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Sample records for prognostically significant classification

  1. Classification of microvascular patterns via cluster analysis reveals their prognostic significance in glioblastoma.

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    Chen, Long; Lin, Zhi-Xiong; Lin, Guo-Shi; Zhou, Chang-Fu; Chen, Yu-Peng; Wang, Xing-Fu; Zheng, Zong-Qing

    2015-01-01

    There are limited researches focusing on microvascular patterns (MVPs) in human glioblastoma and their prognostic impact. We evaluated MVPs of 78 glioblastomas by CD34/periodic acid-Schiff dual staining and by cluster analysis of the percentage of microvascular area for distinct microvascular formations. The distribution of 5 types of basic microvascular formations, that is, microvascular sprouting (MS), vascular cluster (VC), vascular garland (VG), glomeruloid vascular proliferation (GVP), and vasculogenic mimicry (VM), was variable. Accordingly, cluster analysis classified MVPs into 2 types: type I MVP displayed prominent MSs and VCs, whereas type II MVP had numerous VGs, GVPs, and VMs. By analyzing the proportion of microvascular area for each type of formation, we determined that glioblastomas with few MSs and VCs had many GVPs and VMs, and vice versa. VG seemed to be a transitional type of formation. In case of type I MVP, expression of Ki-67 and p53 but not MGMT was significantly higher as compared with those of type II MVP (P < .05). Survival analysis showed that the type of MVPs presented as an independent prognostic factor of progression-free survival (PFS) and overall survival (OS) (both P < .001). Type II MVP had a more negative influence on PFS and OS than did type I MVP. We conclude that the heterogeneous MVPs in glioblastoma can be categorized properly by certain histopathologic and statistical analyses and may influence clinical outcome. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Significance analysis of prognostic signatures.

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    Andrew H Beck

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

  3. A novel classification of frontal bone fractures: The prognostic significance of vertical fracture trajectory and skull base extension.

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    Garg, Ravi K; Afifi, Ahmed M; Gassner, Jennifer; Hartman, Michael J; Leverson, Glen; King, Timothy W; Bentz, Michael L; Gentry, Lindell R

    2015-05-01

    The broad spectrum of frontal bone fractures, including those with orbital and skull base extension, is poorly understood. We propose a novel classification scheme for frontal bone fractures. Maxillofacial CT scans of trauma patients were reviewed over a five year period, and frontal bone fractures were classified: Type 1: Frontal sinus fracture without vertical extension. Type 2: Vertical fracture through the orbit without frontal sinus involvement. Type 3: Vertical fracture through the frontal sinus without orbit involvement. Type 4: Vertical fracture through the frontal sinus and ipsilateral orbit. Type 5: Vertical fracture through the frontal sinus and contralateral or bilateral orbits. We also identified the depth of skull base extension, and performed a chart review to identify associated complications. 149 frontal bone fractures, including 51 non-vertical frontal sinus (Type 1, 34.2%) and 98 vertical (Types 2-5, 65.8%) fractures were identified. Vertical fractures penetrated the middle or posterior cranial fossa significantly more often than non-vertical fractures (62.2 v. 15.7%, p = 0.0001) and had a significantly higher mortality rate (18.4 v. 0%, p fractures with frontal sinus and orbital extension, and fractures that penetrated the middle or posterior cranial fossa had the strongest association with intracranial injuries, optic neuropathy, disability, and death (p bone fractures carry a worse prognosis than frontal bone fractures without a vertical pattern. In addition, vertical fractures with extension into the frontal sinus and orbit, or with extension into the middle or posterior cranial fossa have the highest complication rate and mortality. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  4. The Usefulness of the TOAST Classification and Prognostic Significance of Pyramidal Symptoms During the Acute Phase of Cerebellar Ischemic Stroke.

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    Dziadkowiak, Edyta; Chojdak-Łukasiewicz, Justyna; Guziński, Maciej; Noga, Leszek; Paradowski, Bogusław

    2016-04-01

    Cerebellar stroke is a rare condition with very nonspecific clinical features. The symptoms in the acute phase could imitate acute peripheral vestibular disorders or a brainstem lesion. The aim of this study was to assess the usefulness of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification in cerebellar stroke and the impact of clinical features on the prognosis. We retrospectively analyzed 107 patients with diagnosed ischemic cerebellar infarction. We studied the clinical features and compared them based on the location of the ischemic lesion and its distribution in the posterior interior cerebellar artery (PICA), superior cerebellar artery (SCA), and anterior inferior cerebellar artery (AICA) territories. According to the TOAST classification, stroke was more prevalent in atrial fibrillation (26/107) and when the lesion was in the PICA territory (39/107). Pyramidal signs occurred in 29/107 of patients and were more prevalent when the lesion was distributed in more than two vascular regions (p = 0.00640). Mortality was higher among patients with ischemic lesion caused by cardiac sources (p = 0.00094) and with pyramidal signs (p = 0.00640). The TOAST classification is less useful in assessing supratentorial ischemic infarcts. Cardioembolic etiology, location of the ischemic lesion, and pyramidal signs support a negative prognosis.

  5. Myelodysplastic syndrome: classification and prognostic systems

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    Rosangela Invernizzi

    2011-12-01

    Full Text Available Myelodysplastic syndromes (MDS are acquired clonal disorders of hematopoiesis, that are characterized most frequently by normocellular or hypercellular bone marrow specimens, and maturation that is morphologically and functionally dysplastic. MDS constitute a complex hematological problem: differences in disease presentation, progression and outcome have made it necessary to use classification systems to improve diagnosis, prognostication and treatment selection. On the basis of new scientific and clinical information, classification and prognostic systems have recently been updated and minimal diagnostic criteria forMDS have been proposed by expert panels. In addition, in the last few years our ability to define the prognosis of the individual patient with MDS has improved. In this paper World Health Organization (WHO classification refinements and recent prognostic scoring systems for the definition of individual risk are highlighted and current criteria are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies.

  6. Improvement of criteria for refractory cytopenia with multilineage dysplasia according to the WHO classification based on prognostic significance of morphological features in patients with refractory anemia according to the FAB classification.

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    Matsuda, A; Germing, U; Jinnai, I; Iwanaga, M; Misumi, M; Kuendgen, A; Strupp, C; Miyazaki, Y; Tsushima, H; Sakai, M; Bessho, M; Gattermann, N; Aul, C; Tomonaga, M

    2007-04-01

    In the criteria of refractory cytopenia with multilineage dysplasia (RCMD) according to the WHO (World Health Organization) classification, the frequency threshold concerning dysplasia of each lineage was defined as 10%. To predict overall survival (OS) and leukemia-free survival (LFS) for patients with refractory anemia (RA) according to the French-American-British (FAB) classification, we investigated prognostic factors based on the morphological features of 100 Japanese and 87 German FAB-RA patients, excluding 5q-syndrome. In the univariate analysis of all patients, pseudo-Pelger-Huet anomalies >or=10% (Pelger+), micromegakaryocytes >or=10% (mMgk+), dysgranulopoiesis (dys G) >or=10% and dysmegakaryopoiesis (dys Mgk) >or=40% were unfavorable prognostic factors for OS and LFS (OS; Por=10% was not correlated with OS and LFS. In the multivariate analysis, mMgk+ and dys Mgk>or=40% were adverse prognostic factors for OS for all patients, and dys G >or=10% and dys Mgk>or=40% were adverse prognostic factors for LFS for all patients. On the basis of the present analysis, we propose the following modified morphological criteria for RCMD. Modified RCMD should be defined as FAB-RA, excluding 5q-syndrome with dys G >or=10%, dys Mgk>or=40% or mMgk+.

  7. Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification.

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    Wetzler, Meir; Mrózek, Krzysztof; Kohlschmidt, Jessica; Dombret, Hervé; Döhner, Hartmut; Pilorge, Sylvain; Krug, Utz; Carroll, Andrew J; Larson, Richard A; Marcucci, Guido; Hiddemann, Wolfgang; Büchner, Thomas; Bloomfield, Clara D

    2014-02-01

    We investigated whether octogenarian patients with acute myeloid leukemia enrolled onto Cooperative Group clinical trials and treated with intensive induction therapy could be cured, and whether karyotype and selected molecular markers had any prognostic significance in these patients. Among 138 patients with cytogenetic information, normal karyotype was the most common (47.1%) followed by complex karyotype (14.5%) and sole +8 (9.4%). Among these patients, the relapse-free survival rate at 1 year was 37% and 13% at 3 years, and the respective overall survival rates were 24% and 8%. Whereas the 90 patients who survived beyond 30 days had the same relapse-free survival rates, their 1-year and 3-year overall survival rates were 36% and 11%, respectively. Of the 66 patients surviving beyond 30 days who could be classified into European LeukemiaNet genetic groups, those in the intermediate-I group had better overall survival than patients in the adverse group (P=0.01). Among patients with cytogenetically normal acute myeloid leukemia who were tested for the European LeukemiaNet-associated molecular alterations, FLT3-internal tandem duplication and NPM1 mutations, it was found that FLT3-internal tandem duplication (detected in 29% of patients) did not associate with overall survival (P=0.31), whereas NPM1 mutations (30%) were associated with a significantly longer overall survival (P=0.002). We conclude that intensive induction is effective and indicated in selected octogenarians with acute myeloid leukemia, that their overall survival varies among the European LeukemiaNet genetic groups and that NPM1 mutations may be of prognostic significance among octogenarian patients with cytogenetically normal acute myeloid leukemia.

  8. [Diagnostics, classification and prognostic criteria of acute myeloid leukemia].

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    Heilmeier, Bernhard; Buske, Christian; Spiekermann, Karsten; Bohlander, Stefan; Feuring-Buske, Michaela; Hiddemann, Wolfgang; Braess, Jan

    2007-04-15

    The continuously growing knowledge about criteria important for biology, pathogenesis, prognosis and treatment of acute myeloid leukemia (AML) necessitates a broad spectrum of diagnostic methods for first diagnosis and for the further course of the disease. Relevant diagnostic techniques (cytomorphology with cytochemistry, immunophenotyping, cytogenetics and molecular genetics, DNA array) are described - with a focus on their mode of operation as well on their clinical significance. Due to the high clinical relevance and growing complexity, AML diagnostics should be performed in specialized laboratories. Compared to the FAB classification which is based primarily on morphological criteria, the classification recommended in 2001 by the WHO additionally takes cytogenetics, molecular genetics and further clinical factors into consideration. Both classifications are described. A wide range of prognostic criteria of AML is discussed on the basis of currently available clinical data. The most important criteria are the karyotype of the leukemic clone and the patient's age.

  9. Prognostic significance of cell surface phenotype in acute lymphoblastic leukemia

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    Shiek Aejaz Aziz

    2015-01-01

    Full Text Available Context: To find out the phenotypic character of lymphoblasts of acute lymphoblastic leukemia (ALL patients in our study cohort and their possible effect on the prognosis. Aims: To investigate the phenotype in ALL in our demographic population and to prognosticate various upfront current protocols employed in our hospital. Settings and Design: The study spanned over a period of 4 years with retrospective and prospective data of January 2008 through December 2011. Materials and Methods: 159 patients of all age groups were enrolled for the study, of which flow cytometry was done in 144 patients. Statistical Analysis Used: Analysis was done using the variables on SPSS (statistical package for social sciences software on computer. Survival curves were estimated by method of Kaplan-Meir. Results: Majority of the patients were of B-cell (68.1% and 30.6% patients were of T-cell lineage. Of these, 80.6% patients were having cALLa positivity. Complete remission (CR was achieved in 59.1%, 16.4% relapsed, and 20.1% patients died. Conclusions: Phenotyping has become an important and integral part of diagnosis, classification, management and prognosticating in ALL. B-cell has been found to have a better survival over T-cell lymphoblastic leukemia. cALLa antigen positivity has good impact in achieving CR in only B-cell lineage, myeloid coexpression has no significant effect on the outcome. BFM (Berlin-Frankfurt-Münster based protocols though showed a higher CR and survival vis-a-vis UKALL-XII. However, patients enrolled in former group being of low risk category and lesser in numbers cannot be compared statistically with a fair degree of confidence.

  10. Prognostic Significance of Melanoma Differentiation and Trans-Differentiation

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    Maddodi, Nityanand; Setaluri, Vijayasaradhi, E-mail: setaluri@wisc.edu [Department of Dermatology, University of Wisconsin School of Medicine and Public Health, 1300 University Avenue, B25, Madison WI 53706 (United States)

    2010-05-26

    Cutaneous malignant melanomas share a number of molecular attributes such as limitless replicative potential that define capabilities acquired by most malignancies. Accordingly, much effort has been focused on evaluating and validating protein markers related to these capabilities to function as melanoma prognostic markers. However, a few studies have also highlighted the prognostic value of markers that define melanocytic differentiation and the plasticity of melanoma cells to trans-differentiate along several other cellular pathways. Here, we provide a comprehensive review and evaluation of the prognostic significance of melanocyte-lineage markers such as MITF and melanogenic proteins, as well as markers of vascular epithelial and neuronal differentiation.

  11. Prognostic significance of delayed structural recovery after macular hole surgery

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    Christensen, Ulrik C; Krøyer, Kristian; Sander, Birgit

    2009-01-01

    PURPOSE: To assess the prognostic significance for visual function of persistent subfoveal fluid and persistent photoreceptor layer discontinuity in eyes in which hole closure had been obtained 3 months after macular hole surgery. DESIGN: Ancillary study of subjects enrolled in a randomized clini...

  12. Prognostic Significance of Prostate-Specific Antigen (PSA) Rate of ...

    African Journals Online (AJOL)

    Aim: To investigate the prognostic significance of Prostate-Specific Antigen (PSA) rate of change in patients with advanced prostate cancer . Patients and Methods: A total of forty-nine male patients aged between 42 and 84 years with advanced prostate cancer receiving therapy of maximum androgen bloackade were ...

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

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

    2013-01-01

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

  14. Clinical and prognostic significance of plasma fibrinogen in lung cancer

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    Chen YS

    2014-01-01

    Full Text Available Objectives: Hyperfibrinogenemia is a common problem associated with various carcinomas. The recent studies have shown that high plasma fibrinogen concentration is associated with invasion, growth and metastases of cancer. Furthermore, the recent studies focus on the prognostic significance of fibrinogen in the patients with advanced NSCLC (stage IIIB -IV. However, the prognostic significance of the plasma fibrinogen levels in early stage NSCLC patients (stage I -IIIA still remains unclear. In addition, it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to the prognosis. The aims of this study were to 1 further explore the relationship between the plasma fibrinogen concentration and the stage and metastases of lung cancer 2 evaluate the prognostic significance of the basal plasma fibrinogen level in patients with lung cancer 3 explore the prognostic value of the change in fibrinogen levels between pre and post-chemotherapy. Methods: In this retrospective study, the data from 370 patients with lung cancer were enrolled into this study. The plasma fibrinogen levels were compared with the clinical and prognostic significance of lung cancer. The association between the plasma fibrinogen level and clinical-prognostic characteristics were analyzed using SPSS 17.0 software. Results: 1 The median pre-treatment plasma fibrinogen levels were 4.20g/L. Pre-treatment plasma fibrinogen levels correlated significantly with gender (p = 0.013. A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.83±1.50 g/L versus 4.15±1.30 g/L; P<0.001, there was a significant association between plasma fibrinogen level and metastases of lung cancer, pointing a higher plasma fibrinogen level in lymph nodes or distant organ metastases (p < 0.001. 2 Patients with low plasma fibrinogen concentration demonstrates higher overall survival compared with those with high plasma fibrinogen

  15. Prognostic significance of XRCC4 expression in hepatocellular carcinoma

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

    2017-01-01

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

  16. Prognostic significance of snail expression in hilar cholangiocarcinoma

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    Kong, Dalu [Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Hexi District, Tianjin (China); Liang, Jun [Department of Oncology, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong Province (China); Li, Rong [Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Hexi District, Tianjin (China); Liu, Shihai [Department of Laboratory Center, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong Province (China); Wang, Jigang [Department of Oncology, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong Province (China); Zhang, Kejun; Chen, Dong [Department of General Surgery, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong Province (China)

    2012-05-11

    Many patients with hilar cholangiocarcinoma (HC) have a poor prognosis. Snail, a transcription factor and E-cadherin repressor, is a novel prognostic factor in many cancers. The aim of this study was to evaluate the relationship between snail and E-cadherin protein expression and the prognostic significance of snail expression in HC. We examined the protein expression of snail and E-cadherin in HC tissues from 47 patients (22 males and 25 females, mean age 61.2 years) using immunohistochemistry and RT-PCR. Proliferation rate was also evaluated in the same cases by the MIB1 index. High, low and negative snail protein expression was recorded in 18 (38%), 17 (36%), and 12 (26%) cases, respectively, and 40.4% (19/47) cases showed reduced E-cadherin protein expression in HC samples. No significant correlation was found between snail and E-cadherin protein expression levels (P = 0.056). No significant correlation was found between snail protein expression levels and gender, age, tumor grade, vascular or perineural invasion, nodal metastasis and invasion, or proliferative index. Cancer samples with positive snail protein expression were associated with poor survival compared with the negative expresser groups. Kaplan-Meier curves comparing different snail protein expression levels to survival showed highly significant separation (P < 0.0001, log-rank test). With multivariate analysis, only snail protein expression among all parameters was found to influence survival (P = 0.0003). We suggest that snail expression levels can predict poor survival regardless of pathological features and tumor proliferation. Immunohistochemical detection of snail protein expression levels in routine sections may provide the first biological prognostic marker.

  17. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials.

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    Grimwade, David; Hills, Robert K; Moorman, Anthony V; Walker, Helen; Chatters, Stephen; Goldstone, Anthony H; Wheatley, Keith; Harrison, Christine J; Burnett, Alan K

    2010-07-22

    Diagnostic karyotype provides the framework for risk-stratification schemes in acute myeloid leukemia (AML); however, the prognostic significance of many rare recurring cytogenetic abnormalities remains uncertain. We studied the outcomes of 5876 patients (16-59 years of age) who were classified into 54 cytogenetic subgroups and treated in the Medical Research Council trials. In multivariable analysis, t(15;17)(q22;q21), t(8;21)(q22;q22), and inv(16)(p13q22)/t(16;16)(p13;q22) were the only abnormalities found to predict a relatively favorable prognosis (P < .001). In patients with t(15;17) treated with extended all-trans retinoic acid and anthracycline-based chemotherapy, additional cytogenetic changes did not have an impact on prognosis. Similarly, additional abnormalities did not have a significant adverse effect in t(8;21) AML; whereas in patients with inv(16), the presence of additional changes, particularly +22, predicted a better outcome (P = .004). In multivariable analyses, various abnormalities predicted a significantly poorer outcome, namely abn(3q) (excluding t(3;5)(q25;q34)), inv(3)(q21q26)/t(3;3)(q21;q26), add(5q)/del(5q), -5, -7, add(7q)/del(7q), t(6;11)(q27;q23), t(10;11)(p11 approximately 13;q23), other t(11q23) (excluding t(9;11)(p21 approximately 22;q23) and t(11;19)(q23;p13)), t(9;22)(q34;q11), -17, and abn(17p). Patients lacking the aforementioned favorable or adverse aberrations but with 4 or more unrelated abnormalities also exhibited a significantly poorer prognosis (designated "complex" karyotype group). These data allow more reliable prediction of outcome for patients with rarer abnormalities and may facilitate the development of consensus in reporting of karyotypic information in clinical trials involving younger adults with AML. This study is registered at http://www.isrctn.org as ISRCTN55678797 and ISRCTN17161961.

  18. PROGNOSTIC SIGNIFICANCE OF CD56 EXPRESSION IN ACUTE LEUKEMIAS

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    B. M. Ahmed

    2014-12-01

    Conclusions. CD56 antigenic expression in AML cases represents an adverse prognostic factor. It should be regularly investigated in cases of AML for better prognostic stratification and assessment. KEY WORDS: CD56; leukemia, myeloid; prognosis

  19. [Prognostic significance of monosomal karyotype in acute myeloid leukemia].

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    Luan, Yanyan; Xu, Junqing; Huang, Baohua; Liu, Xiaoqian; Liu, Yinghui; Chen, Liming; Chu, Xiaoxia

    2015-04-01

    To explore the prognostic significance of monosomal karyotype (MK) in patients with acute myeloid leukemia (AML). The clinical data of 498 AML patients were analyzed retrospectively. Of the 498 patients, 233 (46.8%) cases had an abnormal karyotype. 42 patients fulfilled the criteria for MK, which were 8.4% of all cases and 18.0% of patients with abnormal karyotype, respectively. The most frequent autosomal monosomies were -7 and -17. 70 patients had complex karyotype (CK), in all patients and patients with abnormal karyotype accounted for 14.1% and 30.0%, respectively. Patients with MK were associated with significantly older (median age 62.5 vs 52 years, P=0.003), and lower HGB concentrations (62.5 vs 77 g/L, P=0.009) and lower WBC counts (7.0×10⁹/L vs 11.7×10⁹/L, P=0.008). Among MK cases, the most frequent chromosome abnormalities were complex karyotype, -7, -5, 7q-, and 5q-. In univariate analysis, MK patients had worse survival than those without MK (7.3 months vs 26.3 months, P<0.001). CK patients also had poorer outcomes than patients without CK (14.8 months vs 26.3 months, P<0.001). In CK patients, survival was worse in MK patients than patients without MK (7.4 months vs 19.2 months, P=0.007). By COX analysis, MK was an independent prognostic factor, beyond NCCN criteria and CK [HR=2.610 (1.632-4.175), P<0.001]. MK was an independent adverse prognostic factor in AML patients.

  20. Prognostic significance of miR-205 in endometrial cancer.

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    Mihriban Karaayvaz

    Full Text Available microRNAs have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. Thus, microRNAs have potential as both cancer biomarkers and/or potential novel therapeutic targets. Although accumulating evidence suggests the role of aberrant microRNA expression in endometrial carcinogenesis, there are still limited data available about the prognostic significance of microRNAs in endometrial cancer. The goal of this study is to investigate the prognostic value of selected key microRNAs in endometrial cancer by the analysis of archival formalin-fixed paraffin-embedded tissues.Total RNAs were extracted from 48 paired normal and endometrial tumor specimens using Trizol based approach. The expression of miR-26a, let-7g, miR-21, miR-181b, miR-200c, miR-192, miR-215, miR-200c, and miR-205 were quantified by real time qRT-PCR expression analysis. Targets of the differentially expressed miRNAs were quantified using immunohistochemistry. Statistical analysis was performed by GraphPad Prism 5.0.The expression levels of miR-200c (P<0.0001 and miR-205 (P<0.0001 were significantly increased in endometrial tumors compared to normal tissues. Kaplan-Meier survival analysis revealed that high levels of miR-205 expression were associated with poor patient overall survival (hazard ratio, 0.377; Logrank test, P = 0.028. Furthermore, decreased expression of a miR-205 target PTEN was detected in endometrial cancer tissues compared to normal tissues.miR-205 holds a unique potential as a prognostic biomarker in endometrial cancer.

  1. Prognostic significance of SOX-1 expression in human hepatocelluar cancer.

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    Lou, Jinshu; Zhang, Kai; Chen, Jing; Gao, Yanping; Wang, Rui; Chen, Long-Bang

    2015-01-01

    Sex-determining region Y (SRY)-box 1 (SOX1) as a member of the SOX gene superfamily is reported to function as a tumor suppressor in hepatocelluar cancer (HCC). However, the clinicopathological and prognostic significance of SOX-1 expression in HCC is unclear. First, semi-quantitative RT-PCR and Western blot assays were performed to detect the expression of SOX-1 mRNA and protein in 15 paired of HCC tissues and corresponding nontumor tissues. Next, immunohistochemistry was performed to detect SOX-1 protein expression in another 96 cases of HCC tissues, and analyze its correlation with clincopathological factors of patients. Finally, the survival was evaluated by the Kaplan-Meier method and proportional hazards model. Results showed that the expression levels of SOX-1 mRNA and protein in HCC tissues were significantly lower than that in the corresponding nontumor tissues. Statistical analyses indicated that low SOX-1 expression was significantly correlated with higher incidence of venous or lymphatic invasion and advanced TNM stage. Also, patients with high SOX-1 expression showed better overall survival than those with low SOX-1 expression, and multivariate analysis with the Cox proportional hazards indicated that status of SOX-1 expression might be an independent prognostic factor in HCC patients. Collectively, our results indicated that downregulation of SOX-1 was correlated with poor prognosis and tumor development in HCC.

  2. Prognostic significance of postoperative empyema in lung cancer.

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    Di Giorgio, A; Sammartino, P; Arnone, P; Canavese, A; Almansour, M

    1996-01-01

    Four hundred sixty patients who had undergone resection for lung cancer, with a minimum follow-up of 10 years, were analyzed retrospectively. Thirty-eight cases developed postoperative empyema. A comparative evaluation of the long-term survival rate was made of two groups: one in which the patients had developed empyema and one in which the patients had developed no empyema complications. The survival rate was estimated by the Kaplan Meyer Product Limit Method. The prognostic significance of empyema and other factors was analyzed by the Log Rank Test, the chi 2 test in homogeneous series of patients and the Cox Hazard Model. Overall, the ten-year survival rate was 23.7% in the empyema group and 15.9% in the control group. After stratification by post-surgical stage, lymphocytic infiltration of primary-tumor (LI), and histological type, no significant differences in survival between the two groups were demonstrated by the Log Rank Test. The same results were found when the survival distribution of the empyema cases was compared with two control groups of patients without empyema, individually paired to the empyema group for Immune Response (LI), post-surgical stage, and histological type. In the end, after multivariate analysis empyema was not shown to be a factor of prognostic significance.

  3. Myelodysplastic syndromes: a scoring system with prognostic significance.

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    Mufti, G J; Stevens, J R; Oscier, D G; Hamblin, T J; Machin, D

    1985-03-01

    141 patients with MDS were classified according to the FAB criteria and followed up for a period of 4-192 months. It was recognized that patients with RAEBT had a uniformly poor prognosis. However, there was a wide variation in survival among the other subgroups. A score of 1 was assigned to each of the following presenting haematological features: bone marrow blasts greater than or equal to 5%, platelets less than or equal to 100 X 10(9)/l, neutrophils less than or equal to 2.5 X 10(9)/l and Hb less than or equal to 10.0 g/dl. Therefore the score for each patient ranged between 0 and 4. There were no statistically significant differences between those patients who scored 0 or 1, or between those who scored 2 and 3. Therefore patients were put into three groups: Group A (score 0 or 1), Group B (score 2 or 3), Group C (score 4). The differences in survival between each of the three groups are highly significant (P less than 0.00001). This system further separates patients with RA, RAS, RAEB into good and bad prognostic groups. This study also confirms that deaths due to cytopenias are more common than those due to transformation to AML. The use of this scoring system in conjunction with the FAB criteria for MDS should serve as a prognostic tool on which to base treatment.

  4. Prognostic significance of platelet count in SLE patients.

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    Abdel Galil, Sahar Mahfouz; Edrees, Azzahra Mohammed; Ajeeb, Afnan Khaled; Aldoobi, Ghadeer Sameer; El-Boshy, Mohamed; Hussain, Waleed

    2017-03-01

    Hematological abnormalities, especially thrombocytopenia (TCP), are highly prevalent among patients with systemic lupus erythematosus (SLE) and at the same time it has been reported as a significant prognostic factor of SLE course. We further investigate the correlation between platelet count and the clinical manifestations and disease activity of SLE, in a cohort of Saudi Arabian female patients. A retrospective analysis was done for the medical records of 100 SLE female patients, selected from all patients diagnosed and treated for SLE at the Rheumatology outpatient clinics in Hera'a General Hospital, Holly Makkah, Saudi Arabia. The data collected from every patient's file included laboratory investigations (complete blood count, platelet parameters, ESR, anti-double-stranded DNA antibody, ANA), clinical manifestations, as well as SLE disease activity index (SLEDAI-2k) scores throughout a period of six sequential follow-up visits. Patients were divided into three groups according to the SLEDAI-2k: mild, moderate, and high-activity group. We found that, out of 100 patients, TCP was the most prevalent hematological abnormality evident in 15%, more than leucopenia (14%) and anemia (2%). TCP was acute in onset and associated with arthritis, neurologic manifestations, and nephritis. Platelet count showed a significant negative correlation with disease activity, in all of the three groups of patients. We concluded that platelet count has a negative correlation with disease activity in SLE patients, whatever the associated manifestations, and it should be considered as a prognostic factor, identifying patients with aggressive disease course.

  5. Prognostic significance of glutathione peroxidase 2 in gastric carcinoma.

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    Liu, Dongzhe; Sun, Liang; Tong, Jinxue; Chen, Xiuhui; Li, Hui; Zhang, Qifan

    2017-06-01

    Increasing evidence suggests that the glutathione peroxidase 2 may actually play important roles in tumorigenesis and progression in various human cancers such as colorectal carcinomas and lung adenocarcinomas. However, the role of glutathione peroxidase 2 in gastric carcinoma remains to be determined. In this study, the expression and prognostic significance of glutathione peroxidase 2 in gastric carcinoma were investigated and the well-known prognostic factor Ki-67 labeling index was also assessed as positive control. Glutathione peroxidase 2 expression levels in the tumor tissue specimens, the matched adjacent normal tissue specimens, and the lymph node metastases of 176 patients with gastric carcinoma were evaluated by quantitative polymerase chain reaction, western blotting, and immunohistochemical staining. The associations between glutathione peroxidase 2 expression levels, as determined by immunohistochemical staining, and multiple clinicopathological characteristics were determined by Pearson's chi-square test and Spearman's correlation analysis. The relationships between glutathione peroxidase 2 expression and other clinicopathological variables and patient prognoses were analyzed further by the Kaplan-Meier method, the log-rank test, and Cox multivariate regression. The quantitative polymerase chain reaction, western blotting, and immunohistochemical staining results showed that glutathione peroxidase 2 expression levels were upregulated in both the primary tumor foci and the lymph node metastases of patients with gastric carcinoma (all p values carcinoma (all p values carcinoma that may be used to devise personalized therapeutic regimens and precision treatments for this disease.

  6. Prognostic significance of age in traumatic brain injury

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    S S Dhandapani

    2012-01-01

    Full Text Available Background: Age is a strong prognostic factor following traumatic brain injury (TBI, with discrepancies defining the critical prognostic age threshold. This study was undertaken to determine the impact of various age thresholds on outcome after TBI. Materials and Methods : The ages of patients admitted with TBI were prospectively studied in relation to mode of injury, Glasgow coma score (GCS, CT category and surgical intervention. Mortality was assessed at 1 month, and neurological outcome was assessed at 6 months. Appropriate statistical analyzes (details in article were performed. Results: Of the total 244 patients enrolled, 144 patients had severe, 38 patients had moderate and 62 patients had mild TBI, respectively. Age had significant association with grade of injury, CT category and surgical intervention (P 59 years respectively (P 40 years in all subgroups, based on GCS and surgical intervention (P < 0.05. Conclusions : In patients with TBI, age demonstrates independent association with unfavorable outcome at 6 months, in stepwise manner centered on a threshold of 40 years.

  7. Comparison of prognostic value of Roper Hall and Dua classification systems in acute ocular burns.

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    Gupta, Noopur; Kalaivani, Mani; Tandon, Radhika

    2011-02-01

    To compare the predictive outcome of ocular burns using two different prognostic classification systems, that is, Dua and Roper Hall classification. In a prospective, randomised, controlled clinical trial, the extent of acute ocular burns in 100 patients was graded by Roper Hall and Dua classifications. Patients were randomised in two groups of 50 each to receive conventional medical therapy alone or additional amniotic membrane transplantation (AMT). Moderate burns were graded similarly (grade II and III) under both systems, while severe burns were classified differently and compared further. Baseline parameters (size of epithelial defect, corneal haze, limbal ischaemia, conjunctival involvement and visual acuity) and outcome variables (healing of epithelial defect, corneal clarity, corneal vascularisation, visual outcome and symblepharon) after 1 year were noted and compared. There was no difference in terms of time taken and rate of healing of epithelial defect, but there was a significant difference in extent of corneal vascularisation between grades IV, V and VI (pburns than either grade V (p=0.045) or grade VI (p=0.024) burns, and final visual acuity was significantly better in these patients (p=0.043). On comparison of patients with grade IV burns (with and without AMT), the outcome in terms of extent of corneal vascularisation was significantly better (p=0.0124) in patients who received AMT. Dua classification by providing further subclassification of grade IV ocular burns by Roper Hall into three separate grades has a superior prognostic predictive value in severe ocular burns.

  8. Prognostic Significance of Nuclear Phospho-ATM Expression in Melanoma.

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    Madhuri Bhandaru

    Full Text Available UV radiation induced genomic instability is one of the leading causes for melanoma. Phosphorylation of Ataxia Telangiectasia Mutated (ATM is one of the initial events that follow DNA damage. Phospho-ATM (p-ATM plays a key role in the activation of DNA repair and several oncogenic pathways as well as in the maintenance of genomic integrity. The present study was therefore performed to understand the significance of p-ATM in melanoma progression and to correlate it with patient prognosis. Tissue microarray and immunohistochemical analysis were employed to study the expression of p-ATM in melanoma patients. A total of 366 melanoma patients (230 primary melanoma and 136 metastatic melanoma were used for the study. Chi-square test, Kaplan-Meier, univariate and multivariate Cox regression analysis were used to elucidate the prognostic significance of p-ATM expression. Results revealed that both loss of, and gain in, p-ATM expression were associated with progression of melanoma from normal nevi to metastatic melanoma. Patients whose samples showed negative or strong p-ATM staining had significantly worse 5-year survival compared to patients who had weak to moderate expression. Loss of p-ATM expression was associated with relatively better 5-year survival, but the corresponding 10-year survival curve almost overlapped with that of strong p-ATM expression. p-ATM expression was found to be an independent prognostic factor for 5-year but not for 10-year patient survival. In conclusion our findings show that loss of p-ATM expression and gain-in p-ATM expression are indicators of worse melanoma patient survival.

  9. The prognostic significance of DAPK1 in bladder cancer.

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    Jian-Yun Xie

    Full Text Available Bladder cancer is one of the leading causes of cancer-related death in men, however, there was only limited effective treatment for invasive bladder cancer. DAPK1 has been shown to play important role in apoptosis and autophagy to suppress cancer progression. Previous results have shown that DAPK1 promoter was hypermethylated in the majority of bladder cancer specimens, however, the prognostic significance of DAPK1 in bladder cancer has yet to be demonstrated. In the present study, we found that DAPK1 expression was negatively associated with tumor stage and a low level expression of DAPK1 in bladder cancer specimens were associated with shorter survival in bladder cancer patients in 3 independent bladder cancer datasets (n = 462. Further investigation showed that FGFR3 knockdown resulted in downregulation of DAPK1 in bladder cancer cell line, suggesting that FGFR3 may be an upstream factor of DAPK1. Further analysis of the 3 independent bladder cancer datasets have identified ACOX1, UPK2, TRAK1, PLEKHG6 and MT1X genes had their expression significantly correlated with that of DAPK1. Knockdown of DAPK1 in bladder cancer T24 cells resulted in downregulation of ACOX1, UPK2 and TRAK1. Interestingly, TRAK1, by itself, was a favorable prognostic marker in the 3 independent bladder cancer datasets. Importantly, by using connectivity mapping with DAPK1-associated gene signature, we found that vemurafenib and trametinib could possibly reverse DAPK1-associated gene signature, suggesting that inhibition of Raf/MEK pathway may be a potential therapeutic approach for bladder cancer. Indeed, treatment of vemurafenib in T24 bladder cancer cells resulted in upregulation of DAPK1 confirming our connectivity mapping, while knockdown of DAPK1 resulted in reduced sensitivity towards inhibition of Braf signaling by vemurafenib. Together, our results suggest that DAPK1 is an important prognostic marker and therapeutic target for bladder cancer and have identified

  10. The prognostic significance of DAPK1 in bladder cancer.

    Science.gov (United States)

    Xie, Jian-Yun; Chen, Peng-Chen; Zhang, Jia-Li; Gao, Ze-Shou; Neves, Henrique; Zhang, Shu-Dong; Wen, Qing; Chen, Wei-Dong; Kwok, Hang Fai; Lin, Yao

    2017-01-01

    Bladder cancer is one of the leading causes of cancer-related death in men, however, there was only limited effective treatment for invasive bladder cancer. DAPK1 has been shown to play important role in apoptosis and autophagy to suppress cancer progression. Previous results have shown that DAPK1 promoter was hypermethylated in the majority of bladder cancer specimens, however, the prognostic significance of DAPK1 in bladder cancer has yet to be demonstrated. In the present study, we found that DAPK1 expression was negatively associated with tumor stage and a low level expression of DAPK1 in bladder cancer specimens were associated with shorter survival in bladder cancer patients in 3 independent bladder cancer datasets (n = 462). Further investigation showed that FGFR3 knockdown resulted in downregulation of DAPK1 in bladder cancer cell line, suggesting that FGFR3 may be an upstream factor of DAPK1. Further analysis of the 3 independent bladder cancer datasets have identified ACOX1, UPK2, TRAK1, PLEKHG6 and MT1X genes had their expression significantly correlated with that of DAPK1. Knockdown of DAPK1 in bladder cancer T24 cells resulted in downregulation of ACOX1, UPK2 and TRAK1. Interestingly, TRAK1, by itself, was a favorable prognostic marker in the 3 independent bladder cancer datasets. Importantly, by using connectivity mapping with DAPK1-associated gene signature, we found that vemurafenib and trametinib could possibly reverse DAPK1-associated gene signature, suggesting that inhibition of Raf/MEK pathway may be a potential therapeutic approach for bladder cancer. Indeed, treatment of vemurafenib in T24 bladder cancer cells resulted in upregulation of DAPK1 confirming our connectivity mapping, while knockdown of DAPK1 resulted in reduced sensitivity towards inhibition of Braf signaling by vemurafenib. Together, our results suggest that DAPK1 is an important prognostic marker and therapeutic target for bladder cancer and have identified possible therapeutic

  11. Child psychiatric symptoms and psychosocial impairment: relationship and prognostic significance.

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    Pickles, A; Rowe, R; Simonoff, E; Foley, D; Rutter, M; Silberg, J

    2001-09-01

    Relatively little is known about the relationships between psychiatric symptoms, diagnosis and psychosocial impairment. To examine these contemporaneous relationships and prognostic significance in a large general population sample. Symptoms of major depression, conduct and oppositional defiant disorders were assessed by interview in two waves of the Virginia Twin Study of Adolescent behavioural Development (2800 children aged 8-16 years). Many children below the DSM-III-R diagnostic threshold, especially for depression, had symptom-related impairment, whereas many children reaching the symptom threshold for conduct and oppositional defiant disorders were little impaired. Impairment score was linearly related to symptom count, with no evidence of any additional impairment at the diagnostic threshold. For depression, only symptoms predicted later symptoms and diagnosis. For conduct and oppositional defiant disorders, impairment was additionally predictive of later symptoms and diagnosis. Impairment, in addition to symptoms, is important for both nosology and prognosis.

  12. Prognostic significance of thrombocytosis in idiopathic sideroblastic anemia.

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    Streeter, R R; Presant, C A; Reinhard, E

    1977-09-01

    In order to determine the prognostic significance of thrombocytosis in idiopathic sideroblastic anemia, the clinical courses of 17 patients were reviewed. Six patients (36%) had thrombocytosis, and none developed acute leukemia. Nine patients (53%) had normal platelet counts, and one developed acute leukemia. Two patients (12%) were thrombocytopenic, and one died of acute leukemia. There was little correlation between survival and platelet count. Sixty-three additional case reports of idiopathic sideroblastic anemia were collected from the literature. Analysis of those patients and the patients in the present study documented transformation to acute leukemia in 5 of 9 (56%) thrombocytopenic patients, 4 of 54 (7.4%) patients with normal platelet counts, and 0 of 17 patients with thrombocytosis (p less than 0.05). Therefore patients with idiopathic sideroblastic anemia and thrombocytosis appear to have a decreased likelihood of leukemic transformation.

  13. Prognostic significance of the prognostic nutritional index in esophageal cancer patients undergoing neoadjuvant chemotherapy.

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    Nakatani, M; Migita, K; Matsumoto, S; Wakatsuki, K; Ito, M; Nakade, H; Kunishige, T; Kitano, M; Kanehiro, H

    2017-08-01

    Nutritional status is one of the most important issues faced by cancer patients. Several studies have shown that a low preoperative nutritional status is associated with a worse prognosis in patients with various types of cancer, including esophageal cancer (EC). Recently, neoadjuvant chemotherapy (NAC) and/or radiotherapy have been accepted as the standard treatment for resectable advanced EC. However, NAC has the potential to deteriorate the nutritional status of a patient. This study aimed to evaluate the prognostic significance of the nutritional status for EC patients who underwent NAC. We retrospectively reviewed 66 squamous cell EC patients who underwent NAC consisting of docetaxel, cisplatin, and 5-fluorouracil followed by subtotal esophagectomy at Nara Medical University Hospital between January 2009 and August 2015. To assess the patients' nutritional status, the prognostic nutritional index (PNI) before commencing NAC and prior to the operation was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count in the peripheral blood (per mm3). The cutoff value of the PNI was set at 45. A multivariable analysis was performed to identify prognostic factors for overall survival (OS) and relapse-free survival (RFS). The mean pre-NAC and preoperative PNI were 50.2 ± 5.7 and 48.1 ± 4.7, respectively (P = 0.005). The PNI decreased following NAC in 44 (66.7%) patients. Before initiating NAC, 9 (13.6%) patients had a low PNI, and 12 (18.2%) patients had a low PNI prior to the operation. The pre-NAC PNI and preoperative PNI were significantly associated with the OS (P = 0.013 and P = 0.004, respectively) and RFS (P = 0.036 and P = 0.005, respectively) rates. The multivariable analysis identified the preoperative PNI as an independent prognostic factor for poor OS and RFS, although the pre-NAC PNI was not an independent predictor. Our results suggest that the preoperative PNI is a useful marker for predicting the long-term outcomes of EC patients

  14. Prognostic considerations of the new World Health Organization classification of lung adenocarcinoma.

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    Borczuk, Alain C

    2016-12-01

    The 2015 World Health Organization (WHO) lung adenocarcinoma classification divides tumours into categories of indolent pre-invasive, minimally invasive and predominantly lepidic and, by examining predominant patterns of invasion, allows for further stratification into intermediate and high-grade tumours. The impact of the 2015 classification on prognosis was reviewed by a PubMed search for search terms "adenocarcinoma", "lung pathology" and "prognosis" and relevant publications reviewed. These were sorted for data on stage and survival as impacted by histological classification, and survival studies were separated into all stage versus stage 1 studies. Predictive aspects of histological classification were also examined, but molecular correlates were not. The separation of adenocarcinoma in situ and minimally invasive adenocarcinoma from invasive subtypes as distinct prognostic entities and the prognostic significance, for disease specific and overall survival for low- and high-grade categories, are discussed. The impact on stage at presentation including risk of node metastasis by histology is examined, as well as histology in relation to recurrence after surgery. Early data with regard to the value of predominant histology in the prediction of chemotherapy response will also be explored. Copyright ©ERS 2016.

  15. Prognostic significance of extensive necrosis in renal cell carcinoma.

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    Collins, Jennifer; Epstein, Jonathan I

    2017-08-01

    Few studies using the current classification of renal cell carcinoma (RCC) have looked at a large number of cases with near total necrosis. We identified 21 cases of resections of RCC with >90% necrosis from the archives of Johns Hopkins Hospital between 2000 and 2015. Patients' mean age was 59 years (43-77) with 16 men (76%); 12 cases (57%) were papillary RCC, 4 clear cell papillary RCC (19%), 4 clear cell RCC (19%), and 1 unclassified with sarcomatoid differentiation (5%). International Society of Urological Pathology (ISUP) nucleolar grade was grade 1 (9 cases) or grade 2 (9 cases). Two cases were ISUP nucleolar grade 3, and 1 case was grade 4. Pathological stage was low (pT1-2) in 20 (95%) with the unclassified RCC with sarcomatoid differentiation RCC stage pT3a. Mean tumor size was 6.3 cm (1.2-17). In 52% (11) of cases, it was difficult to identify viable tumor, requiring multiple sections; 4 cases of papillary RCC were diagnosed in part due to necrotic tumor "ghost" architecture. Follow-up was available in 17 cases (81%) with a mean follow-up of 59 months. Thirteen patients (62%) are alive without disease. The patient with unclassified carcinoma with sarcomatoid differentiation died of cancer, and 2 died due to causes unrelated to cancer. One patient (5%) with low-grade clear cell RCC developed metastases but had a contralateral RCC. In the setting of a low-grade RCC, extensive necrosis does not have an adverse prognosis. In summary, our data, together with a prior study from our institution, comprise one of the largest cohorts of extensively (>90%) necrotic RCCs and suggests that in the setting of a low-grade RCC, it portends a good prognosis (only 2/36 cases showing progression (6%) on follow-up). However, we did identify a single case of high-grade RCC with an adverse prognosis and therefore, careful attention to tumor grade and classification is critical. The presence of tumor necrosis as a prognosticator in RCCs is complex, and despite its well

  16. Prognostic classification of fifth metatarsal stress fracture using plantar gap.

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    Lee, Kyung Tai; Park, Young Uk; Jegal, Hyuk; Park, Jong Won; Choi, Jung Pil; Kim, Jin Su

    2013-05-01

    There have been diverse results even in same Torg type of fifth metatarsal stress fractures. Eighty-six cases with a fifth metatarsal stress fracture that were treated with modified tension band wiring from January 2003 to May 2009 were evaluated retrospectively. Each case was classified according to Torg's classification and a new classification. Using the new proposed classification, cases were subdivided into complete fracture and incomplete fracture. The cases of incomplete fracture were subdivided based on presence or absence of plantar gap more than 1 mm. After surgery, bone union was determined by CT. Statistical analysis of the Torg classification and time for bone union as well as the proposed new classification and time for bone union was performed. There was a significant difference in the time for bone union among the three Torg types (P = 0.004). The mean time for bone union in group A (complete fracture, n = 32) was 67.5 ± 28.8, and it was 103.2 ± 47.7 for group B (incomplete fracture, n = 54). There was a significant difference in time for bone union between them (P fracture, plantar gap less than 1 mm, n = 16) was 73.9 ± 26.7, and it was 115.5 ± 45.4 for group B2 (incomplete fracture, plantar gap 1 mm or more, n = 38). There was a significant difference in time for bone union between them (P stress fractures. Level III, retrospective comparative series.

  17. Optic disc hemorrhage in glaucoma: pathophysiology and prognostic significance.

    Science.gov (United States)

    Kim, Ko Eun; Park, Ki Ho

    2017-03-01

    This article reviews the recent findings with regard to the pathophysiology and clinical significance of optic disc hemorrhage in glaucoma. Even though the pathophysiology of disc hemorrhage has been investigated in depth, its underlying mechanism remains unclear. The key disc hemorrhage mechanisms currently under discussion are mechanical vascular disruption and associated vascular susceptibilities. Recent technical advances in spectral-domain optical coherence tomography have yielded more compelling evidence of mechanical vascular disruption behind the pathogenesis of disc hemorrhage in glaucoma. Studies show that disc hemorrhage is associated with structural and functional glaucoma progression. Furthermore, recent findings suggest that disc hemorrhage can have different significances according to its location, recurrence, and associated underlying mechanism. The underlying mechanism of disc hemorrhage is complex like that of glaucoma. The ongoing controversy respecting the role of disc hemorrhage as a risk factor for glaucoma progression notwithstanding, special attention entailing closer follow-up and/or treatment escalation is recommended for patients with disc hemorrhage. Further studies investigating the unrevealed pathogenesis of disc hemorrhage and its prognostic value in glaucoma are warranted.

  18. Prognostic significance of urinary NGAL in chronic kidney disease

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    Patel ML

    2015-10-01

    Full Text Available Munna Lal Patel,1 Rekha Sachan,2 Ravi Misra,3 Ritul Kamal,4 Radhey Shyam,5 Pushpalata Sachan6 1Department of Medicine, King George Medical University, Lucknow, India; 2Department of Obstetrics and Gynaecology, King George Medical University, Lucknow, India; 3Department of Internal Medicine, King George Medical University, Lucknow, India; 4Epidemiology Division, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR, Lucknow, India; 5Department of Geriatric Intensive Care Unit, King George Medical University, Lucknow, India; 6Department of Physiology, Career Institute of Medical Sciences, Lucknow, India Background: Chronic kidney disease (CKD is a worldwide public health problem. Recently urinary NGAL (uNGAL has been proven to be a useful (potentially ideal biomarker for early detection of CKD. The aim of the present study was to examine the correlation of uNGAL with severity of renal impairment in CKD and to evaluate its prognostic value in these subjects. Methods: This was a prospective study carried out over a period of 24 months in subjects with CKD due to primary chronic glomerulonephritis. New cases of CKD stage II, III, IV aged between 18 and 65 years were enrolled as per KDIGO (Kidney Disease: Improving Global Outcomes guidelines 2012. A total of 90 subjects completed the study up to the end-point. The primary follow-up end-point was 18 months, or decreased glomerular filtration rate of less than 15 mL/min. Secondary follow-up end-point was the number of subjects who expired during this period. Results: Multiple regression model of estimated glomerular filtration rate showed significant associations with log uNGAL (β=0.38, P<0.001, Ca×PO4 (β=0.60, P<0.001, hemoglobin (β=0.37, P<0.001, urine protein (β=0.34, P<0.001, serum albumin (β=0.48, P<0.001, and systolic blood pressure (β=0.76, P<0.001. Receiver operator curve for uNGAL considering the progression of CKD showed area under the curve

  19. TP53 Mutation and Its Prognostic Significance in Waldenstrom's Macroglobulinemia.

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    Poulain, Stéphanie; Roumier, Christophe; Bertrand, Elisabeth; Renneville, Aline; Caillault-Venet, Aurélie; Doye, Emmanuelle; Geffroy, Sandrine; Sebda, Sheherazade; Nibourel, Olivier; Nudel, Morgane; Herbaux, Charles; Renaud, Loic; Tomowiak, Cécile; Guidez, Stéphanie; Tricot, Sabine; Roche-Lestienne, Catherine; Quesnel, Bruno; Preudhomme, Claude; Leleu, Xavier

    2017-10-15

    Purpose:TP53 is a tumor-suppressor gene that functions as a regulator influencing cellular responses to DNA damage, and TP53 alterations are associated with pejorative outcome in most B-lymphoid disorders. Little is known regarding TP53 alteration in Waldenstrom's macroglobulinemia (WM).Experimental Design: Here, we have explored the incidence of TP53 alteration using Sanger sequencing and ultradeep-targeted sequencing in 125 WM and 10 immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance (MGUS), along with the clinical features and the associated genomic landscape using single-nucleotide polymorphism array and mutational landscape in an integrative study.Results: Overall, we have identified alteration of TP53 locus including mutation, deletion, and copy-neutral LOH in 11.2% of WM. TP53 mutation was acquired in 7.3% of patients with WM at diagnosis, being absent in IgM MGUS, and was highly correlated to deletion 17p. No correlation with CXCR4 mutations was observed. Patients with TP53 alteration had a greater number of genomic abnormalities. Importantly, WM with TP53 alteration had a significantly shorter overall survival, particularly in symptomatic WM, and independently of the international prognostic scoring system for Waldenstrom macroglobulinemia (IPSSWM) score. Specific treatment for WM with TP53 may have to be studied. Nutlin-3a-targeted p53 signaling induced cytotoxicity preclinically, along with new compounds such as ibrutinib, PrimaMet, or CP31398 that bypass p53 pathway in WM, paving the path for future treatment-tailored options.Conclusions: Our results highlight the clinical significance of detection of TP53 alteration in WM to determine the prognosis of WM and guide the treatment choice. Clin Cancer Res; 23(20); 6325-35. ©2017 AACR. ©2017 American Association for Cancer Research.

  20. Prognostic significance of delayed intraventricular haemorrhage in the INTERACT studies.

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    Moullaali, Tom J; Sato, Shoichiro; Wang, Xia; Rabinstein, Alejandro A; Arima, Hisatomi; Carcel, Cheryl; Chen, Guofang; Robinson, Thompson; Heeley, Emma; Chan, Edward; Delcourt, Candice; Stapf, Christian; Cordonnier, Charlotte; Lindley, Richard I; Chalmers, John; Anderson, Craig S

    2017-01-01

    Intraventricular extension of intracerebral haemorrhage (ICH) predicts poor outcome, but the significance of delayed intraventricular haemorrhage (dIVH) is less well defined. We determined the prognostic significance of dIVH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2). Pooled analyses of the INTERACT CT substudies-international, multicentre, prospective, open, blinded end point, randomised controlled trials of patients with acute spontaneous ICH and elevated systolic blood pressure (SBP)-randomly assigned to intensive (<140 mm Hg) or guideline-based (<180 mm Hg) SBP management. Participants had blinded central analyses of baseline and 24 h CTs, with dIVH defined as new intraventricular haemorrhage (IVH) on the latter scan. Outcomes of death and major disability were defined by modified Rankin Scale scores at 90 days. There were 349 (27%) of 1310 patients with baseline IVH, and 107 (11%) of 961 initially IVH-free patients who developed dIVH. Significant associations of dIVH were prior warfarin anticoagulation, high (≥15) baseline National Institutes of Health Stroke Scale score, larger (≥15 mL) ICH volume, greater ICH growth and higher achieved SBP over 24 h. Compared with those who were IVH-free, dIVH had greater odds of 90-day death or major disability versus initial IVH (adjusted ORs 2.84 (95% CI 1.52 to 5.28) and 1.87 (1.36 to 2.56), respectively (p trend <0.0001)). Although linked to factors determining greater ICH growth including poor SBP control, dIVH is independently associated with poor outcome in acute small to moderate-size ICH. NCT00226096 and NCT00716079. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  1. Diagnostic and prognostic significance of cytogenetics in adult primary myelodysplastic syndromes.

    Science.gov (United States)

    Jotterand, M; Parlier, V

    1996-10-01

    Cytogenetic analysis has proven to be a mandatory part of the diagnosis of myelodysplastic syndromes (MDS) as well as a major indicator for predicting clinical course and outcome. This review concentrates on the cytogenetic classifications, the incidence and types of chromosome defects and the prognostic significance of the karyotype in adult primary MDS. Two cytogenetic classifications are currently used: one is based on the karyotype complexity (normal, single, double or complex defects), the other on clonal status (all metaphases normal, abnormal or admixture of normal and abnormal clones). Chromosome abnormalities are of both numerical and structural types. Aside from the 5q-syndrome, no specific clinico-cytogenetic entity has been reported. However, several distinct clinical and cellular features have been identified that correlate with the presence of specific chromosome defects such as inv(3)/t(3;3), +6, t(5;12), del(17p) and del(20q). The presence of complex defects is associated with reduced survival and a high risk of leukemic transformation. Among single defects, specific abnormalities may define distinct prognostic groups. Patients with del(5q) as a sole chromosome defect and a refractory anemia without excess of blasts have a favourable prognosis. For patients with trisomy 8 or monosomy 7 there may be distinct types of clinical evolution. Most patients with the 3q21q26 syndrome have a short survival. The presence of two chromosome defects may constitute an independent cytogenetic entity probably associated with relative poor prognosis. Karyotypic evolution generally represents a poor risk factor. The combination of cytogenetics with clinical and hematological features has proven to provide for a better prediction of patients' survival, leukemic transformation and response to treatment. Several scoring systems have been developed. They have to be improved by the study of new patients according to strict clinical and cytogenetic criteria and by the

  2. BLZF1 expression is of prognostic significance in hepatocellular carcinoma

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    Huang, Run-Yue, E-mail: ry_huang@hotmail.com [Department of Rheumatology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510006 (China); Su, Shu-Guang [Department of Pathology, The Affiliated Hexian Memorial Hospital of Southern Medical University, Guangzhou (China); Wu, Dan-Chun [Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou (China); Fu, Jia [Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060 (China); Zeng, Xing, E-mail: zengxing-china@163.com [Department of Rheumatology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510006 (China)

    2015-11-20

    BLZF1, a member of b-ZIP family, has been implicated in epigenetic regulation and Wnt/β-catenin signaling. Its expression and clinical significance in human cancers remain largely unknown. In this study, we showed that BLZF1 expression was reduced in hepatocellular carcinoma (HCC) tissues, compared to the paracarcinoma tissues, at both mRNA and protein levels. Results of immunohistochemistry revealed that BLZF1 was presented in both nuclear and cytoplasm. Decreased expression of nuclear and cytosolic BLZF1 in HCC was depicted in 68.2% and 79.2% of the 634 cases. Nuclear BLZF1 expression was significantly associated with tumor multiplicity (P = 0.048) and tumor capsule (P = 0.028), while cytosolic BLZF1 expression was correlated with serum AFP level (P = 0.017), tumor differentiation (P = 0.001) and tumor capsule (P = 0.003). Kaplan–Meier analysis indicated both nuclear and cytosolic BLZF1 expression was associated with poor overall survival. Low nuclear BLZF1 also indicated unfavorable disease-free survival and high tendency of tumor recurrence. Furthermore, multiple Cox regression analysis revealed nuclear BLZF1 as an independent factor for overall survival (Hazard Ratio (HR) = 0.827, 95% confident interval (95%CI): 0.697–0.980, P = 0.029). The prognostic value of BLZF1 was further confirmed by stratified analyses. Collectively, our data suggest BLZF1 is a novel unfavorable biomarker for prognosis of patients with HCC. - Highlights: • BLZF1 expression was much lower in HCC tissues. • Low BLZF1 expression was associated with poor outcomes in a cohort of 634 HCC patients. • Multiple Cox regression analysis indicated nuclear BLZF1 as an independent predictor for overall survival.

  3. Prognostic Significance Of QT Interval Prolongation In Adult ...

    African Journals Online (AJOL)

    Prognostic survival studies for heart-rate corrected QT interval in patients with chronic heart failure are few; although these patients are known to have a high risk of sudden cardiac death. This study was aimed at determining the mortality risk associated with prolonged QTc in Nigerians with heart failure. Ninety-six ...

  4. Prognostic significance of elevated cardiac troponin I after heart surgery.

    Science.gov (United States)

    Adabag, A Selcuk; Rector, Thomas; Mithani, Salima; Harmala, John; Ward, Herbert B; Kelly, Rosemary F; Nguyen, John T; McFalls, Edward O; Bloomfield, Hanna E

    2007-05-01

    Cardiac troponin I (cTnI) measured after heart surgery has been associated with operative mortality. We sought to determine whether measuring cTnI after heart surgery provides additional prognostic information beyond that provided by validated preoperative risk scores, the Veterans Affairs (VA) risk score and the European System for Cardiac Operative Risk Evaluation (EuroSCORE). We retrospectively collected cTnI levels measured 24 hours after surgery in 1,186 patients who underwent coronary artery bypass graft surgery (n = 696) or valve surgery (n = 490). The outcomes were operative death and perioperative myocardial infarction. The ability of the cTnI and the risk scores to discriminate patients who did or did not have the study outcomes was assessed by the area under the receiver operating curve (c-index). Mean age was 66 +/- 10 years. Median cTnI was 38 ng/mL after valve surgery versus 18 ng/mL after coronary artery bypass graft surgery (p < 0.0001). There were 51 operative deaths (4.3%) and 142 perioperative myocardial infarctions (12%). For every 50 ng/mL increase in cTnI, the odds of operative death increased by 40% (odds ratio, 1.4; 95% confidence interval: 1.2 to 1.6) after coronary artery bypass graft surgery and by 30% (odds ratio, 1.3; 95% confidence interval: 1.1 to 1.5) after valve surgery. Cardiac troponin I was a significant independent correlate of perioperative myocardial infarction and death (p < 0.0001) with a c-index of 0.70 for death. Addition of cTnI improved the c-indexes of the risk scores for predicting death (from 0.75 to 0.79 for the VA risk score; p = 0.1; and from 0.69 to 0.77 for the EuroSCORE; p = 0.005). Postoperative cTnI measured 24 hours after heart surgery is independently associated with operative death and perioperative myocardial infarction and improves the ability to predict operative mortality in comparison with preoperative risk scores alone.

  5. Prognostic significance of NGAL in early stage chronic kidney disease.

    Science.gov (United States)

    Basturk, Taner; Sari, Ozlem; Koc, Yener; Eren, Nezaket; Isleem, Mahmoud; Kara, Ekrem; Sevinc, Mustafa; Sakaci, Tamer; Ahbap, Elbis; Hasbal, Nuri B; Bayrakdar Caglayan, Feyza; Unsal, Abdulkadir

    2017-06-01

    Neutrophilgelatinase-associated lipocalin (NGAL) has been proven to be a useful biomarker for early detection of acute kidney injury, but it is not known whether adding NGAL measurements to conventional risk factors will improve the risk assessment in the setting of chronic kidney disease (CKD). The aim of the present study was to examine the correlation of NGAL with early stage renal impairment in CKD and to evaluate its prognostic value in these subjects. This is a prospective observational cohort study of 54 patients with early stage (stage 1-2) CKD. Patients aged between 18 and 65 years with stable disease were enrolled in this study. Patients with a history of primary glomerulonephritis, diabetes mellitus, acute kidney injury, systemic diseases and stage 3-4-5 CKD were excluded from the study group. Estimated glomerular filtration (eGFR) rate was calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. The patients were followed for two years to determine the ability of baseline NGAL for prediction of renal outcome. In our study disease progression was defined as changes in eGFR (ΔeGFR) and proteinuria (Δproteinuria). Patients divided into two groups according to NGAL cut-off value as group 1 (N.=23, NGAL ≤98.71 ng/mL) and group 2 (N.=31, NGAL >98.71 ng/mL). Out of 54 patients (mean age: 45.6±7.6 years, 64.8% female, baseline eGFR: 84.6±16.8 mL/min/1.73 m2, baseline NGAL level: 157.47±121.52 ng/mL); 18 patients were stage 1 and 36 patients were stage 2 CKD. In the ROC analysis, we found that the optimal cut-off value of NGAL for predicting stage 2 CKD was 98.71ng/mL (P=0.005) with the 72.2% sensitivity and 72.2% specificity. In correlation analysis, we evaluated significantly positive correlations between NGAL and CKD stage (r=0.389, P=0.004), baseline/last serum creatinine level (r=0.530, Pearly stage CKD. But further studies stated in different patient groups may also explain the usability of NGAL in clinical practice.

  6. [Study on karyotypic abnormalities and its prognostic significance in Chinese patients with primary myelodysplastic syndromes].

    Science.gov (United States)

    Li, Lin; Liu, Xu-Ping; Nie, Ling; Yu, Ming-Hua; Zhang, Yue; Qin, Tie-Jun; Xiao, Zhi-Jian

    2009-04-01

    To investigate the features and prognostic significance of chromosomal karyotype in patients with primary myelodysplastic syndromes (MDS). Results of chromosomal karyotypes of 351 adult patients with primary MDS were retrospectively analyzed. Two hundred and thirty-seven cases (67.5%) had karyotypic abnormalities. Of them, 99 (41.7%) were numerical, 70 (29.5%) were structural, and 68 (28.8%) were complex abnormalities. In addition, among the 237 patients with chromosomal abnormalities, 130 (54.8%) showed single abnormality, 54 (22.8%) double abnormalities and 53 (22.4%) complex abnormalities (> or = 3 two independent aberrations). Four cases (1.7%) were multiploid. Aneuploidy or of chromosomal arm anomaly were detected all of the 46 chromosomes and the aberrations in frequent order were +8, -20/20q-, -7/7q-, -5/5q-, -18, -11/11q-/, +21, -Y, -21, -10, -16, -22, +9, del(12)(p12). The incidence of -5/5q- (5.1%) was lower in our series than in western countries (8.7% -23.4%) and 5q- syndrome was even less (0.3%). The incidences of +8 (19.1%) and -20/20q- (9.4%) were higher in our series than in western countries (1.2% -7.0%, 2.0% -3.5%, respectively). Chromosome translocations were detected in 31 cases (13.1%), including 12 novel translocations that have not been reported in MDS patients before. In addition, i(17)(q10) was detected in 9 cases (3.8%) of which 6 were simplex abnormality. Chromosomal duplication presented in 7 cases (3.0%) with 4 cases involved chromosome 1. According to IPSS chromosomal prognostic classification, the incidence of poor-risk karyotypes was increased in the advanced WHO subtypes (P chromosomal prognostic classification, the median OS of patients with good, intermediate and poor-risk cytogenetic subgroup were 51 (95% CI 25-77), 35 (95% CI 5-65) and 13 (95% CI 9-17) months, respectively (P = 0.004) and for NN-AN-AA karyotype classification, the median OS of NN, AN and AA were 51 (95% CI 24-78), 36 (95% CI 0.3-71) and 23 (95% CI 10-35) months

  7. A novel volume-age-KPS (VAK) glioblastoma classification identifies a prognostic cognate microRNA-gene signature.

    Science.gov (United States)

    Zinn, Pascal O; Sathyan, Pratheesh; Mahajan, Bhanu; Bruyere, John; Hegi, Monika; Majumder, Sadhan; Colen, Rivka R

    2012-01-01

    Several studies have established Glioblastoma Multiforme (GBM) prognostic and predictive models based on age and Karnofsky Performance Status (KPS), while very few studies evaluated the prognostic and predictive significance of preoperative MR-imaging. However, to date, there is no simple preoperative GBM classification that also correlates with a highly prognostic genomic signature. Thus, we present for the first time a biologically relevant, and clinically applicable tumor Volume, patient Age, and KPS (VAK) GBM classification that can easily and non-invasively be determined upon patient admission. We quantitatively analyzed the volumes of 78 GBM patient MRIs present in The Cancer Imaging Archive (TCIA) corresponding to patients in The Cancer Genome Atlas (TCGA) with VAK annotation. The variables were then combined using a simple 3-point scoring system to form the VAK classification. A validation set (N = 64) from both the TCGA and Rembrandt databases was used to confirm the classification. Transcription factor and genomic correlations were performed using the gene pattern suite and Ingenuity Pathway Analysis. VAK-A and VAK-B classes showed significant median survival differences in discovery (P = 0.007) and validation sets (P = 0.008). VAK-A is significantly associated with P53 activation, while VAK-B shows significant P53 inhibition. Furthermore, a molecular gene signature comprised of a total of 25 genes and microRNAs was significantly associated with the classes and predicted survival in an independent validation set (P = 0.001). A favorable MGMT promoter methylation status resulted in a 10.5 months additional survival benefit for VAK-A compared to VAK-B patients. The non-invasively determined VAK classification with its implication of VAK-specific molecular regulatory networks, can serve as a very robust initial prognostic tool, clinical trial selection criteria, and important step toward the refinement of genomics-based personalized therapy

  8. A novel volume-age-KPS (VAK glioblastoma classification identifies a prognostic cognate microRNA-gene signature.

    Directory of Open Access Journals (Sweden)

    Pascal O Zinn

    Full Text Available BACKGROUND: Several studies have established Glioblastoma Multiforme (GBM prognostic and predictive models based on age and Karnofsky Performance Status (KPS, while very few studies evaluated the prognostic and predictive significance of preoperative MR-imaging. However, to date, there is no simple preoperative GBM classification that also correlates with a highly prognostic genomic signature. Thus, we present for the first time a biologically relevant, and clinically applicable tumor Volume, patient Age, and KPS (VAK GBM classification that can easily and non-invasively be determined upon patient admission. METHODS: We quantitatively analyzed the volumes of 78 GBM patient MRIs present in The Cancer Imaging Archive (TCIA corresponding to patients in The Cancer Genome Atlas (TCGA with VAK annotation. The variables were then combined using a simple 3-point scoring system to form the VAK classification. A validation set (N = 64 from both the TCGA and Rembrandt databases was used to confirm the classification. Transcription factor and genomic correlations were performed using the gene pattern suite and Ingenuity Pathway Analysis. RESULTS: VAK-A and VAK-B classes showed significant median survival differences in discovery (P = 0.007 and validation sets (P = 0.008. VAK-A is significantly associated with P53 activation, while VAK-B shows significant P53 inhibition. Furthermore, a molecular gene signature comprised of a total of 25 genes and microRNAs was significantly associated with the classes and predicted survival in an independent validation set (P = 0.001. A favorable MGMT promoter methylation status resulted in a 10.5 months additional survival benefit for VAK-A compared to VAK-B patients. CONCLUSIONS: The non-invasively determined VAK classification with its implication of VAK-specific molecular regulatory networks, can serve as a very robust initial prognostic tool, clinical trial selection criteria, and important step toward

  9. The prognostic significance of cancer-associated fibroblasts in esophageal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Sang Yun Ha

    Full Text Available BACKGROUND: Cancer-associated fibroblasts (CAF are activated fibroblasts in the cancer stroma and play an important role in cancer progression. Some reports have indicated the correlation between the expression of CAF markers and adverse prognosis in several cancers. However, no reports have studied CAF phenotype and its clinical relevance in esophageal squamous cell carcinoma (ESCC. METHODS: We investigated CAF phenotype of ESCC based on histology and immunohistochemical expressions of five CAF markers such as fibroblast activation protein (FAP, smooth muscle actin (SMA, fibroblast-specific protein-1 (FSP1, platelet-derived growth factor receptor (PDGFRα, and PDGFRβ in 116 ESCC tissue samples. Besides, we also examined the correlation of the CAF phenotype with clinical relevance as well as other cancer-microenvironment related factors. RESULTS: Histologically immature CAF phenotype was correlated with poor prognosis (p<0.001 and associated with increased microvessel density, increased tumor associated macrophages, and epithelial to mesenchymal transition. CAF markers were characteristically expressed in stromal fibroblast close to tumor cells and the expression pattern of 5 CAF markers was highly heterogeneous in every individual cases. Of five CAF markers, SMA, FSP1, and PDGFRα were unfavorable prognostic indicators of ESCC. The number of positive CAF markers was greater in ESCC with immature CAFs than in those with mature ones. CONCLUSIONS: Our results demonstrate that histologic classification of CAF phenotype is a reliable and significant prognostic predictor in ESCC. CAF markers have the potential to be diagnostic and therapeutic targets in ESCC.

  10. Prognostic significance of cardiovascular biomarkers and renal dysfunction in outpatients with systolic heart failure

    DEFF Research Database (Denmark)

    Bosselmann, Helle; Egstrup, Michael; Rossing, Kasper

    2013-01-01

    To assess whether the prognostic significance of cardiovascular (CV) biomarkers, is affected by renal dysfunction (RD) in systolic heart failure (HF).......To assess whether the prognostic significance of cardiovascular (CV) biomarkers, is affected by renal dysfunction (RD) in systolic heart failure (HF)....

  11. [Expression and prognostic significance of microenvironment related prognostic factors in patients with classical Hodgkin's lymphoma].

    Science.gov (United States)

    Wang, T T; Li, S X; Xia, B; Zhao, H F; Xu, W; Yang, H L; Wang, X F; Yu, Y; Sun, B C; Zhang, Y Z

    2017-05-16

    Objective: To observe the expression of three microenvironment related prognostic factors, i. e. programmed death 1 (PD-1), forkhead box protein 3(FOXP3) and colony-stimulating factor 1 receptor(CSF-1R) protein in classical Hodgkin's lymphoma (CHL) patients, and to explore the correlation between the protein expression and the prognosis of the patients. Methods: A total of 45 cases of CHL patients, who had been admitted to the Tianjin Medical University Cancer Institute and Hospital and Chinese PLA General Hospital from February 2005 to August 2010 were analyzed, including clinical features, prognostic factors, and treatment regimens. CHL patients' specimens were collected and the expression of PD-1, FOXP3, and CSF-1R proteins analyzed by immunohistochemical staining. Epstein-Barr virus encoded mRNA (EBER) was detected by in situ hybridization analysis. The relationship between the protein expression of PD-1, FOXP3 and CSF-1R and the patients' outcome was analyzed with clinical and follow-up data. Survival analysis was performed by Kaplan-Meier method, the Cox proportional hazard model was used to perform multivariate analysis. Results: In this cohort of 45 CHL patients, PD-1 positive was found in 7 cases (15.6%), FOXP3 high expression in 23 cases (51.1%), CSF-1R positive in 18 cases (40.0%). In the univariate analysis, the expression of FOXP3 and CSF-1R, International Prognostic Index (IPI) score, Ann Arbor stage and EBER were related with the patients' 5-year overall survival (OS); IPI score, the expression of FOXP3 and EBER were related with the patients' 5-year progress-free survival (PFS). Multivariate analysis indicated that CSF-1R protein expression was the independent prognostic factor affecting the patients' 5-year OS(HR: 8.918, P=0.020), and FOXP3 protein expression was the independent prognostic factor affecting the patients' 5-year PFS (HR: 0.122, PCSF-1R and EBV may be independent prognostic factors of CHL and this study may provide novel strategies

  12. Prognostic significance of transient myocardial ischaemia after first acute myocardial infarction: five year follow up study

    DEFF Research Database (Denmark)

    Mickley, H; Nielsen, J R; Berning, J

    1995-01-01

    OBJECTIVE: To assess the five year prognostic significance of transient myocardial ischaemia on ambulatory monitoring after a first acute myocardial infarction, and to compare the diagnostic and long term prognostic value of ambulatory ST segment monitoring, maximal exercise testing, and echocard...

  13. Prognostic Significance of the Proportion of Tall Cell Components in Papillary Thyroid Carcinoma.

    Science.gov (United States)

    Ito, Yasuhiro; Hirokawa, Mitsuyoshi; Miyauchi, Akira; Higashiyama, Takuya; Kihara, Minoru; Miya, Akihiro

    2017-03-01

    Tall cell variant (TCV) of papillary thyroid carcinoma (PTC) shows a poorer prognosis than conventional PTC. The World Health Organization (WHO) classification defines TCV as the tall cell component (TCC) in ≥50% of PTC lesions. We investigated whether and how the proportion of TCC affects the prognosis of patients with PTC with TCC. Seventy patients with TCC in ≥30% of their PTC lesions and 210 age- and gender-matched controls with no TCC who underwent locally curative surgery at Kuma Hospital (2006-2014) were enrolled. The 70 PTC patients were divided into two categories: TCC ≥50% (TCC-major, n = 19) and TCC 30-49% (TCC-minor, n = 51). We performed univariate and multivariate analyses of the relationships between disease-free survival (DFS) and variables including the TCC proportion in 276 patients who had no distant metastases at surgery (median follow-up 64 months). In the univariate analysis, TCC-major, TCC-minor, old age (≥65 years), clinical node metastasis, significant extrathyroid extension (Ex), and high Ki-67 labeling index (≥5%) significantly affected the DFS. In the multivariate analysis, TCC-major and Ex independently affected the DFS, but TCC-minor did not. In an analysis excluding TCC-major patients, TCC-minor was not an independent prognostic factor for DFS. Studies or larger patient series with longer follow-ups are necessary, but we speculate that in PTC with TCC, TCC-major significantly and independently affects the DFS, whereas TCC-minor does not. Our findings indicate that the WHO definition of TCV is appropriate and that the prognostic impact of TCC-minor is limited.

  14. Pathohistological classification systems in gastric cancer: diagnostic relevance and prognostic value.

    Science.gov (United States)

    Berlth, Felix; Bollschweiler, Elfriede; Drebber, Uta; Hoelscher, Arnulf H; Moenig, Stefan

    2014-05-21

    Several pathohistological classification systems exist for the diagnosis of gastric cancer. Many studies have investigated the correlation between the pathohistological characteristics in gastric cancer and patient characteristics, disease specific criteria and overall outcome. It is still controversial as to which classification system imparts the most reliable information, and therefore, the choice of system may vary in clinical routine. In addition to the most common classification systems, such as the Laurén and the World Health Organization (WHO) classifications, other authors have tried to characterize and classify gastric cancer based on the microscopic morphology and in reference to the clinical outcome of the patients. In more than 50 years of systematic classification of the pathohistological characteristics of gastric cancer, there is no sole classification system that is consistently used worldwide in diagnostics and research. However, several national guidelines for the treatment of gastric cancer refer to the Laurén or the WHO classifications regarding therapeutic decision-making, which underlines the importance of a reliable classification system for gastric cancer. The latest results from gastric cancer studies indicate that it might be useful to integrate DNA- and RNA-based features of gastric cancer into the classification systems to establish prognostic relevance. This article reviews the diagnostic relevance and the prognostic value of different pathohistological classification systems in gastric cancer.

  15. Reproducibility and prognostic significance of morphologic dysplasia in de novo acute myeloid leukemia.

    Science.gov (United States)

    Weinberg, Olga K; Pozdnyakova, Olga; Campigotto, Federico; DeAngelo, Daniel J; Stone, Richard M; Neuberg, Donna; Hasserjian, Robert P

    2015-07-01

    The 2008 WHO classification of acute myeloid leukemia includes a category of acute myeloid leukemia with myelodysplasia-related changes; however, the significance of multilineage dysplasia alone is controversial and its reproducibility has not been evaluated in acute myeloid leukemia. We performed an in-depth analysis of morphologic dysplasia in 159 de novo acute myeloid leukemia cases lacking myelodysplasia-related cytogenetic abnormalities. Using the 2008 WHO criteria, there were 89 acute myeloid leukemia-not otherwise specified (56%) and 43 acute myeloid leukemia with myelodysplasia-related changes (27%), while 27 cases were ambiguous as to myelodysplasia-related changes status due to limited maturing cells (acute myeloid leukemia-not evaluable, 17%). On multivariable analysis, neither acute myeloid leukemia with myelodysplasia-related changes nor acute myeloid leukemia-not evaluable showed significantly different event-free survival compared with acute myeloid leukemia-not otherwise specified in the 137 patients treated with induction chemotherapy. When individual dysplastic features were analyzed, only micromegakaryocytes and hypogranulated myeloid cells emerged as factors significantly associated with shorter event-free survival in a multivariable analysis that included the other significant covariates of age, white blood count, platelet count, abnormal karyotype and stem-cell transplantation. Our findings indicate that the current 2008 WHO definition of multilineage dysplasia in acute myeloid leukemia in its current form is not optimal, and that the use of a more restricted definition of morphologic dysplasia results in more relevant risk stratification that is independent of other conventional prognostic factors.

  16. Aneurysmal subarachnoid hemorrhage prognostic decision-making algorithm using classification and regression tree analysis.

    Science.gov (United States)

    Lo, Benjamin W Y; Fukuda, Hitoshi; Angle, Mark; Teitelbaum, Jeanne; Macdonald, R Loch; Farrokhyar, Forough; Thabane, Lehana; Levine, Mitchell A H

    2016-01-01

    Classification and regression tree analysis involves the creation of a decision tree by recursive partitioning of a dataset into more homogeneous subgroups. Thus far, there is scarce literature on using this technique to create clinical prediction tools for aneurysmal subarachnoid hemorrhage (SAH). The classification and regression tree analysis technique was applied to the multicenter Tirilazad database (3551 patients) in order to create the decision-making algorithm. In order to elucidate prognostic subgroups in aneurysmal SAH, neurologic, systemic, and demographic factors were taken into account. The dependent variable used for analysis was the dichotomized Glasgow Outcome Score at 3 months. Classification and regression tree analysis revealed seven prognostic subgroups. Neurological grade, occurrence of post-admission stroke, occurrence of post-admission fever, and age represented the explanatory nodes of this decision tree. Split sample validation revealed classification accuracy of 79% for the training dataset and 77% for the testing dataset. In addition, the occurrence of fever at 1-week post-aneurysmal SAH is associated with increased odds of post-admission stroke (odds ratio: 1.83, 95% confidence interval: 1.56-2.45, P tree was generated, which serves as a prediction tool to guide bedside prognostication and clinical treatment decision making. This prognostic decision-making algorithm also shed light on the complex interactions between a number of risk factors in determining outcome after aneurysmal SAH.

  17. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.

    Directory of Open Access Journals (Sweden)

    Laetitia Marisa

    adjusting for age, sex, stage, and the emerging prognostic classifier Oncotype DX Colon Cancer Assay recurrence score (hazard ratio 1.5, 95% CI 1.1-2.1, p = 0.0097. However, a limitation of this study is that information on tumor grade and number of nodes examined was not available.We describe the first, to our knowledge, robust transcriptome-based classification of CC that improves the current disease stratification based on clinicopathological variables and common DNA markers. The biological relevance of these subtypes is illustrated by significant differences in prognosis. This analysis provides possibilities for improving prognostic models and therapeutic strategies. In conclusion, we report a new classification of CC into six molecular subtypes that arise through distinct biological pathways.

  18. The occurrence and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarction. TRACE Study group. TRAndolapril Cardiac Evalution

    DEFF Research Database (Denmark)

    Pedersen, O D; Bagger, H; Køber, L

    1999-01-01

    AIMS: To investigate the occurrence and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarction. METHODS AND RESULTS: The occurrence and prognostic significance of atrial fibrillation/-flutter were studied in 6676 consecutive patients with acute myocardial in...

  19. Prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma.

    Science.gov (United States)

    Che, Keying; Zhao, Yang; Qu, Xiao; Pang, Zhaofei; Ni, Yang; Zhang, Tiehong; Du, Jiajun; Shen, Hongchang

    2017-01-01

    Gastric carcinoma (GC) is a highly aggressive cancer and one of the leading causes of cancer-related deaths worldwide. Histopathological evaluation pertaining to invasiveness is likely to provide additional information in relation to patient outcome. In this study, we aimed to evaluate the prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma. Hematoxylin and eosin-stained slides generated from 296 gastric adenocarcinoma patients with full clinical and pathological and follow-up information were systematically reviewed. The patients were grouped on the basis of tumor budding, single cell invasion, large cell invasion, mitotic count, and fibrosis. The association between histopathological parameters, different classification systems, and overall survival (OS) was statistically analyzed. Among the 296 cases that were analyzed, high-grade tumor budding was observed in 49.0% (145) of them. Single cell invasion and large cell invasion were observed in 62.8% (186) and 16.9% (50) of the cases, respectively. Following univariate analysis, patients with high-grade tumor budding had shorter OS than those with low-grade tumor budding (hazard ratio [HR]: 2.260, Ptumor budding and single cell invasion were observed to be independent risk factors for gastric adenocarcinoma (PTumor budding and single cell invasion in gastric adenocarcinoma are associated with an unfavorable prognosis.

  20. Prognostic significance of metallothionein in B-cell lymphomas

    DEFF Research Database (Denmark)

    Poulsen, Christian Bjørn; Borup, Rehannah; Borregaard, Niels

    2006-01-01

    We have investigated metallothionein (MT) I and II mRNA and protein in B-cell lymphomas with particular reference to diffuse large B-cell lymphoma (DLBCL). The mRNA profiling was performed on Affymetrix arrays and showed up-regulated MT mRNA in 15 of 48 DLBCLs, including 12 of 23 activated B......-cell (ABC) and 3 of 9 type-3 lesions. In contrast, MT mRNA was low to undetectable in 16 germinal center B-cell (GCB)-type DLBCLs. Only 1 of 15 patients with up-regulated MT mRNA achieved a sustained remission, suggesting that up-regulated MT mRNA constitutes a significant risk factor for treatment failure....... This was confirmed in 2 independent series, which showed significantly shorter 5-year survival in DLBCL with high versus low MT-IIa levels. By immunohistology, MT was shown to be present in both macrophages and lymphoma cells. The proportion of MT-positive macrophages did not correlate with the survival. In contrast...

  1. Prognostic Value of Subclassification Using MRI in the T4 Classification Nasopharyngeal Carcinoma Intensity-Modulated Radiotherapy Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Chen Lei [State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou (China); Liu Lizhi [State Key Laboratory of Oncology in South China, Imaging Diagnosis and Interventional Center, Sun Yat-sen University Cancer Center, Guangzhou (China); Chen Mo; Li Wenfei; Yin Wenjing [State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou (China); Lin Aihua [Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou (China); Sun Ying [State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou (China); Li Li [State Key Laboratory of Oncology in South China, Imaging Diagnosis and Interventional Center, Sun Yat-sen University Cancer Center, Guangzhou (China); Ma Jun, E-mail: majun2@mail.sysu.edu.cn [State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou (China)

    2012-09-01

    Purpose: To subclassify patients with the T4 classification nasopharyngeal carcinoma (NPC), according to the seventh edition of the American Joint Committee on Cancer staging system, using magnetic resonance imaging (MRI), and to evaluate the prognostic value of subclassification after intensity-modulated radiotherapy (IMRT). Methods and Materials: A total of 140 patients who underwent MRI and were subsequently histologically diagnosed with nondisseminated classification T4 NPC received IMRT as their primary treatment and were included in this retrospective study. T4 patients were subclassified into two grades: T4a was defined as a primary nasopharyngeal tumor with involvement of the masticator space only; and T4b was defined as involvement of the intracranial region, cranial nerves, and/or orbit. Results: The 5-year overall survival (OS) rate and distant metastasis-free survival (DMFS) rate for T4a patients (82.5% and 87.0%, respectively), were significantly higher than for T4b patients (62.6% and 66.8%; p = 0.033 and p = 0.036, respectively). The T4a/b subclassification was an independent prognostic factor for OS (hazard ratio = 2.331, p = 0.032) and DMFS (hazard ratio = 2.602, p = 0.034), and had no significant effect on local relapse-free survival. Conclusions: Subclassification of T4 patients, as T4a or T4b, using MRI according to the site of invasion, has prognostic value for the outcomes of IMRT treatment in NPC.

  2. Expression of EGFRvIII in Glioblastoma: Prognostic Significance Revisited

    Directory of Open Access Journals (Sweden)

    Nicola Montano

    2011-12-01

    Full Text Available The epidermal growth factor receptor variant III (EGFRvIII is associated with increased proliferation of glioma cells. However, the impact of EGFRvIII on survival of patients with glioblastoma (GBM has not been definitively established. In the present study, we prospectively evaluated 73 patients with primary GBM treated with surgical resection and standard radio/chemotherapy. The EGFRvIII was assessed by reverse transcription–polymerase chain reaction (PCR, O6-methylguanine methyltransferase (MGMT promoter methylation was assessed by methylation-specific PCR, and phosphatase and tension homolog (PTEN expression was assessed by immunohistochemistry. In 14 patients of this series, who presented with tumor recurrence, EGFRvIII was determined by real-time PCR. Sensitivity to temozolomide (TMZ was assessed in vitro on GBM neurosphere cell cultures with different patterns of EGFRvIII expression. Age 60 years or younger, preoperative Karnofsky Performance Status score of 70 or higher, recursive partitioning analysis score III and IV, methylated MGMT, and Ki67 index of 20% or less were significantly associated with longer overall survival (OS; P = .0069, P =.0035, P = .0007, P = .0437, and P = .0286, respectively. EGFRvIII identified patients with significantly longer OS (P = .0023 and the association of EGFRvIII/Ki67 of 20% or less, EGFRvIII/normal PTEN, EGFRvIII/methylated MGMT, and EGFRvIII/normal PTEN/methylated MGMT identified subgroups of GBM patients with better prognosis. In recurred GBMs, EGFRvIII expression was approximately two-fold lower than in primary tumors. In vitro, the EGFRvIII-negative GBM neurosphere cells were more resistant to TMZ than the positive ones. In conclusion, in contrast with previous studies, we found that EGFRvIII is associated with prolonged survival of GBM patients treated with surgery and radio/chemotherapy. Depletion of EGFRvIII in recurrent GBMs as well as differential sensitivity to TMZ in vitro indicates that

  3. Prognostic significance and therapeutic implications of centromere protein F expression in human nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Cao Jing-Yan

    2010-09-01

    Full Text Available Abstract Background Our recent cDNA microarray data showed that centromere protein F (CENP-F is significantly upregulated in primary cultured nasopharyngeal carcinoma (NPC tumor cells compared with normal nasopharyngeal epithelial cells. The goal of this study was to further investigate the levels of CENP-F expression in NPC cell lines and tissues to clarify the clinical significance of CENP-F expression in NPC as well as the potential therapeutic implications of CENP-F expression. Methods Real-time RT-PCR and western blotting were used to examine CENP-F expression levels in normal primary nasopharyngeal epithelial cells (NPEC, immortalized nasopharyngeal epithelial cells and NPC cell lines. Levels of CENP-F mRNA were determined by real-time RT-PCR in 23 freshly frozen nasopharyngeal biopsy tissues, and CENP-F protein levels were detected by immunohistochemistry in paraffin sections of 202 archival NPC tissues. Statistical analyses were applied to test for prognostic associations. The cytotoxicities of CENP-F potential target chemicals, zoledronic acid (ZOL and FTI-277 alone, or in combination with cisplatin, in NPC cells were determined by the MTT assay. Results The levels of CENP-F mRNA and protein were higher in NPC cell lines than in normal and immortalized NPECs. CENP-F mRNA level was upregulated in nasopharyngeal carcinoma biopsy tissues compared with noncancerous tissues. By immunohistochemical analysis, CENP-F was highly expressed in 98 (48.5% of 202 NPC tissues. Statistical analysis showed that high expression of CENP-F was positively correlated with T classification (P P P P = 0.012 inversely correlated with the overall survival time in NPC patients. Multivariate analysis showed that CENP-F expression was an independent prognostic indicator for the survival of the patient. Moreover, we found that ZOL or FTI-277 could significantly enhance the chemotherapeutic sensitivity of NPC cell lines (HONE1 and 6-10B with high CENP-F expression to

  4. Computerized three-class classification of MRI-based prognostic markers for breast cancer

    Science.gov (United States)

    Bhooshan, Neha; Giger, Maryellen; Edwards, Darrin; Yuan, Yading; Jansen, Sanaz; Li, Hui; Lan, Li; Sattar, Husain; Newstead, Gillian

    2011-09-01

    The purpose of this study is to investigate whether computerized analysis using three-class Bayesian artificial neural network (BANN) feature selection and classification can characterize tumor grades (grade 1, grade 2 and grade 3) of breast lesions for prognostic classification on DCE-MRI. A database of 26 IDC grade 1 lesions, 86 IDC grade 2 lesions and 58 IDC grade 3 lesions was collected. The computer automatically segmented the lesions, and kinetic and morphological lesion features were automatically extracted. The discrimination tasks—grade 1 versus grade 3, grade 2 versus grade 3, and grade 1 versus grade 2 lesions—were investigated. Step-wise feature selection was conducted by three-class BANNs. Classification was performed with three-class BANNs using leave-one-lesion-out cross-validation to yield computer-estimated probabilities of being grade 3 lesion, grade 2 lesion and grade 1 lesion. Two-class ROC analysis was used to evaluate the performances. We achieved AUC values of 0.80 ± 0.05, 0.78 ± 0.05 and 0.62 ± 0.05 for grade 1 versus grade 3, grade 1 versus grade 2, and grade 2 versus grade 3, respectively. This study shows the potential for (1) applying three-class BANN feature selection and classification to CADx and (2) expanding the role of DCE-MRI CADx from diagnostic to prognostic classification in distinguishing tumor grades.

  5. Prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Che K

    2017-02-01

    Full Text Available Keying Che,1,* Yang Zhao,2,3,* Xiao Qu,1 Zhaofei Pang,1 Yang Ni,4 Tiehong Zhang,4 Jiajun Du,1,5 Hongchang Shen4 1Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 2Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Collaborative Innovation Center of Cancer Medicine, Fudan University Shanghai Cancer Center, 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 4Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, 5Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Purpose: Gastric carcinoma (GC is a highly aggressive cancer and one of the leading causes of cancer-related deaths worldwide. Histopathological evaluation pertaining to invasiveness is likely to provide additional information in relation to patient outcome. In this study, we aimed to evaluate the prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma.Materials and methods: Hematoxylin and eosin-stained slides generated from 296 gastric adenocarcinoma patients with full clinical and pathological and follow-up information were systematically reviewed. The patients were grouped on the basis of tumor budding, single cell invasion, large cell invasion, mitotic count, and fibrosis. The association between histopathological parameters, different classification systems, and overall survival (OS was statistically analyzed.Results: Among the 296 cases that were analyzed, high-grade tumor budding was observed in 49.0% (145 of them. Single cell invasion and large cell invasion were observed in 62.8% (186 and 16.9% (50 of the cases, respectively. Following univariate analysis, patients with high-grade tumor budding had shorter OS than those with low-grade tumor budding (hazard ratio [HR]: 2.260, P<0

  6. Development of prognostic indicators using Classification And Regression Trees (CART) for survival

    Science.gov (United States)

    Nunn, Martha E.; Fan, Juanjuan; Su, Xiaogang; McGuire, Michael K.

    2014-01-01

    The development of an accurate prognosis is an integral component of treatment planning in the practice of periodontics. Prior work has evaluated the validity of using various clinical measured parameters for assigning periodontal prognosis as well as for predicting tooth survival and change in clinical conditions over time. We critically review the application of multivariate Classification And Regression Trees (CART) for survival in developing evidence-based periodontal prognostic indicators. We focus attention on two distinct methods of multivariate CART for survival: the marginal goodness-of-fit approach, and the multivariate exponential approach. A number of common clinical measures have been found to be significantly associated with tooth loss from periodontal disease, including furcation involvement, probing depth, mobility, crown-to-root ratio, and oral hygiene. However, the inter-relationships among these measures, as well as the relevance of other clinical measures to tooth loss from periodontal disease (such as bruxism, family history of periodontal disease, and overall bone loss), remain less clear. While inferences drawn from any single current study are necessarily limited, the application of new approaches in epidemiologic analyses to periodontal prognosis, such as CART for survival, should yield important insights into our understanding, and treatment, of periodontal diseases. PMID:22133372

  7. Assessing the prognostic features of a pain classification system in advanced cancer patients.

    Science.gov (United States)

    Arthur, Joseph; Tanco, Kimberson; Haider, Ali; Maligi, Courtney; Park, Minjeong; Liu, Diane; Bruera, Eduardo

    2017-09-01

    The Edmonton Classification System for Cancer Pain (ECS-CP) has been shown to predict pain management complexity based on five features: pain mechanism, incident pain, psychological distress, addictive behavior, and cognitive function. The main objective of our study was to explore the association between ECS-CP features and pain treatment outcomes among outpatients managed by a palliative care specialist-led interdisciplinary team. Initial and follow-up clinical information of 386 eligible supportive care outpatients were retrospectively reviewed and analyzed. Between the initial consultation and the first follow-up visit, the median ESAS pain intensity improved from 6 to 4.5 (p feature (p = 0.006) used a higher number of adjuvant medications. At follow-up, patients with neuropathic pain were less likely to achieve their personalized pain goal (PPG) (29 vs 72%, p = 0.015). No statistically significant association was found between increasing sum of ECS-CP features and any of the pain treatment outcomes at follow-up. Neuropathy was found to be a poor prognostic feature in advanced cancer pain management. Increasing sum of ECS-CP features was not predictive of pain management complexity at the follow-up visit when pain was managed by a palliative medicine specialist. Further research is needed to further explore these observations.

  8. Prevalence and prognostic significance of hyponatraemia in outpatients with chronic heart failure

    DEFF Research Database (Denmark)

    Balling, Louise; Schou, Morten; Videbæk, Lars

    2011-01-01

    Hyponatraemia has been reported to be a potent predictor of poor outcome in patients hospitalized for heart failure (HF). The aim of the study was to determine the prevalence and prognostic significance of hyponatraemia in a large cohort of HF outpatients followed in clinics participating...... in the Danish Heart Failure Clinics Network....

  9. The prognostic significance of the axillary apex biopsy in clinically operable breast cancer

    NARCIS (Netherlands)

    van Tienhoven, G.; Borger, J. H.; Passchier, D. H.; Hart, A. A.; Rutgers, E. J.; van Dongen, J. A.; Bartelink, H.

    1995-01-01

    To evaluate the prognostic significance of the axillary apex biopsy and its impact on clinical practice, a retrospective analysis was performed in 875 patients with clinically operable breast cancer who underwent this procedure from 1977 to 1985 (165 TNM stage I; 512 TNM stage II; 198 TNM stage

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

    LENUS (Irish Health Repository)

    Mohan, Helen M

    2013-06-01

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

  11. Frequency and Prognostic Significance of Hemoptysis in Pediatric Pulmonary Arterial Hypertension

    NARCIS (Netherlands)

    Roofthooft, Marcus T. R.; Douwes, Johannes M.; Vrijlandt, Elianne J. L. E.; Berger, Rolf M. F.

    2013-01-01

    Data concerning the prevalence, risk factors, and prognostic significance of hemoptysis in pediatric pulmonary arterial hypertension (PAH) are scarce. A Dutch national cohort of 74 children with either idiopathic or heritable PAH (IPAH/HPAH, n = 43) or PAH associated with congenital heart disease

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

    Directory of Open Access Journals (Sweden)

    Sheng-Na Li

    2016-01-01

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

  13. Prevalence and Prognostic Significance of Runs of Premature Atrial Complexes in Ischemic Stroke Patients

    DEFF Research Database (Denmark)

    Høeg Vinther, Kristina; Tveskov, Claus; Möller, Sören

    2016-01-01

    BACKGROUND AND PURPOSE: Runs of premature atrial complexes (PACs) are common in stroke patients and perceived to be clinically insignificant, but their prognostic significance is unclear. This study investigated the association between runs of PACs in ischemic stroke patients and the risk...

  14. The prognostic significance of computerised tomography findings in women with liver metastases from breast cancer.

    Science.gov (United States)

    Mhlanga, J C; Evans, A E; Doyle, S; James, J J; Cornford, E J; Balls, G; Chan, S Y; Ellis, I

    2011-10-01

    While computerised tomography (CT) is used for diagnosis and assessing response to treatment little work has been performed on the prognostic significance of the CT findings in women with liver metastases. The aim of this study was to assess if the CT findings in women diagnosed with liver metastases at the time of first presentation with metastatic breast cancer have any prognostic significance. The staging CT scans of 78 consecutive women diagnosed with liver metastases at the time of first presentation of metastatic breast cancer were reviewed independently by two radiologists who were blinded to survival and the histological features of the tumour. The number and enhancement characteristics of liver metastases, whether metastases were solitary, multiple or diffuse, the diameter of the largest and the sum of the diameter of the five largest lesions, an estimate of % involvement (50%), and the presence of metastases at other sites were assessed. HER-2 and ER status and histological grade of the patient's primary breast cancer were also recorded. Survival was ascertained from hospital records. The prognostic significance of these factors was assessed in a univariate and multivariate fashion. At univariate analysis, number of liver metastases, sum of the diameter of the five largest lesions, percentage estimated involvement, presence of ascites, chest metastases and HER-2 status were significantly associated with reduced survival. Liver metastasis pattern (i.e. whether discrete or multiple), enhancement characteristics, ER status and histological grade were not associated with a significant outcome. At multivariate analysis estimated percentage liver involvement and the presence of chest metastases retained prognostic significance. Estimated percentage involvement was reproducible with 90% concordance between the two observers. The CT appearances of patients with liver metastases at first presentation with metastatic breast cancer provide prognostic information

  15. Prognostic classification of MDS is improved by the inclusion of FISH panel testing with conventional cytogenetics.

    Science.gov (United States)

    Kokate, Prajakta; Dalvi, Rupa; Koppaka, Neeraja; Mandava, Swarna

    2017-10-01

    Cytogenetics is a critical independent prognostic factor in myelodysplastic syndromes (MDS). Conventional cytogenetics (CC) and Fluorescence in situ hybridization (FISH) Panel Testing are extensively used for the prognostic stratification of MDS, although the FISH test is not yet a bona fide component of the International Prognostic Scoring System (IPSS). The present study compares the utility of CC and FISH to detect chromosomal anomalies and in prognostic categorization. GTG-Banding and FISH Panel Testing specifically for -5/-5q, -7/-7q, +8 and -20q was performed on whole blood or bone marrow samples from 136 patients with MDS. Chromosomal anomalies were found in 40 cases by CC, including three novel translocations. FISH identified at least one anomaly in 54/136 (39.7%) cases. More than one anomaly was found in 18/54 (33.3%) cases, therefore, overall FISH identified 75 anomalies of which 32 (42.6%) were undetected by CC. FISH provided additional information in cases with CC failure and in cases with a normal karyotype. Further, in ten cases with an abnormal karyotype, FISH could identify additional anomalies, increasing the number of abnormalities per patient. Although CC is the gold standard in the cytogenetic profiling of MDS, FISH has proven to be an asset in identifying additional abnormalities. The number of anomalies per patient can predict the prognosis in MDS and hence, FISH contributed towards prognostic re-categorization. The FISH Panel testing should be used as an adjunct to CC, irrespective of the adequacy of the number of metaphases in CC, as it improves the prognostic classification of MDS. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Prognostic significance of elevated endothelin-1 levels in patients with colorectal cancer.

    Science.gov (United States)

    Arun, C; London, N J M; Hemingway, D M

    2004-01-01

    Prognostic factors from clinical, laboratory and pathological data of patients with colorectal cancer are essential to identify high-risk groups to whom beneficial adjuvant therapy could be given. Endothelin-1, a growth factor, has been associated with the development and spread of solid tumours. This prospective study was performed to determine whether preoperative plasma big ET-1 levels might be useful as a prognostic indicator in patients with colorectal carcinoma. Sixty-five consecutive patients with colorectal cancer confirmed by biopsy were included prospectively into this study over a 12-month period. Plasma samples from a peripheral vein were obtained prior to surgery. Univariate analysis of survival using age ( 70 years), sex, Dukes' stage (A&B versus C), tumour size ( 50 mm), vascular invasion and plasma big ET-1 levels was performed and significant factors were then analysed with the Cox regression model. Three variables, age, Dukes' tumour stage and plasma big ET-1 levels, were found to have prognostic significance (p70 years (p=0.02), Dukes' C tumours (p=0.04) and plasma big ET-1 levels >4.2 pg/mL (p=0.02). The Cox regression model identified the same three variables as having independent prognostic value for overall survival. Preoperative plasma big ET-1 levels may be useful in predicting overall survival in patients with colorectal cancer. Plasma big ET-1 levels may be useful in the selection of high-risk lymph node-negative patients with colorectal cancer for adjuvant therapy.

  17. Prognostics

    Data.gov (United States)

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

  18. Clinicopathological significance and prognostic role of EZH2 expression in non-small cell lung cancer.

    Science.gov (United States)

    Kim, Nae Yu; Pyo, Jung-Soo

    2017-07-01

    The aim of this study was to investigate the clinicopathological characteristics and prognostic role of enhancer of zeste homologue 2 (EZH2) expression in non-small cell lung cancer (NSCLC). The correlation between EZH2 expression and the clinicopathological characteristics, including sex, smoking history, tumor differentiation, histologic type, tumor stage, and lymph node metastasis, was evaluated through a meta-analysis. In addition, the prognostic value of EZH2 expression was elucidated. This study included 1,932 patients with NSCLC from 11 eligible studies. The overall rate of EZH2 expression was 0.548 [95% confidence interval (CI) 0.491-0.604]. There were significant correlations between EZH2 expression and male sex and smoking history. The expression rate of EZH2 was significantly lower in adenocarcinoma than in other histologic types. Furthermore, EZH2 expression rates were higher in NSCLC with moderately and poorly differentiation and nodal disease than in well-differentiated NSCLC without nodal disease. There was a significant correlation between EZH2 expression and worse overall and disease-free survival [hazard ratio (HR) 1.938, 95% CI 1.617-2.323 and HR 1.713, 95% CI 1.366-2.149, respectively]. Subgroup analysis revealed no significant difference for the prognostic effect of EZH2 expression between histologic types or detection methods. Our data collectively suggest that EZH2 expression is significantly correlated with aggressive tumor behavior and poor prognosis in NSCLC. Copyright © 2017 Elsevier GmbH. All rights reserved.

  19. The prognostic significance of UCA1 for predicting clinical outcome in patients with digestive system malignancies.

    Science.gov (United States)

    Liu, Fang-Teng; Dong, Qing; Gao, Hui; Zhu, Zheng-Ming

    2017-06-20

    Urothelial Carcinoma Associated 1 (UCA1) was an originally identified lncRNA in bladder cancer. Previous studies have reported that UCA1 played a significant role in various types of cancer. This study aimed to clarify the prognostic value of UCA1 in digestive system cancers. The meta-analysis of 15 studies were included, comprising 1441 patients with digestive system cancers. The pooled results of 14 studies indicated that high expression of UCA1 was significantly associated with poorer OS in patients with digestive system cancers (HR: 1.89, 95 % CI: 1.52-2.26). In addition, UCA1 could be as an independent prognostic factor for predicting OS of patients (HR: 1.85, 95 % CI: 1.45-2.25). The pooled results of 3 studies indicated a significant association between UCA1 and DFS in patients with digestive system cancers (HR = 2.50; 95 % CI = 1.30-3.69). Statistical significance was also observed in subgroup meta-analysis. Furthermore, the clinicopathological values of UCA1 were discussed in esophageal cancer, colorectal cancer and pancreatic cancer. A comprehensive retrieval was performed to search studies evaluating the prognostic value of UCA1 in digestive system cancers. Many databases were involved, including PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure and Wanfang database. Quantitative meta-analysis was performed with standard statistical methods and the prognostic significance of UCA1 in digestive system cancers was qualified. Elevated level of UCA1 indicated the poor clinical outcome for patients with digestive system cancers. It may serve as a new biomarker related to prognosis in digestive system cancers.

  20. Application of different prognostic scoring systems and comparison of the FAB and WHO classifications in Korean patients with myelodysplastic syndrome.

    Science.gov (United States)

    Lee, J-H; Lee, J-H; Shin, Y-R; Lee, J-S; Kim, W-K; Chi, H-S; Park, C-J; Seo, E-J; Lee, K-H

    2003-02-01

    We retrospectively studied 227 patients with MDS (1) to identify the prognostic factors of survival and acute leukemia evolution in Korean patients with MDS, (2) to apply different prognostic scoring systems to the same group of patients, and (3) to compare the FAB with the WHO classification. Six scoring systems were applied to the patients, and the FAB and WHO classifications were compared. The patients' median age was 57 years. The median survival time was 21 months, and age, dysgranulopoiesis and the IPSS cytogenetic groups were independent prognostic factors for survival. Acute leukemia occurred in 34 patients, and the cumulative incidence was 27.1% at 3 years. Marrow blast percentage was the only independent prognostic factor for acute leukemia evolution. Most scoring systems successfully discriminated risk groups for survival and acute leukemia evolution, but patient distribution into risk groups varied according to the scoring systems. Refractory cytopenia with multilineage dysplasia and RAEB II seemed to have different prognoses from RA or RARS and RAEB I, respectively. In summary, our MDS patients had different disease natures from those of Western countries regarding clinical features, prognostic factors and cytogenetic profiles. Although the WHO classification seems to improve the FAB classification, further studies are warranted to validate the utility of the WHO classification before it is accepted for routine clinical use. Our study has the limitations of retrospective analysis, and our results should be verified in future prospective studies.

  1. Prognostic significance of tumour vascularisation on survival of patients with advanced ovarian carcinoma

    OpenAIRE

    Labiche, Alexandre; Elie, Nicolas; Herlin, Paulette; Denoux, Yves; Crouet, Hubert; Heutte, Natacha; Joly, Florence; Héron, Jean-François; Gauduchon, Pascal; Henry-Amar, Michel

    2009-01-01

    Objective. The prognostic significance of microvessel density in ovarian cancer is still a matter of debate. Classically, the degree of vascularisation is assessed in areas of high vascular density (hot spots), considered as regions of increased probability of metastasis. Since ovarian tumours have a particular progression and dissemination behaviour, vascularisation outside hot spots may also contribute to their evolution. Methods. In the present study, the degree of ...

  2. The prognostic significance of extramural deposits and extracapsular lymph node invasion in colon cancer.

    LENUS (Irish Health Repository)

    Al Sahaf, Osama

    2011-08-01

    The status of resected lymph nodes in colon cancer determines prognosis and further treatment. The American Joint Committee on Cancer staging system has designated extramural nodules as nonnodal disease and classified them as extensions of the T category in the sixth edition and as site-specific tumor deposits in the seventh edition. Extracapsular lymph node extension is an established poor prognostic indicator in many cancers. Its significance in colon cancer has not been extensively investigated.

  3. [Clinical significance of WHO classification and MDS 2000 classification in myelodysplastic syndromes].

    Science.gov (United States)

    Akiba, M; Matsuda, A; Misumi, M; Yagasaki, F; Bessho, M

    2001-12-01

    Excluding chronic myelomonocytic leukemia, a total of 92 consecutive patients with myelodysplastic syndrome showing less than 20% blasts in the bone marrow were analyzed. We evaluated the clinical significance of the WHO and MDS 2000 classifications by reviewing each MDS patient according to the classification. The WHO criteria classified the MDS patients into 36 with RA, 22 with RCMD and 33 with RAEB, whereas according to the MDS 2000 criteria there were 19 RAEB-I patients and 15 RAEB-II patients. Based on the WHO classification, the RCMD patients had higher platelet counts and percentages of blasts among BM cells than the RA patients (P = 0.0018, P = 0.0001). Twenty percent of the RA patients, 44.8% of the RCMD patients, and 70.8% of the RAEB patients had cytogenetic abnormalities. Among them, the poor karyotype was present in 6.7% of the RA patients, 21.0% of the RCMD patients and 41.6% of the RAEB patients. The rate of acute leukemia death was 14.3% in the RA patients, 67.7% in the RAEB patients and 50.0% in the RCMD patients. Analysis of survival times revealed significant differences between RA and RCMD patients (P = 0.0482). The clinical features of RCMD patients were intermediate between those of RAEB and RA patients. There was no difference between the clinical features of the RAEB-I and RAEB-II patients in the MDS 2000 classification.

  4. Coronary thrombus in patients undergoing primary PCI for STEMI: Prognostic significance and management.

    Science.gov (United States)

    Vecchio, Sabine; Varani, Elisabetta; Chechi, Tania; Balducelli, Marco; Vecchi, Giuseppe; Aquilina, Matteo; Ricci Lucchi, Giulia; Dal Monte, Alessandro; Margheri, Massimo

    2014-06-26

    Acute ST-elevation myocardial infarction (STEMI) usually results from coronary atherosclerotic plaque disruption with superimposed thrombus formation. Detection of coronary thrombi is a poor prognostic indicator, which is mostly proportional to their size and composition. Particularly, intracoronary thrombi impair both epicardial blood flow and myocardial perfusion, by occluding major coronary arteries and causing distal embolization, respectively. Thus, although primary percutaneous coronary intervention is the preferred treatement strategy in STEMI setting, the associated use of adjunctive antithrombotic drugs and/or percutaneous thrombectomy is crucial to optimize therapy of STEMI patients, by improving either angiographical and clinical outcomes. This review article will focus on the prognostic significance of intracoronary thrombi and on current antithrombotic pharmacological and interventional strategies used in the setting of STEMI to manage thrombotic lesions.

  5. Prognostic significance of vascularity in cutaneous melanoma: pilot study using in vivo confocal scanning laser microscopy.

    Science.gov (United States)

    Humphrey, Shannon; Walsh, Noreen M; Delaney, Laura; Propperova, Iva; Langley, Richard G B

    2006-01-01

    Tumor vascularity may be of strong prognostic significance in cutaneous melanoma. We are the first to use a novel, noninvasive, in vivo confocal scanning laser microscope (CSLM) to evaluate vascularity in cutaneous melanoma. Our purpose was to apply a CSLM to assess vascularity in melanoma and to evaluate the prognostic significance of these findings. Patients with a suspicious pigmented lesion were prospectively recruited to undergo CSLM prior to skin biopsy, and those diagnosed with melanoma were included in this study. A blinded observer graded tumor vascularity from still digital CSLM images. The CSLM vascularity grading was correlated to tumor thickness and ulceration as a proxy for clinical prognosis. Sixty-six patients and 67 lesions underwent imaging with CSLM. Eleven patients were diagnosed with melanoma, including six in situ and five invasive melanomas. Prominent vascularity was observed in all advanced melanomas. There was an overall increase in mean tumor thickness between the absent (x = 0.315 mm) to prominent (x = 1.51 mm) categories. In this pilot study, vascularity was readily detected in cutaneous melanomas using CSLM. Prominent vascularity was observed in patients with advanced cutaneous melanomas. Our preliminary results are encouraging and indicate potential for the use of CSLM to assess vascularity in cutaneous melanoma, with potential prognostic and therapeutic implications.

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

    Directory of Open Access Journals (Sweden)

    Minna M Boström

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

  7. Important prognostic significance of lymph node density in patients with node positive oral tongue cancer.

    Science.gov (United States)

    Lieng, Hester; Gebski, Val J; Morgan, Gary J; Veness, Michael J

    2016-09-01

    Lymph node density (LND) has been described as a prognostic factor for survival in patients with head and neck squamous cell carcinoma, particularly of the oral cavity. The aim of this study was to determine the prognostic significance of LND in patients with node positive oral tongue squamous cell carcinoma (OTSCC). Patients with pathological node positive OTSCC were identified in a retrospective review of prospectively collected data. The optimal cut-point for LND was determined using the minimum P-value method and the log-rank test. The impact of this LND cut-point on time to disease progression and overall survival was determined. In 72 patients with OTSCC, an LND of 14.3% was found to have the greatest separation using the log-rank test (P 14.3% (hazard ratio: 3.43; 95% confidence interval: 1.76-6.70; P 14.3% (hazard ratio: 3.28; 95% confidence interval: 1.61-6.68; P = 0.001). Patients with an LND >14.3% experienced a higher rate of regional recurrence. Our findings confirm the prognostic significance of LND in patients with node positive OTSCC, with a similar LND cut-point value to other published series. Improving regional control in these high-risk patients may improve outcome. © 2016 Royal Australasian College of Surgeons.

  8. Prognostic significance of number of nodes removed in patients with node-negative early cervical cancer.

    Science.gov (United States)

    Mao, Siyue; Dong, Jun; Li, Sheng; Wang, Yiqi; Wu, Peihong

    2016-10-01

    The aim of this study was to investigate whether the number of removed lymph nodes was associated with survival of patients with node-negative early cervical cancer and to analyze the prognostic significance of clinical and pathologic features in these patients. Patients with FIGO stage IA-IIB cervical cancer who underwent radical hysterectomy with lymphadenectomy without receiving preoperative therapy were reviewed retrospectively. Patients were all proved to have lymph-node-negative disease and classified into five groups based on the number of nodes removed. The Kaplan-Meier method and Cox's proportional hazards regression model were used in prognostic analysis. The final dataset included 359 patients: 45 (12.5%) patients had ≤10 nodes removed, 93 (25.9%) had 11-15, 98 (27.3%) had 16-20, 64 (17.8%) had 21-25, and 59 (16.4%) had >25 nodes removed. There was no association between the number of nodes removed and survival of patients with node-negative early cervical cancer (χ 2  = 6.19, P = 0.185). Similarly, subgroup analyses for FIGO stage IB1-IIB also showed that the number of lymph nodes was not significantly related to survival in each stage. Multivariate analyses showed that histology and depth of invasion were independent prognostic factors for survival in these patients. If a standardized lymphadenectomy is performed, the number of lymph nodes removed is not an independent prognostic factor for patients with node-negative early cervical cancer. Our study suggests that there is inconclusive evidence to support survival benefit of complete lymphadenectomy among these patients. © 2016 Japan Society of Obstetrics and Gynecology.

  9. [Significance of WHO classification for acute leukemia and myelodysplastic syndrome].

    Science.gov (United States)

    Sugiura, Aya; Takeshita, Akihiro

    2006-11-01

    The FAB classification, proposed in 1976, is basically a morphological classification of leukemia and is now used worldwide. However, according to chromosome and genetic research development, some important data have been revealed to influence the prognosis of leukemia. Recently, the World Health Organization (WHO), in conjunction with the Society for Hematopathology and the European Association of Hematopathology, published a new classification. The WHO classification incorporated the results of chromosome and genetic analyses of leukemia. Some leukemias and lymphomas revealed genetic abnormalities, establishing a new disease entity in the WHO classification, and several genetic abnormalities affect drug sensitivity and prognosis. As the WHO classification is going to be used worldwide, we should update our understanding of its contents.

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

    Directory of Open Access Journals (Sweden)

    Sura Aziz

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

  11. The prognostic significance of angina pectoris experienced during the first month following acute myocardial infarction

    DEFF Research Database (Denmark)

    Jespersen, C M

    1997-01-01

    on study treatment 1 month after discharge. Of these patients, 311 (39%) reported chest pain during the first month following discharge. RESULTS: Patients with angina pectoris had a significantly increased risk of reinfarction [hazard 1.71; 95%-confidence limit (CL): 1.09, 2.69] and increased mortality......BACKGROUND: Angina pectoris accompanied by transient ST-segment changes during the in-hospital phase of acute myocardial infarction (AMI) is a well established marker of subsequent cardiac death and reinfarction. HYPOTHESIS: This study was undertaken to record the prognostic significance of angina...

  12. [Clinical and prognostic relevance of the Kiel classification of non-Hodgkin lymphomas].

    Science.gov (United States)

    Brittinger, G; Bartels, H; Common, H; Dühmke, E; Engelhard, M; Fülle, H H; Gunzer, U; Gyenes, T; Heinz, R; König, E

    1986-04-01

    The Kiel classification provides a new subdivision of non-Hodgkin lymphomas into distinct entities showing different clinical and prognostic properties. In comparison with earlier classifications this system defines additional types of lymphoma (e.g. CC lymphoma, LP immunocytoma) (for abbreviations see text) which are to be considered separate entities also from a clinical point of view. By data derived from a multicenter prospective observation study (1,127 patients recruited from 1975 to 1980, follow-up until 1985) a precise definition of the clinical features of each lymphoma entity (e.g. frequency, age and sex distribution, patterns of initial involvement and spread of disease) was possible. In addition, the effect of radio- and/or chemotherapeutic measures was evaluated. Strictly localized disease (stage I/IE according to the Ann Arbor classification) occurred in 1.5 to 8% of patients with NHL of low-grade malignancy (comprising 69.4% of cases studied) and in 8 to 17% of patients with high-grade malignant NHL (comprising 30.2% of cases studied). Loco-regional irradiation alone was able to induce complete remission in 86 to 89% (CB and IB lymphomas) and in 100% (LP immunocytoma, CB-CC and CC lymphomas), respectively, of stage I/IE patients. Only CC and IB lymphomas showed a relevant risk of relapse (40% and 50%, respectively). Total lymphoid irradiation as able to induce stable complete remissions in about 50% of patients with stage III of CB-CC lymphoma. Probabilities of survival of patients with initial stages III and IV treated by several types of chemotherapy reflect different prognostic features of individual lymphoma entities.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Prognostic significance of metastatic lymph node ratio in squamous cell carcinoma of the cervix

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    Li C

    2016-06-01

    Full Text Available Chen Li,1 Wenhui Liu,2 Yufeng Cheng1 1Department of Radiation Oncology, QiLu Hospital of Shandong University, 2School of Public Health, Shandong University, Jinan, Shandong, People’s Republic of China Purpose: Metastatic lymph node ratio (MLNR was reported to be an important prognostic factor in several tumors. However, depth of primary tumor invasion is also important in cervical cancer prognostic analysis. In this study, the objective was to determine if MLNR can be used to define a high-risk category of patients with squamous cell carcinoma of the cervix (SCC. And we combined MLNR and depth of invasion to investigate whether prognosis of SCC can be predicted better.  Patients and methods: We performed a retrospective review of patients with SCC who underwent radical hysterectomy and pelvic lymphadenectomy at QiLu Hospital of Shandong University from January 2007 to December 2009. Prognostic factors for disease-free survival (DFS and overall survival (OS were identified by univariate and multivariate analyses.  Results: One hundred and ninety-eight patients met the inclusion criteria and were included in the analysis. By cut-point survival analysis, MLNR cutoff was designed as 0.2. On multivariate analysis, an MLNR >0.2 was associated with a worse OS (hazard ratio [HR] =2.560, 95% CI 1.275–5.143, P=0.008 and DFS (HR =2.404, 95% CI 1.202–4.809, P=0.013. Depth of invasion cutoff was designed as invasion >1/2 cervix wall and was associated with a worse OS (HR =1.806, 95% CI 1.063–3.070, P=0.029 and DFS (HR =1.900, 95% CI 1.101–3.279, P=0.021. In addition, subgroup analysis revealed significant difference in OS and DFS rates between different MLNR categories within the same depth of invasion category (P<0.05, however, not between different depth of invasion categories within the same MLNR category (P>0.05.  Conclusion: MLNR may be used as the independent prognostic parameter in patients with SCC. Combined MLNR and depth of invasion

  14. Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer.

    Science.gov (United States)

    Prat, Aleix; Cheang, Maggie Chon U; Martín, Miguel; Parker, Joel S; Carrasco, Eva; Caballero, Rosalía; Tyldesley, Scott; Gelmon, Karen; Bernard, Philip S; Nielsen, Torsten O; Perou, Charles M

    2013-01-10

    Current immunohistochemical (IHC)-based definitions of luminal A and B breast cancers are imperfect when compared with multigene expression-based assays. In this study, we sought to improve the IHC subtyping by examining the pathologic and gene expression characteristics of genomically defined luminal A and B subtypes. Gene expression and pathologic features were collected from primary tumors across five independent cohorts: British Columbia Cancer Agency (BCCA) tamoxifen-treated only, Grupo Español de Investigación en Cáncer de Mama 9906 trial, BCCA no systemic treatment cohort, PAM50 microarray training data set, and a combined publicly available microarray data set. Optimal cutoffs of percentage of progesterone receptor (PR) -positive tumor cells to predict survival were derived and independently tested. Multivariable Cox models were used to test the prognostic significance. Clinicopathologic comparisons among luminal A and B subtypes consistently identified higher rates of PR positivity, human epidermal growth factor receptor 2 (HER2) negativity, and histologic grade 1 in luminal A tumors. Quantitative PR gene and protein expression were also found to be significantly higher in luminal A tumors. An empiric cutoff of more than 20% of PR-positive tumor cells was statistically chosen and proved significant for predicting survival differences within IHC-defined luminal A tumors independently of endocrine therapy administration. Finally, no additional prognostic value within hormonal receptor (HR) -positive/HER2-negative disease was observed with the use of the IHC4 score when intrinsic IHC-based subtypes were used that included the more than 20% PR-positive tumor cells and vice versa. Semiquantitative IHC expression of PR adds prognostic value within the current IHC-based luminal A definition by improving the identification of good outcome breast cancers. The new proposed IHC-based definition of luminal A tumors is HR positive/HER2 negative/Ki-67 less than 14

  15. Prognostic significance of thymidylate synthase (TS) expression in cutaneous malignant melanoma.

    Science.gov (United States)

    Shimizu, A; Kaira, K; Yasuda, M; Asao, T; Ishikawa, O

    2016-01-01

    Thymidylate synthase (TS) plays an essential role in the pathogenesis and development of cancer, and TS-targeting agents have been widely used against different types of cancers. However, it remains still unclear whether or not TS is expressed in malignant melanoma. We conducted the clinicopathological study to investigate the prognostic significance of TS expression in cutaneous malignant melanoma. Ninety-nine patients with surgically resected cutaneous malignant melanoma were assessed. Tumor sections were stained by immunohistochemistry for TS, Ki-67, and microvessel density (MVD) determined by CD34. TS was positively expressed in 26% (26 out of 99). The expression of TS was significantly associated with T factor, cell proliferation (Ki-67) and MVD (CD34). By Spearman's rank test, TS expression was significantly correlated with Ki67 and CD34. By univariate analysis, ulceration, disease stage, TS, Ki-67 and CD34 had a significant relationship with survival. Multivariate analysis confirmed that TS was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The positive expression of TS could be a useful marker for predicting poor prognosis in patients with cutaneous malignant melanoma, and TS-targeting agents may be worth trying for the treatment of this dismal disease.

  16. Prognostic significance of clinical seizures after cardiac arrest and target temperature management

    DEFF Research Database (Denmark)

    Lybeck, Anna; Friberg, Hans; Aneman, Anders

    2017-01-01

    AIM: Clinical seizures are common after cardiac arrest and predictive of a poor neurological outcome. Seizures may be myoclonic, tonic-clonic or a combination of seizure types. This study reports the incidence and prognostic significance of clinical seizures in the target temperature management......-findings, and long-term neurological outcome. The trial randomised 939 comatose survivors to TTM at 33°C or 36°C with strict criteria for withdrawal of life-sustaining therapies. Sensitivity, specificity and false positive rate for poor outcome were reported for different types of seizures. RESULTS: Clinical...

  17. [Cardio-hepatic Syndrome in Heart Failure: Prevalence, Pathogenesis and Prognostic Significance].

    Science.gov (United States)

    Kobalava, Zh D; Villevalde, S V; Soloveva, A E

    2016-12-01

    In a framework of the concept of organ interactions great attention has been paid during recent years to interaction of the heart and liver. The term cardio-hepatic syndrome (CHS) designates the combination of clinical-laboratory signs of liver dysfunction and acute or chronic cardiac pathology. In this article, we present mechanisms and characteristics of CHS in acute and chronic heart failure (HF), data of large clinical studies and registries on prevalence, associations, and prognostic significance of cardiogenic disturbances of liver function in patients with HF.

  18. Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients.

    Science.gov (United States)

    Vincenzi, Bruno; Cremolini, Chiara; Sartore-Bianchi, Andrea; Russo, Antonio; Mannavola, Francesco; Perrone, Giuseppe; Pantano, Francesco; Loupakis, Fotios; Rossini, Daniele; Ongaro, Elena; Bonazzina, Erica; Dell'Aquila, Emanuela; Imperatori, Marco; Zoccoli, Alice; Bronte, Giuseppe; De Maglio, Giovanna; Fontanini, Gabriella; Natoli, Clara; Falcone, Alfredo; Santini, Daniele; Onetti-Muda, Andrea; Siena, Salvatore; Tonini, Giuseppe; Aprile, Giuseppe

    2015-10-13

    Activating mutations of K-Ras gene have a well-established role as predictors of resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. Their prognostic value is controversial, and no data regarding the prognostic value of mutation rate, defined as the percentage of mutated alleles/tumor sample, are available. We aimed to evaluate the prognostic value of K-Rasmutation rate in a homogenous cohort of mCRC patients receiving first-line doublet plus bevacizumab. This retrospective study enrolled 397 K-Ras mutant mCRC patients from 6 Italian centers, and 263 patients were fully evaluable for our analysis. K-Ras mutation rate was assessed by pyrosequencing. Patients with less than 60% of cancer cells in tumor tissue were excluded. No patients received anti-EGFR containing anticancer therapy, at any time. Median mutation rate was 40% and was adopted as cut-off. The primary and secondary endpoints were PFS and OS respectively. At univariate analysis, K-Ras mutation rate higher than 40% was significantly associated with lower PFS (7.3 vs 9.1 months; P < 0.0001) and OS (21 vs 31 months; P = 0.004). A multivariate model adjusted for age at diagnosis, site of origin of tumor tissue (primary vs metastases), referral center, number of metastatic sites, and first-line chemotherapy backbone, showed that K-Ras mutation rate remained a significant predictor of PFS and OS in the whole population. Our data demonstrate an association between K-Ras mutation rate and prognosis in mCRC patients treated with bevacizumab-containing first-line therapy. These data deserve to be verified in an independent validation set.

  19. Prognostic Significance of DNA Cytometry in Carcinoma of the Uterine Cervix FIGO Stage IB and II

    Directory of Open Access Journals (Sweden)

    Hans Jürgen Grote

    2001-01-01

    Full Text Available Objective: To assess the prognostic value of DNA‐image cytometry in cervical carcinoma of the uterus and its relation to other established prognostic factors. Study design: The study included 116 cases of cervical carcinoma FIGO stages IB and II which were treated with radical abdominal hysterectomy. The median follow‐up was 55 months (range 1–162 months. DNA image cytometry was performed on cytologic specimens prepared by enzymatic cell separation from formalin‐fixed, paraffin‐embedded tissues. DNA stemline ploidy, DNA stemline aneuploidy, 5c exceeding rate, 9c exceeding rate, 2c deviation index, and DNA malignancy grade were computed. DNA‐variables as well as various clinical and histological variables were related to survival rates. Results: In multivariate statistical analysis DNA stemline ploidy using 2.2c as a cut‐off value and FIGO stage showed to be statistically significant available presurgery predictors of survival, whereas the postsurgical parameters lymphonodal status, tumor size and parametrial involvement were significantly correlated with survival. The synopsis of all parameters in a multivariate Cox model indicated that – with declining relevance – the number of positive pelvic lymph nodes, DNA stemline ploidy using a cut‐off level at a modal value of 2.2c, largest pelvic lymph node, 5c exceeding rate, and ratio of carcinoma area to cervix area, were of predictive value for survival. Conclusions: Our results suggest that prognostic information deducted from classical staging parameters is successfully complemented by DNA image cytometry which can be applied pretherapeutically.

  20. Prognostic value of the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification in stage IB lung adenocarcinoma.

    Science.gov (United States)

    Xu, C-h; Wang, W; Wei, Y; Hu, H-d; Zou, J; Yan, J; Yu, L-k; Yang, R-s; Wang, Y

    2015-10-01

    Patients with pathological stage IB lung adenocarcinoma have a variable prognosis, even if received the same treatment. This study investigated the prognostic value of the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification in resected stage IB lung adenocarcinoma. We identified 276 patients with pathological stage IB adenocarcinoma who had undergone surgical resection at the Nanjing Chest Hospital between 2005 and 2010. The histological subtypes of all patients were classified according to the 2011 IASLC/ATS/ERS international multidisciplinary lung adenocarcinoma classification. Kaplan-Meier and Cox regression analyses were used to analyze the correlation between the IASLC/ATS/ERS classification and patients' prognosis. Two hundred and seventy-six patients with pathological stage IB adenocarcinoma had an 86.2% 5-year overall survival (OS) and 80.4% 5-year disease-free survival (DFS). Patients with micropapillary and solid predominant tumors had a significantly worse OS and DFS as compared to those with other subtypes predominant tumors (p = 0.003 and 0.001). Multivariate analysis revealed that the new classification was an independent prognostic factor for both OS and DFS of pathological stage IB adenocarcinoma (p = 0.009 and 0.003). Our study revealed that the new IASLC/ATS/ERS classification was an independent prognostic factor of pathological stage IB adenocarcinoma. This new classification is valuable of screening out high risk patients to receive postoperative adjuvant therapy. Copyright © 2015. Published by Elsevier Ltd.

  1. Prognostic significance of neutrophil-lymphocyteratio/platelet-lymphocyteratioin lung cancers: a meta-analysis.

    Science.gov (United States)

    Yang, Hong-Bo; Xing, Meng; Ma, Lei-Na; Feng, Ling-Xin; Yu, Zhuang

    2016-11-22

    For now, hematological markers of inflammatory response have emerged as prognostic factors for patients with cancer. Many articles have confirm that neutrophil to lymphocyte ratio(NLR) and platelet-lymphocyte ratio (PLR) are relate with poor prognosis in various types of tumors. To investigate the association between NLR/PLR and progression free survival (PFS), overall survival (OS) and clinicopathologic parameters in lung cancer patients. We performed relevant searches in PubMed database, Google Scholar, Springer Link. We included retrospective cohort studies that reported hazard ratios with 95% confidence intervals for the NLR or PLR and PFS or OS. Both high NLR (P < 0.00001) and high PLR (P = 0.01) were significantly predictive of poorer OS. It also demonstrated that elevated NLR predicted poorer PFS (P = 0.0002). High NLR was significantly associated with deeper Invasive of tumor, (P = 0.006) extensive lymph nodetastasis(N2-3) (P = 0.01), poor differentiation (P = 0.0002) and vascular invasion(P = 0.002).There was no evidence of publication bias. Subgroup analysis indicated that little evidence of heterogeneity. However, PLR has no prognostic significance for SCLC. We provides further evidence in support of elevated NLR and PLR were predictors of poor OS and PFS in patients with lung cancer. Given this, NLR and PLR may be markers to report treatment outcomes.

  2. Prognostic significance of low microRNA-218 expression in patients with different types of cancer

    Science.gov (United States)

    Duan, Fujiao; Wang, Kaijuan; Dai, Liping; Zhao, Xia; Feng, Yajing; Song, Chunhua; Cui, Shuli; Wang, Chengzeng

    2016-01-01

    Abstract Background: Mounting evidence showed that microRNAs may be useful as prognostic biomarkers of cancer. Therefore, we summarize the predictive role of microRNA-218 (miR-218) for survival in patients with various cancers. Methods: We performed a systematic literature review and assessed the quality of included studies based on Meta-analysis of Observational Studies in Epidemiology group (MOOSE). Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated to assess the correlation between miR-218 expression and prognosis of different cancers. Results: We identified 10 studies for pooled analyses. For overall survival, a lower expression levels of miR-218 significantly predicted poorer survival, with the pooled HR of 2.61 (95% CI: 2.11–3.22, P < 0.001). For disease-free survival/progressive-free survival/recurrence-free survival (DFS/PFS/RFS), a lower expression level of miR-218 significantly predicted worse DFS/PFS/RFS in various carcinomas, with the pooled HR of 2.73 (95% CI: 2.08–3.58, P < 0.001). Similarly, subgroup analysis by detection method, ethnicity and cancer subtype analysis suggested that lower expression of miR-218 correlated with. Conclusion: Our data demonstrated that lower miR-218 expression is significantly associated with poorer overall survival (OS) and DFS/PFS/RFS and may be a novel prognostic biomarker in some cancer types. PMID:27631228

  3. Prognostic significance of venous tumour thrombus consistency in patients with renal cell carcinoma (RCC).

    Science.gov (United States)

    Weiss, Valerie L; Braun, Martin; Perner, Sven; Harz, Andreas; Vorreuther, Roland; Kristiansen, Glen; Müller, Stefan C; Ellinger, Jörg

    2014-02-01

    To identify the prognostic impact of venous tumour thrombus (VTT) in locally advanced renal cell carcinomas (RCCs). To further differentiate the clinical course of patients with VTT who have similar clinicopathological characteristics. We determined the VTT consistency (solid vs friable) in a retrospective cohort of 200 patients with RCC who had undergone nephrectomy between 1994 and 2011. We examined the correlation of VTT consistency in these patients with clinical and pathological variables. A total of 65% of the patients had solid VTT and 35% had friable VTT, which has a significantly lower amount of cell-cell adhesion molecules and connective tissue than solid VTT. We found that friable VTT was associated with advanced pT stage, higher VTT level, papillary RCC subtype and a lower age. Patients with friable VTT had a significantly shorter median overall survival than those with solid VTT (29 vs 89 months), but VTT consistency was not found to be an independent predictor of patients' survival in the multivariate Cox analysis. We found that VTT consistency was an independent significant predictor of overall survival in patients without evidence of distant and nodal metastases (N = 119). The VTT consistency is caused by the tumour and not by different surgical handling. Friable VTT is an important adverse prognostic predictor of overall survival in patients with non-metastatic RCC. © 2013 The Authors. BJU International © 2013 BJU International.

  4. Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    Mahmoud Moustafa

    2004-09-01

    Full Text Available Abstract Background Colorectal cancer is a common cancer all over the world. Aberrations in the cell cycle checkpoints have been shown to be of prognostic significance in colorectal cancer. Methods The expression of cyclin D1, cyclin A, histone H3 and Ki-67 was examined in 60 colorectal cancer cases for co-regulation and impact on overall survival using immunohistochemistry, southern blot and in situ hybridization techniques. Immunoreactivity was evaluated semi quantitatively by determining the staining index of the studied proteins. Results There was a significant correlation between cyclin D1 gene amplification and protein overexpression (concordance = 63.6% and between Ki-67 and the other studied proteins. The staining index for Ki-67, cyclin A and D1 was higher in large, poorly differentiated tumors. The staining index of cyclin D1 was significantly higher in cases with deeply invasive tumors and nodal metastasis. Overexpression of cyclin A and D1 and amplification of cyclin D1 were associated with reduced overall survival. Multivariate analysis shows that cyclin D1 and A are two independent prognostic factors in colorectal cancer patients. Conclusions Loss of cell cycle checkpoints control is common in colorectal cancer. Cyclin A and D1 are superior independent indicators of poor prognosis in colorectal cancer patients. Therefore, they may help in predicting the clinical outcome of those patients on an individual basis and could be considered important therapeutic targets.

  5. Prognostic significance of soluble mesothelin in malignant pleural mesothelioma: a meta-analysis.

    Science.gov (United States)

    Tian, Long; Zeng, Rujun; Wang, Xin; Shen, Cheng; Lai, Yutian; Wang, Mingming; Che, Guowei

    2017-07-11

    Soluble mesothelin is beneficial to detect the progression and the treatment response of malignant pleural mesothelioma. However, the prognostic value of soluble mesothelin in malignant pleural mesothelioma remains unclear. Hazard ratio with 95% CI was used to evaluate the prognostic value of soluble mesothelin and the effect of clinicopathological characteristics on the survival of malignant pleural mesothelioma. Eight eligible studies involving 579 patients were selected for this meta-analysis. The results showed that soluble mesothelin level was significantly correlated with the survival of malignant pleural mesothelioma (pooled HR: 1.958, 95%CI: 1.531-2.504, p = 0.000; heterogeneity test: I2 = 1.1%, p = 0.421). In addition, the survival of malignant pleural mesothelioma was significantly correlated with some clinicopathological characteristics such as tumor histology (HR = 3.214, 95% CI = 2.071-4.988, p = 0.000; heterogeneity test: I2 = 0.0%, p = 0.623) and tumor stage (HR = 2.007; 95% CI = 1.477-2.727; p = 0.000; heterogeneity test: I2 = 0.0%, p = 0.966). The survival of malignant pleural mesothelioma is significantly correlated with tumor histology and tumor stage. Furthermore, high soluble mesothelin level may lead to a poor prognosis for malignant pleural mesothelioma patients.

  6. Identification of a 24-gene prognostic signature that improves the European LeukemiaNet risk classification of acute myeloid leukemia: an international collaborative study.

    Science.gov (United States)

    Li, Zejuan; Herold, Tobias; He, Chunjiang; Valk, Peter J M; Chen, Ping; Jurinovic, Vindi; Mansmann, Ulrich; Radmacher, Michael D; Maharry, Kati S; Sun, Miao; Yang, Xinan; Huang, Hao; Jiang, Xi; Sauerland, Maria-Cristina; Büchner, Thomas; Hiddemann, Wolfgang; Elkahloun, Abdel; Neilly, Mary Beth; Zhang, Yanming; Larson, Richard A; Le Beau, Michelle M; Caligiuri, Michael A; Döhner, Konstanze; Bullinger, Lars; Liu, Paul P; Delwel, Ruud; Marcucci, Guido; Lowenberg, Bob; Bloomfield, Clara D; Rowley, Janet D; Bohlander, Stefan K; Chen, Jianjun

    2013-03-20

    To identify a robust prognostic gene expression signature as an independent predictor of survival of patients with acute myeloid leukemia (AML) and use it to improve established risk classification. Four independent sets totaling 499 patients with AML carrying various cytogenetic and molecular abnormalities were used as training sets. Two independent patient sets composed of 825 patients were used as validation sets. Notably, patients from different sets were treated with different protocols, and their gene expression profiles were derived using different microarray platforms. Cox regression and Kaplan-Meier methods were used for survival analyses. A prognostic signature composed of 24 genes was derived from a meta-analysis of Cox regression values of each gene across the four training sets. In multivariable models, a higher sum value of the 24-gene signature was an independent predictor of shorter overall (OS) and event-free survival (EFS) in both training and validation sets (P classification of AML, and patients in three new risk groups classified by the integrated risk classification showed significantly (P classification incorporating this gene signature provides a better framework for risk stratification and outcome prediction than the ELN classification.

  7. Evaluation and prognostic significance of ACAT1 as a marker of prostate cancer progression.

    Science.gov (United States)

    Saraon, Punit; Trudel, Dominique; Kron, Ken; Dmitromanolakis, Apostolos; Trachtenberg, John; Bapat, Bharati; van der Kwast, Theodorus; Jarvi, Keith A; Diamandis, Eleftherios P

    2014-04-01

    Prostate cancer is the second leading cause of cancer-related death among men in North America. While a majority of prostate cancer cases remain indolent, subsets of patients develop aggressive cancers, which may lead to death. The current methods of detection include digital rectal examination and the serum PSA test. However, due to lack of specificity, neither of these approaches is able to accurately discriminate between indolent and aggressive cancer, which is why there is a need for additional prognostic factors. Previously, we identified enzymes of the ketogenic pathway, particularly ACAT1, to be elevated in aggressive prostate cancer. In the current study, we assessed the diagnostic and prognostic potential of ACAT1 by analyzing its expression using immunohistochemistry on a tissue microarray consisting of 251 clinically localized prostate cancer patients who have undergone radical prostatectomy. Using quantitative digital imaging software, we found that ACAT1 expression was significantly greater in cancerous cores compared to adjacent benign cores (P cancers versus GS≤6 cancers (P cancers versus GS7 cancers (P = 0.001), as well as pT3/pT4 versus pT2 cancers (P = 0.001). In addition, ACAT1 predicted biochemical recurrence in univariate (HR, 1.81, CI = 1.13-2.9, P = 0.0128), and multivariate models (HR, 1.69, CI = 1.01-2.81, P = 0.0431) including pre-operative PSA level, Gleason score and pathological stage. In univariate time-to-recurrence analysis, ACAT1 expression predicted recurrence in ERG negative cases (P = 0.0025), whereas ERG positive cases did not display any differences. Taken together, these findings indicate that ACAT1 expression could serve as a potential prognostic marker in prostate cancer, specifically in differentiating indolent and aggressive forms of cancer. © 2013 Wiley Periodicals, Inc.

  8. Prognostic significance of centromere 17 copy number gain in breast cancer depends on breast cancer subtype.

    Science.gov (United States)

    Lee, Kyuongyul; Jang, Min Hye; Chung, Yul Ri; Lee, Yangkyu; Kang, Eunyoung; Kim, Sung-Won; Kim, Yu Jung; Kim, Jee Hyun; Kim, In Ah; Park, So Yeon

    2017-03-01

    Increased copy number of chromosome enumeration probe (CEP) targeting centromere 17 is frequently encountered during HER2 in situ hybridization (ISH) in breast cancer. The aim of this study was to clarify the clinicopathologic significance of CEP17 copy number gain in a relatively large series of breast cancer patients. We analyzed 945 cases of invasive breast cancers whose HER2 fluorescence ISH reports were available from 2004 to 2011 at a single institution and evaluated the association of CEP17 copy number gain with clinicopathologic features of tumors and patient survival. We detected 186 (19.7%) cases of CEP17 copy number gain (CEP17≥3.0) among 945 invasive breast cancers. In survival analysis, CEP17 copy number gain was not associated with disease-free survival of the patients in the whole group. Nonetheless, it was found to be an independent adverse prognostic factor in the HER2-negative group but not in the HER2-positive group. In further subgroup analyses, CEP17 copy number gain was revealed as an independent poor prognostic factor in HER2-negative and hormone receptor-positive breast cancers, and it was associated with aggressive histologic variables including high T stage, high histologic grade, lymphovascular invasion, p53 overexpression, and high Ki-67 proliferative index. In conclusion, we found that elevated CEP17 count can serve as a prognostic marker in luminal/HER2-negative subtype of invasive breast cancer. We advocate the use of the dual-colored fluorescence ISH using CEP17 rather than the single-colored one because it gives additional valuable information on CEP17 copy number alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Histopathological Significance and Prognostic Impact of Tumor Budding in Colorectal Cancer.

    Science.gov (United States)

    Mehta, Anurag; Goswami, Malini; Sinha, Rupal

    2017-03-01

    Colorectal cancer (CRC) is a heterogeneous disease with complex etiology. New prognostic factors for this group of disease need to be investigated. This study evaluated the histopathological significance and prognostic impact of tumor budding in CRC. A total of 60 treatment naive consecutive patients undergoing surgical resection for CRC during the period of January 2011 to December 2013 were included in the study. Details of each patient related to their demographic and tumor profile were recorded. Pan Cytokeratin immunohistochemistry was applied on chosen sections and tumor budding was assessed. The most frequent site of involvement was rectosigmoid and sigmoid colon (31.6%). The majority of the cases were moderately differentiated (75%) in morphology, and showed tumor invasion into the pericolic/subserosal fat (66.6%), and were stage III (38.3%). Nodal involvement was present in 50% cases. Correlations between tumor budding and nodal involvement (p-value 0.039) and AJCC stage (p-value 0.021) were found to be statistically significant. Tumor budding may be a promising and powerful predictor of lymphnodal metastasis and a higher stage of tumor and can be used as a marker for assessing the aggressiveness of CRC. Routine hemotoxylin-eosin staining supported by cytokeratin immunostain can aid in the grading of tumor budding in CRC. © 2017 by the Association of Clinical Scientists, Inc.

  10. Expression of Fra-1 in human hepatocellular carcinoma and its prognostic significance.

    Science.gov (United States)

    Gao, Xiao-Qiang; Ge, Yong-Sheng; Shu, Qing-Hua; Ma, Hua-Xing

    2017-06-01

    This study aimed to explore the clinical significance and prognostic value of Fra-1 in hepatocellular carcinoma patients after curative resection. Fra-1 expression was investigated using a combination of techniques: immunohistochemistry for 66 samples of hepatocellular carcinoma and quantitative real-time polymerase chain reaction and western blotting assays for 19 matched hepatocellular carcinoma specimens. Fra-1 was present in 38 of 66 (57.6%) tumor tissues, with intense staining in the nuclei. There was also positive staining in 14 of 66 (21.2%) adjacent peritumoral tissues, with weak staining in the cytoplasm. Quantitative real-time polymerase chain reaction and western blotting assays confirmed higher expression of Fra-1 messenger RNA and Fra-1 protein in tumor tissues than adjacent non-tumor tissues for 19 hepatocellular carcinoma samples (p expression of Fra-1 was significantly related to vascular invasion and serum alpha-fetoprotein. Kaplan-Meier survival analysis found that overexpressed Fra-1 was correlated with poor overall survival and disease-free survival. Multivariate analysis identified Fra-1 as an independent prognostic factor. Fra-1 may be involved in the progress of hepatocellular carcinoma and could be a promising molecular candidate in the diagnosis and treatment of hepatocellular carcinoma.

  11. Clinicopathological and prognostic significance of HER-2/neu and VEGF expression in colon carcinomas

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    Li Jing

    2011-06-01

    Full Text Available Abstract Background HER-2/neu and VEGF expression is correlated with disease behaviors in various cancers. However, evidence for their expression in colon cancer is rather contradictory both for the protein expression status and prognostic value. HER-2/neu is found to participate in VEGF regulation, and has known correlation with VEGF expression in some tumors. In this study, we investigated HER-2/neu and VEGF expression in Chinese colon patients and explored whether there was any correlation between their expression patterns. Methods HER-2/neu and VEGF were investigated immunohistochemically using tumor samples obtained from 317 colon cancer patients with all tumor stages. Correlation of the degree of staining with clinicopathological parameters and survival was investigated. Results Positive expression rates of HER-2/neu and VEGF in colon cancer were 15.5% and 55.5% respectively. HER-2/neu expression was significantly correlated with tumor size and distant metastases (P (P > 0.05. Expression of VEGF was significantly correlated with tumor size, tumor stage, lymph node metastases, and distant metastases (P (P = 0.146. No correlation between HER-2/neu and VEGF expression was detected (P = 0.151. Conclusions HER-2/neu and VEGF are not important prognostic markers of colon cancer. The present results do not support any association between HER2/neu and VEGF expression in this setting.

  12. Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis.

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    Figarella-Branger, Dominique; Mokhtari, Karima; Colin, Carole; Uro-Coste, Emmanuelle; Jouvet, Anne; Dehais, Caroline; Carpentier, Catherine; Villa, Chiara; Maurage, Claude-Alain; Eimer, Sandrine; Polivka, Marc; Vignaud, Jean-Michel; Laquerriere, Annie; Sevestre, Henri; Lechapt-Zalcman, Emmanuelle; Quintin-Roué, Isabelle; Aubriot-Lorton, Marie-Hélène; Diebold, Marie-Danièle; Viennet, Gabriel; Adam, Clovis; Loussouarn, Delphine; Michalak, Sophie; Rigau, Valérie; Heitzmann, Anne; Vandenbos, Fanny; Forest, Fabien; Chiforeanu, Danchristian; Tortel, Marie-Claire; Labrousse, François; Chenard, Marie-Pierre; Nguyen, Anh Tuan; Varlet, Pascale; Kemeny, Jean Louis; Levillain, Pierre-Marie; Cazals-Hatem, Dominique; Richard, Pomone; Delattre, Jean-Yves

    2015-07-01

    Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO. © 2014 International Society of Neuropathology.

  13. Histological Subtype Remains a Significant Prognostic Factor for Survival Outcomes in Patients With Appendiceal Mucinous Neoplasm With Peritoneal Dissemination.

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    Huang, Yeqian; Alzahrani, Nayef A; Chua, Terence C; Morris, David L

    2017-04-01

    It has been increasingly recognized that appendiceal mucinous neoplasm with peritoneal dissemination is not a homogenous disease. This study aimed to examine the impact of different histological subtypes on survival of a large cohort of patients with appendiceal mucinous neoplasms uniformly treated by cytoreductive surgery and intraperitoneal chemotherapy. This was a retrospective study of prospectively collected data of patients with peritoneal dissemination of appendiceal neoplasm who underwent cytoreductive surgery and intraperitoneal chemotherapy. The study was conducted by 1 surgical team at St. George Hospital. A total of 444 patients formed the cohort of this study. Histological diagnoses were categorized based on Carr criteria to include acellular mucin, disseminated peritoneal adenomucinosis, peritoneal mucinous neoplasms without signet ring cells, and peritoneal mucinous carcinomatosis with signet cells. Patients with low-grade appendiceal mucinous neoplasms with neoplastic epithelium absent tended to have lower CEA, CA19-9, and CA125 levels preoperatively (p = 0.109, 0.008, and 0.034). Factor analysis showed that histological diagnosis was an independent prognostic factor for survival outcomes (HR = 3.13 (95% CI, 2.34-4.39); p 20, completeness of cytoreductive score ≥2, use of early postoperative intraperitoneal chemotherapy, transfusion units, CEA >7.0 mg/L, CA19-9 >24.0 U/mL, and CA125 >24 U/mL. This study was limited by its retrospective nature, lack of uniform classifications of appendiceal mucinous neoplasms in early years, and the heterogeneity of this study cohort given the long study period. Histological subtype remains a significant prognostic factor for survival outcomes in patients with appendiceal mucinous neoplasms. It should be taken into account when selecting patients for cytoreductive surgery, tailoring appropriate adjuvant therapies and follow-up surveillance plan.

  14. Prognostic Value of Gai′s Plaque Score and Agatston Coronary Artery Calcium Score for Functionally Significant Coronary Artery Stenosis

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    Chuang Zhang; Shuang Yang; Lu-Yue Gai; Zhi-Qi Han; Qian Xin; Xiao-Bo Yang; Jun-Jie Yang; Qin-Hua Jin

    2016-01-01

    Background: The prognostic values of the coronary computed tomography angiography (CCTA) score for predicting future cardiovascular events have been previously demonstrated in numerous studies. However, few studies have used the rich information available from CCTA to detect functionally significant coronary lesions. We sought to compare the prognostic values of Gai's plaque score and the coronary artery calcium score (CACS) of CCTA for predicting functionally significant coronary lesions, us...

  15. Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients.

    Science.gov (United States)

    Liu, Ning Qing; De Marchi, Tommaso; Timmermans, Annemieke; Trapman-Jansen, Anita M A C; Foekens, Renée; Look, Maxime P; Smid, Marcel; van Deurzen, Carolien H M; Span, Paul N; Sweep, Fred C G J; Brask, Julie Benedicte; Timmermans-Wielenga, Vera; Foekens, John A; Martens, John W M; Umar, Arzu

    2016-08-25

    We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways associated to its expression through gene set enrichment analysis (GSEA). A total of 461 TNBC paraffin-embedded tissues were collected from different academic hospitals in Europe, incorporated into tissue micro-arrays (TMA), and stained for CMPK1 expression. We also collected gene expression data of 60 samples, which were also present in the TMA, for GSEA correlation analysis. CMPK1 IHC staining showed both cytoplasmic and nuclear components. While cytoplasmic CMPK1 did not show any association to metastasis free survival (MFS), nuclear CMPK1 was associated to poor prognosis independently from other prognostic factors in stratified Cox regression analyses. GSEA correlation analysis of the nuclear CMPK1-stratified gene expression dataset showed a significant enrichment of extracellular matrix (ECM; positive correlation) and cell cycle (negative correlation) associated genes. We have shown here that nuclear CMPK1 is indicative of poor prognosis in TNBCs and that its expression may be related to dysregulation of ECM and cell cycle molecules.

  16. Prognostic Significance of BMI-1 But Not MEL-18 Expression in Pulmonary Squamous Cell Carcinoma.

    Science.gov (United States)

    Abe, Sosei; Yamashita, Shin-Ichi; Miyahara, S O; Wakahara, Junichi; Yamamoto, Leona; Mori, Ryo; Imamura, Naoko; Yoshida, Yasuhiro; Waseda, Ryuichi; Hiratsuka, Masafumi; Shiraishi, Takeshi; Nabeshima, Kazuki; Iwasaki, Akinori

    2017-04-01

    We investigated the possibility of BMI-1 and MEL-18 to predict survival in patients with pulmonary squamous cell carcinoma. One hundred and ninety-nine patients underwent surgery in our Institute between 1995 and 2005. We used immunohistochemical (IHC) analysis to determine the expressions of BMI-1 and MEL-18 and compared them with clinicopathological factors and survival. Forty-one of 199 cases (21%) were BMI-1-positive. No correlation was found between BMI-1 and MEL-18 expression by IHC and clinicopathological factors. Five-year overall survival in the BMI-1-positive group (66.8%), but not MEL-18, was significantly better than that in the negative group (45.5%, p=0.04). In multivariate analysis, positive BMI-1 was a better prognostic factor of overall survival (hazard ratio (HR)=0.561, 95% confidence interval (CI)=0.271-1.16, p=0.12). BMI-1 expression, but not MEL-18, is associated with a favorable prognosis and is a possible prognostic factor of pulmonary squamous cell carcinoma. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  17. Prognostic significance of new immunohistochemical markers in refractory classical Hodgkin lymphoma: a study of 59 cases.

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    Danielle Canioni

    Full Text Available Although most classical Hodgkin lymphoma patients are cured, a significant minority fail after primary therapy and may die as result of their disease. To date, there is no consensus on biological markers that add value to usual parameters (which comprise the International Prognostic Score used at diagnosis to predict outcome. We evaluated 59 patients (18 with primary refractory or early relapse disease and 41 responders for bcl2, Ki67, CD20, TiA1 and c-kit expression by semi-quantitative immunohistochemical study and correlated the results with the response to treatment.The results showed that expression of bcl2 and CD20 in Hodgkin and Reed Sternberg cells, and expression of TiA1 in micro-environmental lymphocytes, and c-kit positive mast cells in microenvironment, were independent prognostic markers. These novel cHL markers could be used in association with clinical parameters to identify newly diagnosed patients with favorable or unfavorable prognosis and to better tailor treatment for different risk groups.

  18. Prognostic significance of tumour vascularisation on survival of patients with advanced ovarian carcinoma.

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    Labiche, Alexandre; Elie, Nicolas; Herlin, Paulette; Denoux, Yves; Crouet, Hubert; Heutte, Natacha; Joly, Florence; Héron, Jean-François; Gauduchon, Pascal; Henry-Amar, Michel

    2009-04-01

    The prognostic significance of microvessel density in ovarian cancer is still a matter of debate. Classically, the degree of vascularisation is assessed in areas of high vascular density (hot spots), considered as regions of increased probability of metastasis. Since ovarian tumours have a particular progression and dissemination behaviour, vascularisation outside hot spots may also contribute to their evolution. In the present study, the degree of tumour vascularisation was estimated both in whole histogical sections and in hot spots, in 235 patients with ovarian carcinoma, using fully automatic image analysis methods. Six parameters were estimated: mean microvessel density (MVD) and mean microvessel surface fraction (MSP) on the whole section, mean and maximum values of MVD and MSP inside hot spots (MVDHS1, MSPHS1 and MVDHS2, MSPHS2). Relationships between vascular parameters and clinicopathologic features were analysed. In stage III-IV patients multivariate analysis showed that stage IV disease (hazards ratio (HR)=1.72, p=0.001), post-surgical residual disease 1cm (HR=2.86, p<0.001), upper MVD tercile (HR=1.45, p<0.022) and medial MVDHS1 tercile (HR=1.36, p=0.060) retained an independent prognostic value upon overall survival. Our results suggest that quantification of blood vessels, both on the whole histological section and in hot spots might be helpful in evaluating prognosis in advanced ovarian carcinomas.

  19. Clinical Significance and Prognostic Value of the Expression of LAMP3 in Oral Squamous Cell Carcinoma

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    Jun Lu

    2017-01-01

    Full Text Available Recent studies demonstrated high expression of lysosome-associated membrane protein 3 (LAMP3 in a variety of malignancies including esophageal squamous cell carcinoma, gastrointestinal cancer, breast cancer, and cervical cancer and its involvement in several biological activities of tumor cells. However, the expression of LAMP3 and its value in oral squamous cell carcinoma (OSCC remain unclear. In this study, we examined the expression of LAMP3 in OSCC tissue samples and investigated the relationship between LAMP3 and clinical characteristics of patients with OSCC. We examined mRNA and protein levels of LAMP3 in OSCC tissues and neighboring normal tissues using quantitative real-time polymerase chain reaction and immunohistochemistry analyses, respectively. Both the mRNA and protein levels of LAMP3 were significantly higher in OSCC tissues than in adjacent normal tissues. Chi-square analysis showed that the high LAMP3 expression was notably linked to the degree of tumor differentiation and advanced TNM stage. Univariate and multivariate analyses showed that the high LAMP3 expression was an independent prognostic marker in OSCC. Our results suggest that LAMP3 might act as a potential anticancer target and a prognostic marker in patients with OSCC.

  20. Prognostic Significance of Aquaporin 5 Expression in Non-small Cell Lung Cancer

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    Young Min Jo

    2016-03-01

    Full Text Available Background: Aquaporins are water channel proteins that play a major role in the movement of water in various human tissues. Recently, it has been found that aquaporins have influence in the carcinogenesis of human malignancies. We analyzed the prognostic impact of aquaporin 5 (AQP5 in non-small lung cancer (NSCLC. Methods: Seventy-six cases of NSCLC were studied, including 44 cases of adenocarcinoma (ADC and 32 cases of squamous cell carcinoma (SQCC. Tissue microarray was constructed and immunohistochemical staining for AQP5 was performed. Results: AQP5 was positive in 59.2% of the total enrolled NSCLCs (63.7% in ADC and 53.1% in SQCC. The difference in expression of AQP5 according to the histologic grade of the tumor was significant (p<.047, but not in a serial order. When ADC and SQCC were separately evaluated, no significant difference was observed according to the histologic grade of the tumor (p=.076 in ADC and p=.631 in SQCC. No difference was observed between AQP5 expression and other demographic data and tumor characteristics. Disease-free survival (DFS was higher in AQP5 negative cases than positive cases in ADC (p=.047, but no significance was found in SQCC (p=.068. We were unable to find a significance between AQP5 overexpression and overall survival in either ADC (p=.210 or SQCC (p=.533. Conclusions: AQP5 expression is associated with DFS in ADC of the lung and tumor grade of NSCLC. The present study suggests that AQP5 can be a prognostic factor of NSCLC.

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

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    Carmen Bellas

    Full Text Available 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.

  2. The new histologic classification of lung primary adenocarcinoma subtypes is a reliable prognostic marker and identifies tumors with different mutation status: the experience of a French cohort.

    Science.gov (United States)

    Mansuet-Lupo, Audrey; Bobbio, Antonio; Blons, Hélène; Becht, Etienne; Ouakrim, Hanane; Didelot, Audrey; Charpentier, Marie-Christine; Bain, Serge; Marmey, Béatrice; Bonjour, Patricia; Biton, Jérôme; Cremer, Isabelle; Dieu-Nosjean, Marie-Caroline; Sautès-Fridman, Catherine; Régnard, Jean-François; Laurent-Puig, Pierre; Alifano, Marco; Damotte, Diane

    2014-09-01

    Histologic classification of lung adenocarcinoma subtype has a prognostic value in most studies. However, lung adenocarcinoma characteristics differ across countries. Here, we aimed at validating the prognostic value of this classification in a large French series of lung adenocarcinoma. We reviewed 407 consecutive lung adenocarcinomas operated on between 2001 and 2005 and reclassified them according to the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification and subsequently graded them into low, intermediate, and high grade. We analyzed the relevance of this classification according to clinical, pathologic, and molecular analysis. Patients (median age, 61 years; 288 men) underwent lobectomy (n = 378) or pneumonectomy (n = 29). Patients' overall survival at 5 and 10 years was 53.2% and 32.6%, respectively. Union for International Cancer Control stage distribution was 189 stage I, 104 stage II, 107 stage III, and seven stage IV. Low-grade tumor was found in one patient, intermediate grade in 275 patients, and high grade in 131 patients. KRAS and EGFR mutations were detected in 34% and 9.6%, respectively. Histologic grade was significantly correlated with extent of resection (P = .01), thyroid transcriptional factor-1 expression (P = .00000001), vascular emboli (P = .03), and EGFR mutations (P = .01). Mucinous adenocarcinomas were associated with KRAS mutations (P = .003). At univariate analysis, age, extent of resection, histologic grade, pleural invasion, vascular emboli, pathologic T and N, and stage were predictive of survival. At multivariate analysis, age (P = .0001), histologic grade (P = .03), and stage (P = .000003) were independent prognostic factors. IASLC/ATS/ERS classification of lung adenocarcinomas predicts survival in French population. Histologic grade correlates with clinical, pathologic and molecular parameters suggesting different oncogenic pathways.

  3. Prognostic Significance of Progesterone Receptor–Positive Tumor Cells Within Immunohistochemically Defined Luminal A Breast Cancer

    Science.gov (United States)

    Prat, Aleix; Cheang, Maggie Chon U.; Martín, Miguel; Parker, Joel S.; Carrasco, Eva; Caballero, Rosalía; Tyldesley, Scott; Gelmon, Karen; Bernard, Philip S.; Nielsen, Torsten O.; Perou, Charles M.

    2013-01-01

    Purpose Current immunohistochemical (IHC)-based definitions of luminal A and B breast cancers are imperfect when compared with multigene expression-based assays. In this study, we sought to improve the IHC subtyping by examining the pathologic and gene expression characteristics of genomically defined luminal A and B subtypes. Patients and Methods Gene expression and pathologic features were collected from primary tumors across five independent cohorts: British Columbia Cancer Agency (BCCA) tamoxifen-treated only, Grupo Español de Investigación en Cáncer de Mama 9906 trial, BCCA no systemic treatment cohort, PAM50 microarray training data set, and a combined publicly available microarray data set. Optimal cutoffs of percentage of progesterone receptor (PR) –positive tumor cells to predict survival were derived and independently tested. Multivariable Cox models were used to test the prognostic significance. Results Clinicopathologic comparisons among luminal A and B subtypes consistently identified higher rates of PR positivity, human epidermal growth factor receptor 2 (HER2) negativity, and histologic grade 1 in luminal A tumors. Quantitative PR gene and protein expression were also found to be significantly higher in luminal A tumors. An empiric cutoff of more than 20% of PR-positive tumor cells was statistically chosen and proved significant for predicting survival differences within IHC-defined luminal A tumors independently of endocrine therapy administration. Finally, no additional prognostic value within hormonal receptor (HR) –positive/HER2-negative disease was observed with the use of the IHC4 score when intrinsic IHC-based subtypes were used that included the more than 20% PR-positive tumor cells and vice versa. Conclusion Semiquantitative IHC expression of PR adds prognostic value within the current IHC-based luminal A definition by improving the identification of good outcome breast cancers. The new proposed IHC-based definition of luminal A

  4. Prognostic value of a novel risk classification of microvascular invasion in patients with hepatocellular carcinoma after resection.

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    Zhao, Hui; Chen, Chuang; Fu, Xu; Yan, Xiaopeng; Jia, Wenjun; Mao, Liang; Jin, Huihan; Qiu, Yudong

    2017-01-17

    The present research aimed to evaluate the prognostic value of a novel risk classification of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) after resection. A total of 295 consecutive HCC patients underwent hepatectomy were included in our study. We evaluated the degree of MVI according to the following three features: the number of invaded microvessels (≤5 vs >5), the number of invading carcinoma cells (≤ 50 vs >50), the distance of invasion from tumor edge (≤1 cm vs >1 cm). All patients were divided into three groups according to the three risk factors of MVI: non-MVI group (n=180), low-MVI group (n=60) and high-MVI group (n=55). The overall survival (OS) and recurrence-free survival (RFS) rates of high-MVI group were significantly poorer than those of low-MVI and non-MVI groups (Prisk factors for OS after hepatectomy. High-MVI, type of resection and tumor size were risk factors for RFS. In subgroup analyses, the OS and RFS rates of low-MVI and non-MVI groups were better than high-MVI group regardless of tumor size. In high-MVI group, anatomical liver resection (n=28) showed better OS and RFS rates compared with non-anatomical liver resection (n=29) (P=0.012 and P=0.002). The novel risk classification of MVI based on histopathological features is valuable for predicting prognosis of HCC patients after hepatectomy.

  5. Significance of MNK1 in prognostic prediction and chemotherapy development of epithelial ovarian cancer.

    Science.gov (United States)

    Hou, S; Du, P; Wang, P; Wang, C; Liu, P; Liu, H

    2017-09-01

    Ovarian cancer is the most lethal gynecologic malignancy worldwide with surgery as the only curative treatment. Long-term overall survival (OS) of ovarian cancer is far from satisfactory, even though significant improvement has been made in post-operative chemotherapy. One of the most important death cause is the chemoresistance due to consecutive chemotherapy. Therefore, understanding the molecular mechanisms involved in ovarian cancer development and identification of novel therapeutic targets are urgently required. Immunohistochemical (IHC) staining was used to explore the expression pattern of mitogen-activated protein kinase (MAPK)-interacting kinase 1 (MNK1) in tumor tissues from 138 epithelial ovarian cancer (EOC) patients. Clinicopathological data were subjected to Kaplan-Meier survival and Cox multivariate analyses to evaluate the prognostic value of MNK1 in EOC. Overexpression and silencing procedures were performed on OVCAR-5 cells to investigate the mechanisms of MNK1 in regulating EOC development. The anti-tumor effects of CGP57380, a specific MNK inhibitor, were examined by cell viability assay. Higher MNK1 expression showed significant relationship with advanced FIGO stage and positive lymph node metastasis of EOC. Univariate and multivariate analyses revealed that MNK1 was an independent prognostic factor for OS of EOC patients. In vitro study demonstrated that MNK1 can promote cell proliferation through regulating the phosphorylation level of eukaryotic initiation factor 4E. In addition, inhibition of MNK1 by CGP57380 significantly down-regulated the OVCAR-5 cell viability. High MNK1 expression in EOC tissues indicates poor clinical outcomes, and MNK1 can act as a potential target for novel chemotherapy development towards EOC.

  6. Prognostic significance of vascular and lymphatic emboli in resected pulmonary adenocarcinoma.

    Science.gov (United States)

    Strano, Salvatore; Lupo, Audrey; Lococo, Filippo; Schussler, Olivier; Loi, Mauro; Younes, Mohamad; Bobbio, Antonio; Damotte, Diane; Regnard, Jean-François; Alifano, Marco

    2013-04-01

    The incidence of vascular and lymphatic emboli in a specimen of resected non-small cell lung cancer is variable according to different authors' experience as well as prognostic significance in patients treated by surgery. We aimed at evaluating these factors in an unselected population of patients with primary pulmonary adenocarcinoma treated by major surgical resection. Clinical and pathology records of all patients treated by lobectomy or pneumonectomy and nodal dissection for pulmonary adenocarcinoma between June 2001 and June 2006 were retrospectively reviewed. Impact on survival of age, sex, tobacco use, history of chronic obstructive pulmonary disease, extent of resection, pathologic stage, and presence of vascular and lymphatic emboli was studied by univariate analysis and multivariate analysis (for factors significantly associated with survival at univariate analysis). Five hundred three patients underwent lobectomy or pneumonectomy with nodal dissection for pathologically proven lung adenocarcinoma. There were 355 men and 148 women; mean age was 61.1 years, and 181 patients were 65 years old or older; 87% were current or former smokers; 90.3% had pulmonary lobectomy; and 9.7% had pneumonectomy. Pathologic stages were I, II, and III/IV in 45%, 17.9%, and 37.1%, respectively. Vascular emboli and lymphatic emboli were found in 183 of 503 patients (36.4%) and 149 of 503 (29.6%), respectively. Overall 5-year survival for the whole population was 50.7%. At univariate analysis, age more than 65 years (p=0.0019), chronic obstructive pulmonary disease (p=0.042), extent of resection (p=0.047), pathologic stage (p<0.0000001), T size (p=0.0020), T and N variables (p=0.0000016 and p<0.0000001, respectively), presence of vascular emboli (p=0.026), and presence of lymphatic emboli (p=0.000021) were associated with worse prognosis. At multivariate analysis, age more than 65 years (p=0.0047, relative risk 1.5), stage I versus II versus III versus IV (p=0.00000032), and

  7. TOURISM AND ITS SIGNIFICANCE: THE EXPERIENCE OF MULTIDIMENSIONAL CLASSIFICATION

    Directory of Open Access Journals (Sweden)

    I. N. Tikunova

    2015-01-01

    Full Text Available The system of indicators, that give an overall picture about market situation of the international tourism in 35 countries of Europe, was characterized. Based on the obtained absolute and relative performance rankings carried out using the evaluation algorithm for automatic classification, identify three groups of countries with similar parameters. Also their geographical characteristics was given. In the second experiment, the countries of Europe were compared with the most famous tourist regions of the world.

  8. Prognostic Significance of Heart Rate and its Long-term Trend in Cardiac Transplant Patients.

    Science.gov (United States)

    Barge-Caballero, Eduardo; Jiménez-López, Jesús; Chávez-Leal, Sergio; Barge-Caballero, Gonzalo; Paniagua-Martin, María Jesús; Marzoa Rivas, Raquel; Grille-Cancela, Zulaika; Cuenca-Castillo, José Joaquín; Castro-Beiras, Alfonso; Crespo-Leiro, María G

    2015-11-01

    The aim of the present study was to examine the prognostic significance of heart rate and its trend in heart transplantation. This observational study enrolled 170 patients who received a bicaval heart transplant between 1995 and 2005; all were in sinus rhythm. The resting heart rate was determined via electrocardiography at the end of the first posttransplant year and annually until the tenth year. Cox analysis was used to evaluate the incidence of adverse events with a mean (standard deviation) follow-up of 8.9 (3.1) years. The primary study end point was the composite outcome of death or graft dysfunction. The resting heart rate at the end of the first posttransplant year was an independent predictor of the primary composite end point (hazard ratio=1.054; 95% confidence interval, 1.028-1.080; P<.001) and was significantly associated with total mortality (hazard ratio=1.058; 95% confidence interval, 1.030-1.087; P<.001) and mortality from cardiac causes (hazard ratio=1.069; 95% confidence interval, 1.026-1.113; P=.001), but not with graft dysfunction (hazard ratio=1.028; 95% confidence interval, 0.989-1.069; P=.161). For patients with a heart rate ≥ 105 or<90 bpm vs those with 90-104 bpm, the hazard ratios of the primary end point were 2.233 (95% confidence interval, 1.250-3.989; P=.007) and 0.380 (95% confidence interval, 0.161-0.895; P=.027), respectively. Heart rate tended to decrease in the first 10 years after transplantation (P=.001). Patients with a net increase in heart rate during follow-up showed a higher incidence of adverse events. An elevated heart rate is an adverse prognostic marker after heart transplantation. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

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    Pistelli, Mirco, E-mail: mirco.pistelli@alice.it; Caramanti, Miriam [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Biscotti, Tommasina; Santinelli, Alfredo [Anatomia Patologica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy)

    2014-06-27

    Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

  10. Beta blocker dose and markers of sympathetic activation in heart failure patients: interrelationships and prognostic significance.

    Science.gov (United States)

    Cohen-Solal, Alain; Jacobson, Arnold F; Piña, Ileana L

    2017-11-01

    Extent of cardiac sympathetic activation can be estimated from physiological parameters, blood biomarkers, and imaging findings. This study examined the prognostic value of three markers of sympathetic activity and their relationship to beta blocker dose in heart failure patients. A post hoc analysis of 858 heart failure subjects in the ADMIRE-HF trial was performed. Variables related to sympathetic activity were plasma norepinephrine, baseline heart rate, the heart to mediastinum (H/M) ratio of 123 I-mIBG uptake, and beta blocker dose. Univariate and multivariate analyses for occurrence of mortality (all-cause and cardiac) and arrhythmic events were performed. Beta blocker dose was significantly related to age, heart rate, b-type natriuretic peptide (negatively), body mass index, body weight and plasma norepinephrine. Univariate predictors of all-cause and cardiac mortality were baseline heart rate (χ2  = 4.5, P = 0.029 and χ2  = 5 .2, P = 0.022, respectively), plasma norepinephrine level (χ2  = 8.9, P = 0.0006 and χ2  = 8.6, P = 0.003, respectively), and H/M (χ = 22.4, P 67 b.p.m. was associated with significantly higher cardiac mortality. Higher beta blocker dose was associated with lower mortality, but of the variables associated with sympathetic activity examined, cardiac 123 I-mIBG uptake was the most powerful prognostic marker in heart failure patients. Elevated heart rate was associated with greater risk for cardiac death. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

  11. VEGF and Id-1 in pancreatic adenocarcinoma: prognostic significance and impact on angiogenesis.

    Science.gov (United States)

    Georgiadou, D; Sergentanis, T N; Sakellariou, S; Filippakis, G M; Zagouri, F; Vlachodimitropoulos, D; Psaltopoulou, T; Lazaris, A C; Patsouris, E; Zografos, G C

    2014-10-01

    The significance of vascular endothelial growth factor (VEGF) and inhibitor of differentiation/DNA synthesis (Id-1) in tumor neoangiogenesis and tumor progression in pancreatic ductal adenocarcinoma (PDAC) is still unclear. Given the central role of VEGF in cancer angiogenesis and the inconclusive results on Id-1 expression in PDAC, it is of great interest to investigate whether Id-1 and VEGF expression are associated with angiogenesis and prognosis in PDAC. Paraffin-embedded specimens from 60 consecutive patients with PDAC were immunostained for VEGF, Id-1 and CD34 and staining quantification was assessed by Image analysis system. The correlations among the expression of individual angiogenic factors and microvessel density (MVD), clinicopathologic features and clinical prognosis were analyzed. Id-1 and VEGF Positive Activity Indices (PAIs) closely correlated with each other. MVD positively correlated with both Id-1 and VEGF expression. More advanced T and N status correlated with more intense expression of Id-1, VEGF and higher MVD. With regard to prognostic significance higher Id-1 PAI (adjusted HR = 1.69, 95%CI: 1.10-2.59, p = 0.017), higher VEGF PAI (adjusted HR = 2.66, 95%CI: 1.09-6.50, p = 0.032), and MVD (adjusted HR = 1.55, 95%CI: 1.27-1.88, p < 0.001) were associated with poorer survival. VEGF and Id-1 overexpression were found to be associated with high MVD and emerged as adverse prognostic factors in terms of patient survival in PDAC. The potential of selective anti-angiogenic targeting therapy for pancreatic malignancies should prompt further validation of the present findings in studies encompassing larger samples and more elaborate techniques. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    Directory of Open Access Journals (Sweden)

    Mirco Pistelli

    2014-06-01

    Full Text Available Background: Triple-negative breast cancers (TNBC are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001 and a lympho-vascular invasion (p = 0.01, but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72 or overall survival (p = 0.93. Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

  13. Diagnostic and prognostic significance of flow cytometry immunophenotyping in patients with leptomeningeal carcinomatosis.

    Science.gov (United States)

    Subirá, D; Simó, M; Illán, J; Serrano, C; Castañón, S; Gonzalo, R; Granizo, J J; Martínez-García, M; Navarro, M; Pardo, J; Bruna, J

    2015-04-01

    Some patients with epithelial-cell cancers develop leptomeningeal carcinomatosis (LC), a severe complication difficult to diagnose and with an adverse prognosis. This study explores the contribution of flow cytometry immunophenotyping (FCI) to the diagnosis and prognosis of LC. Cerebrospinal fluid (CSF) samples from patients diagnosed with LC were studied using FCI. Expression of the epithelial-cell adhesion molecule (EpCAM) was the criterion used to identify the epithelial cells. To test the diagnostic precision, 144 patients (94 diagnosed with LC) were included. The prognostic value of FCI was evaluated in 72 patients diagnosed with LC and eligible for therapy. Compared with cytology, FCI showed greater sensitivity and negative predictive value (79.79 vs. 50%; 68.85 vs. 51.55%, respectively), but lower specificity and positive predictive value (84 vs. 100%; 90.36 vs. 100%, respectively). The multivariate analysis revealed that the percentage of CSF EpCAM+ cells predicted an increased risk of death (HR: 1.012, 95% CI 1.000-1.023; p=0.041). A cut-off value of 8% EpCAM+ cells in the CSF distinguished two groups of patients with statistically significant differences in overall survival (OS) (p=0.018). This cut-off value kept its statistical significance regardless of the absolute CSF cell-count. The FCI study of the CSF improved the sensitivity for diagnosing LC, but refinement of the technique is needed to improve specificity. Furthermore, quantification of CSF EpCAM+ cells was revealed to be an independent prognostic factor for OS in patients with LC eligible for therapy. An 8% cut-off value contributed to predicting clinical evolution before initiation of therapy.

  14. Prognostic significance of Epstein-Barr virus (EBV) infection in Hodgkin lymphoma patients.

    Science.gov (United States)

    Myriam, Ben Dhiab; Sonia, Ziadi; Hanene, Saad; Teheni, Louhichi; Mounir, Trimeche

    2017-03-01

    The prognostic significance of Epstein-Barr virus (EBV) infection in Hodgkin lymphoma (HL) is still controversial. In this work we sought to examine the prognostic differences between EBV-positive and -negative HL through a series of 131 cases from Tunisia. The status of EBV was assessed by EBV-encoded RNA (EBER) in situ hybridization. Results were correlated to patients' characteristics and outcome. EBV was detected in the malignant cells in 62 of 131 HL cases (47.3%). EBV-positive HL was associated with extreme age classes (≤15 and > 45 years; p = 0.0001), male gender (p = 0.008), mixed cellularity histologic subtype (p = 0.03), and inversely with leukocytosis (white blood cells ≥15000/mm3) (p = 0.004) and bulky mediastinum (mediastinal-thoracic ratio≥ 0.35) (p = 0.0001). On analysis of all patients, no significant difference between survival rates was found between EBV-positive and EBV-negative HL. In contrast, subgroups analysis revealed a negative effect of EBV infection in terms of overall survival in patients with Ann Arbor stages I/II (p = 0.03) and nodular sclerosis HL subgroup (p = 0.01), and in terms of event free survival in patients with mediastinal-thoracic ratio less than 0.35 (p = 0.03). These results suggest that EBV infection affects the survival of particular subgroups of HL, especially those with early-stage of the disease. Copyright © 2016. Published by Elsevier Ltd.

  15. Clinicopathological and prognostic significance of survivin expression in renal cancer patients: a meta-analysis.

    Science.gov (United States)

    Ma, Chengquan; Lu, Bingxin; Sun, Erlin

    2017-04-01

    Survivin has been reported to play a role in the diagnosis and prognosis of renal cell carcinoma (RCC); however, published data on this subject are conflicting. To conduct a meta-analysis to evaluate the impact of survivin as a prognostic marker and its association with clinicopathological variables in patients with RCC. Comprehensive searches of electronic databases (PubMed, ISI Web of Knowledge Embase, Google Scholar Web and the Cochrane Library) were updated to June 2016 to retrieve eligible studies. The association strength was measured with relative risks (RRs) and pooled HRs with 95% CIs, which were extracted and pooled to determine the association between survivin expression and patient survival and clinicopathological features. Ten studies with 1063 cases of RCC were included. Positive survivin expression in RCC was associated with the TNM stage (pooled RR 1.49; 95% CI 1.07 to 2.07) or Fuhrman grade (pooled RR 1.63; 95% CI 1.15 to 2.32) in patients. The correlation between survivin expression and gender was not significant (pooled RR 0.97; 95% CI 0.83 to 1.15). In addition, a considerable association was found between survivin expression and overall survival for patients with RCC (pooled HR 1.94; 95% CI 1.24 to 3.05 (multivariate model) and 5.41; 95% CI 4.08 to 7.17 (univariate model)). Our results indicate that survivin is of prognostic significance in patients with RCC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. The prognostic significance of HOTAIR for predicting clinical outcome in patients with digestive system tumors.

    Science.gov (United States)

    Ma, Gaoxiang; Wang, Qiaoyan; Lv, Chunye; Qiang, Fulin; Hua, Qiuhan; Chu, Haiyan; Du, Mulong; Tong, Na; Jiang, Yejuan; Wang, Meilin; Zhang, Zhengdong; Wang, Jian; Gong, Weida

    2015-12-01

    Although some studies have assessed the prognostic value of HOTAIR in patients with digestive system tumors, the relationship between the HOTAIR and outcome of digestive system tumors remains unknown. The PubMed was searched to identify the eligible studies. Here, we performed a meta-analysis with 11 studies, including a total of 903 cases. Pooled hazard ratios (HRs) and 95 % confidence interval (CI) of HOTAIR for cancer survival were calculated. We found that the pooled HR elevated HOTAIR expression in tumor tissues was 2.36 (95 % CI 1.88-2.97) compared with patients with low HOTAIR expression. Moreover, subgroup analysis revealed that HOTAIR overexpression was also markedly associated with short survival for esophageal squamous cell carcinoma (HR 2.19, 95 % CI 1.62-2.94) and gastric cancer (HR 1.66, 95 % CI 1.02-2.68). In addition, up-regulated HOTAIR was significantly related to survival of digestive system cancer among the studies with more follow-up time (follow time ≥ 5 years) (HR 2.51, 95 % CI 1.99-3.17). When stratified by HR resource and number of patients, the result indicated consistent results with the overall analysis. Subgroup analysis on ethnicities did not change the prognostic influence of elevated HOTAIR expression. Additionally, we conducted an independent validation cohort including 71 gastric cancer cases, in which patients with up-regulated HOTAIR expression had an unfavorable outcome with HR of 2.10 (95 % CI 1.10-4.03). The results suggest that aberrant HOTAIR expression may serve as a candidate positive marker to predict the prognosis of patients with carcinoma of digestive system.

  17. MicroRNAs at the human 14q32 locus have prognostic significance in osteosarcoma

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    Sarver Aaron L

    2013-01-01

    Full Text Available Abstract Background Deregulation of microRNA (miRNA transcript levels has been observed in many types of tumors including osteosarcoma. Molecular pathways regulated by differentially expressed miRNAs may contribute to the heterogeneous tumor behaviors observed in naturally occurring cancers. Thus, tumor-associated miRNA expression may provide informative biomarkers for disease outcome and metastatic potential in osteosarcoma patients. We showed previously that clusters of miRNAs at the 14q32 locus are downregulated in human osteosarcoma. Methods Human and canine osteosarcoma patient’s samples with clinical follow-up data were used in this study. We used bioinformatics and comparative genomics approaches to identify miRNA based prognostic biomarkers in osteosarcoma. Kaplan-Meier survival curves and Whitney Mann U tests were conducted for validating the statistical significance. Results Here we show that an inverse correlation exists between aggressive tumor behavior (increased metastatic potential and accelerated time to death and the residual expression of 14q32 miRNAs (using miR-382 as a representative of 14q32 miRNAs in a series of clinically annotated samples from human osteosarcoma patients. We also show a comparable decrease in expression of orthologous 14q32 miRNAs in canine osteosarcoma samples, with conservation of the inverse correlation between aggressive behavior and expression of orthologous miRNA miR-134 and miR-544. Conclusions We conclude that downregulation of 14q32 miRNA expression is an evolutionarily conserved mechanism that contributes to the biological behavior of osteosarcoma, and that quantification of representative transcripts from this family, such as miR-382, miR-134, and miR-544, provide prognostic and predictive markers that can assist in the management of patients with this disease.

  18. Prognostic significance of a positive surgical margin in pathologically organ-confined prostate cancer.

    Science.gov (United States)

    Ahyai, Sascha A; Zacharias, Mario; Isbarn, Hendrik; Steuber, Thomas; Eichelberg, Christian; Köllermann, Jens; Fisch, Margit; Karakiewicz, Pierre I; Huland, Hartwig; Graefen, Markus; Chun, Felix K-H

    2010-08-01

    To identify risk factors of a positive surgical margin (PSM) and the significance of a PSM after radical prostatectomy (RP) on biochemical recurrence (BCR) in exclusively pathologically confirmed organ-confined (OC) prostate cancer, as despite an excellent prognosis after RP, some patients with pathologically confirmed OC disease have BCR, and the prognostic significance of a PSM in these men remains unclear. We assessed 932 men with pathologically OC disease who were treated with RP by nine different surgeons between 1992 and 2004. The prognostic significance of clinical and pathological variables, including tumour volume (TV) and percentage of high-grade TV (%HGTV) were assessed. Logistic and Cox regression models were fitted to identify risk factors of a PSM and BCR. BCR was defined as a prostate-specific antigen (PSA) level of 0.1 ng/mL and increasing after an undetectable PSA level. The total PSM rate was 12.9% (120 men); the mean TV (P < 0.001), but not %HGTV (P= 0.2) was significantly higher in patients with PSM. TV, nerve-sparing RP technique and surgical volume were independent risk factors for a PSM (P= 0.03). After a median follow-up of 35 months the overall BCR rate was 8.8% (82 men). Patients with a PSM had significantly higher BCR rates (21.7% vs 6.9%; P < 0.001). In univariable analysis, a high %HGTV (70.4%) was the most informative risk factor of BCR, followed by RP Gleason score (65.8%) and PSM (65.7%). Removal of PSM from a multivariable Cox model decreased the accuracy by 12.1% (P < 0.001). Our findings show that in OC prostate cancer, the risk of a PSM depends on TV, surgical technique and surgical volume. PSM is a significant risk factor for BCR. However, only 20% men with OC disease and a PSM develop BCR; conversely, 80% of men are cured despite a PSM. Therefore, adjuvant therapy must be considered, with caution to avoid unnecessary overtreatment.

  19. Transglutaminase 2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma

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    Min Jee Park

    2015-01-01

    Full Text Available Background: A few recent studies have demonstrated a possible role of transglutaminase 2 (TG2 in tumorigenesis or progression of renal cell carcinoma (RCC. The aim of this study was to examine TG2 expression and its clinicopathologic significance in a large number of human clear cell RCCs (CCRCCs. Methods: We analyzed 638 CCRCC patients who underwent partial or radical nephrectomy between 1995 and 2005. The expression of TG2 was determined by immunohistochemistry and categorized into four groups, according to staining intensity: negative (0, mild (1+, moderate (2+, and strong (3+. Results: TG2 staining intensity was negative in 8.5% of CCRCC (n=54, 1+ in 32.6% (n=208, 2+ in 50.5% (n=322, and 3+ in 8.5% (n=54. Strong TG2 expression was correlated with high Fuhrman nuclear grade (p=.011, high T category (p=.049, metastasis (p=.043 and male sex (p<.001 but not with N category.The survival analysis showed a significant association between strong TG2 expression and worse overall and cancer-specific survival (p=.027 and p=.010, respectively. On multivariate analysis, strong TG2 expression was a marginally significant prognostic indicator for Fuhrman nuclear grade and TNM staging (p=.054. Conclusions: Our study is the first to demonstrate the clinicopathologic significance of TG2 expression in a large number of human CCRCC samples. Strong TG2 expression was associated with high nuclear grade and poor prognosis.

  20. Clinical and Prognostic Significance of Lupus Anticoagulant Measurement in Patients With Lung Cancer.

    Science.gov (United States)

    Fei, Xianming; Wang, Huan; Jiang, Lei; Zhao, Tongwei; Cheng, Maoliang; Yuan, Wufeng

    2017-01-01

    Lupus anticoagulants is related to both recurrent thrombosis and cancer. Thrombotic complications occur more frequently in patients with lung cancer. The aim of this study is to investigate the association of lupus anticoagulants with hypercoagulability and thrombotic complications, as well as prognostic significance of lupus anticoagulants for patients with lung cancer. The study comprised 205 patients with non-small cell lung cancer. Plasma normalized LAC ratio, D-dimer, fibrinogen, activities of antithrombin, and FVIII before treatment were analyzed by coagulation analyzer, and routine hematologic and biochemical parameters were also evaluated. In patients, normalized LAC ratio, D-dimer, fibrinogen, and procoagulant activity of coagulating factor VIII levels significantly increased, whereas antithrombin activity significantly decreased compared with healthy controls ( P LAC ratio was positively correlated with D-dimer, fibrinogen, and procoagulant activity of coagulating factor VIII, and negatively correlated with antithrombin activity, respectively ( P LAC ratio patients than in normal ones, respectively ( P LAC ratio level in patients with deep venous thrombosis and/or metastasis ( P LAC ratio level and the incidence of deep venous thrombosis and metastasis were higher than those in survivors, respectively ( P LAC ratio was independently associated with short survival time in patients with non-small cell lung cancer (hazard regression: 2.871, 95%confidence interval: 1.704-4.835; χ2: 19.130; P lupus anticoagulants is a useful marker to predict thrombotic complications and prognosis in patient with lung cancer.

  1. Occult pneumothoraces in Chinese patients with significant blunt chest trauma: radiological classification and proposed clinical significance.

    Science.gov (United States)

    Lee, Ryan K L; Graham, Colin A; Yeung, Janice H H; Ahuja, Anil T; Rainer, Timothy H

    2012-12-01

    vs. 1, p=0.02) than apical OPs. All apical and non-apical/basal OPs were successfully managed expectantly without associated mortality. This TCT classification of OP is proposed to help clinicians to decide on subsequent management of the OP. Basal OPs are significantly larger in size, and both basal and bilateral OPs are associated with higher severity of injury and longer hospital stay. These groups of patient may benefit from prophylactic tube thoracostomy instead of conservative treatment. On the other hand, apical and non-apical/basal groups is smaller in size, less severely injured and thus can be successfully managed expectantly. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Molecular correlates and prognostic significance of SATB1 expression in colorectal cancer

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    Nodin Björn

    2012-08-01

    Full Text Available Abstract Background Special AT-rich sequence-binding protein 1 (SATB1 is a global gene regulator that has been reported to confer malignant behavior and associate with poor prognosis in several cancer forms. SATB1 expression has been demonstrated to correlate with unfavourable tumour characteristics in rectal cancer, but its association with clinical outcome in colorectal cancer (CRC remains unclear. In this study, we examined the prognostic impact of SATB1 expression in CRC, and its association with important molecular characteristics; i.e. beta-catenin overexpression, microsatellite instability (MSI screening status, and SATB2 expression. Methods Immunohistochemical expression of SATB1 and beta-catenin was assessed in tissue microarrays with tumours from 529 incident CRC cases in the prospective population-based Malmö Diet and Cancer Study, previously analysed for SATB2 expression and MSI screening status. Spearmans Rho and Chi-Square tests were used to explore correlations between SATB1 expression, clinicopathological and investigative parameters. Kaplan Meier analysis and Cox proportional hazards modelling were used to explore the impact of SATB1 expression on cancer specific survival (CSS and overall survival (OS. Results SATB1 was expressed in 222 (42% CRC cases and negative, or sparsely expressed, in adjacent colorectal mucosa (n = 16. SATB1 expression was significantly associated with microsatellite stable tumours (p interaction = 0.011 for CSS and HR = 2.31; 95% CI 1.32-4.04; pinteraction = 0.015 for OS, remaining significant in multivariable analysis. Conclusions The results of this study demonstrate that SATB1 expression in CRC is significantly associated with beta-catenin overexpression, microsatellite stability and SATB2 expression. Furthermore, SATB1 expression is a factor of poor prognosis in SATB2 negative tumours. Altogether, these data indicate an important role for SATB1 in colorectal carcinogenesis and

  3. The prognostic significance of the immunohistochemical expression of P53 and BCL-2 in endometrial cancer

    Directory of Open Access Journals (Sweden)

    Lech Chyczewski

    2012-01-01

    Full Text Available The objective of this study was to verify the frequency of P53 and BCL-2 immunohistochemical expression in 98 patients with endometrial carcinoma, and to correlate it with clinical stage and patient survival. A significant difference was found regarding the frequency of P53 expression when comparing type I and II tumors (23.7% and 54.5%, respectively; p = 0.006. A positive correlation was observed between P53 immunoexpression and patient survival in type I and II tumors (p = 0.009 and p = 0.036, respectively. BCL-2 expression was significantly more frequent in early clinical stages in both types of endometrial cancer (p < 0.001 and 0.002 and correlated with a decrease in overall survival in type I endometrial cancer (p = 0.014. Thus, the prognostic value of these biomarkers in endometrial cancer needs to be further investigated. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 631–635

  4. p53 immunohistochemistry in high-grade urothelial carcinoma of the bladder is prognostically significant.

    Science.gov (United States)

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

    2017-08-01

    TP53 mutations are characteristic of the high-grade pathway in the dual pathway of urothelial carcinogenesis. These mutations have been correlated with aberrant accumulation of p53 protein; however the definition and significance of this vary in the literature. The aim of this study was to assess p53 immunostaining in a cohort of high-grade urothelial carcinomas by using standard published cut-offs and a novel binarized method that included assessment of the null phenotype. Each scoring method was correlated with oncological outcome. A triplicate core tissue microarray was constructed from 207 cases of high-grade urothelial carcinoma treated by cystectomy, and was stained with p53. The percentage nuclear staining was recorded for each core and averaged for every case (206 cases were evaluable). Cases were categorized as positive/negative according to published cut-offs (10%, 40%) or by binarizing them as abnormal (null phenotype or >50% positivity) and wild type (1-49% positivity). Correlation with disease-specific survival was not significant according to standard definitions of p53 positivity. When a 40% cut-off was used, a correlation with relapse-free survival was significant on univariate analysis (P = 0.038) but not on multivariate analysis (P = 0.079). Abnormal p53 expression showed a near-significant trend for association with disease-specific survival (P = 0.052) and was a significant predictor for relapse-free survival on both univariate analysis (P = 0.047) and multivariate analysis (P = 0.035). Prior to this study, the p53 null phenotype was not well described in urothelial carcinoma of the bladder. Abnormal p53 immunoexpression (null staining pattern or staining in >50% of cells) is prognostic in terms of oncological outcome. © 2017 John Wiley & Sons Ltd.

  5. Prognostic significance of CD44s expression in resected non-small cell lung cancer

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    Ko Yoon

    2011-08-01

    Full Text Available Abstract Background CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC. Methods Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n = 82 and squamous cell carcinoma (SCC; n = 77. Additionally, the immunoreactivity of cyclooxygenase (COX-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically. Results High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7% than in those with AC histology (P 0.001. Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P = 0.021. In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P P = 0.046, and high CD44s expression (P = 0.014. For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P = 0.015. No significant association was found between CD44s and clinical outcome (P = 0.311. Conclusions High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage.

  6. Prognostic Significance of Creeping Proteinuria in the First Year After Transplantation.

    Science.gov (United States)

    Calabuig, Asunción Sancho; Martínez, Eva Gavela; Berga, Julia Kanter; Catalán, Sandra Beltrán; Bernabeu, Ana Isabel Avila; Mateu, Luis Manuel Pallardó

    2015-12-01

    Proteinuria changes have a prognostic significance in proteinuric nephropathies. Proteinuria has been related to kidney transplant outcomes, but there are no information about the impact of increasing proteinuria during the first year on long-term graft and patient survival. Retrospective cohort study of 591 kidney transplants to analyze the effect on long-term prognosis of: proteinuria at 3 (n = 591) and 12 (n = 583) months (no proteinuria: 150-299 mg/24 hours, 300-999 mg/24 hours, and ≥1 g/24 hours), and changes in proteinuria during the first year in such patients with proteinuria at 3 months (reduction ≥50% of proteinuria from 3 to 12 months, variation proteinuria") (n = 283). Higher levels of proteinuria, at both 3 and 12 months, were progressively related to lower graft survival (P Proteinuria at 12 months was related to mortality (P = 0.026). Creeping proteinuria, which was present in 35 patients (12.4%), was related to graft failure (P proteinuria at 3 months. De novo HLA antibody development was the only factor related to creeping proteinuria (hazard ratio, 2.946; 95% confidence interval, 1.158-7.491; P = 0.023). Creeping proteinuria during the first year was associated with long-term graft failure and mortality and could be considered as a surrogate of kidney disease progression in the renal transplant population, as it is in proteinuric nephropathies. It could also be viewed as an expression of immunological damage.

  7. The Prognostic and Clinicopathological Significance of IGF-1R in NSCLC: a Meta-Analysis

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    Jun Zhao

    2017-09-01

    Full Text Available Background/Aims: Accumulating studies have reported that IGF-1R (Insulin-like growth factor-1 receptor is aberrantly expressed in NSCLC (non-small cell lung cancer, but the role of IGF-1R in NSCLC remains controversial. The present paper assessed the precise role of IGF-1R in NSCLC. Methods: We comprehensively searched PubMed, EMBASE, and Web of Science in March 2017. Combined HRs and ORs were used to evaluate the prognostic and clinicopathological significance of IGF-1R in NSCLC respectively. Results: A total of 10 eligible studies including 8 on overall survival, and 10 on clinicopathological features were identified from the databases. The results showed that high expression of IGF-1R was associated with shorter OS (overall survival of NSCLC patients (pooled HR 1.17,95 % CI 1.00–1.36. In addition, we found that IGF-1R was related to smoking status (OR=1.82, 95 % CI=1.35-2.44 and IGF-1R tended to be highly expressed in SCC (squamous cell carcinoma (OR=3.40 95 % CI: 1.95-5.95. Conclusions: In summary, this meta-analysis revealed that high expression of IGF-1R was associated with poor prognosis in NSCLC.

  8. Prognostic significance of TBL1XR1 in predicting liver metastasis for early stage colorectal cancer.

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    Liu, Hongda; Xu, Yunfei; Zhang, Qun; Yang, Hui; Shi, Weichen; Liu, Zhaochen; Li, Kangshuai; Gong, Zheng; Ning, Shanglei; Li, Shuo; Chen, Yuxin

    2017-03-01

    Liver metastasis is the leading cause of lethal colorectal cancer (CRC). For patients with early stage CRC, metachronous liver metastasis is the primary risk for poor prognosis. Accordingly, identification of prospective biomarkers for metachronous liver metastasis would be invaluable in evaluating patients' clinical outcomes and developing personal treatment therapy. Here we investigated the role of transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) in predicting liver metastasis for early stage CRC. To accomplish this goal, a multi-center retrospective study was performed which included three stages: exploration stage (43 patients), identification stage (162 patients) and validation stage (38 patients). TBL1XR1 expression was evaluated using immunohistochemical staining and RT-qPCR. The prognostic significance of TBL1XR1 in both stage IV CRC patients and early stage CRC patients were evaluated by Kaplan-Meier survival analysis and multivariate analysis, respectively. For stage IV CRC patients, TBL1XR1 expression was correlated with the number of liver metastases (P = 0.036), and high levels of TBL1XR1 in liver metastases indicated poor overall survival (P = 0.028). Moreover, high expressions of TBL1XR1 can serve as a predictor for liver metastasis in early stage CRC patients (P = 0.003). TBL1XR1 is a promising biomarker for predicting liver metastasis in early stage CRC patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Risk factors and prognostic significance of altered left ventricular geometry in preterm infants.

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    Choudhry, Swati; Salter, Amber; Cunningham, Tyler W; Levy, Philip T; Hackett, Brian P; Singh, Gautam K; Johnson, Mark C

    2018-02-06

    Left ventricular (LV) hypertrophy (LVH) predicts adverse cardiac events in adults. We sought to determine the risk factors and prognostic significance of altered LV geometry in preterm infants. In an echocardiographic, single-center, retrospective case-control study we investigated the risk factors and outcomes in patients with altered LV geometry (either increased left ventricular mass index (LVMI) or increased relative wall thickness (RWT)) from a cohort of 503 preterm infants ≤2 kg. Altered LV geometry was seen in 180 patients and was predicted by postnatal steroids and small for gestational age. Hospital stay was longer in the elevated RWT cases. Altered LV geometry resolved in 129 of the 131 cases with follow-up echocardiogram. Fifteen of 94 patients with elevated RWT died compared to 3/90 controls (P = 0.004). Altered LV geometry in preterm infants is associated with postnatal steroid use and small for gestational age. Elevated RWT is associated with longer hospital stay and increased mortality.

  10. Assessment of prognostic significance of cytoplasmic survivin expression in advanced oesophageal cancer.

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    G Wallner

    2004-10-01

    Full Text Available Survivin is a member of the family of proteins, which inhibit apoptosis (inhibitor of apoptosis proteins - IAP. Expression of survivin was found in colorectal cancer, neuroblastoma, bladder cancer, non-small cell lung cancer, and breast cancer. There is some recent data indicating the correlation of poor prognosis and worse response to chemotherapy in patients with oesophageal squamous cell carcinoma (OSCC expressing survivin. The aim of the present study was to assess survivin expression in cancerous tissue of patients with advanced OSCC and to test the potential correlation between survivin expression and clinicopathological data. Forty two patients (mean age 58.36+/-8.97 yrs, who were oesophagectomised due to squamous cell carcinoma of the thoracic oesophagus between 1998 and 2000, were retrospectively analysed. Cytoplasmic survivin expression, examined immunohistochemically, was found in 35 (83.33% cases. No statistically significant correlation between survivin expression in the tumour and patients' gender, TNM stage, or vascular involvement was noted. The mean survival of patients with cytoplasmic survivin expression (17.81+/-5.51 months was not statistically different to those with negative survivin staining (16+/-6.28 months as assessed by Mantel-Cox test (p=0.49. Univariate regression analysis revealed UICC staging as the only predictor of survival in the analysed group (p<0.05. These results indicate that the cytoplasmic survivin expression does not seem to be the prognostic factor in advanced cases of OSCC.

  11. Evaluation of Prognostic and Predictive Significance of Circulating MicroRNAs in Ovarian Cancer Patients.

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    Halvorsen, Ann Rita; Kristensen, Gunnar; Embleton, Andy; Adusei, Cybil; Barretina-Ginesta, Maria Pilar; Beale, Philip; Helland, Åslaug

    2017-01-01

    Ovarian cancer patients are recognized with poor prognosis. This study aimed to identify microRNAs in plasma for predicting response to treatment and outcome. We have investigated microRNAs in plasma from ovarian cancer patients enrolled in a large multicenter study (ICON7), investigating the effect of adding bevacizumab to standard chemotherapy in patients diagnosed with epithelial ovarian cancer. Patients with different histology, grade, and FIGO stages were included (n = 207) in this study. Screening of 754 unique microRNAs was performed in the discovery phase (n = 91) using TaqMan Low Density Arrays. The results were validated using single assays and RT-qPCR. Low levels of miR-200b, miR-1274A (tRNALys5), and miR-141 were significantly associated with better survival, confirmed with log-rank test in the validation set. The level of miR-1274A (tRNALys5) correlated with outcome was especially pronounced in the high-grade serous tumors. Interestingly, low level of miR-200c was associated with 5-month prolongation of PFS when treated with bevacizumab compared to standard chemotherapy. We found prognostic significance of miR-200b, miR-141, and miR-1274A (tRNALys5) in all histological types, where miR-1274A (tRNALys5) may be a specific marker in high-grade serous tumors. The level of miR-200c may be predictive of effect of treatment with bevacizumab. However, this needs further validation.

  12. Serum nucleosomes during neoadjuvant chemotherapy in patients with cervical cancer. Predictive and prognostic significance

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    Cetina Lucely

    2005-06-01

    Full Text Available Abstract Background It has been shown that free DNA circulates in serum plasma of patients with cancer and that at least part is present in the form of oligo- and monucleosomes, a marker of cell death. Preliminary data has shown a good correlation between decrease of nucleosomes with response and prognosis. Here, we performed pre- and post-chemotherapy determinations of serum nucleosomes with an enzyme-linked immunosorbent assay (ELISA method in a group of patients with cervical cancer receiving neoadjuvant chemotherapy. Methods From December 2000 to June 2001, 41 patients with cervical cancer staged as FIGO stages IB2-IIIB received three 21-day courses of carboplatin and paclitaxel, both administered at day 1; then, patients underwent radical hysterectomy. Nucleosomes were measured the day before (baseline, at day seven of the first course and day seven of the third course of chemotherapy. Values of nucleosomes were analyzed with regard to pathologic response and to time to progression-free and overall survival. Results All patients completed chemotherapy, were evaluable for pathologic response, and had nucleosome levels determined. At a mean follow-up of 23 months (range, 7–26 months, projected progression time and overall survival were 80.3 and 80.4%, respectively. Mean differential values of nucleosomes were lower in the third course as compared with the first course (p >0.001. The decrease in the third course correlated with pathologic response (p = 0.041. Survival analysis showed a statistically significant, better progression-free and survival time in patients who showed lower levels at the third course (p = 0.0243 and p = 0.0260, respectively. Cox regression analysis demonstrated that nucleosome increase in the third course increased risk of death to 6.86 (95% confidence interval [CI 95%], 0.84–56.0. Conclusion Serum nucleosomes may have a predictive role for response and prognostic significance in patients with cervical cancer

  13. Prognostic significance of EBV latent membrane protein 1 expression in lymphomas: evidence from 15 studies.

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    Yuan Mao

    Full Text Available BACKGROUND: Epstein-Barr virus (EBV infection has been associated with lymphoma development. EBV latent membrane protein 1 (LMP1 is essential for EBV-mediated transformation and progression of different human cells, including lymphocytes. This meta-analysis investigated LMP1 expression with prognosis of patients with lymphoma. METHODS: The electronic databases of PubMed, Embase, and Chinese Biomedicine Databases were searched. There were 15 published studies available for a random effects model analysis. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale for cohort studies. A funnel plot was used to investigate publication bias, and sources of heterogeneity were identified by meta-regression analysis. The combined hazard ratios (HR and their corresponding 95% confidence intervals of LMP1 expression were calculated by comparison to the overall survival. RESULTS: Overall, there was no statistical significance found between LMP1 expression and survival of lymphoma patients (HR 1.25 [95% CI, 0.92-1.68]. In subgroup analyses, LMP1 expression was associated with survival in patients with non-Hodgkin lymphoma (NHL (HR = 1.84, 95% CI: 1.02-3.34, but not with survival of patients with Hodgkin disease (HD (HR = 1.03, 95% CI: 0.74-1.44. In addition, significant heterogeneity was present and the meta-regression revealed that the outcome of analysis was mainly influenced by the cutoff value. CONCLUSIONS: This meta-analysis demonstrated that LMP1 expression appears to be an unfavorable prognostic factor for overall survival of NHL patients. The data suggested that EBV infection and LMP1 expression may be an important factor for NHL development or progression.

  14. Management and prognostic significance of pathological fractures through chondrosarcoma of the femur.

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    Albergo, Jose I; Gaston, Czar L; Jeys, Lee M; Khajuria, Arun; Carter, Simon R; Tillman, Roger M; Abudu, Adesegun T; Grimer, Robert J

    2015-05-01

    The aim of the study was to report overall survival, local recurrence and development of metastasis in a group of patients with femur chondrosarcoma that presented with or without a pathological fracture. A retrospective review was performed, and 182 patients (39 pathological fractures) that had been treated by oncologic surgery for femoral chondrosarcoma were included. The mean age of the series was 50 years (range, eight to 90) and 114 patients were male (63%). Mean follow-up was 113 months (range, three to 216). Cancer-specific overall survival, development of metastasis and local recurrence were analysed, grouping patients by grade (grade I / grade 2-3 / dedifferentiated). Disease-specific survival in the entire group of chondrosarcoma of the femur was 69% (CI95% 63-76) at 5 years. Five-year disease-specific survival in the fracture group was 49% lower than in the control group 75% (p = 0.0001). Survival of patients with grade 1 chondrosarcoma with fracture was significantly less than those without fracture (p = 0.02) but there was no difference in those with grade 2-3 (p = 0.49) and dedifferentiated tumours (p = 0.09). The local recurrence rate of the entire series was 27%. Only dedifferentiated chondrosarcomas with an associated pathological fracture had a significantly higher rate of local recurrence. There was no relationship between development of metastases and fracture. A pathological fracture of the femur has a negative prognostic influence in grade 1 chondrosarcoma and increases the risk of local recurrence in dedifferentiated femur chondrosarcomas.

  15. Evaluation of Prognostic and Predictive Significance of Circulating MicroRNAs in Ovarian Cancer Patients

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    Ann Rita Halvorsen

    2017-01-01

    Full Text Available Ovarian cancer patients are recognized with poor prognosis. This study aimed to identify microRNAs in plasma for predicting response to treatment and outcome. We have investigated microRNAs in plasma from ovarian cancer patients enrolled in a large multicenter study (ICON7, investigating the effect of adding bevacizumab to standard chemotherapy in patients diagnosed with epithelial ovarian cancer. Patients with different histology, grade, and FIGO stages were included (n=207 in this study. Screening of 754 unique microRNAs was performed in the discovery phase (n=91 using TaqMan Low Density Arrays. The results were validated using single assays and RT-qPCR. Low levels of miR-200b, miR-1274A (tRNALys5, and miR-141 were significantly associated with better survival, confirmed with log-rank test in the validation set. The level of miR-1274A (tRNALys5 correlated with outcome was especially pronounced in the high-grade serous tumors. Interestingly, low level of miR-200c was associated with 5-month prolongation of PFS when treated with bevacizumab compared to standard chemotherapy. We found prognostic significance of miR-200b, miR-141, and miR-1274A (tRNALys5 in all histological types, where miR-1274A (tRNALys5 may be a specific marker in high-grade serous tumors. The level of miR-200c may be predictive of effect of treatment with bevacizumab. However, this needs further validation.

  16. Concordance of immune checkpoints within tumor immune contexture and their prognostic significance in gastric cancer.

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    Dai, Congqi; Geng, Ruixuan; Wang, Chenchen; Wong, Angela; Qing, Min; Hu, Jianjun; Sun, Yu; Lo, A W I; Li, Jin

    2016-12-01

    Checkpoint blockade therapy has emerged as a novel approach for cancer immunotherapy in several malignancies. However, patient prognosis and disease progression relevant to immune checkpoints in gastric tumor microenvironment are not defined. This study aims to investigate the expression and prognostic significance of immune checkpoints within gastric cancer. In the study, a cohort of 398 cancer tissues from stage I to IV gastric cancer patients were assessed for programmed cell death 1 ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) infiltration using immunohistochemistry to ascertain their survival correlation. The data revealed that higher TIL density correlated with less risk of disease progression, and exhibited survival benefits in gastric cancer patients, and PD-L1 positivity showed a significant association with the presence of high TIL infiltration. Furthermore, real-time quantitative polymerase chain reaction was performed to detect expression of multiple immune checkpoints with the relation to clinical outcome in 139 samples randomly selected from the same cohort, and higher messenger RNA levels of most immune checkpoints were associated with favorable outcome, while consistently showing a positive correlation with interferon gamma levels. In situ hybridization was used to determine the localization of Epstein-Barr virus (EBV) in 97 specimens, and showed EBV-positive gastric cancer samples correlated with PD-L1 expression and increased TIL density. These results suggest that induction of immune checkpoint within gastric cancer patients reflects a high immune infiltration density, especially in those with EBV-associated gastric cancer, which may direct patient selection for checkpoint blockade therapy. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  17. Incidence and prognostic significance of new onset atrial fibrillation/flutter in acute pericarditis.

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    Imazio, Massimo; Lazaros, George; Picardi, Elisa; Vasileiou, Panagiotis; Orlando, Fabrizio; Carraro, Mara; Tsiachris, Dimitris; Vlachopoulos, Charalambos; Georgiopoulos, George; Tousoulis, Dimitrios; Belli, Riccardo; Gaita, Fiorenzo

    2015-09-01

    Data on the incidence of new onset atrial fibrillation and flutter (AF/f) in patients with acute pericarditis are limited. We sought to determine the incidence and prognostic significance of AF/f in this setting. Between January 2006 and June 2014, consecutive new cases of acute pericarditis were included in two urban referral centres for pericardial diseases. All new cases of AF/f defined as episodes lasting ≥30 s were recorded. Events considered during follow-up consisted of AF/f and pericarditis recurrence, cardiac tamponade, pericardial constriction and death. 822 consecutive new cases of acute pericarditis (mean age 53±15 years, 444 men) were analysed. AF/f was detected in 35 patients (4.3%, mean age 66.5±11.3 years, 18 men). Patients with AF/f were significantly older (p=0.017) and presented more frequently with pericardial effusion (ppericarditis onset in 91.4% of cases, lasted >24 h in 25.7% and spontaneously converted in 74.3% of patients. Underlying structural heart disease was present in 17% of AF/f cases. In a 30-month follow-up, patients with history of AF/f at the initial episode had a higher rate of arrhythmia occurrence (34.3% vs 0.9%, ppericarditis identifies a predisposed population to AF/f with a high recurrence risk (about 35%): in these patients, pericarditis may act as an arrhythmic trigger and oral anticoagulation should be seriously considered according to guidelines. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Prognostic significance of stromal microinvasion in the intestinal type of ovarian mucinous adenocarcinoma.

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    Kong, Kun-Young; Park, Jeong-Yeol; Kim, Dae-Yeon; Kim, Jong-Hyeok; Kim, Yong-Man; Kim, Kyu-Rae; Kim, Young-Tak; Nam, Joo-Hyun

    2011-11-01

    The purpose of this study was to assess clinical outcomes with respect to the extent of stromal invasion in patients with stage I ovarian mucinous adenocarcinoma (MAC) of the intestinal type. We retrospectively reviewed the medical records and pathologic slides of 113 patients with stage I ovarian MACs who were treated at the Asan Medical Center from January 1994 to July 2009. According to the recent histopathologic criteria, MACs were classified into 3 groups: intraepithelial carcinoma without invasion (IEC), intraepithelial carcinoma with microinvasion (IECMI), and mucinous adenocarcinoma with extensive invasion (MACEI). Stromal invasion was confined to the tumors showing severe cytologic atypia in the invasive foci. Therefore, cases showing mucin granulomas composed only of macrophages without malignant cells were excluded from the definition of invasion. Of the 113 patients, 54 (47.8%) had IEC, 15 (13.3%) had IECMI, and 44 (38.9%) had MACEI. There were no differences among groups in age, menopausal status, CA-125 level, surgical procedures, stage, capsular and lymphovascular space invasion. The 5-year disease-free-survival rates in the IEC, IECMI, and MACEI groups were 97.7%, 77.3%, and 79.9%, respectively (IEC vs IECMI, P=0.004; IEC vs MACEI, P=0.012; IECMI vs MACEI, P=0.555). Prognosis was significantly poorer for patients with IECMI than for those with IEC, but not different between patients with IECMI and MACEI. Stromal microinvasion in ovarian MAC is a significant prognostic factor. Therefore, diligent search for "stromal microinvasion" with adequate sampling of tumor tissue are important at the time of histopathologic diagnosis, and patients with IECMI should no longer be treated identically to those with IEC.

  19. Neoadjuvant radiochemotherapy and surgery for advanced rectal cancer. Prognostic significance of tumor regression

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    Eich, Hans Theodor; Stepien, Anna; Zimmermann, Christian; Mueller, Rolf-Peter [Koeln Univ. (Germany). Dept. of Radiation Oncology; Hellmich, Martin [Koeln Univ. (Germany). Inst. of Medical Statistics, Informatics, and Epidemiology; Metzger, Ralf; Hoelscher, Arnulf [Koeln Univ. (Germany). Dept. of General, Visceral and Cancer Surgery

    2011-04-15

    Purpose: Preoperative radiochemotherapy is widely used in the treatment of locally advanced rectal cancer. The predictive value of response to neoadjuvant treatment remains uncertain. We retrospectively evaluated the impact of downstaging and tumor regression as prognostic factors and its influence on the ability to perform sphincter-sparing surgery. Patients and Methods: A total of 72 consecutive patients with advanced rectal cancer were included in this retrospective analysis. All patients were treated with preoperative 5-fluorouracil-based chemotherapy and pelvic radiation with a total dose of 50.4 Gy followed by surgery 6 weeks later. Results: A sphincter-preserving procedure could be performed on 42 patients, and in all 72 patients complete resection (R0) was achieved. A pathological complete response (ypT0, ypN0) was achieved in 8 (11%) patients. None of the patients showing a complete pathological response relapsed or died during the follow-up period. At a median follow-up of 28 months, 65 patients were alive, none of these patients had local recurrence and 15 patients had metastatic disease. Patients showing a complete pathological response had a significantly better 2-year disease-free survival compared to patients with {>=} 10% residual tumor cells (p = 0.024). Patients < 65 years showed a significantly better response rate, compared with those > 65 years of age (p = 0.036). Acute toxicity was moderate. Conclusion: Preoperative radiochemotherapy is an effective and safe treatment for patients with locally advanced rectal cancer. Pathological parameters after preoperative radiochemotherapy, including tumor regression grading, could be correlated with disease-free survival. The impact of tumor regression grading needs to be further validated in prospective clinical trials. (orig.)

  20. Urinary prognostic biomarkers and classification of IgA nephropathy by high resolution mass spectrometry coupled with liquid chromatography.

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    Shiva Kalantari

    Full Text Available IgA nephropathy is the most common cause of primary glomerulonephritis. There are different pathologic biopsy-based scoring systems in use, but there is no consensus among nephrologists yet regarding the best classification method. Our aim was to test urine proteomics as a non-invasive method for classification of IgA nephropathy. This aim was pursued by discovering novel prognostic protein biomarkers in urine, and linking them to pathogenesis of the disease through known signaling and metabolic pathways. 13 urine samples of the patients with biopsy-proven IgA nephropathy were analyzed via two proteomics approaches: nanoflow LC-MS/MS and GeLC-MS/MS. The results of label-free quantification were subjected to multivariate statistical analysis, which could classify patients into two groups, broadly corresponding to the primary and advance stages. The proteome classification correlated well with biopsy-based scoring systems, especially endocapillary hypercellularity score of the Oxford's classification. Differentially excreted candidate proteins were found as potential prognostic biomarkers: afamin, leucine-rich alpha-2-glycoprotein, ceruloplasmin, alpha-1-microgolbulin, hemopexin, apolipoprotein A-I, complement C3, vitamin D-binding protein, beta-2-microglobulin, and retinol-binding protein 4. Pathway analysis suggested impairment of Extra Cellular Matrix (ECM-Receptor Interaction pathways as well as activation of complement and coagulation pathway in progression of IgA nephropathy.

  1. Classification, Molecular Characterization, and the Significance of Pten Alteration in Leiomyosarcoma

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    Allie H. Grossmann

    2012-01-01

    Full Text Available Leiomyosarcoma is a malignant smooth muscle neoplasm with a complicated histopathologic classification scheme and marked differences in clinical behavior depending on the anatomic site of origin. Overlapping morphologic features of benign and borderline malignant smooth muscle neoplasms further complicate the diagnostic process. Likewise, deciphering the complex and heterogeneous patterns of genetic changes which occur in this cancer has been challenging. Preliminary studies suggest that reproducible molecular classification may be possible in the near future and new prognostic markers are emerging. Robust recapitulation of leiomyosarcoma in mice with conditional deletion of Pten in smooth muscle and the simultaneous discovery of a novel role for Pten in genomic stability provide a fresh perspective on the mechanism of leiomyosarcomagenesis and promise for therapeutic intervention.

  2. Inhibitors of apoptosis proteins (IAPs expression and their prognostic significance in hepatocellular carcinoma

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    Roncalli Massimo

    2009-04-01

    Full Text Available Abstract Background Similarly to other tumor types, an imbalance between unrestrained cell proliferation and impaired apoptosis appears to be a major unfavorable feature of hepatocellular carcinoma (HCC. The members of IAP family are key regulators of apoptosis, cytokinesis and signal transduction. IAP survival action is antagonized by specific binding of Smac/DIABLO and XAF1. This study aimed to investigate the gene and protein expression pattern of IAP family members and their antagonists in a series of human HCCs and to assess their clinical significance. Methods Relative quantification of IAPs and their antagonist genes was assessed by quantitative Real Time RT-PCR (qPCR in 80 patients who underwent surgical resection for HCC. The expression ratios of XIAP/XAF1 and of XIAP/Smac were also evaluated. Survivin, XIAP and XAF1 protein expression were investigated by immunohistochemistry. Correlations between mRNA levels, protein expression and clinicopathological features were assessed. Follow-up data were available for 69 HCC patients. The overall survival analysis was estimated according to the Kaplan-Meier method. Results Survivin and Livin/ML-IAP mRNAs were significantly over-expressed in cancer tissues compared to non-neoplastic counterparts. Although Survivin immunoreactivity did not correlate with qPCR data, a significant relation was found between higher Survivin mRNA level and tumor stage, tumor grade and vascular invasion. The mRNA ratio XIAP/XAF1 was significantly higher in HCCs than in cirrhotic tissues. Moreover, high XIAP/XAF1 ratio was an indicator of poor prognosis when overall survival was estimated and elevated XIAP immunoreactivity was significantly associated with shorter survival. Conclusion Our study demonstrates that alterations in the expression of IAP family members, including Survivin and Livin/ML-IAP, are frequent in HCCs. Of interest, we could determine that an imbalance in XIAP/XAF1 mRNA expression levels correlated

  3. Prognostic Significance of p16 Expression in Advanced Cervical Cancer Treated With Definitive Radiotherapy

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    Schwarz, Julie K., E-mail: jschwarz@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States); Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Lewis, James S. [Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States); Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Pfeifer, John [Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States); Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Huettner, Phyllis [Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States); Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO (United States); Grigsby, Perry [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States); Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO (United States); Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States)

    2012-09-01

    Purpose: The purpose of this study was to evaluate the prognostic significance of p16 immunohistochemistry (IHC) in patients with advanced cervical cancer treated with radiation therapy. Materials and Methods: This was a retrospective study of 126 patients with International Federation of Gynecology and Obstetrics Stages Ib1-IVb cervical cancer treated with radiation. Concurrent cisplatin chemotherapy was given to 108 patients. A tissue microarray (TMA) was constructed from the paraffin-embedded diagnostic biopsy specimens. Immunoperoxidase staining was performed on the TMA and a p16 monoclonal antibody was utilized. IHC p16 extent was evaluated and scored in quartiles: 0 = no staining, 1 = 1-25% of cells staining, 2 = 26 to 50%, 3 = 51 to 75%, and 4 = 76 to 100%. Results: The p16 IHC score was 4 in 115 cases, 3 in 1, 2 in 3 and 0 in 7. There was no relationship between p16 score and tumor histology. Patients with p16-negative tumors were older (mean age at diagnosis 65 vs. 52 years for p16-positive tumors; p = 0.01). The 5-year cause-specific survivals were 33% for p16-negative cases (score = 0) compared with 63% for p16-positive cases (scores 1, 2, 3 or 4; p = 0.07). The 5-year recurrence-free survivals were 34% for those who were p16-negative vs. 57% for those who were p16-positive (p = 0.09). In addition, patients with p16-positive tumors (score > 0) were more likely to be complete metabolic responders as assessed by the 3-month posttherapy 18 [F]-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomograph compared with patients with p16-negative tumors (p = 0.03). Conclusion: p16 expression is predictive of improved survival outcome after chemoradiation therapy for advanced-stage invasive cervical carcinoma. Further testing will be needed to evaluate p16-negative cervical tumors.

  4. The clinicopathologic characteristics and prognostic significance of triple-negativity in node-negative breast cancer

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    Rhee, Jiyoung; Han, Sae-Won; Oh, Do-Youn; Kim, Jee Hyun; Im, Seock-Ah; Han, Wonshik; Ae Park, In; Noh, Dong-Young; Bang, Yung-Jue; Kim, Tae-You

    2008-01-01

    Background Triple-negative (TN) breast cancer, which is defined as being negative for the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER-2), represents a subset of breast cancer with different biologic behaviour. We investigated the clinicopathologic characteristics and prognostic indicators of lymph node-negative TN breast cancer. Methods Medical records were reviewed from patients with node-negative breast cancer who underwent curative surgery at Seoul National University Hospital between Jan. 2000 and Jun. 2003. Clinicopathologic variables and clinical outcomes were evaluated. Results Among 683 patients included, 136 had TN breast cancer and 529 had non-TN breast cancer. TN breast cancer correlated with younger age (< 35 y, p = 0.003), and higher histologic and nuclear grade (p < 0.001). It also correlated with a molecular profile associated with biological aggressiveness: negative for bcl-2 expression (p < 0.001), positive for the epidermal growth factor receptor (p = 0.003), and a high level of p53 (p < 0.001) and Ki67 expression (p < 0.00). The relapse rates during the follow-up period (median, 56.8 months) were 14.7% for TN breast cancer and 6.6% for non-TN breast cancer (p = 0.004). Relapse free survival (RFS) was significantly shorter among patients with TN breast cancer compared with those with non-TN breast cancer (4-year RFS rate 85.5% vs. 94.2%, respectively; p = 0.001). On multivariate analysis, young age, close resection margin, and triple-negativity were independent predictors of shorter RFS. Conclusion TN breast cancer had higher relapse rate and more aggressive clinicopathologic characteristics than non-TN in node-negative breast cancer. Thus, TN breast cancer should be integrated into the risk factor analysis for node-negative breast cancer. PMID:18947390

  5. Prognostic and clinical significance of newly acquired complete right bundle branch block in Japan Airline pilots.

    Science.gov (United States)

    Taniguchi, Masayuki; Nakano, Hajime; Kuwahara, Koichiro; Masuda, Izuru; Okawa, Yasuhiro; Miyazaki, Hiroshi; Okoshi, Hirofumi; Kaji, Masanobu; Noguchi, Yoshiko; Asukata, Ichiro

    2003-01-01

    The purpose of this study was to evaluate the prognostic and clinical significance of newly acquired complete right bundle branch block (CRBBB) in airline pilots. This study included pilots with acquired CRBBB, identified from a group of over 2,700 Japan Airline pilots. When the pilots applied for employment, a past medical history, physical examination, electrocardiogram, and chest radiograph were obtained. The pilots with ECG abnormality including CRBBB were not included in the study because of hiring requirements. Thirty-six pilots with CRBBB were identified between 1983 and 2002. All pilots with CRBBB were evaluated for the presence of ischemic heart disease by treadmill exercise testing, echocardiogram and exercise thallium scintigraphy. Twelve individuals underwent coronary angiography. The mean age of pilots was 44.4 +/- 5.8 years. The mean observation period was 10.9 +/- 5.7 years. For each of the 36 study subjects, Holter electrocardiogram and echocardiogram were obtained every 6 months after the CRBBB was detected. Exercise stress testing was performed every year. Exercise thallium scintigraphy was performed every 2 years to detect ischemic heart disease. During the observation period, two pilots stopped flying temporarily because of frequent ventricular premature beats and one pilot stopped flying permanentaly because of atrial fibrillation. During the follow-up period, no cardiovascular events were observed in pilots with CRBBB who had no underlying ischemic heart disease. Acquired CRBBB does not confer a poor prognosis, particularly in young men working as a pilot if there is no evidence of ischemia on exercise stress testing, echocardiography and exercise thallium scintigraphy.

  6. The Prognostic Significance of Right Bundle Branch Block: A Meta-analysis of Prospective Cohort Studies.

    Science.gov (United States)

    Xiong, Yunyun; Wang, Lian; Liu, Wenyan; Hankey, Graeme J; Xu, Biao; Wang, Shang

    2015-10-01

    The prognostic significance of right bundle branch block (RBBB) is inconsistent across studies. We aimed to assess the association between RBBB (in general population and patients with heart disease) and risk of all-cause mortality, cardiac death, acute myocardial infarction (MI), and heart failure (HF). RBBB may be associated with increased risk of death. PubMed, EMBASE, and the Cochrane Library up to February 2015 were searched for prospective cohort studies that reported RBBB at baseline and all-cause mortality, cardiac death, MI, and HF at follow-up. A meta-analysis of published data was undertaken primarily by means of fixed-effects models. Nineteen cohort studies including 201 437 participants were included with a mean follow-up period ranging from 1 to 246 months. For general population with RBBB, the pooled adjusted hazard ratio (HR) for all-cause mortality was 1.17 (95% confidence interval [CI]: 1.03-1.33) compared with no BBB. General population with RBBB had an increased risk of cardiac death (HR: 1.43, 95% CI: 1.17-1.74). For patients with RBBB and acute MI, the pooled risk ratio was 2.31 (95% CI: 2.13-2.49) for in-hospital mortality, 2.85 (95% CI: 2.46-3.30) for 30-day mortality, and 1.96 (95% CI: 1.59-2.42) for longer-term mortality. For acute HF patients, the pooled risk ratio of all-cause mortality was 1.11 (95% CI: 1.06-1.16), and for chronic HF patients it was 1.75 (95% CI: 1.38-2.22). Right bundle branch block is associated with an increased risk of mortality in general population and patients with heart disease. © 2015 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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. © 2015 Wiley Periodicals, Inc.

  8. Gene Expression Programs in Response to Hypoxia: Cell Type Specificity and Prognostic Significance in Human Cancers.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available BACKGROUND: Inadequate oxygen (hypoxia triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF, plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis

  9. Gene expression programs in response to hypoxia: cell type specificity and prognostic significance in human cancers.

    Directory of Open Access Journals (Sweden)

    Jen-Tsan Chi

    2006-03-01

    Full Text Available Inadequate oxygen (hypoxia triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF, plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases.We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use.The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis in breast and ovarian cancer.

  10. Profiles of serum cytokines in acute drug-induced liver injury and their prognostic significance.

    Directory of Open Access Journals (Sweden)

    Nury M Steuerwald

    Full Text Available Drug-induced liver injury (DILI is the most common cause of acute liver failure in the United-States. The aim of the study was to describe serum immune profiles associated with acute DILI, to investigate whether there are profiles associated with clinical features or types of DILI and/or with prognosis, and to assess temporal changes in levels. Twenty-seven immune analytes were measured in the sera of 78 DILI subjects in the Drug-Induced Liver Injury Network (DILIN and compared with 40 healthy controls. Immune analytes (14 cytokines, 7 chemokines and 6 growth factors were measured by BioPlex multiplex ELISA at DILI onset and after 6 months. A modeling process utilizing immune principles was used to select a final set of variables among 27 immune analytes and several additional clinical lab values for prediction of early death (within 6 months of DILI onset. Nineteen of the 27 immune analytes were differentially expressed among healthy control, DILI onset and 6-month cohorts. Disparate patterns of immune responses, especially innate and adaptive cellular (mostly TH17 immunity were evident. Low values of four immune analytes (IL-9, IL-17, PDGF-bb and RANTES and serum albumin are predictive of early death [PPV = 88% (95% CI, 65%-100%, NPV = 97% (95% CI, 93%-100%, accuracy = 96% (95% CI, 92%-100%].Acute DILI is associated with robust and varying immune responses. High levels of expression of cytokines associated with innate immunity are associated with a poor prognosis, whereas high levels of expression of adaptive cytokines are associated with good long-term prognosis and eventual recovery. Serum immune analyte profiles at DILI onset appear to be of prognostic, and perhaps, diagnostic significance.

  11. Prognostic significance of circulating tumor cells in esophageal carcinoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Qiao GL

    2016-03-01

    Full Text Available Guang-Lei Qiao,1 Wei-Xiang Qi,2 Wei-Hua Jiang,1 Ying Chen,1 Li-Jun Ma1 1Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 2Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of China Purpose: The prognostic significance of circulating tumor cells (CTCs in esophageal carcinoma (EC is controversial. We aim to assess its association with clinicopathological and prognostic relevance in EC by using a meta-analysis.Methods: We searched PubMed, Cochrane Database, Embase databases, and the references in relevant studies that assessed the clinicopathological or prognostic relevance of CTCs in peripheral blood of patients with EC. Statistical analyses were conducted by using Stata software to calculate the pooled odds ratio (OR, hazard ratio (HR, and 95% confidence intervals (CIs using fixed or random-effects models according to the heterogeneity of included studies. The subgroup analyses were performed according to ethnicity, histological type, and detection method.Results: Sixteen trials containing 1,260 patients were included for analysis. Pooled results showed that presence of CTCs was significantly associated with poor overall survival (HR =1.71, 95% CI [1.30, 2.12], P<0.001 and progression-free survival (HR =1.67, 95% CI [1.19, 2.15], P<0.001 in EC patients. Subgroup analysis indicated that presence of CTCs was closely associated with worse overall survival (Asian: HR =1.66, 95% CI [1.24, 2.08], P<0.001; squamous cell carcinoma [SCC]: HR =1.66, 95% CI [1.24, 2.08], P<0.001; no polymerase chain reaction [PCR]: HR =2.08, 95% CI [1.40, 2.76], P<0.001 and progression-free survival (Asian: HR =1.63, 95% CI [1.15, 2.12], P<0.001; SCC: HR =1.63, 95% CI [1.15, 2.12], P<0.001; PCR: HR =1.63, 95% CI [1.15, 2.12], P<0.001. Additionally, ORs showed that presence of CTCs was significantly correlated with tumor node metastasis (TNM staging (overall: OR =1

  12. Prognostic significance of thymidylate synthase in postoperative non-small cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Zhao HY

    2014-07-01

    Full Text Available Hong-Yun Zhao,1,* Guo-Wei Ma,1,* Ben-Yan Zou,1,* Mei Li,1 Su-Xia Lin,1 Li-Ping Zhao,2 Ying Guo,1 Yan Huang,1 Ying Tian,1 Dan Xie,1 Li Zhang1 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Department of Medical Oncology, Zhongshan Hospital of Sun Yat-Sen University, Zhongshan People’s City Hospital, Zhongshan, People’s Republic of China *The first three authors contributed equally to this work Abstract: The aim of the present study was to investigate the clinicopathologic/prognostic significance of thymidylate synthase (TS, orotate phosphoribosyltransferase (OPRT, and thymidine phosphorylase (TP proteins in postoperative non-small cell lung cancer (NSCLC patients. Microarray slides from a set of 178 NSCLC patients were used for the detection of TS, OPRT, and TP expression by immunohistochemistry. The correlation between clinicopathologic factors and protein expression of three proteins was analyzed. Ninety seven carcinomas (57.4% were TS-positive, 90 carcinomas (53.9% were OPRT-positive, and 102 carcinomas (69.4% were TP-positive. Compared with the TS-positive patients, the overall survival (OS was significantly lower in the TS-negative patients (hazard ratio [HR] =1.766, 95% confidence interval [CI] =1.212–2.573, P=0.003. Significant differences between TS-positive and TS-negative patients was also observed in the following stratified analyses: 1 adenocarcinoma subgroup (HR =2.079, 95% CI =1.235–3.500, P=0.006; 2 less than 60-year-old subgroup (HR =1.890, 95% CI =1.061–3.366, P=0.031; 3 stage II/III subgroup (HR =1.594, 95% CI =1.036–2.453, P=0.034; and 4 surgery plus adjuvant therapy subgroup (HR =1.976, 95% CI =1.226–3.185, P=0.005. However, the OS was not significantly correlated with OPRT or TP protein expression. This study demonstrates that the TS level in tumor tissues may be a useful marker

  13. The presence and prognostic significance of human papillomavirus in squamous cell carcinoma of the larynx.

    Science.gov (United States)

    Erkul, Evren; Yilmaz, Ismail; Narli, Gizem; Babayigit, Mustafa Alparslan; Gungor, Atila; Demirel, Dilaver

    2017-07-01

    prognosis, additional studies may be needed, since our results were not statistically significant. We believed that HPV is not an adequate biomarker for diagnostic and prognostic purposes in laryngeal squamous cell carcinoma.

  14. Prognostic significance of del 17p, ZAP-70 and CD38 as ...

    African Journals Online (AJOL)

    Nihal S. El-Kinawy

    2012-04-29

    Apr 29, 2012 ... Abstract Prognostic markers as CD38 and ZAP-70 and specific chromosomal abnormalities as del. 17p have ... Early treatment of the former could lead to therapy- ... Chest X-ray, abdomino-pelvic ultrasound, CT scan for clin-.

  15. Coronary thrombus in patients undergoing primary PCI for STEMI: Prognostic significance and management

    OpenAIRE

    Vecchio, Sabine; Varani, Elisabetta; Chechi, Tania; Balducelli, Marco; Vecchi, Giuseppe; Aquilina, Matteo; Ricci Lucchi, Giulia; Dal Monte, Alessandro; Margheri, Massimo

    2014-01-01

    Acute ST-elevation myocardial infarction (STEMI) usually results from coronary atherosclerotic plaque disruption with superimposed thrombus formation. Detection of coronary thrombi is a poor prognostic indicator, which is mostly proportional to their size and composition. Particularly, intracoronary thrombi impair both epicardial blood flow and myocardial perfusion, by occluding major coronary arteries and causing distal embolization, respectively. Thus, although primary percutaneous coronary...

  16. Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients

    DEFF Research Database (Denmark)

    Liu, Ning Qing; De Marchi, Tommaso; Timmermans, Annemieke

    2016-01-01

    We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways...

  17. Intratumoral genetic heterogeneity and number of cytogenetic aberrations provide additional prognostic significance in chronic lymphocytic leukemia.

    Science.gov (United States)

    Yi, Shuhua; Li, Zengjun; Zou, Dehui; An, Gang; Cui, Rui; Zhong, Shizhen; Li, Heng; Xiong, Wenjie; Li, Chenwen; Chen, Weiwei; Liu, Wei; Lv, Rui; Yu, Zhen; Wang, Huijun; Xu, Yan; Zhou, Keshu; Ru, Kun; Wang, Jianxiang; Cheng, Tao; Qiu, Lugui

    2017-02-01

    Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with cytogenetic aberrations that are still considered the gold standard of prognostic factors. However, heterogeneity remains within each cytogenetic group, especially in patients with concomitant cytogenetic aberrations. A panel of DNA probes was used to detect cytogenetic aberrations, including RB1/D13S25 at 13q14, ATM at 11q22, TP53 at 17p13, CEP12 and IGH translocation at 14q32, by fluorescence in situ hybridization. A comprehensive method integrating the number of cytogenetic aberrations and intratumoral genetic heterogeneity was used to analyze the prognosis for patients with concomitant aberrations. Within the conventional favorable or neutral prognostic groups (i.e., with del 13q, trisomy 12, and/or t(14q32)), the coincidence of these three aberrations worsened survival in terms of time to first therapy, progression-free survival, and overall survival. However, within the conventional unfavorable prognostic group (i.e., del 11q or del 17p), patients with a minor unfavorable clone had an unexpected survival advantage compared with patients with a major unfavorable clone. A new cytogenetic prognostic system that integrates the number of cytogenetic aberrations and intratumoral genetic subclones was more precise than the conventional system. The number of cytogenetic aberrations and the size of intratumoral genetic subclones should be comprehensively considered to determine the prognosis for CLL.Genet Med 19 2, 182-191.

  18. Prognostic significance of ALCAM (CD166/MEMD) expression in cutaneous melanoma patients.

    Science.gov (United States)

    Donizy, Piotr; Zietek, Marcin; Halon, Agnieszka; Leskiewicz, Marek; Kozyra, Cyprian; Matkowski, Rafal

    2015-07-02

    ALCAM (activated leukocyte cell adhesion molecule, CD166, MEMD) is a transmembrane protein of immunoglobulin superfamily (Ig-SF) and plays an important role in human malignant melanoma progression and formation of locoregional and distant metastases. The study using melanoma cell lines showed that overexpression of ALCAM is directly related with the increase of cytoaggregation and the ability to form cell nests. The aim of the study was to assess the expression and intracellular localization of ALCAM in primary skin melanomas and metastatic lesions from regional lymph nodes. Also, prognostic significance of ALCAM expression in primary tumor cells and metastatic lesion cells was evaluated in the context of 5-year observation. Formalin-fixed paraffin-embedded tissue specimens from 104 primary cutaneous melanomas and 16 regional lymph nodes metastases were studied for the expression of ALCAM measured by immunohistochemistry. We demonstrate that high ALCAM expression in primary melanoma cells (IRS ≥8) is strongly correlated with unfavorable prognosis as compared with patients with lower ALCAM immunoreactivity in tumor compartment as regards cancer specific overall survival (CSOS) (P = 0.001) and disease free survival (DFS) (P < 0.001). Additionally lower ALCAM immunoreactivity in nodal metastatic foci was significantly statistically correlated with deeper melanoma invasion in the primary tumor according to Clark scale (P = 0.032). It was also found that decreased ALCAM expression (IRS <8) in nodal metastases shows a trend related with a correlation with shorter cancer specific overall survival (P = 0.083). Statistically significant correlations were also demonstrated between the presence of ulceration and decreased intensity of lymphocytic inflammatory infiltration and a high percentage of ALCAM-positive cells (P = 0.035, P = 0.01, respectively). High ALCAM expression in melanoma cells of the primary tumor can be used as a marker of negative

  19. Prognostic Significance of Promoter DNA Hypermethylation of cysteine dioxygenase 1 (CDO1 Gene in Primary Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Naoko Minatani

    Full Text Available Using pharmacological unmasking microarray, we identified promoter DNA methylation of cysteine dioxygenase 1 (CDO1 gene in human cancer. In this study, we assessed the clinicopathological significance of CDO1 methylation in primary breast cancer (BC with no prior chemotherapy. The CDO1 DNA methylation was quantified by TaqMan methylation specific PCR (Q-MSP in 7 BC cell lines and 172 primary BC patients with no prior chemotherapy. Promoter DNA of the CDO1 gene was hypermethylated in 6 BC cell lines except SK-BR3, and CDO1 gene expression was all silenced at mRNA level in the 7 BC cell lines. Quantification of CDO1 methylation was developed using Q-MSP, and assessed in primary BC. Among the clinicopathologic factors, CDO1 methylation level was not statistically significantly associated with any prognostic factors. The log-rank plot analysis elucidated that the higher methylation the tumors harbored, the poorer prognosis the patients exhibited. Using the median value of 58.0 as a cut-off one, disease specific survival in BC patients with CDO1 hypermethylation showed significantly poorer prognosis than those with hypomethylation (p = 0.004. Multivariate Cox proportional hazards model identified that CDO1 hypermethylation was prognostic factor as well as Ki-67 and hormone receptor status. The most intriguingly, CDO1 hypermethylation was of robust prognostic relevance in triple negative BC (p = 0.007. Promoter DNA methylation of CDO1 gene was robust prognostic indicator in primary BC patients with no prior chemotherapy. Prognostic relevance of the CDO1 promoter DNA methylation is worthy of being paid attention in triple negative BC cancer.

  20. Acute Phase Hyperglycemia among Patients Hospitalized with Acute Coronary Syndrome: Prevalence and Prognostic Significance

    Directory of Open Access Journals (Sweden)

    Hameed Laftah Wanoose

    2011-03-01

    Full Text Available AbstractObjectives: Regardless of diabetes status, hyperglycemia on arrival for patients presenting with acute coronary syndrome, has been associated with adverse outcomes including death. The aim of this study is to look at the frequency and prognostic significance of acute phase hyperglycemia among patients attending the coronary care unit with acute coronary syndrome over the in-hospital admission days.Methods: The study included 287 consecutive patients in the Al- Faiha Hospital in Basrah (Southern Iraq during a one year period from December 2007 to November 2008. Patients were divided into two groups with respect to admission plasma glucose level regardless of their diabetes status (those with admission plasma glucose of <140 mg/dl (7.8 mmol/L and those equal to or more than that. Acute phase hyperglycemia was defined as a non-fasting glucose level equal to or above 140 mg/dl (7.8 mmol/L regardless of past history of diabetes.Results: Sixty one point seven percent (177 of patients were admitted with plasma glucose of ≥140 mg/dl (7.8 mmol/L. There were no differences were found between both groups regarding the mean age, qualification, and smoking status, but males were predominant in both groups. A family history of diabetes, and hypertension, were more frequent in patients with plasma glucose of ≥140 mg/dl (7.8 mmol/L. There were no differences between the two groups regarding past history of ischemic heart disease, stroke, lipid profile, troponin-I levels or type of acute coronary syndrome. Again heart failure was more common in the admission acute phase hyperglycemia group, but there was no difference regarding arrhythmia, stroke, or death. Using logistic regression with heart failure as the dependent variable we found that only the admission acute phase hyperglycemia (OR=2.1344, 95�0CI=1.0282-4.4307; p=0.0419 was independently associated with heart failure. While male gender, family history of diabetes mellitus, hypertension and

  1. Prognostic significance of CDH13 hypermethylation and mRNA in NSCLC

    Directory of Open Access Journals (Sweden)

    Xue R

    2014-10-01

    Full Text Available Ruilin Xue,1 Cuili Yang,1 Fang Zhao,2 Dejia Li1 1Global Health Institute, School of Public Health, 2Zhongnan Hospital, Wuhan University, Wuhan, People's Republic of ChinaAbstract: Aberrant methylation of CpG dinucleotides is a commonly observed epigenetic modification in human cancer. Thus, detection of aberrant gene promoter methylation as a tool for diagnosis of tumors or as a prognostic marker has been widely described for many types of cancers, including nonsmall cell lung cancer (NSCLC. Emerging evidence indicates that CDH13 is a candidate tumor suppressor in several types of human tumors, including NSCLC. However, the correlation between CDH13 hypermethylation and clinicopathological characteristics of NSCLC remains unclear. In the current study, we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of CDH13 hypermethylation on the incidence of NSCLC and clinicopathological characteristics. Final analysis of 803 NSCLC patients from eleven eligible studies was performed. CDH13 hypermethylation was observed to be significantly higher in NSCLC than in normal lung tissue, with the pooled odds ratio (OR from seven studies including 448 NSCLC and 345 normal lung tissue (OR, 7.85; 95% confidence interval, 5.12–12.03; P<0.00001. CDH13 hypermethylation was also associated with pathological types. The pooled OR was obtained from four studies, including 111 squamous cell carcinoma and 106 adenocarcinoma (OR, 0.35; 95% confidence interval, 0.19–0.66; P=0.001, which indicated that CDH13 hypermethylation plays a more important role in the pathogenesis of adenocarcinoma. NSCLC with CDH13 hypermethylation was found more frequently in poorly differentiated NSCLC patients. NSCLC patients with CDH13 hypermethylation had a lower survival rate than those without CDH13 hypermethylation. In addition, CDH13 mRNA high expression was found to correlate with better overall survival for all NSCLC patients followed for 20 years

  2. Prognostic significance of TGF beta 1 and TGF beta 3 in human breast carcinoma.

    Science.gov (United States)

    Ghellal, A; Li, C; Hayes, M; Byrne, G; Bundred, N; Kumar, S

    2000-01-01

    Transforming growth factor beta s (TGF beta s) are multifunctional growth factors which show differential expression both temporally and spatially and exert pleiotropic effects during carcinogenesis. Although all three mammalian isoforms of TGF beta share considerable sequence similarity, they appear to have distinct functions in health and disease, such as embryogenesis, wound healing and tumourigenesis. Much of our knowledge about the relationship between TGF beta s and breast cancer is based on publications on TGF beta 1 but the role of TGF beta 3 in the progression of breast cancer has not been well documented. In the present study, the expression of TGF beta 1 and TGF beta 3 was assessed by immunohistochemistry. Of the 153 invasive breast cancer tissues, TGF beta 1 was expressed strongly in 25 and moderately in 98 cases. The immunoreactivity of TGF beta 3 was comparable with TGF beta 1, which was expressed strongly in 21 and moderately in 104 cases. The two isoforms were coexpressed in 111 (72.5%) tumours and were absent in 16 cases (10%). Immunostaining for TGFb3 but not TGF beta 1 was inversely correlated with overall survival (p = 0.0204). When combined with lymph node involvement, TGFb3 became an even more significant prognostic factor for overall survival (p = 0.0003), i.e. patients with node metastasis and positive TGFb3 expression had a worse prognosis: the risk of death for these patients was thirteen-fold greater than those who had no node involvement. The fact that it has been reported previously that high TGF beta 3 plasma levels in patients with untreated early stage breast cancer were correlated with subsequent lymph node metastasis and it was observed in the present study too, that TGF beta 3 expression in breast tumours was an independent predictor of overall survival, led us to suggest that the simultaneous measurement of TGF beta 3 in plasma and its expression in resected tumour tissues in the same cohort of patients may prove to be an

  3. utomated real-time classification of functional states: the significance of individual tuning stage

    Directory of Open Access Journals (Sweden)

    Galatenko, Vladimir V.

    2013-09-01

    Full Text Available Automated classification of a human functional state is an important problem, with applications including stress resistance evaluation, supervision over operators of critical infrastructure, teaching and phobia therapy. Such classification is particularly efficient in systems for teaching and phobia therapy that include a virtual reality module, and provide the capability for dynamic adjustment of task complexity. In this paper, a method for automated real-time binary classification of human functional states (calm wakefulness vs. stress based on discrete wavelet transform of EEG data is considered. It is shown that an individual tuning stage of the classification algorithm — a stage that allows the involvement of certain information on individual peculiarities in the classification, using very short individual learning samples, significantly increases classification reliability. The experimental study that proved this assertion was based on a specialized scenario in which individuals solved the task of detecting objects with given properties in a dynamic set of flying objects.

  4. The prognostic significance of lung function in stable heart failure outpatients

    DEFF Research Database (Denmark)

    Plesner, Louis Lind; Dalsgaard, Morten; Schou, Morten

    2017-01-01

    BACKGROUND: This study investigated the impact on all-cause mortality of airflow limitation indicative of chronic obstructive pulmonary disease or restrictive spirometry pattern (RSP) in a stable systolic heart failure population. HYPOTHESIS: Decreased lung function indicates poor survival in heart...... independent prognostic factors (pmarker when using LLN criteria (HR 1.74 [1.17-2.59] p=0.006). RSP was independently associated...

  5. Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer.

    Directory of Open Access Journals (Sweden)

    Milosz Wilczynski

    Full Text Available Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients' clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034. These results indicate potential clinical utility of miRNA-205 as a prognostic marker.

  6. Expression and prognostic significance of thymidylate synthase (TS) in pancreatic head and periampullary cancer.

    Science.gov (United States)

    van der Zee, J A; van Eijck, C H J; Hop, W C J; van Dekken, H; Dicheva, B M; Seynhaeve, A L B; Koning, G A; Eggermont, A M M; Ten Hagen, T L M

    2012-11-01

    Pancreatic cancer has a dismal prognosis. Attempts have been made to improve outcome by several 5-FU based adjuvant treatment regimens. However, the results are conflicting. There seems to be a continental divide with respect to the use of 5-FU based chemoradiotherapy (CRT). Furthermore, evidence has been presented showing a different response of pancreatic head and periampullary cancer to 5-FU based CRT. Expression of thymidylate synthase (TS) has been associated with improved outcome following 5-FU based adjuvant treatment in gastrointestinal cancer. This prompted us to determine the differential expression and prognostic value of TS in pancreatic head and periampullary cancer. TS protein expression was studied by immunohistochemistry on original paraffin embedded tissue from 212 patients following microscopic radical resection (R0) of pancreatic head (n = 98) or periampullary cancer (n = 114). Expression was investigated for associations with recurrence free (RFS), cancer specific (CSS) and overall survival (OS), and conventional prognostic factors. High cytosolic TS expression was present in 26% of pancreatic head tumours and 37% of periampullary tumours (p = .11). Furthermore, TS was an independent factor predicting favourable outcome following curative resection of pancreatic head cancer (p = .003, .001 and .001 for RFS, CSS and OS, respectively). In contrast, in periampullary cancer, TS was not associated with outcome (all p > .10). TS, was found to be poorly expressed in both pancreatic head and periampullary cancer and identified as an independent prognostic factor following curative resection of pancreatic head cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. The Prognostic Significance of the Serum p53 Protein Concentration in Chinese Patients with Non-Hodgkin Lymphoma

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    Min Zhou

    2012-12-01

    Full Text Available OBJECTIVE: To investigate the prognostic significance of cytogenetic abnormalities, staging, patient factors, and the serum p53 protein concentration in Chinese non-Hodgkin lymphoma (NHL patients. METHODS: The study included 43 patients with NHL that were identified between August 2003 and December 2008. Patient clinical characteristics patients were determined based on morphological, immunohistochemical, and cytogenetic analysis, and the serum p53 protein concentration was measured quantitatively. RESULTS: Following conventional chemotherapy, the complete/partial remission (CR/PR rate was significantly higher and overall survival (OS was significantly longer in the patients with early-stage (stage I-II lymphoma, normal karyotype, and a low serum p53 protein concentration than in those with advanced-stage (stage III-IV lymphoma, cytogenetic abnormalities, and a high serum p53 protein concentration (≥0.35 U/mL. Bone marrow infiltration was also a predictor of poor response and OS. There weren’t any significant differences in disease remission between the male and female patients, older and younger patients (aged <70 years vs. ≥70 years, or B-cell lymphoma and T-cell lymphoma patients. CONCLUSION: Staging is an effective means of assessing the severity of NHL. Cytogenetic examination can provide useful information for diagnosis, staging, and prognostication. The serum p53 protein level may be a potential prognostic marker in patients with NHL.

  8. Basal Serum Cortisol Levels are not Predictive of Response to Corticotropin but Have Prognostic Significance in Patients with Septic Shock

    OpenAIRE

    Kwon, Yong Soo; Suh, Gee Young; Kang, Eun-Hae; Koh, Won-Jung; Chung, Man Pyo; Kim, Hojoong; Kwon, O Jung

    2007-01-01

    Because high levels of cortisol are frequently observed in patients with septic shock, low levels of serum cortisol are considered indicative of relative adrenal insufficiency (RAI). This study was performed to investigate whether pretest clinical characteristics, including basal serum cortisol levels, are predictive of serum cortisol response to corticotropin and whether basal cortisol levels have a prognostic significance in patients with septic shock. We performed a retrospective analysis ...

  9. Prognostic value of clinical and Doppler echocardiographic findings in children and adolescents with significant rheumatic valvular disease

    Directory of Open Access Journals (Sweden)

    Fátima Derlene da Rocha Araújo

    2012-01-01

    Conclusions: Our study suggests that the use of Doppler echocardiography during RF helps to identify prognostic factors regarding the development of significant valvular heart disease. Initial severe carditis is an important factor in the long-term prognosis of chronic RHD, whereas arthritis and chore during the initial episode of RF appears to be protective. Strict secondary prophylaxis should be mandatory in high risk patients.

  10. The prognostic significance of postchemoradiotherapy high-resolution MRI and histopathology detected extramural venous invasion in rectal cancer.

    Science.gov (United States)

    Chand, Manish; Evans, Jessica; Swift, Robert I; Tekkis, Paris P; West, Nicholas P; Stamp, Gordon; Heald, Richard J; Brown, Gina

    2015-03-01

    This study aimed to determine the prognostic significance of extramural venous invasion (EMVI) after chemoradiotherapy (CRT) by both magnetic resonance imaging (MRI) (ymrEMVI) and histopathology (ypEMVI). EMVI is a prognostic factor in rectal cancer but whether this remains so after CRT preoperative is unknown. Histopathological definitions of EMVI are variable and lead to underreporting particularly after CRT. All consecutive patients staged on initial MRI as EMVI-positive undergoing preoperative CRT and curative surgery between Jan 2006 and Jan 2012 were included. Posttreatment EMVI status (yEMVI) was reevaluated for both MRI and pathology. The primary endpoint of disease-free survival (DFS) for ymrEMVI and ypEMVI was calculated using the Kaplan-Meier product limit and compared with a Mantel-Cox log-rank test. A P histopathology tumor characteristics. A total of 188 patients who had evidence of EMVI on initial baseline MRI staging were included. MRI detected significantly more patients with persistent EMVI than histopathology (53% vs 19%) but both were prognostic for worse survival-ymrEMVI (HR 1.97) and ypEMVI (HR 2.39). Patients with persistent ymrEMVI-positivity had significantly worse DFS at 3 years (42.7%) compared with ymrEMVI-negative tumors (79.8%); DFS for was 36.9% versus 65.9% positive and negative ypEMVI, respectively. Detection of EMVI post-CRT is prognostically significant whether detected by MRI or histopathology. EMVI status after treatment may be used to counsel patients regarding ongoing risks of metastatic disease, implications for surveillance, and systemic chemotherapy.

  11. Prognostic significance of tumour burden in Hodgkin's disease PS I and II

    DEFF Research Database (Denmark)

    Specht, L; Nissen, N I

    1986-01-01

    of infradiaphragmatic lymph nodes), while the other 47 had been treated with mantle field irradiation plus 6 cycles of combination chemotherapy (MOPP or an equivalent regimen). Of the patients treated with radiotherapy alone, 13 relapsed whereas only 1 of the patients treated with radiotherapy plus combination...... chemotherapy relapsed. The initial tumour burden of each patient was estimated, combining tumour size of each involved area and number of sites involved. For patients treated with radiotherapy alone, a large tumour burden singled out the patients destined to relapse more accurately than other prognostic...

  12. Diagnostic and Prognostic Significance of DSM-5 Attenuated Psychosis Syndrome in Services for Individuals at Ultra High Risk for Psychosis.

    Science.gov (United States)

    Fusar-Poli, Paolo; De Micheli, Andrea; Cappucciati, Marco; Rutigliano, Grazia; Davies, Cathy; Ramella-Cravaro, Valentina; Oliver, Dominic; Bonoldi, Ilaria; Rocchetti, Matteo; Gavaghan, Lauren; Patel, Rashmi; McGuire, Philip

    2017-05-17

    The diagnostic and prognostic significance of the DSM-5-defined Attenuated Psychosis Syndrome (DSM-5-APS) in individuals undergoing an ultra high risk (UHR) clinical assessment for suspicion of psychosis risk is unknown. Prospective cohort study including all consecutive help-seeking individuals undergoing both a DSM-5-APS and a Comprehensive Assessment of At Risk Mental States (CAARMS 12/2006) assessment for psychosis risk at the Outreach and Support in South London (OASIS) UHR service (March 2013-April 2014). The diagnostic significance of DSM-5-APS was assessed with percent overall agreement, prevalence bias adjusted kappa, Bowker's test, Stuart-Maxwell test, residual analysis; the prognostic significance with Cox regression, Kaplan-Meier failure function, time-dependent area under the curve (AUC) and net benefits analysis. The impact of specific revisions of the DSM-5-APS was further tested. In 203 help-seeking individuals undergoing UHR assessment, the agreement between the DSM-5-APS and the CAARMS 12/2006 was only moderate (kappa 0.59). Among 142 nonpsychotic cases, those meeting DSM-5-APS criteria had a 5-fold probability (HR = 5.379) of developing psychosis compared to those not meeting DSM-5-APS criteria, with a 21-month cumulative risk of psychosis of 28.17% vs 6.49%, respectively. The DSM-5-APS prognostic accuracy was acceptable (AUC 0.76 at 24 months) and similar to the CAARMS 12/2006. The DSM-5-APS designation may be clinically useful to guide the provision of indicated interventions within a 7%-35% (2-year) range of psychosis risk. The removal of the criterion E or C of the DSM-5-APS may improve its prognostic performance and transdiagnostic value. The DSM-5-APS designation may be clinically useful in individuals accessing clinical services for psychosis prevention.

  13. Clinicopathological and prognostic significance of OCT4 in patients with hepatocellular carcinoma: a meta-analysis

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    Liang CJ

    2017-12-01

    Full Text Available Chaojie Liang,* Yingchen Xu,* Hua Ge, Guangming Li, Jixiang Wu Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China *These authors contributed equally to this work Background and aims: Octamer-binding transcription factor 4 (OCT4 has been implicated in the development of hepatocellular carcinoma (HCC, although the findings are controversial. We conducted a meta-analysis to assess the correlation between OCT4 and the clinicopathological characteristics and the prognostic value in HCC.Methods: An electronic search for relevant articles was conducted in PubMed, Cochrane Library, Web of Science, EMBASE database, Chinese CNKI, and Chinese WanFang database. Correlations between OCT4 expression and clinicopathological features and survival outcomes were analyzed. Pooled odds ratios and hazard ratios with 95% CIs were calculated using STATA 14.2 software.Results: A total of 10 trials with 985 patients were included. Positive OCT4 expression was correlated with tumor size, tumor numbers, differentiation, and TNM stage. OCT4 expression was not correlated with gender, age, hepatitis B surface antigen, alfa-fetoprotein, liver cirrhosis, vascular invasion, or tumor encapsulation. OCT4 expression was associated with poor 3- and 5-year overall survival, and disease-free survival rate.Conclusion: OCT4 expression was associated with tumor size, tumor numbers, differentiation, and TNM stage in HCC. OCT4 may be a useful prognostic biomarker for HCC. Keywords: octamer-binding transcription factor 4, hepatocellular carcinoma, prognosis, meta-analysis

  14. DC-SCRIPT: nuclear receptor modulation and prognostic significance in primary breast cancer.

    Science.gov (United States)

    Ansems, M; Hontelez, S; Looman, M W G; Karthaus, N; Bult, P; Bonenkamp, J J; Jansen, J H; Sweep, F C G J; Span, P N; Adema, Gosse J

    2010-01-06

    Nuclear receptors, including estrogen receptor (ER), progesterone receptor (PR)-B, peroxisome proliferator-activated receptor gamma, and retinoic acid receptor alpha, have been implicated in breast cancer etiology and progression. We investigated the role of dendritic cell-specific transcript (DC-SCRIPT) as coregulator of these nuclear receptors and as a prognostic factor in breast cancer. The effect of DC-SCRIPT on the transcriptional activity of nuclear receptors was assessed by luciferase reporter assays. DC-SCRIPT expression in normal and tumor tissue from breast cancer patients was analyzed by polymerase chain reaction and immunohistochemistry. The prognostic value of tumor DC-SCRIPT mRNA expression was assessed in three independent cohorts of breast cancer patients: a discovery group (n = 47) and a validation group (n = 97) (neither of which had received systemic adjuvant therapy) and in a tamoxifen-treated validation group (n = 68) by using a DC-SCRIPT to porphobilinogen deaminase transcript ratio cutoff of 0.15 determined in the discovery group. Univariate and multivariable Cox proportional hazards model analyses were performed. All statistical tests were two-sided. DC-SCRIPT suppressed ER- and PR-mediated transcription in a ligand-dependent fashion, whereas it enhanced the retinoic acid receptor alpha- and peroxisome proliferator-activated receptor gamma-mediated transcription. In breast tissue samples from nine patients, DC-SCRIPT mRNA was expressed at lower levels in the tumor than in the corresponding normal tissue (P = .010). Patients in the discovery group with high tumor DC-SCRIPT mRNA levels (66%) had a longer disease-free interval than those with a low DC-SCRIPT mRNA level (34%) (hazard ratio [HR] of recurrence for high vs low DC-SCRIPT level = 0.23, 95% confidence interval [CI] = 0.06 to 0.93, P = .039), which was confirmed in the validation group (HR of recurrence = 0.50, 95% CI = 0.26 to 0.95, P = .034). This prognostic value was confined to

  15. Machine learning classification with confidence: application of transductive conformal predictors to MRI-based diagnostic and prognostic markers in depression.

    Science.gov (United States)

    Nouretdinov, Ilia; Costafreda, Sergi G; Gammerman, Alexander; Chervonenkis, Alexey; Vovk, Vladimir; Vapnik, Vladimir; Fu, Cynthia H Y

    2011-05-15

    There is rapidly accumulating evidence that the application of machine learning classification to neuroimaging measurements may be valuable for the development of diagnostic and prognostic prediction tools in psychiatry. However, current methods do not produce a measure of the reliability of the predictions. Knowing the risk of the error associated with a given prediction is essential for the development of neuroimaging-based clinical tools. We propose a general probabilistic classification method to produce measures of confidence for magnetic resonance imaging (MRI) data. We describe the application of transductive conformal predictor (TCP) to MRI images. TCP generates the most likely prediction and a valid measure of confidence, as well as the set of all possible predictions for a given confidence level. We present the theoretical motivation for TCP, and we have applied TCP to structural and functional MRI data in patients and healthy controls to investigate diagnostic and prognostic prediction in depression. We verify that TCP predictions are as accurate as those obtained with more standard machine learning methods, such as support vector machine, while providing the additional benefit of a valid measure of confidence for each prediction. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Distribution of p53 expression in tissue from 774 Danish ovarian tumour patients and its prognostic significance in ovarian carcinomas

    DEFF Research Database (Denmark)

    Hogdall, E.V.S.; Christensen, L.; Frederiksen, K.

    2008-01-01

    The clinical roles played by normal and altered p53 in cancer are under intensive investigation, but larger studies describing the pattern as well as the prognostic value are still needed. The aim of this study was, using tissue array (TA), to examine the overexpression of p53 protein in 774...... epithelial ovarian tumour tissues from Danish women and to evaluate whether p53 tissue expression levels correlate with clinicopathological parameters and prognosis. The distribution of p53 expression levels at different stages of disease, in different histological subtypes, and the prognostic value of p53...... tissue expression were examined. Overall, p53 was expressed in 24/189 (13%) low malignant potential ovarian tumours (LMP) and in 278/585 (48%) ovarian cancers (OC). No significant difference in frequency of p53 tissue expression in LMP tissue was noted with increasing tumour stage (p=0.98). By contrast...

  17. Molecular Classification Substitutes for the Prognostic Variables Stage, Age, and MYCN Status in Neuroblastoma Risk Assessment

    Directory of Open Access Journals (Sweden)

    Carolina Rosswog

    2017-12-01

    Full Text Available BACKGROUND: Current risk stratification systems for neuroblastoma patients consider clinical, histopathological, and genetic variables, and additional prognostic markers have been proposed in recent years. We here sought to select highly informative covariates in a multistep strategy based on consecutive Cox regression models, resulting in a risk score that integrates hazard ratios of prognostic variables. METHODS: A cohort of 695 neuroblastoma patients was divided into a discovery set (n = 75 for multigene predictor generation, a training set (n = 411 for risk score development, and a validation set (n = 209. Relevant prognostic variables were identified by stepwise multivariable L1-penalized least absolute shrinkage and selection operator (LASSO Cox regression, followed by backward selection in multivariable Cox regression, and then integrated into a novel risk score. RESULTS: The variables stage, age, MYCN status, and two multigene predictors, NB-th24 and NB-th44, were selected as independent prognostic markers by LASSO Cox regression analysis. Following backward selection, only the multigene predictors were retained in the final model. Integration of these classifiers in a risk scoring system distinguished three patient subgroups that differed substantially in their outcome. The scoring system discriminated patients with diverging outcome in the validation cohort (5-year event-free survival, 84.9 ± 3.4 vs 63.6 ± 14.5 vs 31.0 ± 5.4; P < .001, and its prognostic value was validated by multivariable analysis. CONCLUSION: We here propose a translational strategy for developing risk assessment systems based on hazard ratios of relevant prognostic variables. Our final neuroblastoma risk score comprised two multigene predictors only, supporting the notion that molecular properties of the tumor cells strongly impact clinical courses of neuroblastoma patients.

  18. Significance of FAB subclassification of "acute myeloid leukemia, NOS" in the 2008 WHO classification: analysis of 5848 newly diagnosed patients.

    Science.gov (United States)

    Walter, Roland B; Othus, Megan; Burnett, Alan K; Löwenberg, Bob; Kantarjian, Hagop M; Ossenkoppele, Gert J; Hills, Robert K; van Montfort, Kees G M; Ravandi, Farhad; Evans, Anna; Pierce, Sherry R; Appelbaum, Frederick R; Estey, Elihu H

    2013-03-28

    The World Health Organization (WHO) classifies acute myeloid leukemia (AML) via genetic, immunophenotypic, biological, and clinical features. Still, "AML, not otherwise specified (NOS)" is further subdivided based on morphologic criteria similar to those of the French-American-British (FAB) classification. We analyzed the relevance of this practice in patients with newly diagnosed "AML, NOS" with available FAB information undergoing curative-intent therapy in trials of 3 cooperative study groups (Dutch-Belgian Cooperative Trial Group for Hematology/Oncology [HOVON], UK Medical Research Council/National Cancer Research Institute [MRC/NCRI], and the US cooperative group Southwest Oncology Group [SWOG]) or at MD Anderson Cancer Center. Ignoring information on NPM1 and CEBPA, 5848 patients met criteria for "AML, NOS." After multivariate adjustment, FAB M0 was independently associated with significantly lower likelihood of achieving complete remission and inferior relapse-free and overall survival as compared with FAB M1, M2, M4, M5, and M6, with inconclusive data regarding M7. However, restricting attention to known NPM1(neg) patients, FAB M0 was no longer associated with worse outcomes; restricting attention to patients known to be NPM1(neg)/CEPBA(neg) (ie, honoring the provisional entities of "AML with mutated NPM1" and "AML with mutated CEBPA") did not affect this result. In conclusion, in the 2008 WHO classification scheme, FAB subclassification does not provide prognostic information for "AML, NOS" cases if data on NPM1 and CEBPA mutations are available.

  19. PROGNOSTIC SIGNIFICANCE OF POSITRON EMISSION TOMOGRAPHY IN AUTOLOGOUS STEM CELL TRANSPLANTATION FOR NON-HODGKIN’S LYMPHOMA

    Directory of Open Access Journals (Sweden)

    V. G. Potapenko

    2016-01-01

    Full Text Available Objective: evaluation and comparison of positron emission tomography (PET prognostic value with other predictors of effectiveness in patients with non-Hodgkin’s lymphoma (NHL receiving high-dose chemotherapy with autologous hematopoietic stem cell transplantation (AHSCT.Materials and methods. The retrospective data on 49 consecutive patients with NHL  receiving high-dose chemotherapy with АHSCT was               analyzed. The median age was 36.2 (7–60  years. Median follow-up is currently 24 (1–82  months. Prognostic factors analyzed included sex, response to the initial chemotherapy, time to relapse, second-line chemotherapy regimen type, B-symptoms on relapse, serum lactate dehydrogenase and albumin levels, response assessed by computer tomography (CT, number of chemotherapy lines, condition regimen, PET-scan results before (PET1, n = 49 and after (PET2, n = 39 AHSCT.Results. Two-year overall and event-free survivals were 74.4 and 79.1 %, respectively. Patients with CT-confirmed progression prior to AH-SCT had the worse prognosis. Prognostic significance of PET-status  was shown in chemosensitive patients (partial/complete response.The overall survival in PET1-negative and PET1-positive patients were 95.4 vs 71.0 % (р = 0.019, respectively. In PET2-positive and PET2-negative patients the overall and event-free survivals were 59.8 vs 100 % (р = 0.001 and 54.4 vs 94.4 % (р = 0.02, respectively.     In combined analysis of PET1 and PET2 statuses prognostic significance of PET2 prevailed over PET1 results significance. The multivariate analysis confirmed only PET1 significance for survival prediction.   Conclusion. Chemosensitivity of the tumor, assessed by CT, is the most important prognostic factor. In chemosensitive patients achievement PET1 or PET2 negativity means better prognosis. The patients with PET positivity prior and after AHSCT have the worst prognosis.

  20. Diagnostic and prognostic significance of ischemic electrocardiographic changes with regadenoson-stress myocardial perfusion imaging.

    Science.gov (United States)

    Doukky, Rami; Olusanya, Adebayo; Vashistha, Raj; Saini, Abhimanyu; Fughhi, Ibtihaj; Mansour, Khaled; Nigatu, Abiy; Confer, Kara; Sims, Shannon A

    2015-08-01

    The diagnostic and prognostic value of regadenoson-induced ST-segment depression (ST↓) is not defined. Due to the low incidence of ST↓ ≥1.0 mm with vasodilator stress, a lower threshold to define ischemic ECG response may provide improved clinical utility. We conducted a retrospective cohort study of patients who underwent regadenoson-stress SPECT myocardial perfusion imaging (MPI) followed by coronary angiography within 6 months. Ischemic ST↓ was defined as ≥0.5 mm. The prevalence of angiographically severe coronary artery disease (CAD) and the rates of major adverse cardiac events (MACE) including cardiac death, myocardial infarction, and coronary revascularization were determined. In a diagnostic cohort of 629 subjects, 117 (18.6%) had ST↓ ≥0.5 mm. Severe CAD was more prevalent in the ST↓ ≥0.5 vs ST regadenoson-induced ST↓ ≥0.5 mm was associated with higher rates of severe CAD and MACE, irrespective of MPI finding.

  1. Prognostic significance of global grading system of Gleason score in patients with prostate cancer with bone metastasis.

    Science.gov (United States)

    Kambara, Tsunehito; Oyama, Tetsunari; Segawa, Atsuki; Fukabori, Yoshitatsu; Yoshida, Ken-Ichiro

    2010-06-01

    To investigate the influence of the revised Gleason grading system (GGS, revised at a consensus conference organized by the International Society of Urological Pathology in 2005) on prediction of prognosis for patients with prostate cancer with bone metastasis. Prostatic needle biopsy specimens from 113 patients with prostate cancer with bone metastasis were scored using the conventional GGS (CGGS), modified global GGS (MGGGS), and modified highest GGS (MHGGS). The patients were divided into two groups (Gleason score or = 8) using each grading system. Prostate-specific antigen failure-free survival after hormone therapy (HT) was estimated retrospectively. The Cox proportional hazard method was used for univariate and multivariate analysis. Patients with a Gleason score of score of > or = 8 according to each GGS. However, the better prognosis patients were detected more precisely by the CGGS and MGGGS than the MHGGS. Multivariate analysis showed that the CGGS and MGGGS were significant prognostic indicators for the outcome of HT after adjustment for other prognostic factors. These results suggest that the CGGS and MGGGS are more useful than the MHGGS as prognostic indicators for HT. Further evaluation in larger series is needed to define its clinical usefulness.

  2. Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy.

    Science.gov (United States)

    Di Caro, Giuseppe; Cortese, Nina; Castino, Giovanni Francesco; Grizzi, Fabio; Gavazzi, Francesca; Ridolfi, Cristina; Capretti, Giovanni; Mineri, Rossana; Todoric, Jelena; Zerbi, Alessandro; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

    2016-10-01

    Tumour-associated macrophages (TAMs) play key roles in tumour progression. Recent evidence suggests that TAMs critically modulate the efficacy of anticancer therapies, raising the prospect of their targeting in human cancer. In a large retrospective cohort study involving 110 patients with pancreatic ductal adenocarcinoma (PDAC), we assessed the density of CD68-TAM immune reactive area (%IRA) at the tumour-stroma interface and addressed their prognostic relevance in relation to postsurgical adjuvant chemotherapy (CTX). In vitro, we dissected the synergism of CTX and TAMs. In human PDAC, TAMs predominantly exhibited an immunoregulatory profile, characterised by expression of scavenger receptors (CD206, CD163) and production of interleukin 10 (IL-10). Surprisingly, while the density of TAMs associated to worse prognosis and distant metastasis, CTX restrained their protumour prognostic significance. High density of TAMs at the tumour-stroma interface positively dictated prognostic responsiveness to CTX independently of T-cell density. Accordingly, in vitro, gemcitabine-treated macrophages became tumoricidal, activating a cytotoxic gene expression programme, inhibiting their protumoural effect and switching to an antitumour phenotype. In patients with human PDAC, neoadjuvant CTX was associated to a decreased density of CD206(+) and IL-10(+) TAMs at the tumour-stroma interface. Overall, our data highlight TAMs as critical determinants of prognostic responsiveness to CTX and provide clinical and in vitro evidence that CTX overall directly re-educates TAMs to restrain tumour progression. These results suggest that the quantification of TAMs could be exploited to select patients more likely to respond to CTX and provide the basis for novel strategies aimed at re-educating macrophages in the context of CTX. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. Multidimensional scaling of diffuse gliomas: application to the 2016 World Health Organization classification system with prognostically relevant molecular subtype discovery.

    Science.gov (United States)

    Cimino, Patrick J; Zager, Michael; McFerrin, Lisa; Wirsching, Hans-Georg; Bolouri, Hamid; Hentschel, Bettina; von Deimling, Andreas; Jones, David; Reifenberger, Guido; Weller, Michael; Holland, Eric C

    2017-05-22

    Recent updating of the World Health Organization (WHO) classification of central nervous system (CNS) tumors in 2016 demonstrates the first organized effort to restructure brain tumor classification by incorporating histomorphologic features with recurrent molecular alterations. Revised CNS tumor diagnostic criteria also attempt to reduce interobserver variability of histological interpretation and provide more accurate stratification related to clinical outcome. As an example, diffuse gliomas (WHO grades II-IV) are now molecularly stratified based upon isocitrate dehydrogenase 1 or 2 (IDH) mutational status, with gliomas of WHO grades II and III being substratified according to 1p/19q codeletion status. For now, grading of diffuse gliomas is still dependent upon histological parameters. Independent of WHO classification criteria, multidimensional scaling analysis of molecular signatures for diffuse gliomas from The Cancer Genome Atlas (TCGA) has identified distinct molecular subgroups, and allows for their visualization in 2-dimensional (2D) space. Using the web-based platform Oncoscape as a tool, we applied multidimensional scaling-derived molecular groups to the 2D visualization of the 2016 WHO classification of diffuse gliomas. Here we show that molecular multidimensional scaling of TCGA data provides 2D clustering that represents the 2016 WHO classification of diffuse gliomas. Additionally, we used this platform to successfully identify and define novel copy-number alteration-based molecular subtypes, which are independent of WHO grading, as well as predictive of clinical outcome. The prognostic utility of these molecular subtypes was further validated using an independent data set of the German Glioma Network prospective glioblastoma patient cohort.

  4. Basal serum cortisol levels are not predictive of response to corticotropin but have prognostic significance in patients with septic shock.

    Science.gov (United States)

    Kwon, Yong Soo; Suh, Gee Young; Kang, Eun-Hae; Koh, Won-Jung; Chung, Man Pyo; Kim, Hojoong; Kwon, O Jung

    2007-06-01

    Because high levels of cortisol are frequently observed in patients with septic shock, low levels of serum cortisol are considered indicative of relative adrenal insufficiency (RAI). This study was performed to investigate whether pretest clinical characteristics, including basal serum cortisol levels, are predictive of serum cortisol response to corticotropin and whether basal cortisol levels have a prognostic significance in patients with septic shock. We performed a retrospective analysis of 68 patients with septic shock who underwent short corticotropin stimulation testing. RAI was defined as an increase in cortisol level significantly higher simplified acute physiology score II (SAPS II) and sequential organ failure assessment (SOFA) scores than the non-RAI group. The incidence of RAI was the same regardless of the basal serum cortisol level (p=0.447). The hospital mortality rate was 58.8% and was not significantly different between the RAI and non-RAI groups. However, a high basal serum cortisol level (> or =30 microgram/dL) was significantly associated with in-hospital mortality. In conclusion, our data suggest that basal serum cortisol levels are not predictive of serum cortisol response to corticotropin but have a significant prognostic value in patients with septic shock.

  5. Prognostic Value of Gai's Plaque Score and Agatston Coronary Artery Calcium Score for Functionally Significant Coronary Artery Stenosis.

    Science.gov (United States)

    Zhang, Chuang; Yang, Shuang; Gai, Lu-Yue; Han, Zhi-Qi; Xin, Qian; Yang, Xiao-Bo; Yang, Jun-Jie; Jin, Qin-Hua

    2016-12-05

    The prognostic values of the coronary computed tomography angiography (CCTA) score for predicting future cardiovascular events have been previously demonstrated in numerous studies. However, few studies have used the rich information available from CCTA to detect functionally significant coronary lesions. We sought to compare the prognostic values of Gai's plaque score and the coronary artery calcium score (CACS) of CCTA for predicting functionally significant coronary lesions, using fractional flow reserve (FFR) as the gold standard. We retrospectively analyzed 107 visually assessed significant coronary lesions in 88 patients (mean age, 59.6 ± 10.2 years; 76.14% of males) who underwent CCTA, invasive coronary angiography, and invasive FFR measurement. An FFR significant coronary stenosis. Lesions were divided into two groups using an FFR cutoff value of 0.80. We compared Gai's plaque scores and CACS between the two groups and evaluated the correlations of these scores with FFR. The statistical methods included unpaired t-test, Mann-Whitney U-test, and Spearman's correlation coefficients. Coronary lesions with FFR Gai's scores than those with FFR ≥0.80. Gai's score had the strongest correlation with FFR (r = -0.48, P arteries and a single artery. Both CACS in a single artery and Gai's plaque score demonstrated a good capacity to assess functionally significant coronary artery stenosis when compared to the gold standard FFR. However, Gai's plaque score was more predictive of FFR Gai's score can be easily calculated in daily clinical practice and could be used when considering revascularization.

  6. A survey of the ASA physical status classification: significant variation in allocation among Finnish anaesthesiologists.

    Science.gov (United States)

    Ranta, S; Hynynen, M; Tammisto, T

    1997-05-01

    The American Society of Anesthesiologists' (ASA) Classification of Physical Health is a widely used grading system for preoperative health of the surgical patient. In previous studies conducted in North America and Great Britain, considerable variation in the ASA classification allocation has been reported. We hypothesised that in smaller and culturally more homogeneous countries there might be less variation in the ASA classification. A postal questionnaire depicting 10 hypothetical patient cases was sent to 249 randomly selected members of the Finnish Society of Anaesthesiologists. Responses of anaesthesiologists working in university teaching and non-teaching hospitals were compared, as well as the answers of specialists and non-specialists. Responses were received from 108 anaesthesiologists (response rate 43%). There was marked variation in the classification of all the 10 cases: 1 case was classified to all five possible grades (ASA grades I-V). In 2 cases, there was significant variation between anaesthesiologists working in university teaching and non-teaching hospitals. There was no difference in the grading between specialist and non-specialist anaesthesiologists. In a small and culturally homogeneous country, like Finland, there exists similar wide variation in the ASA classification as has been previously reported from larger and culturally more heterogeneous countries. The significant variation should always be considered when using this classification in clinical or scientific work.

  7. Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance.

    Science.gov (United States)

    Stål, Per

    2015-10-21

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD.

  8. Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy.

    Science.gov (United States)

    Rogers, Ailín C; Gibbons, David; Hanly, Ann M; Hyland, John M P; O'Connell, P Ronan; Winter, Desmond C; Sheahan, Kieran

    2014-01-01

    Tumor budding is an increasingly important prognostic feature for pathologists to recognize. The aim of this study was to correlate intra-tumoral budding in pre-treatment rectal cancer biopsies with pathological response to neoadjuvant chemoradiotherapy and with long-term outcome. Data from a prospectively maintained database were acquired from patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. Pre-treatment rectal biopsies were retrospectively reviewed for evidence of intra-tumoral budding. Multivariate logistic regression was used to identify factors contributing to cancer-specific death, expressed as hazard ratios with 95% confidence intervals. Of the 185 patients with locally advanced rectal cancer, 89 patients met the eligibility criteria, of whom 18 (20%) exhibited budding in a pre-treatment tumor biopsy. Intra-tumoral budding predicted a poor pathological response to neoadjuvant chemoradiotherapy (higher ypT stage, P=0.032; lymph node involvement, P=0.018; lymphovascular invasion, P=0.004; and residual poorly differentiated tumors, P=0.005). No patient with intra-tumoral budding exhibited a tumor regression grade 1 or complete pathological response, providing a 100% specificity and positive predictive value for non-response to neoadjuvant chemoradiotherapy. Intra-tumoral budding was associated with a lower disease-free 5-year survival rate (33 vs 78%, Ptumoral budding at diagnosis of rectal cancer identifies those who will poorly respond to neoadjuvant chemoradiotherapy and those with a poor prognosis.

  9. Prognostic significance of contrast-enhanced CT attenuation value in extrahepatic cholangiocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Asayama, Yoshiki [Kyushu University, Department of Advanced Imaging and Interventional Radiology, Graduate School of Medical Sciences, Fukuoka (Japan); Nishie, Akihiro; Ishigami, Kousei; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Fujita, Nobuhiro; Honda, Hiroshi [Kyushu University, Departments of Clinical Radiology, Fukuoka (Japan); Ohtsuka, Takao [Kyushu University, Departments of Surgery and Oncology, Fukuoka (Japan); Yoshizumi, Tomoharu [Kyushu University, Departments of Surgery and Sciences, Fukuoka (Japan); Aishima, Shinichi [Saga University, Pathology and Microbiology, Faculty of Medicine, Saga (Japan); Kyushu University, Departments of Anatomic Pathology, Graduate School of Medical Sciences, Fukuoka (Japan); Oda, Yoshinao [Kyushu University, Departments of Anatomic Pathology, Graduate School of Medical Sciences, Fukuoka (Japan)

    2017-06-15

    To determine whether washout characteristics of dynamic contrast-enhanced computed tomography (CT) could predict survival in patients with extrahepatic cholangiocarcinoma (EHC). This study collected 46 resected cases. All cases were examined by dynamic contrast study on multidetector-row CT. Region-of-interest measurements were obtained at the non-enhanced, portal venous phase and delayed phase in the tumour and were used to calculate the washout ratio as follows: [(attenuation value at portal venous phase CT - attenuation value at delayed enhanced CT)/(attenuation value at portal venous phase CT - attenuation value at unenhanced CT)] x 100. On the basis of the median washout ratio, we classified the cases into two groups, a high-washout group and low-washout group. Associations between overall survival and various factors including washout rates were analysed. The median washout ratio was 29.4 %. Univariate analysis revealed that a lower washout ratio, venous invasion, lymphatic permeation and lymph node metastasis were associated with shorter survival. Multivariate analysis identified the lower washout ratio as an independent prognostic factor (hazard ratio, 3.768; p value, 0.027). The washout ratio obtained from the contrast-enhanced CT may be a useful imaging biomarker for the prediction of survival of patients with EHC. (orig.)

  10. Prognostic significance of osteopontin expression in non-small-cell lung cancer: A meta-analysis.

    Science.gov (United States)

    Zou, Xue-Lin; Wang, Chun; Liu, K E; Nie, Wen; Ding, Zhen-Yu

    2015-05-01

    Osteopontin (OPN) plays an important role in the progression and metastasis of cancer. However, the role of OPN as a prognostic factor in non-small-cell lung cancer (NSCLC) remains controversial. The aim of this study was to investigate the association between OPN expression and prognosis in patients with NSCLC using a meta-analysis. Based on PubMed, Ovid Medline, Embase, ISI, ScienceDirect and SpringerLink databases, related articles published prior to January, 2013 were collected. A meta-analysis was conducted to investigate the association of OPN expression with overall survival (OS) and progression-free survival (PFS) in patients with NSCLC. Hazard ratio (HR) with 95% confidence interval (CI) was used to assess the strength of this association. A total of 6 studies, including 776 patients, were found to be eligible for the meta-analysis. No heterogeneity was observed in OS or PFS, whereas low OPN expression was found to be correlated with better OS (HR=0.57, 95% CI: 0.46-0.70) and PFS (HR=0.62, 95% CI: 0.49-0.77). This meta-analysis demonstrated an association of OPN with poor prognosis in NSCLC patients. However, prospective studies are required to confirm these findings.

  11. Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1, 2 and 3 in Periampullary Adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Jacob Elebro

    Full Text Available Periampullary adenocarcinoma, including pancreatic cancer, is a heterogeneous group of tumours with dismal prognosis, for which there is an urgent need to identify novel treatment strategies. The human epithelial growth factor receptors EGFR, HER2 and HER3 have been studied in several tumour types, and HER-targeting drugs have a beneficial effect on survival in selected types of cancer. However, these effects have not been evident in pancreatic cancer, and remain unexplored in other types of periampullary cancer. The prognostic impact of HER-expression in these cancers also remains unclear. The aim of this study was therefore to examine the expression and prognostic value of EGFR, HER2 and HER3 in periampullary cancer, with particular reference to histological subtype. To this end, protein expression of EGFR, HER2 and HER3, and HER2 gene amplification was assessed by immunohistochemistry and silver in situ hybridization, respectively, on tissue microarrays with tumours from 175 periampullary adenocarcinomas, with follow-up data on recurrence-free survival (RFS and overall survival (OS for up to 5 years. EGFR expression was similar in pancreatobiliary (PB and intestinal (I type tumours, but high HER2 and HER3 expression was significantly more common in I-type tumours. In PB-type cases receiving adjuvant gemcitabine, but not in untreated cases, high EGFR expression was significantly associated with a shorter OS and RFS, with a significant treatment interaction in relation to OS (pinteraction = 0.042. In I-type cases, high EGFR expression was associated with a shorter OS and RFS in univariable, but not in multivariable, analysis. High HER3 expression was associated with a prolonged RFS in univariable, but not in multivariable, analysis. Neither HER2 protein expression nor gene amplification was prognostic. The finding of a potential interaction between the expression of EGFR and response to adjuvant chemotherapy in PB-type tumours needs validation

  12. Feature selection based on SVM significance maps for classification of dementia

    NARCIS (Netherlands)

    E.E. Bron (Esther); M. Smits (Marion); J.C. van Swieten (John); W.J. Niessen (Wiro); S. Klein (Stefan)

    2014-01-01

    textabstractSupport vector machine significance maps (SVM p-maps) previously showed clusters of significantly different voxels in dementiarelated brain regions. We propose a novel feature selection method for classification of dementia based on these p-maps. In our approach, the SVM p-maps are

  13. No prognostic significance of antimitochondrial antibody profile testing in primary biliary cirrhosis.

    Science.gov (United States)

    Vleggaar, Frank P; van Buuren, Henk R

    2004-01-01

    The rate of disease progression varies considerably between individuals with primary biliary cirrhosis (PBC). On the basis of serological subtyping 4 antimitochondrial antibody (AMA) profiles (A, B, C and D) can be defined. The finding of previous studies that profile C/D is associated with a progressive course, in contrast to profile A/B, is a question of debate. The aim of the study was to investigate whether AMA profiles predicted the course for a cohort of Dutch PBC patients. Patients with an established diagnosis of AMA-positive PBC, AMA-negative PBC patients, non-PBC decompensated cirrhotics and healthy volunteers. Serum samples from 38 AMA-positive progressive patients, 31 AMA-positive patients without evidence of progression for at least 6 years, 5 AMA-negative PBC patients, 5 non-PBC decompensated cirrhotics and 5 healthy volunteers were assessed. AMA profiles were determined without knowledge of the clinical data. In the progressive AMA-positive group, 13% had profile A/B and 84% had profile C/D. In the non-progressive group, 13% had profile A/B, 77% profile C/D; 10% had no profile. During follow-up, a change from profile A/B to profile C/D or vice versa was not observed. This study found that not only PBC patients with AMA profile C/D but also patients with profile A/B may run a progressive course and therefore does not support the suggestion that AMA profiles can be used as independent prognostic indicator. The divergent results of this and previous studies may be explained by the selection of different patient populations.

  14. Prognostic significance of serum creatinine and its change patterns in patients with acute coronary syndromes.

    Science.gov (United States)

    Marenzi, Giancarlo; Cabiati, Angelo; Cosentino, Nicola; Assanelli, Emilio; Milazzo, Valentina; Rubino, Mara; Lauri, Gianfranco; Morpurgo, Marco; Moltrasio, Marco; Marana, Ivana; De Metrio, Monica; Bonomi, Alice; Veglia, Fabrizio; Bartorelli, Antonio

    2015-03-01

    In acute coronary syndromes (ACS), serum creatinine (sCr) levels have short- and long-term prognostic value. However, it is possible that repeated evaluations of sCr during hospitalization, rather than measuring sCr value at admission only, might improve risk assessment. We investigated the relationship between sCr baseline value, its changes, and in-hospital mortality in patients hospitalized with ACS. In 2,756 ACS patients, sCr was measured at hospital admission and then daily, until discharge from coronary care unit. Patients were grouped according to the maximum sCr change observed: <0.3 mg/dL change from baseline (stable renal function [SRF] group), ≥0.3 mg/dL decrease (improved renal function [IRF] group), and ≥0.3 mg/dL increase (worsening renal function [WRF] group). Of the 2,756 patients, 2,163 (78%) had SRF, 292 (11%) had IRF, and 301 (11%) had WRF. In-hospital mortality in the 3 groups was 0.5%, 2%, and 14% (P < .001), respectively. Peak sCr value was a more powerful predictor of mortality (area under the curve 0.86, 95% CI 0.81-0.92) than the initial sCr value (area under the curve 0.69, 95% CI 0.63-0.77; P < .001). When sCr and its change patterns during coronary care unit stay were evaluated together, improved mortality risk stratification was found. In ACS patients, daily sCr value and its change pattern are stronger predictors of in-hospital mortality than the initial sCr value only; thus, their combined evaluation provides a more accurate and dynamic stratification of patients' risk. Finally, the intermediate mortality risk of IRF patients possibly reflects acute kidney injury started before hospitalization. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Invasion front-specific expression and prognostic significance of microRNA in colorectal liver metastases.

    Science.gov (United States)

    Kahlert, Christoph; Klupp, Fee; Brand, Karsten; Lasitschka, Felix; Diederichs, Sven; Kirchberg, Johanna; Rahbari, Nuh; Dutta, Shamik; Bork, Ulrich; Fritzmann, Johannes; Reissfelder, Christoph; Koch, Moritz; Weitz, Juergen

    2011-10-01

    The tumor edge of colorectal cancer and its adjacent peritumoral tissue is characterized by an invasion front-specific expression of genes that contribute to angiogenesis or epithelial-to-mesenchymal transition. Dysregulation of these genes has a strong impact on the invasion behavior of tumor cells. However, the invasion front-specific expression of microRNA (miRNA) still remains unclear. Therefore, the aim of the present study was to investigate miRNA expression patterns at the invasion front of colorectal liver metastases. Laser microdissection of colorectal liver metastases was performed to obtain separate tissue compartments from the tumor center, tumor invasion front, liver invasion front and pure liver parenchyma. Microarray expression analysis revealed 23 miRNA downregulated in samples from the tumor invasion front with respect to the same miRNA in the liver, the liver invasion front or the tumor center. By comparing samples from the liver invasion front with samples from pure liver parenchyma, the tumor invasion front and the tumor center, 13 miRNA were downregulated. By quantitative RT-PCR, we validated the liver invasion front-specific downregulation of miR-19b, miR-194, let-7b and miR-1275 and the tumor invasion front-specific downregulation of miR-143, miR- 145, let-7b and miR-638. Univariate analysis demonstrated that enhanced expression of miR-19b and miR-194 at the liver invasion front, and decreased expression of let-7 at the tumor invasion front, is an adverse prognostic marker of tumor recurrence and overall survival. In conclusion, the present study suggests that invasion front-specific downregulation of miRNA in colorectal liver metastases plays a pivotal role in tumor progression.

  16. Changes of 2015 WHO Histological Classification of Lung Cancer 
and the Clinical Significance

    Directory of Open Access Journals (Sweden)

    Xin YANG

    2016-06-01

    Full Text Available Due in part to remarkable advances over the past decade in our understanding of lung cancer, particularly in area of medical oncology, molecular biology, and radiology, there is a pressing need for a revised classification, based not on pathology alone, but rather on an integrated multidisciplinary approach to classification of lung cancer. The 2015 World Health Organization (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart has just been published with numerous important changes from the 2004 WHO classification. The revised classification has been greatly improved in helping advance the field, increasing the impact of research, improving patient care and assisting in predicting outcome. The most significant changes will be summarized in this paper as follows: (1 main changes of lung adenocarcinoma as proposed by the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS classification, (2 reclassifying squamous cell carcinomas into keratinizing, nonkeratinizing, and basaloid subtypes with the nonkeratinizing tumors requiring immunohistochemistry proof of squamous differentiation, (3 restricting the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation with reclassification of the remaining former large cell carcinoma subtypes into different categories, (4 grouping of neuroendocrine tumors together in one category, (5 and the current viewpoint of histologic grading of lung cancer.

  17. Prognostic Significance of Remote Myocardium Alterations Assessed by Quantitative Noncontrast T1 Mapping in ST-Segment Elevation Myocardial Infarction.

    Science.gov (United States)

    Reinstadler, Sebastian J; Stiermaier, Thomas; Liebetrau, Johanna; Fuernau, Georg; Eitel, Charlotte; de Waha, Suzanne; Desch, Steffen; Reil, Jan-Christian; Pöss, Janine; Metzler, Bernhard; Lücke, Christian; Gutberlet, Matthias; Schuler, Gerhard; Thiele, Holger; Eitel, Ingo

    2017-06-09

    This study assessed the prognostic significance of remote zone native T1 alterations for the prediction of clinical events in a population with ST-segment elevation myocardial infarction (STEMI) who were treated by primary percutaneous coronary intervention (PPCI) and compared it with conventional markers of infarct severity. The exact role and incremental prognostic relevance of remote myocardium native T1 mapping alterations assessed by cardiac magnetic resonance (CMR) after STEMI remains unclear. We included 255 consecutive patients with STEMI who were reperfused within 12 h after symptom onset. CMR core laboratory analysis was performed to assess left ventricular (LV) function, standard infarct characteristics, and native T1 values of the remote, noninfarcted myocardium. The primary endpoint was a composite of death, reinfarction, and new congestive heart failure within 6 months (major adverse cardiac events [MACE]). Patients with increased remote zone native T1 values (>1,129 ms) had significantly larger infarcts (p = 0.012), less myocardial salvage (p = 0.002), and more pronounced LV dysfunction (p = 0.011). In multivariable analysis, remote zone native T1 was independently associated with MACE after adjusting for clinical risk factors (p = 0.001) or other CMR variables (p = 0.007). In C-statistics, native T1 of remote myocardium provided incremental prognostic information beyond clinical risk factors, LV ejection fraction, and other markers of infarct severity (all p infarct size, and myocardial salvage index) led to net reclassification improvement of 0.82 (95% confidence interval: 0.46 to 1.17; p Myocardial Damage in STEMI [LIPSIA-COND]; NCT02158468). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. Histological grading of papillary urothelial carcinoma of the bladder: prognostic value of the 1998 WHO/ISUP classification system and comparison with conventional grading systems

    NARCIS (Netherlands)

    Oosterhuis, J. W. A.; Schapers, R. F. M.; Janssen-Heijnen, M. L. G.; Pauwels, R. P. E.; Newling, D. W.; ten Kate, F.

    2002-01-01

    AIM: To test the prognostic value of the 1998 WHO/ISUP (World Health Organisation/International Society of Urologic Pathology) consensus classification system in Ta papillary urothelial neoplasms of the bladder. METHODS: The histological slides of 322 patients with a primary Ta tumour were

  19. A clinically based prognostic index for diffuse large B-cell lymphoma with a cut-off at 70 years of age significantly improves prognostic stratification

    DEFF Research Database (Denmark)

    Gang, Anne O.; Pedersen, Michael; d'Amore, Francesco

    2015-01-01

    subtypes. We applied IPI factors to a population-based rituximab-treated cohort of 1990 patients diagnosed 2000-2010 and explored new factors and the optimal prognostic age cut-off for DLBCL. Multivariate-analyses (MVA) confirmed the prognostic value of all IPI factors except the presence of > 1 extranodal...... lesion. The optimal age cut-off was 70 years. In a MVA of albumin, lymphocyte count, sex, immunoglobulin G, bulky disease, hemoglobin and B-symptoms, only albumin was prognostic. We propose: (1) a modified DLBCL prognostic index (DLBCL-PI) including: age (70 years), performance status (PS), lactate...... dehydrogenase (LDH), stage and albumin level, and (2) a separate age-adjusted DLBCL-PI for patients 1 extranodal lesion, however excluding stage....

  20. Prognostic utility of the 2011 GOLD classification and other multidimensional tools in Asian COPD patients: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Chan HP

    2016-04-01

    Full Text Available Hiang Ping Chan,1,2 Amartya Mukhopadhyay,1,2 Pauline Lee Poh Chong,1,2 Sally Chin,1,2 Xue Yun Wong,1,2 Venetia Ong,1,2 Yiong Huak Chan,3 Tow Keang Lim,1,2 Jason Phua1,2 1Division of Respiratory and Critical Care Medicine, University Medicine Cluster, National University Health System, 2Department of Medicine, 3Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Background: How well the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD classification prognosticates for Asian patients with COPD is unknown.Objective: The authors aimed to study the predictive utility of the GOLD 2011 classification for exacerbations and mortality as compared with other multidimensional tools in an Asian population.Methods: In all, 1,110 COPD patients were prospectively followed between March 2008 and March 2013. They were classified using the 2011 and 2007 GOLD guidelines, modified Medical Research Council score, St. George’s Respiratory Questionnaire (SGRQ, and Body mass index, Obstruction, Dyspnea (BOD index. Outcome measures were exacerbations and mortality. Multivariable survival analyses and receiver operating characteristic (ROC curves were used to assess the different classification systems.Results: Time-to-event analyses demonstrated earlier exacerbations in 2011’s GOLD D when compared with GOLD A (hazard ratio [HR] 0.54, 95% confidence interval [CI]: 0.31–0.95, P=0.032 and GOLD B (HR 0.62, 95% CI: 0.45–0.85, P=0.003 and higher mortality when compared with GOLD A (HR 0.37, 95% CI: 0.16–0.88, P=0.025 and GOLD B (HR 0.46, 95% CI: 0.31–0.70, P<0.001. The areas under the ROC curve for GOLD 2011, GOLD 2007, modified Medical Research Council, St. George’s Respiratory Questionnaire, and BOD index were 0.62, 0.59, 0.61, 0.60, and 0.61, respectively, for the prediction of exacerbations and 0.71, 0.70, 0.71, 0.71, and 0.72, respectively, for the prediction of mortality (ROC comparator, P>0

  1. Clinical and Prognostic Significance of Preoperative Plasma Fibrinogen Levels in Patients with Operable Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Yu Mei

    Full Text Available Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer.Two hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS and overall survival (OS. Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS.Elevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001, menopause (yes vs. no, p<0.001, tumor size (T1&T2 vs. T3&T4, p = 0.033, tumor stage (I vs. II vs. III, p = 0.034 and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001, but not with histological grade, molecular type and other Immunohistochemical parameters (ER, PR, HER2 and Ki-67. In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/p<0.001 and plasma fibrinogen (p<0.001/p<0.001 levels were associated with disease-free and overall survival, but just lymph nodes involvement (p<0.001, hazard ratio [HR] = 2.9, 95% confidence interval [CI] = 1.6-5.3/p = 0.006, HR = 3.2, 95% CI = 1.4-7.3 and plasma fibrinogen levels (p = 0.006, HR = 3.4, 95% CI = 1.4-8.3/p = 0.002, HR = 10.1, 95% CI = 2.3-44.6 were associated with disease-free and overall survival in a multivariate survival analysis, respectively.This study demonstrates that elevated preoperative plasma fibrinogen levels are associated with breast cancer progression and are independently associated with a poor prognosis in patients with operable breast cancer.

  2. An enhanced topologically significant directed random walk in cancer classification using gene expression datasets

    Directory of Open Access Journals (Sweden)

    Choon Sen Seah

    2017-12-01

    Full Text Available Microarray technology has become one of the elementary tools for researchers to study the genome of organisms. As the complexity and heterogeneity of cancer is being increasingly appreciated through genomic analysis, cancerous classification is an emerging important trend. Significant directed random walk is proposed as one of the cancerous classification approach which have higher sensitivity of risk gene prediction and higher accuracy of cancer classification. In this paper, the methodology and material used for the experiment are presented. Tuning parameter selection method and weight as parameter are applied in proposed approach. Gene expression dataset is used as the input datasets while pathway dataset is used to build a directed graph, as reference datasets, to complete the bias process in random walk approach. In addition, we demonstrate that our approach can improve sensitive predictions with higher accuracy and biological meaningful classification result. Comparison result takes place between significant directed random walk and directed random walk to show the improvement in term of sensitivity of prediction and accuracy of cancer classification.

  3. The occurrence and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarction. TRACE Study group. TRAndolapril Cardiac Evalution.

    Science.gov (United States)

    Pedersen, O D; Bagger, H; Køber, L; Torp-Pedersen, C

    1999-05-01

    To investigate the occurrence and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarction. The occurrence and prognostic significance of atrial fibrillation/-flutter were studied in 6676 consecutive patients with acute myocardial infarction screened in 27 centres in Denmark for inclusion into the TRAndolapril Cardiac Evaluation (TRACE) study. Information about occurrence of atrial fibrillation/-flutter during hospitalization was prospectively collected for the following three periods: day 1-2, day 3-4 and from day 5 until discharge. A total of 1395 patients (21%) suffered from atrial fibrillation/-flutter in one or more of the specified periods during hospitalization. Patients with atrial fibrillation/-flutter were significantly older, a significantly greater proportion were women, left ventricular systolic dysfunction was more extensive, thrombolytic therapy was received less frequently, and anterior Q wave myocardial infarction was experienced more frequently than patients without atrial fibrillation/-flutter. History of acute myocardial infarction and/or angina pectoris was similar in patients with and without atrial fibrillation/-flutter, whereas significantly more patients with atrial fibrillation/-flutter had a history of hypertension, congestive heart failure, diabetes mellitus, pulmonary disease and stroke. The unadjusted in-hospital mortality rate was significantly higher in patients with atrial fibrillation/-flutter in one or more of the specified periods during hospitalization (18%) than in patients without atrial fibrillation/-flutter (9%), P<0.001. After adjustment for baseline characteristics, the presence of atrial fibrillation/-flutter was still associated with increased in-hospital mortality; odds ratio=1.5 (95% Cl: 1.2-1.8), P<0.001. In patients surviving hospitalization, the unadjusted 5-year mortality rate was also significantly higher in patients suffering from atrial fibrillation/-flutter (56%) than in

  4. Prognostic significance of occult lymph node micrometastasis in gastric cancer: a histochemical and immunohistochemical study based on 1997 UICC TNM and 1998 JGCA classifications Significância prognóstica das micrometástases ocultas em linfonodos no câncer gástrico: estudo histoquímico e imunoistoquímico baseado nas classificações UICC TNM de 1997 e JCGCA de 1998

    Directory of Open Access Journals (Sweden)

    Nelson Fausto Dell'Aquila Jr

    2008-12-01

    Full Text Available BACKGROUND: Micrometastasis is a single or a cluster of malignant cells inside the lymph node that are not detected by routine histopathological sections. Micrometastasis is related to poorer prognosis in many gastric cancer studies the real significance of these cells is still controversial. AIM: To evaluate if lymph node micrometastasis is a significant independent prognostic factor and important risk factor for recurrence in gastric cancer. METHODS: A total of 1290 lymph nodes from 28 patients with gastric cancer, since 1998 until 2003, treated by radical resection (D2 and modified D3 lymphadenectomies were studied. Three sections per lymph node were stained by Hematoxilin-Eosin, histochemical (AB-PAS and immunohistochemical (AE1-AE3 techniques. Kaplan-Meier's survival curves and Log-rank/Cox tests were used in order to compares lymph node micrometastasis positivity, depth (pT and location of tumor in gastric wall, histologic type, lymphatic, vascular and perineural invasion, lymph node status (pN and stage. RESULTS: There were worse prognosis and recurrence in patients with positive lymph node micrometastasis related to vascular and perineural invasions, advanced lymph node status and advanced stages. CONCLUSION: Lymph node micrometastasis seems to be a significant independent prognostic factor and important risk factor for recurrence in gastric cancer, in a context of radical D2 lymphadenectomyRACIONAL: Micrometástases são um conjunto de células malignas dentro de linfonodo que não são detectadas pelos exames histopatológicos de rotina. Elas são relacionadas a prognóstico mais pobre em muitos estudos sobre câncer gástrico, mas a real significância dessas células permanece controversa. OBJETIVO: Avaliar se micrometástase linfonodal é um fator independente de prognóstico e importante para detectar a recurrência do câncer gástrico. MÉTODOS: Um total de 1290 lifonodos de 28 pacientes com câncer gástrico, de 1998 a 2003

  5. Prognostic significance of precordial ST segment depression during inferior myocardial infarction in the thrombolytic era: Results in 16,521 patients

    NARCIS (Netherlands)

    E.D. Peterson; W.R. Hathaway; K.M. Zabel; K.S. Pieper (Karen); C.B. Granger (Christopher); G.S. Wagner (Galen); E.J. Topol (Eric); E.R. Bates (Eric); M.L. Simoons (Maarten); R.M. Califf (Robert)

    1996-01-01

    textabstractObjectives. We examined the prognostic significance of precordial ST segment depression among patients with an acute inferior myocardial infarction. Background. Although precordial ST segment depression has been associated with a poor prognosis, this correlation has not been adequately

  6. Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers.

    Science.gov (United States)

    Becht, Etienne; Giraldo, Nicolas A; Germain, Claire; de Reyniès, Aurélien; Laurent-Puig, Pierre; Zucman-Rossi, Jessica; Dieu-Nosjean, Marie-Caroline; Sautès-Fridman, Catherine; Fridman, Wolf H

    2016-01-01

    The outcome of tumors results from genetic and epigenetic modifications of the transformed cells and also from the interactions of the malignant cells with their tumor microenvironment (TME), which includes immune and inflammatory cells. For a given cancer type, the composition of the immunological TME is not homogeneous. Heterogeneity is found between different cancer types and also between tumors from patients with the same type of cancer. Some tumors exhibit a poor infiltration by immune cells, and others are highly infiltrated by lymphocytes. Among the latter, the architecture of the TME, with the localization of immune cells in the invasive front and the center of the tumor, the presence of tumor-adjacent organized lymphoid aggregates, and the type of inflammatory context, determines the prognostic impact of the infiltrating cells. The description and the understanding of the immune and inflammatory landscape in human tumors are of paramount importance at different levels of patient's care. It completes the mutational, transcriptional, and epigenetic patterns of the malignant cells and open paths to understand how tumor cells shape their immune microenvironment and are shaped by the immune reaction. It provides prognostic and theranostic markers, as well as novel targets for immunotherapies. © 2016 Elsevier Inc. All rights reserved.

  7. Defining a new aggressiveness classification and using NFATc1 localization as a prognostic factor in cherubism.

    Science.gov (United States)

    Kadlub, Natacha; Sessiecq, Quentin; Dainese, Linda; Joly, Aline; Lehalle, Daphne; Marlin, Sandrine; Badoual, Cecile; Galmiche, Louise; Majoufre-Lefebvre, Claire; Berdal, Ariane; Deckert, Marcel; Vazquez, Marie-Paule; Descroix, Vianney; Coudert, Amélie E; Picard, Arnaud

    2016-12-01

    Cherubism is a rare genetic disease characterized by bilateral giant cell reparative granuloma of the jaws consisting of a fibrotic stroma with giant multinucleated cells (GMCs) and osteoclastic features. Cherubism severity is highly variable, and recurrence after surgery is the most important risk. Currently, there are no prognostic indicators. The aims of this study were to evaluate the osteoclastogenesis phenotype by histologic examination of nuclear factor of activated T cells 1 (NFATc1) localization and tartrate-resistant acid phosphatase (TRAP) activity and to correlate the results to disease aggressiveness to define prognostic indicators. Based on cherubism evolution 1 year after surgery, 3 classes of cherubism aggressiveness were identified: mild (group A), moderate (group B), and severe (group C). Histologically, in grade A and B cherubism lesions, GMCs were negative for both TRAP activity and NFATc1 nuclear localization. In contrast, in grade C cherubism lesions, GMCs were all positive for TRAP activity and NFATc1 nuclear localization and displayed osteoclast-like features. Other histopathologic findings were not different among the 3 groups. Our results establish that TRAP activity and NFTAc1 nuclear localization are associated with aggressive cherubism and therefore could be added to routine pathologic examination to aid in prognosis and management of the disease. The finding of NFATc1 nuclear localization in aggressive tumors supports the addition of anticalcineurin treatment to the therapeutic arsenal for cherubism. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Prognostic significance of APACHE II score and plasma suPAR in Chinese patients with sepsis: a prospective observational study.

    Science.gov (United States)

    Liu, Xuan; Shen, Yong; Li, Zhihua; Fei, Aihua; Wang, Hairong; Ge, Qinmin; Pan, Shuming

    2016-07-29

    Timely risk stratification is the key strategy to improve prognosis of patients with sepsis. Previous study has proposed to develop a powerful risk assessment rule by the combination of Acute Physiology and Chronic Health Evaluation II (APACHE II) score and plasma soluble urokinase plasminogen activator receptor (suPAR). That reaffirmation of suPAR as a prognostic marker in Chinese patients with severe sepsis is the aim of the study. A total of 137 consecutive Chinese patients with sepsis were enrolled in a prospective study cohort. Demographic and clinical characteristics, conventional risk factors and important laboratory data were prospectively recorded. Sequential plasma suPAR concentrations were measured by an enzymeimmunoabsorbent assay on days 1, 3, and 7 after admission to the intensive care unit (ICU). Receiver operating characteristic (ROC) curves and Cox regression analysis were used to examine the performance of suPAR in developing a rule for risk stratification. The results showed that plasma suPAR concentrations remained relatively stable within survivors and non-survivors during the first week of disease course. Regression analysis indicated that APACHE II ≥15 and suPAR ≥10.82 ng/mL were independently associated with unfavorable outcome. With the above cutoffs of APACHE II and suPAR, strata of disease severity were determined. The mortality of each stratum differed significantly from the others. Combination of APACHE II score and suPAR may supply the powerful prognostic utility for the mortality of sepsis.

  9. Proposal and validation of prognostic scoring systems for IgG and IgA monoclonal gammopathies of undetermined significance.

    Science.gov (United States)

    Rossi, Francesca; Petrucci, Maria Teresa; Guffanti, Andrea; Marcheselli, Luigi; Rossi, Davide; Callea, Vincenzo; Vincenzo, Federico; De Muro, Marianna; Baraldi, Alessandra; Villani, Oreste; Musto, Pellegrino; Bacigalupo, Andrea; Gaidano, Gianluca; Avvisati, Giuseppe; Goldaniga, Maria; Depaoli, Lorenzo; Baldini, Luca

    2009-07-01

    The presenting clinico-hematologic features of 1,283 patients with IgG and IgA monoclonal gammopathies of undetermined significance (MGUS) were correlated with the frequency of evolution into multiple myeloma (MM). Two IgG MGUS populations were evaluated: a training sample (553 patients) and a test sample (378 patients); the IgA MGUS population consisted of 352 patients. Forty-seven of the 553 training group patients and 22 of 378 test group IgG patients developed MM after a median follow-up of 6.7 and 3.6 years, respectively. Multivariate analysis showed that serum monoclonal component (MC) levels of sample. Thirty of the 352 IgA patients developed MM after a median follow-up of 4.8 years, and multivariate analysis showed that hemoglobin levels of <12.5 g/dL and reduced serum polyclonal immunoglobulin correlated with progression. A pooled statistical analysis of all of the patients confirmed the validity of Mayo Clinic risk model showing that IgA class, serum MC levels, and light-chain proteinuria are the most important variables correlated with disease progression. Using simple variables, we validated a prognostic model for IgG MGUS. Among the IgA cases, the possible prognostic role of hemoglobin emerged in addition to a decrease in normal immunoglobulin levels.

  10. Significance of stromal-1 and stromal-2 signatures and biologic prognostic model in diffuse large B-cell lymphoma

    Science.gov (United States)

    Abdou, Asmaa Gaber; Asaad, Nancy; Kandil, Mona; Shabaan, Mohammed; Shams, Asmaa

    2017-01-01

    Objective : Diffuse Large B Cell Lymphoma (DLBCL) is a heterogeneous group of tumors with different biological and clinical characteristics that have diverse clinical outcomes and response to therapy. Stromal-1 signature of tumor microenvironment of DLBCL represents extracellular matrix deposition and histiocytic infiltrate, whereas stromal-2 represents angiogenesis that could affect tumor progression. Methods : The aim of the present study is to assess the significance of stromal-1 signature using SPARC-1 and stromal-2 signature using CD31 expression and then finally to construct biologic prognostic model (BPM) in 60 cases of DLBCL via immunohistochemistry. Results : Microvessel density (PBPM showed that 42 cases (70%) were of low biologic score (0–1) and 18 cases (30%) were of high biologic score (2–3). Low BPM cases showed less probability for splenic involvement (P=0.04) and a higher rate of complete response to therapy compared with high score cases (P=0.08). Conclusions : The DLBCL microenvironment could modulate tumor progression behavior since angiogenesis and SPARC positive stromal cells promote dissemination by association with spleen involvement and capsular invasion. Biologic prognostic models, including modified BPM, which considered cell origin of DLBCL and stromal signature pathways, could determine DLBCL progression and response to therapy. PMID:28607806

  11. Prognostic Significance of Spot Urine Na/K for Longitudinal Changes in Blood Pressure and Renal Function: The Nagahama Study.

    Science.gov (United States)

    Tabara, Yasuharu; Takahashi, Yoshimitsu; Setoh, Kazuya; Kawaguchi, Takahisa; Kosugi, Shinji; Nakayama, Takeo; Matsuda, Fumihiko

    2017-09-01

    Urinary sodium-to-potassium ratio (Na/K) represents a simple measure of sodium load and has been reported to be associated with blood pressure (BP) levels in a cross-sectional setting even with spot measurements. The aim of the present large-scale cohort study is to determine prognostic significance of spot urine Na/K for longitudinal changes in BP levels and renal function. The present study population consisted of 7,063 individuals from the general population. Clinical parameters were measured at baseline and at a follow-up interval of 5 years. Mean systolic BP was slightly increased during the follow-up period (overall, 124 ± 17 to 125 ± 18 mm Hg; nontreated participants, 119 ± 15 to 122 ± 17 mm Hg). Although, the urinary Na/K demonstrated a linear association with BP in a cross-sectional analysis (P K * time interaction, i.e., an intraindividual effect, as an inverse determinant (F = 76.9, P K values at baseline. Spot urine Na/K values were found to be positively associated with renal function in a cross-sectional analysis (P K * time interaction showed inverse associated with renal functional decline (F = 85.8, P K may have limited utility as a prognostic marker of longitudinal BP change, as well as renal functional decline.

  12. Impact of the degree of anemia on the outcome of patients with myelodysplastic syndrome and its integration into the WHO classification-based Prognostic Scoring System (WPSS).

    Science.gov (United States)

    Malcovati, Luca; Della Porta, Matteo G; Strupp, Corinna; Ambaglio, Ilaria; Kuendgen, Andrea; Nachtkamp, Kathrin; Travaglino, Erica; Invernizzi, Rosangela; Pascutto, Cristiana; Lazzarino, Mario; Germing, Ulrich; Cazzola, Mario

    2011-10-01

    Anemia is an established negative prognostic factor in myelodysplastic syndromes but the relationship between its degree and clinical outcome is poorly defined. We, therefore, studied the relationship between severity of anemia and outcome in myelodysplastic syndrome patients. We studied 840 consecutive patients diagnosed with myelodysplastic syndromes at the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, and 504 patients seen at the Heinrich-Heine-University Hospital, Düsseldorf, Germany. Hemoglobin levels were monitored longitudinally and analyzed by means of time-dependent Cox's proportional hazards regression models. Hemoglobin levels lower than 9 g/dL in males (HR 5.56, P=0.018) and 8 g/dL in females (HR=5.35, P=0.026) were independently related to reduced overall survival, higher risk of non-leukemic death and cardiac death (Panemia, defined as hemoglobin below these thresholds, was found to be as effective as transfusion-dependency in the prognostic assessment. After integrating this definition of severe anemia into the WHO classification-based Prognostic Scoring System, time-dependent regression and landmark analyses showed that the refined model was able to identify risk groups with different survivals at any time during follow up. Accounting for severity of anemia through the WHO classification-based Prognostic Scoring System provides an objective criterion for prognostic assessment and implementation of risk-adapted treatment strategies in myelodysplastic syndrome patients.

  13. Does the RIFLE Classification Improve Prognostic Value of the APACHE II Score in Critically Ill Patients?

    Science.gov (United States)

    Wahrhaftig, Kátia M; Correia, Luis C L; Matias, Denise; De Souza, Carlos A M

    2013-01-01

    Introduction. The RIFLE classification defines three severity criteria for acute kidney injury (AKI): risk, injury, and failure. It was associated with mortality according to the gradation of AKI severity. However, it is not known if the APACHE II score, associated with the RIFLE classification, results in greater discriminatory power in relation to mortality in critical patients. Objective. To analyze whether the RIFLE classification adds value to the performance of APACHE II in predicting mortality in critically ill patients. Methods. An observational prospective cohort of 200 patients admitted to the ICU from July 2010 to July 2011. Results. The age of the sample was 66 (±16.7) years, 53.3% female. ICU mortality was 23.5%. The severity of AKI presented higher risk of death: class risk (RR = 1.89 CI:0.97-3.38, P = 0.001), grade injury (RR = 3.7 CI:1.71-8.08, P = 0.001), and class failure (RR = 4.79 CI:2.10-10.6, P = 0.001). The APACHE II had C-statistics of 0.75, 95% (CI:0.68-0.80, P = 0.001) and 0.80 (95% CI:0.74 to 0.86, P = 0.001) after being incorporated into the RIFLE classification in relation to prediction of death. In the comparison between AUROCs, P = 0.03. Conclusion. The severity of AKI, defined by the RIFLE classification, was a risk marker for mortality in critically ill patients, and improved the performance of APACHE II in predicting the mortality in this population.

  14. Does the RIFLE Classification Improve Prognostic Value of the APACHE II Score in Critically Ill Patients?

    Directory of Open Access Journals (Sweden)

    Kátia M. Wahrhaftig

    2013-01-01

    Full Text Available Introduction. The RIFLE classification defines three severity criteria for acute kidney injury (AKI: risk, injury, and failure. It was associated with mortality according to the gradation of AKI severity. However, it is not known if the APACHE II score, associated with the RIFLE classification, results in greater discriminatory power in relation to mortality in critical patients. Objective. To analyze whether the RIFLE classification adds value to the performance of APACHE II in predicting mortality in critically ill patients. Methods. An observational prospective cohort of 200 patients admitted to the ICU from July 2010 to July 2011. Results. The age of the sample was 66 (±16.7 years, 53.3% female. ICU mortality was 23.5%. The severity of AKI presented higher risk of death: class risk (RR = 1.89 CI:0.97–3.38, , grade injury (RR = 3.7 CI:1.71–8.08, , and class failure (RR = 4.79 CI:2.10–10.6, . The APACHE II had C-statistics of 0.75, 95% (CI:0.68–0.80, and 0.80 (95% CI:0.74 to 0.86, after being incorporated into the RIFLE classification in relation to prediction of death. In the comparison between AUROCs, . Conclusion. The severity of AKI, defined by the RIFLE classification, was a risk marker for mortality in critically ill patients, and improved the performance of APACHE II in predicting the mortality in this population.

  15. Prognostic value of clinical and Doppler echocardiographic findings in children and adolescents with significant rheumatic valvular disease.

    Science.gov (United States)

    Araújo, Fátima Derlene da Rocha; Goulart, Eugênio Marcos Andrade; Meira, Zilda Maria Alves

    2012-07-01

    The diagnosis of acute rheumatic fever (RF) is based on clinical findings. However, during the chronic phase of the disease, the clinical approach is not sufficient for the follow-up of the patients and the Doppler echocardiography is a tool for the diagnosis of cardiac involvement. Prognostic variables that influence long-term outcomes are not well known. 462 patients with RF according to Jones criteria were studied, and followed-up from the initial attack to 13.6 ± 4.6 years. All patients underwent clinical assessment and Doppler echocardiography for the detection of heart valve involvement in the acute and chronic phases. Multivariate logistic regression analysis was used to identify the factors influencing long-term heart valve disease. Carditis occurred in 55.8% and subclinical valvulitis in 35.3% patients. In the chronic phase, 33% of the patients had significant valvular heart disease. No normal Doppler echocardiography exam was observed on patients who had severe valvulitis, although heart auscultation had become normal in 13% of these. In the multivariate analysis, only the severity of carditis and the mitral and/or aortic valvulitis were associated with significant valvular heart disease. Chorea or arthritis were protective factors for significant valvular heart disease, odds ratio 0.41 (95% C.I. 0.22 - 0.77) and 0.43 (95% C.I. 0.23 - 0.82), respectively. Our study suggests that the use of Doppler echocardiography during RF helps to identify prognostic factors regarding the development of significant valvular heart disease. Initial severe carditis is an important factor in the long-term prognosis of chronic RHD, whereas arthritis and chore during the initial episode of RF appears to be protective. Strict secondary prophylaxis should be mandatory in high risk patients.

  16. Prognostic significance of lymphovascular invasion in radical cystectomy on patients with bladder cancer: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hwanik Kim

    Full Text Available PURPOSE: The objective of the present study was to conduct a systematic review and meta-analysis of published literature to appraise the prognostic value of lymphovascular invasion (LVI in radical cystectomy specimens. MATERIALS AND METHODS: Following the PRISMA statement, PubMed, Cochrane Library, and SCOPUS database were searched from the respective dates of inception until June 2013. RESULTS: A total of 21 articles met the eligibility criteria for this systematic review, which included a total of 12,527 patients ranging from 57 to 4,257 per study. LVI was detected in 34.6% in radical cystectomy specimens. LVI was associated with higher pathological T stage and tumor grade, as well as lymph node metastasis. The pooled hazard ratio (HR was statistically significant for recurrence-free survival (pooled HR, 1.61; 95% confidence interval [CI], 1.26-2.06, cancer-specific survival (pooled HR, 1.67; 95% CI, 1.38-2.01, and overall survival (pooled HR, 1.67; 95% CI, 1.38-2.01, despite the heterogeneity among included studies. On sensitivity analysis, the pooled HRs and 95% CIs were not significantly altered when any one study was omitted. The funnel plot for overall survival demonstrated a certain degree of asymmetry, which showed slight publication bias. CONCLUSIONS: This meta-analysis indicates that LVI is significantly associated with poor outcome in patients with bladder cancer who underwent radical cystectomy. Adequately designed prospective studies are required to provide the precise prognostic significance of LVI in bladder cancer.

  17. Prognostic significance of PD-L1 expression in patients with gastric cancer in East Asia: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Liu YX

    2016-05-01

    Full Text Available Yong-Xuan Liu, Xin-Shuai Wang, Yu-Feng Wang, Xiao-Chen Hu, Jun-Qiang Yan, Ya-Li Zhang, Wei Wang, Rui-Jie Yang, Ying-Ying Feng, She-Gan Gao, Xiao-Shan Feng Department of Oncology, Cancer Institute, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, People’s Republic of China Abstract: The overexpression of programmed cell death-ligand 1(PD-L1 has been observed in gastric cancer (GC. However, whether the expression of PD-L1 in tumor cells or blood serum is associated with the prognosis of patients with GC remains unclear. Therefore, we performed a meta-analysis to evaluate the prognostic significance of PD-L1 expression in GC. Electronic databases were searched systematically. Studies that met the inclusion criteria were included in the meta-analysis. Data concerning the hazard ratio (HR for overall survival and disease-free survival with a 95% confidence interval (CI according to the expression status of PD-L1 evaluated by immunohistochemistry or enzyme-linked immunosorbent assay were extracted. The data were analyzed using a random effects model. Subgroup analyses were proposed. Our results showed that eight studies with 950 patients met the inclusion criteria and were included in the meta-analysis. The pooled HR for overall survival indicated that patients with PD-L1-positive expression had significantly shorter survival time compared with the PD-L1-negative group (HR 1.60, 95% CI 1.09–2.36, P=0.012. The pooled HR for disease-free survival demonstrated that the difference between the two groups was not statistically significant (HR 1.02, 95% CI 0.32–3.20, P=0.98. In conclusion, our results indicate that the evaluation of PD-L1 overexpression in GC tissue or blood serum may be useful in the future as a novel prognostic factor. Keywords: PD-L1, gastric cancer, prognostic, meta-analysis, OS, immunohistochemistry

  18. Wound classification in pediatric general surgery: significant variation exists among providers.

    Science.gov (United States)

    Snyder, Rebecca A; Johnson, Lisa; Tice, Jamie; Wingo, Tammy; Williams, Dana; Wang, Li; Blakely, Martin L

    2013-11-01

    Risk-adjusted rates of surgical site infections (SSI) are used as a quality metric to facilitate improvement within a hospital system and allow comparison across institutions. The NSQIP-Pediatric, among others, uses surgical wound classification as a variable in models designed to predict risk-adjusted postoperative morbidity, including SSI rates. The purpose of this study was to measure the level of agreement in wound classification assignment among 3 providers: surgeons, operating room (OR) nurses, and NSQIP surgical clinical reviewers (SCR). An analysis was performed of pediatric general surgery operations from 2010 to 2011. Wound classification was assigned at the time of operation by the OR nurse and surgeon, and by the NSQIP SCR postoperatively, according to NSQIP methodology. Disagreement was defined as any discrepancy in classification among the 3 providers, and the level of agreement was determined using the kappa statistic. For the 374 procedures reviewed, there was an overall disagreement of 48% among all providers, kappa 0.48 (95% CI 0.43 to 0.53). When comparing wound classification by surgeon and NSQIP SCR, 23% of cases were in disagreement, kappa 0.74 (95% CI 0.68 to 0.78). Disagreement between OR nurse and either surgeon or NSQIP SCR was higher: 38%, kappa 0.45 (95% CI 0.38 to 0.53) and 40%, kappa 0.44 (95% CI 0.37 to 0.51). Fundoplication, appendectomy, and cholecystectomy demonstrated the highest overall disagreement (73%, 71%, and 60%, respectively). There is significant variation in assigning surgical wound classification among health care providers. For future SSI comparative analyses, it will be critical to improve uniformity and understanding of wound class assignment among providers and institutions. Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Prognostic significance of neurological signs in high-risk infants - a systematic review

    NARCIS (Netherlands)

    Hamer, E.G.; Hadders-Algra, M.

    2016-01-01

    The aim of this paper was to systematically review the literature on the significance of specific neurological signs in infancy, in particular in infants at risk for developmental problems such as cerebral palsy (CP). A literature search was performed using the databases PubMed, Embase, Web of

  20. Prognostic significance of neurological signs in high-risk infants : a systematic review

    NARCIS (Netherlands)

    Hamer, Elisa G.; Hadders-Algra, Mijna

    The aim of this paper was to systematically review the literature on the significance of specific neurological signs in infancy, in particular in infants at risk for developmental problems such as cerebral palsy (CP). A literature search was performed using the databases PubMed, Embase, Web of

  1. Prognostic significance of the TREK-1 K2P potassium channels in prostate cancer

    OpenAIRE

    Zhang, Gui-Ming; Wan, Fang-Ning; Qin, Xiao-Jian; Cao, Da-Long; Zhang, Hai-Liang; Zhu, Yao; Dai, Bo; Shi, Guo-Hai; Ye, Ding-wei

    2015-01-01

    Background TREK-1 channels belong to the two-pore domain potassium channel superfamily and play an important role in central nervous system diseases. However, few studies have examined their role in carcinogenesis. Methods In this study, we assessed the expression of TREK-1 in 100 prostate cancer (PCa) tissues using immunohistochemistry and further analyzed its clinicopathological significance. Next, cell proliferation and cell cycle analysis were carried out on human PCa PC-3 cell lines wher...

  2. Prognostic significance of heart rate turbulence parameters in patients with chronic heart failure

    OpenAIRE

    Yin, De-Chun; Wang, Zhao-Jun; Guo, Shuai; Xie, Hong-Yu; Sun, Lin; Feng, Wei; Qiu, Wei; Qu, Xiu-Fen

    2014-01-01

    Background This study is aimed to evaluate the clinical significance of heart rate turbulence (HRT) parameters in predicting the prognosis in patients with chronic heart failure (CHF). Methods From June 2011 to December 2012, a total of 104 CHF patients and 30 healthy controls were enrolled in this study. We obtained a 24-hour Holter ECG recording to assess the HRT parameters, included turbulence onset (TO), turbulence slope (TS), standard deviation of N-N intervals (SDNN), and resting heart ...

  3. Thyroid Gland Involvement in Carcinoma Larynx and Hypopharynx-Predictive Factors and Prognostic Significance.

    Science.gov (United States)

    Iype, Elizabeth Mathew; Jagad, Vijay; Nochikattil, Santhosh Kumar; Varghese, Bipin T; Sebastian, Paul

    2016-02-01

    Intraoperative management of thyroid gland in laryngeal and hypopharyngeal cancer is controversial. The objectives of this study were to determine the incidence of thyroid gland invasion in patients undergoing surgery for laryngeal or hypopharyngeal carcinoma, to assess predictive factors and to assess the prognosis in patients with and without thyroid gland invasion. One hundred and thirty-three patients who underwent surgery for carcinoma larynx and hypopharynx from 2006 to 2010 were reviewed retrospectively. Surgical specimens were examined to determine the incidence of thyroid gland invasion and predictive factors were analysed. The recurrence rate and the survival in patients with and without thyroid gland invasion were also analysed. Out of the 133 patients with carcinoma larynx and hypopharynx who underwent surgery, histological thyroid gland invasion was observed in 28/133 (21%) patients. Significant relationship was found between histological thyroid gland invasion and preoperative evidence of thyroid cartilage erosion by CT scan and also when gross thyroid gland involvement observed during surgery. There is significant association between thyroid gland invasion when there is upper oesophageal or subglottic involvement. After analysing the retrospective data from our study, we would like to suggest that thyroid gland need not be removed routinely in all laryngectomies, unless there is advanced disease with thyroid cartilage erosion and gross thyroid gland involvement or disease with significant subglottic or oesophageal involvement.

  4. Prognostic significance of the expression of MUC1 and collagen type IV in advanced gastric carcinoma.

    Science.gov (United States)

    Ando, H; Aihara, R; Ohno, T; Ogata, K; Mochiki, E; Kuwano, H

    2009-08-01

    Scirrhous gastric carcinoma is characterized by excessive deposition of collagen in the stroma. However, the clinical significance of this fibrosis of the stomach has not been clarified. The aim of this study was to examine the fibrotic mechanism in several histological types of gastric carcinoma, and the combination of MUC1 and collagen type IV as a possible predictor of patient survival. One hundred and two paraffin-embedded specimens of gastric carcinoma were examined by immunohistochemical staining using monoclonal antibodies against collagen type IV and MUC1. Collagen type IV-positive expression was significantly associated with depth of wall penetration (P = 0.025) and stage (P = 0.023). There was a significant relationship between MUC1-positive expression and interstitial collagen type IV-positive expression (P = 0.035). Survival was shorter for patients with the combination of MUC1-positive expression and interstitial collagen type IV-negative expression than for those with other expression patterns. In patients with differentiated-type advanced gastric carcinoma, the combination of MUC1-positive and interstitial collagen type IV-negative expression may be a marker of unfavourable prognosis. Copyright 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  5. Expression and prognostic significance of ELL-associated factor 2 in human prostate cancer.

    Science.gov (United States)

    Zang, Yachen; Dong, Yun; Yang, Dongrong; Xue, Boxin; Li, Feng; Gu, Peng; Zhao, Haifeng; Wang, Shaoxiong; Zhou, Songlin; Ying, Rong; Wang, Zhou; Shan, Yuxi

    2016-05-01

    ELL-associated factor 2 (EAF2) is an androgen-regulated tumor suppressor in the prostate. The purpose of this study was to investigate the expression of EAF2 protein in human prostate cancer specimens along with BPH specimens as a control, and to evaluate potential association of EAF2 expression with clinical characteristics and overall survival of the prostate cancer patients. The expression of EAF2 was evaluated in 44 prostate cancer and 23 BPH tissue specimens using immunohistochemistry. The relationships of EAF2 expression with clinical characteristics and overall survival rates were analyzed by Chi-square test and Kaplan-Meier method. The immunostaining intensity of EAF2 in BPH specimens was significantly higher than that in prostate cancer (p < 0.05). EAF2 expression decreased significantly in high-grade and advanced-stage human prostate tumors and inversely correlated with PSA level, Gleason scores, bone metastasis and tumor stage. Importantly, loss of EAF2 expression was associated with a significant decrease in patient survival. Expression of EAF2 is decreased in prostate carcinogenesis, and EAF2 loss is associated with high-risk patients and poor survival.

  6. Prognostic Significance of Forkhead Box M1 (FOXM1) Expression and Antitumor Effect of FOXM1 Inhibition in Angiosarcoma.

    Science.gov (United States)

    Ito, Takamichi; Kohashi, Kenichi; Yamada, Yuichi; Iwasaki, Takeshi; Maekawa, Akira; Kuda, Masaaki; Hoshina, Daichi; Abe, Riichiro; Furue, Masutaka; Oda, Yoshinao

    2016-01-01

    The prognosis of angiosarcoma is poor and a novel treatment option for the disease is desired. The aim of this study was to investigate the prognostic significance of Forkhead box M1 (FOXM1), a transcription factor that regulates cell-cycle progression and various crucial processes in tumor progression, and its potential as a new therapeutic target. We investigated 125 angiosarcoma clinical samples (94 primary lesions and 31 metastatic lesions in 94 patients) and a human angiosarcoma cell line (HAMON) using immunohistochemical staining and molecular biological approaches. FOXM1 expression in angiosarcoma samples was also compared with that in Kaposi's sarcomas (n = 13), epithelioid hemangioendotheliomas (n = 13) and benign hemangiomas (n = 10). Patients with FOXM1-overexpressing angiosarcoma had significantly shorter survival (both for disease-specific survival [DSS] and event-free survival [EFS]) than other patients (5-year DSS, 23.5% vs. 47.1%, P = 0.013; and 5-year EFS, 5.5% vs. 28.7%, P = 0.004). FOXM1 overexpression was also an independent prognostic factor for both DSS and EFS in Cox multivariate analyses (hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.10-5.81, P = 0.039; and HR 4.16, 95%CI 2.03-8.67, P = 0.0001, respectively). FOXM1 inhibition using both small interfering RNA and a specific inhibitor (thiostrepton) suppressed cell proliferation of the angiosarcoma cell line. Furthermore, FOXM1 inhibition improved the chemosensitivity to docetaxel in vitro. FOXM1 inhibition may be a potential therapeutic option for angiosarcoma.

  7. Clinicopathological and prognostic significance of epidermal growth factor receptor overexpression in patients with esophageal adenocarcinoma: a meta-analysis.

    Science.gov (United States)

    Guo, Y-M; Yu, W-W; Zhu, M; Guo, C-Y

    2015-01-01

    The prognostic significance of epidermal growth factor receptor (EGFR) overexpression in patients with esophageal adenocarcinoma (EAC) remains controversial. Eligible studies that investigated the association between survival in EAC and the expression status of EGFR were identified by an electronic search of PubMed, EMBASE, and ISI Web of Science. A meta-analysis was performed to clarify the impact of EGFR overexpression on clinicopathological parameters or overall survival (OS) in EAC. A total of seven studies including 1028 patients were subjected to the final analysis. The overall results suggested that overexpression of EGFR was significantly correlated with not only the depth of invasion, lymph node status, and tumors stage of EAC, with a pooled odds ratio of 2.99 (95% confidence interval [CI]: 1.07-8.35; Z = 2.09; P = 0.037), 3.05 (95% CI: 1.77-5.27; Z = 4.00; P < 0.001), and 5.37 (95% CI: 2.49-11.57; Z = 4.29; P < 0.001), respectively, but also the poorer OS with a pooled hazard ratio of 2.20 (95% CI: 1.47-3.31; Z = 3.79; P < 0.001). Overexpression of EGFR correlates with not only the clinicopathological features, but also the worse OS, and it might be useful as a predictive biomarker in clinical practice, yet the clinicopathological and prognostic role of EGFR in EAC still needs further confirmation by well-designed prospective studies. © 2014 International Society for Diseases of the Esophagus.

  8. Clinical and prognostic significance of eosinophilia and inv(16)/t(16;16) in pediatric acute myelomonocytic leukemia (AML-M4).

    Science.gov (United States)

    Klein, Kim; de Haas, Valérie; Bank, Ingrid E M; Beverloo, H Berna; Zwaan, C Michel; Kaspers, Gertjan L

    2017-10-01

    The cytogenetic aberrations inv(16)(p13.1q22)/t(16;16)(p13.1;q22), frequently detected in acute myelomonocytic leukemia with eosinophilia (FAB type M4eo), are generally considered a prognostically favorable subgroup. M4eo comprises a distinct morphology compared to M4 without eosinophilia (M4eo-) and therefore may be indicative for a different pathogenesis. Morphology and cytogenetic/molecular analyses of a Dutch cohort of pediatric acute myelomonocytic leukemia (AML-M4) patients were performed and studied in order to analyze the association between the presence of eosinophilia morphology (M4eo+), inv(16)/t(16;16) (inv(16)+), clinical features, and outcome. Of the 119 included patients with available combined morphological and cytogenetic results, 60% had M4eo- without inv(16) (inv(16)-), 10% had M4eo-/inv(16)+, 13% had M4eo+/inv(16)-, and 17% had M4eo+/inv(16)+. M4eo+ was significantly associated with the presence of inv(16)/t(16;16) (P morphology with eosinophilia probably relies on its association with inv(16)/t(16;16). Simultaneous presence of both eosinophilia and inv(16) was not associated with superior outcome in our study. These results may be relevant for risk-group classification and risk-group adapted treatment and underline the importance of accurate cytogenetic analysis. © 2017 Wiley Periodicals, Inc.

  9. Prognostic significance of anti-diabetic medications in pancreatic cancer: A meta-analysis.

    Science.gov (United States)

    Zhou, Dong-Chu; Gong, Hui; Tan, Chong-Qing; Luo, Jian-Quan

    2017-09-22

    The role of anti-diabetic medications in pancreatic cancer remains conflicting. We carried out a systematic search of Pubmed and Embase databases for studies published before August 2016, which assessed the associations between anti-diabetic medications (metformin, sulfonylureas, thiazolidinediones and insulin) intake and pancreatic cancer prognosis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). Fourteen studies enrolling 94778 participants were eligible for inclusion, with 12 cohort studies and 2 randomized controlled trials (RCTs). Significant association between metformin (adjusted HR=0.77, 95% CI=0.68-0.87) use and OS was found in cohort studies, whereas no significant association between metformin use and PFS (HR=1.22; 95% CI=0.76-1.95) or OS (HR=1.20, 95% CI=0.84-1.72) in RCTs. No significant survival benefits were identified for insulin (HR=1.18, 95% CI=0.83-1.69), sulfonylureas (HR=1.03, 95% CI=0.81-1.30), or thiazolidinediones (HR=0.84, 95% CI=0.58-1.22). The trim-and-fill method and subgroup analyses stratified by the study characteristics confirmed the robustness of the results. Our findings provide strong evidence that metformin is associated with improved OS in pancreatic cancer patients in cohort studies. However, the effect of other anti-diabetic medications should be interpreted with caution owing to the limited number of studies.

  10. DIAGNOSTIC AND PROGNOSTIC SIGNIFICANCE OF INTRATHECAL SYNTHESIS OF IMMUNOGLOBULIN FREE LIGHT CHAINS IN MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    V. D. Nazarov

    2015-01-01

    Full Text Available Increased intrathecal synthesis and oligoclonal banding of immunoglobulins (Ig in cerebrospinal fluid (CSF are major immunological findings in multiple sclerosis. Free light chains are fragments of Ig molecules that are produced in parallel to oligoclonal Ig, and their production reflects total Ig synthesis within central nervous system. Assessment of intrathecal kappaand lambda free light chain production within CNS compartment will help to improve diagnosis and prediction of outcomes in multiple sclerosis. Concentrations of kappa and lambda free light chains and clonality of immunoglobulin pattern synthesis were studied in paired CSF and serum samples of 151 patients, including 92 patients with multiple sclerosis, and 33 patients with clinically isolated syndrome which later was transformed into the definite multiple sclerosis. A control group consisted of 26 patients with other inflammatory diseases of central nervous system. Several Ig parameters have been determined in the patients, i.e., Ig clonality in CSF; concentrations of free light chains (both kappaand lambda- in CSF; as well as their indexes and ratios. It was established that synthesis of kappa free light chains were significantly elevated in patients with multiple sclerosis. Moreover, the amounts of free light Ig chains in patients with positive oligoclonality test were significantly higher than in cases without intrathecal oligoclonal synthesis. With respect to diagnostic significance, the kappa quotient proved the best available option for diagnosis of multiple sclerosis. Its combination with Ig oligoclonality assays caused a decrease in false-negative diagnostics by 42%. Diagnostic benefit of the kappa quotient could be also confirmed by the data of ROC analysis. Also concentration of lambda free light chains in cerebrospinal fluid showed a negative correlation with conversion terms of clinically isolated syndrome to evident multiple sclerosis. Therefore, the indexes of free Ig

  11. Angiogenesis in non-Hodgkin's lymphoma: clinico-pathological correlations and prognostic significance in specific subtypes

    DEFF Research Database (Denmark)

    Jørgensen, J M; Sørensen, Flemming Brandt; Bendix, K

    2007-01-01

    The aim of the study was to evaluate angiogenesis in different subtypes of non-Hodgkin's lymphoma (NHL) and to correlate angiogenic scores to clinical endpoints. Pre-therapeutic lymph node biopsies from 308 patients with NHL [107 follicular B-cell lymphoma (FL), 94 diffuse large B-cell lymphoma...... (DLBCL), 107 peripheral T-cell lymphoma (PTCL)] were studied. Microvessels were scored according to the Chalkley and microvessel density method (MVD) methods. Vascular endothelial growth factor (VEGF) protein expression was evaluated by immunohistochemistry. Both Chalkley and MVD methods showed......, that the lymphoma subtypes differed significantly in angiogenic scores (P

  12. Prognostic significance of the TREK-1 K2P potassium channels in prostate cancer.

    Science.gov (United States)

    Zhang, Gui-Ming; Wan, Fang-Ning; Qin, Xiao-Jian; Cao, Da-Long; Zhang, Hai-Liang; Zhu, Yao; Dai, Bo; Shi, Guo-Hai; Ye, Ding-Wei

    2015-07-30

    TREK-1 channels belong to the two-pore domain potassium channel superfamily and play an important role in central nervous system diseases. However, few studies have examined their role in carcinogenesis. In this study, we assessed the expression of TREK-1 in 100 prostate cancer (PCa) tissues using immunohistochemistry and further analyzed its clinicopathological significance. Next, cell proliferation and cell cycle analysis were carried out on human PCa PC-3 cell lines where TREK-1 was stably knockdown. We found that compared with normal prostate tissues, PCa tissues showed overexpressed TREK-1 levels and TREK-1 levels were positively associated with Gleason score and T staging. High level of TREK-1 expression was related to shorter castration resistance free survival (CRFS). Furthermore, knockdown of TREK-1 significantly inhibited PCa cell proliferation in vitro and in vivo, and induced a G1/S cell cycle arrest. Our results suggest that TREK-1 might be a biomarker in CRFS judgment of PCa, as well as a potential therapeutic target.

  13. The Prognostic Significance of Different Definitions for Angiosome-Targeted Lower Limb Revascularization.

    Science.gov (United States)

    Špillerová, Kristýna; Biancari, Fausto; Settembre, Nicla; Albäck, Anders; Venermo, Maarit

    2017-04-01

    The definition of angiosome-targeted revascularization is confusing, especially when a tissue lesion affects several angiosomes. Two different definitions of direct revascularization exist in the literature. The study aim was (1) to compare the 2 definitions of direct revascularization in patients with foot lesions involving more than one angiosome and (2) to evaluate which definition better predicts clinical outcome. This study cohort comprises 658 patients with Rutherford 5-6 foot lesions who underwent infrapopliteal endovascular or surgical revascularization between January 2010 and July 2013. We compared the 2 angiosome-targeted definitions using multivariate analysis; the impact of each angiosome-targeted definition was adjusted for a propensity score obtained by means of nonparsimonious logistic regression. Direct revascularization according to definition A was performed in 367 cases (55.8%) versus 198 cases (30.1%) with definition B. The propensity-score-adjusted analysis showed that definition A of direct revascularization was associated with significantly better wound healing (P revascularization according to definition A was confirmed in a Cox proportional hazard analysis. Definition A of direct revascularization was associated with a significantly higher wound healing and leg salvage rate than indirect revascularization in both series. Therefore, it seems that, if the wound spreads over several angiosomes in the forefoot or heel, any angiosome involved in the wound can be targeted. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Hypoglycorrhachia in adults with community-acquired meningitis: etiologies and prognostic significance.

    Science.gov (United States)

    Shrikanth, Vandana; Salazar, Lucrecia; Khoury, Nabil; Wootton, Susan; Hasbun, Rodrigo

    2015-10-01

    Hypoglycorrhachia (cerebrospinal fluid (CSF) glucose meningitis. The differential diagnosis of hypoglycorrhachia and its clinical significance was analyzed in the present study. This was a retrospective study of 620 adult patients with community-acquired meningitis (CSF white blood cell count >5 × 10(6) cells/l and absence of a CSF shunt or recent neurosurgical procedure (meningitis, 116 (19%) had hypoglycorrhachia. Etiologies of hypoglycorrhachia were idiopathic (n=40), bacterial (n=27), cryptococcal (n=26), viral (n=15), and tuberculous (n=4). Patients with hypoglycorrhachia were more likely to be immunosuppressed, have a history of intravenous drug use, and present with a vesicular or petechial rash, nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status, and focal neurological deficits compared to those patients without hypoglycorrhachia (pmeningitis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Clinical Significance and Prognostic Relevance of Microsatellite Instability in Sporadic Colorectal Cancer Patients

    Directory of Open Access Journals (Sweden)

    Angelika Copija

    2017-01-01

    Full Text Available Microsatellite instability (MSI is a marker of the replication error phenotype. It is caused by impaired DNA mismatch repair processes (MMR, resulting in ineffectiveness of the mechanisms responsible for the DNA replication precision and postreplicative DNA repair. MSI underlies the pathogenesis of 10%–20% of colorectal cancer (CRC cases. The data about the potential value of MMR status as a predictive factor for 5-fluorouracil (FU-based chemotherapy remain unclear. According to National Comprehensive Cancer Network updated guidelines, MSI testing is recommended for all patients with stage II CRC because patients with MSI-H (high-frequency MSI tumour may have a good prognosis and obtain no benefit from 5-FU-based adjuvant chemotherapy. The significance of the MSI status as a predictive factor for patients with metastatic disease was not confirmed. The association between the MSI status and the efficacy of the therapy based on anti-programmed death-1 receptor inhibitors requires further studies.

  16. Clinical Significance and Prognostic Relevance of Microsatellite Instability in Sporadic Colorectal Cancer Patients

    Science.gov (United States)

    Copija, Angelika; Waniczek, Dariusz; Witkoś, Andrzej; Walkiewicz, Katarzyna; Nowakowska-Zajdel, Ewa

    2017-01-01

    Microsatellite instability (MSI) is a marker of the replication error phenotype. It is caused by impaired DNA mismatch repair processes (MMR), resulting in ineffectiveness of the mechanisms responsible for the DNA replication precision and postreplicative DNA repair. MSI underlies the pathogenesis of 10%–20% of colorectal cancer (CRC) cases. The data about the potential value of MMR status as a predictive factor for 5-fluorouracil (FU)-based chemotherapy remain unclear. According to National Comprehensive Cancer Network updated guidelines, MSI testing is recommended for all patients with stage II CRC because patients with MSI-H (high-frequency MSI) tumour may have a good prognosis and obtain no benefit from 5-FU-based adjuvant chemotherapy. The significance of the MSI status as a predictive factor for patients with metastatic disease was not confirmed. The association between the MSI status and the efficacy of the therapy based on anti-programmed death-1 receptor inhibitors requires further studies. PMID:28067827

  17. Prognostic significance of heart rate turbulence parameters in patients with chronic heart failure.

    Science.gov (United States)

    Yin, De-Chun; Wang, Zhao-Jun; Guo, Shuai; Xie, Hong-Yu; Sun, Lin; Feng, Wei; Qiu, Wei; Qu, Xiu-Fen

    2014-04-13

    This study is aimed to evaluate the clinical significance of heart rate turbulence (HRT) parameters in predicting the prognosis in patients with chronic heart failure (CHF). From June 2011 to December 2012, a total of 104 CHF patients and 30 healthy controls were enrolled in this study. We obtained a 24-hour Holter ECG recording to assess the HRT parameters, included turbulence onset (TO), turbulence slope (TS), standard deviation of N-N intervals (SDNN), and resting heart rate (RHR). The relationships between HRT parameters and the prognosis of CHF patients were determined. The assessment follow-up period lasted until January 31, 2013. The overall mortality of CHF patients was 9.6% (10/104). Our results revealed that CHF patients had higher levels of TO than those of healthy subjects, but the TS levels of CHF patients were lower than that of the control group. CHF patients with NYHA grade IV had higher HRT1/2 rate than those with NYHA grade II/III. There were statistical differences in TS, LVEF, SDNN and RHR between the non-deteriorating group and the non-survivor group. Significant differences in TS among the three groups were also found. Furthermore, CHF patients in the non-survivor group had lower levels of TS than those in the deteriorating group. Correlation analyses indicated that TO negatively correlate with SDNN, while TS positively correlated with SDNN and left ventricular ejection fraction (LVEF). We also observed negative correlations between TS and left ventricular end-diastolic cavity dimension (LVEDD), RHR, homocysteine (Hcy) and C-reactive protein (CRP). Multivariate Cox regression analysis further confirmed that LVEF (≤30%), HRT2, SDNN and RHR were independent risk factors which can indicate poor prognosis in CHF patients. Our findings indicate that HRT may have good clinical predictive value in patients with CHF. Thus, quantifying HRT parameters could be a useful tool for predicting mortality in CHF patients.

  18. Genomics-based Approach and Prognostic Stratification Significance of Gene Mutations in Intermediate-risk Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Bian-Hong Wang

    2015-01-01

    Conclusions: NGS represents a pioneering and helpful approach to prognostic risk stratification of IR-AML patients. Further large-scale studies for comprehensive molecular analysis are needed to provide guidance and a theoretical basis for IR-AML prognostic stratification and clinical management.

  19. Study of prognostic significance of antenatal ultrasonography and renin angiotensin system activation in predicting disease severity in posterior urethral valves

    Directory of Open Access Journals (Sweden)

    Divya Bhadoo

    2015-01-01

    Full Text Available Aims: Study on prognostic significance of antenatal ultrasonography and renin angiotensin system activation in predicting disease severity in posterior urethral valves. Materials and Methods: Antenatally diagnosed hydronephrosis patients were included. Postnatally, they were divided into two groups, posterior urethral valve (PUV and non-PUV. The studied parameters were: Gestational age at detection, surgical intervention, ultrasound findings, cord blood and follow up plasma renin activity (PRA values, vesico-ureteric reflux (VUR, renal scars, and glomerular filtration rate (GFR. Results: A total of 25 patients were included, 10 PUV and 15 non-PUV. All infants with PUV underwent primary valve incision. GFR was less than 60 ml/min/1.73 m 2 body surface area in 4 patients at last follow-up. Keyhole sign, oligoamnios, absent bladder cycling, and cortical cysts were not consistent findings on antenatal ultrasound in PUV. Cord blood PRA was significantly higher (P < 0.0001 in PUV compared to non-PUV patients. Gestational age at detection of hydronephrosis, cortical cysts, bladder wall thickness, and amniotic fluid index were not significantly correlated with GFR while PRA could differentiate between poor and better prognosis cases with PUV. Conclusions: Ultrasound was neither uniformly useful in diagnosing PUV antenatally, nor differentiating it from cases with non-PUV hydronephrosis. In congenital hydronephrosis, cord blood PRA was significantly higher in cases with PUV compared to non-PUV cases and fell significantly after valve ablation. Cord blood PRA could distinguish between poor and better prognosis cases with PUV.

  20. Prognostic significance of weight changes in Parkinson's disease: the Park-weight phenotype.

    Science.gov (United States)

    Sharma, Jagdish C; Vassallo, Michael

    2014-01-01

    Neurodegenerative Parkinson's disease (PD) is associated with a changing profile of weight as the disease advances. Whilst some patients gain weight, a significant proportion of patients lose weight. PD patients have a lower body weight as compared with non-PD controls. Weight loss is not a benign phenomenon. Patients with lower initial body weight and weight losers have a higher risk of developing dyskinesia. There is a relationship between body weight and levodopa dose, patients with higher levodopa dose per kilogram are at a higher risk of dyskinesia, the risk escalates above 6 mg per kilogram. Lower weight patients have risk of undernutrition and the associated disease pathology due to frailty. Weight losers are at risk of higher mortality and poor quality of life. PD patients should be assessed for body weight and the dose of levodopa be adjusted according to periodic weight changes, supplemented by other dopaminergic medications. Patients at risk of weight loss may be identified by their severe loss of olfaction since there seems to exist the olfaction-weight-dyskinesia phenotype. Measures should be taken to prevent weight loss in at-risk patients to prevent low-weight-related adverse outcomes in PD patients. These measures may protect PD patients from motor and non-motor adverse effects as the disease advances.

  1. BRCA1 and BRCA2 expression patterns and prognostic significance in digestive system cancers.

    Science.gov (United States)

    Wang, Gui-Hua; Zhao, Chun-Mei; Huang, Ying; Wang, Wei; Zhang, Shu; Wang, Xudong

    2017-11-07

    The role of BRCA1 and BRCA2 genes is mainly to maintain genome integrity in response to DNA damage through different mechanisms. Deregulation of BRCA1 and BRCA2 is associated with the development of tumor and altered sensitivity to chemotherapeutic agents. In this study, we determined protein expression of BRCA1 and BRCA2 in four digestive system cancers (gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic cancer) by immunohistochemistry (IHC) on tissue microarrays. A total of 1546 samples of four types of cancer tissues, their matched adjacent non-tumor tissues, and corresponding benign tissues were studied respectively. IHC expression patterns of the two proteins and their correlation with patients' clinical parameters and overall survival were analyzed. The results showed that low expression of cytoplasmic BRCA1 and BRCA2 were commonly associated with advanced TNM stage, while high expression of nuclear BRCA1 was generally correlated with advanced tumor stages in these cancers. High expression of cytoplasmic BRCA1 and BRCA2 had significantly favorable overall survival in digestive system cancers; in contrast, BRCA1 nuclear expression usually predicted poor outcomes. We conclude that BRCA1 and BRCA2 could be used as clinicopathological biomarkers to evaluate the prognosis of digestive system cancers. Copyright © 2017. Published by Elsevier Inc.

  2. [Relationship between microsatellite instability and hepatocyte growth factor expression and their prognostic significance in colorectal cancer].

    Science.gov (United States)

    Yang, G; Zheng, H X; Wu, L N; Wan, H L; Li, N; Yang, G C; Liang, J F

    2016-04-01

    To investigate the expression of hepatocyte growth factor (HGF) and its relationship with microsatellite instability (MSI) and their influence on survival in patients with colorectal cancer. Immunohistochemistry (IHC) was used to detect the expression of HGF and MSI in 98 specimens of colorectal cancer. Tumors lacking protein expression of any of the four mismatch repair genes (MLH1, PMS2, MSH2 or MSH6) were labelled as MSI, and the rest were considered as microsatellite stable (MSS). The associations between expression and clinicopathological factors were assessed using Chi-square tests. Kaplan-Meier curves, log-rank test, and Cox regression were used to analyze the association between biomarker expressions and overall survival. The incidence rate of MSI in 98 colorectal specimens was 32.7%, and was statistically significantly correlated with the location of tumor and differentiation degree (Pcolorectal cancer (Pcolorectal cancer patients with microsatellite instability. Both microsatellite instability and HGF are independent factors affecting the prognosis in patient with colorectal cancer.

  3. Prognostic significance of MYH9 expression in resected non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Ken Katono

    Full Text Available Myosin-9 (MYH9 belongs to the myosin superfamily of actin-binding motor protein. Recently, MYH9 has been thought to be associated with cancer cell migration, invasion, and metastasis. The aims of this study were to immunohistochemically examine MYH9 expression in surgically resected non-small cell lung cancer (NSCLC, and evaluate its correlations with clinicopathological parameters and the prognosis of patients.MYH9 expression was immunohistochemically studied in 266 consecutive resected NSCLCs, and its associations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of MYH9 expression on survival.MYH9 expression was detected in 102 of 266 (38.3% NSCLCs. MYH9 expression was significantly correlated with the adenocarcinoma histology (P = 0.014, poorer differentiation ((P = 0.033, intratumoral vascular invasion and lymphatic invasion ((P = 0.013 and P = 0.045 respectively, and a poorer prognosis ((P = 0.032. In addition, multivariable analysis revealed that MYH9 expression independently predicted a poorer survival (HR, 2.15; 95%CI, 1.17-3.92; (P = 0.01.The present study revealed that MYH9 is expressed in a subset of NSCLC with a more malignant nature, and its expression is an indicator of a poorer survival probability.

  4. [Significance of subtype pattern of antimitochondrial antibodies in primary biliary cirrhosis for prognostic parameters and response to ursodeoxycholic acid].

    Science.gov (United States)

    Wirth, H P; Zala, G; Meyenberger, C; Ammann, R

    1995-04-15

    Antimitochondrial antibodies are of considerable importance for the diagnosis of primary biliary cirrhosis. Several subtypes of antimitochondrial antibodies have been identified and the pattern has been associated with prognosis of the disease in the long term course. 22 patients with primary biliary cirrhosis (19 female, 3 male; age 29-66, mean 49 years) were examined for the occurrence of the subtypes of antimitochondrial antibodies anti M2, anti M4 and anti M9. Diagnosis of primary biliary cirrhosis was based on elevated cholestatic enzymes, antimitochondrial antibodies, histology and exclusion of other chronic liver disease in all patients and elevated serum IgM concentration in 18/22 patients. Most patients were included in a study protocol of the Swiss Association for the Study of the Liver and treated with 10 mg/kg/day oral ursodeoxycholic acid. According to the subtype pattern of antimitochondrial antibodies, patients were divided into 4 groups A to D (A: anti M2-, anti M4-, anti M9+; B: anti M2+, anti M4-, anti M9+; C: anti M2+, anti M4-, anti M9- and D: anti M2+, anti M4+, anti M9-). The groups were compared with respect to the prognostically relevant parameters age, bilirubin, albumin, prothrombin time and peripheral edema, as well as the occurrence of granulomas in liver biopsy, galactose elimination capacity and response to treatment with ursodeoxycholic acid during one year. Treatment response was expressed as decrease of the serum concentration of IgM, GPT, alkaline phosphatase, gamma glutamyl transpeptidase and bilirubin. No significant differences between the four groups were found with respect to the prognostically relevant parameters, histology and galactose elimination capacity at study entry.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. The prognostic significance of metaplastic carcinoma of the breast (MCB)--a case controlled comparison study with infiltrating ductal carcinoma.

    Science.gov (United States)

    Lai, Hung-Wen; Tseng, Ling-Ming; Chang, Tsai-Wang; Kuo, Yao-Lung; Hsieh, Chia-Ming; Chen, Shou-Tung; Kuo, Sou-Jen; Su, Chin-Cheng; Chen, Dar-Ren

    2013-10-01

    Metaplastic carcinoma of the breast (MCB) is a rare histological subtype of breast cancer with an incidence of less than 0.1%-0.5%. Due to its rarity, the clinical characteristics and prognostic significance of MCB compared with other common breast cancers (like infiltrating ductal carcinoma [IDC], and infiltrating lobular carcinoma [ILC]) are not clear, and controversial among different reports. We performed a collective comparison study of multi-institutional cases to evaluate the clinical characteristics and prognostic status of MCB to compare with IDC and ILC. A case control analysis was performed to minimize the bias from clinicopathologic factors between IDC and MCB. Disease free survival (DFS) and overall survival (OS) between groups were compared. Forty-five MCB patients were enrolled from the 4 medical centers and compared with 1777 IDC and 53 ILC patients from the CCH cancer registry database comprise the current study. Compared with IDC, MCB was associated with older age, larger tumor size, a lesser lymph node positive rate, a higher likelihood of distant metastasis, higher tumor grade, lower ER-positive tumor, and higher triple negative breast cancer subtype (TNBC). MCB was associated with worse OS (p = 0.031) than IDC, but no difference in DFS (p = 0.071); however, MCB was not statistically different from ILC in both DFS and OS (p = 0.289 and 0.132, respectively). Compared with the case-controlled IDC group, MCB patients had poorer OS (p = 0.040), but no difference in DFS (p = 0.439). MCB is associated with poorer OS than IDC, and this was related to tumor behavior rather than clinicopathologic factors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Prognostic significance of pleural fluid data in patients with malignant effusion.

    Science.gov (United States)

    Bielsa, Silvia; Salud, Antonieta; Martínez, Montserrat; Esquerda, Aureli; Martín, Antonio; Rodríguez-Panadero, Francisco; Porcel, José M

    2008-07-01

    To determine the effects of the biochemical and cytological properties of the pleural fluid (PF) on the survival of patients with malignant pleural effusion (MPE). A retrospective study of 284 patients with MPE was performed, which measured overall survival, survival of patients with different types of primary tumors, and survival as a function of PF biochemical variables transformed into quartiles. Median overall survival of MPE patients was 5.4 months following diagnosis. Survival varied significantly depending on the type of the primary tumor: 17.4 months for mesothelioma, 13.2 months for breast cancer, 7 months for lymphoma and 2.6 months for lung cancer. A multivariate analysis of PF biochemical parameters showed that survival was lower as the concentration of lactate dehydrogenase (LDH) increased (11.3 months if LDH was between 140 U/L and 358 U/L vs 2.8 months if LDH was between 1027 U/L and 10,110 U/L) or the concentration of pleural proteins decreased (9.4 months if proteins were between 4.92 g/dL and 7.94 g/dL vs 2.2 months if proteins were between 0.97 g/dL and 3.85 g/dL). We also found that when mesotheliomas were excluded from the analysis, survival was lower in patients with a PF pH lower than 7.3 (2.4 months vs 6.8 months, p=0.03). Tumor type as well as some biochemical features of the pleural fluid, such as pH and concentrations of proteins and LDH, influence survival in patients with MPE.

  7. Vascular dysfunction by myofibroblast activation in patients with idiopathic pulmonary fibrosis and prognostic significance

    Directory of Open Access Journals (Sweden)

    E.R. Parra

    2012-07-01

    Full Text Available In this study, we demonstrated the importance of telomerase protein expression and determined the relationships among telomerase, endothelin-1 (ET-1 and myofibroblasts during early and late remodeling of parenchymal and vascular areas in usual interstitial pneumonia (UIP using 27 surgical lung biopsies from patients with idiopathic pulmonary fibrosis (IPF. Telomerase+, myofibroblasts α-SMA+, smooth muscle cells caldesmon+, endothelium ET-1+ cellularity, and fibrosis severity were evaluated in 30 fields covering normal lung parenchyma, minimal fibrosis (fibroblastic foci, severe (mural fibrosis, and vascular areas of UIP by the point-counting technique and a semiquantitative score. The impact of these markers was determined in pulmonary functional tests and follow-up until death from IPF. Telomerase and ET-1 expression was significantly increased in normal and vascular areas compared to areas of fibroblast foci. Telomerase and ET-1 expression was inversely correlated with minimal fibrosis in areas of fibroblast foci and directly associated with severe fibrosis in vascular areas. Telomerase activity in minimal fibrosis areas was directly associated with diffusing capacity of the lung for oxygen/alveolar volume and ET-1 expression and indirectly associated with diffusing capacity of the lungs for carbon monoxide and severe fibrosis in vascular areas. Cox proportional hazards regression revealed a low risk of death for females with minimal fibrosis displaying high telomerase and ET-1 expression in normal areas. Vascular dysfunction by telomerase/ET-1 expression was found earlier than vascular remodeling by myofibroblast activation in UIP with impact on IPF evolution, suggesting that strategies aimed at preventing the effect of these mediators may have a greater impact on patient outcome.

  8. The Prognostic Significance of Metabolic Response Heterogeneity in Metastatic Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Alain Hendlisz

    Full Text Available Tumoral heterogeneity is a major determinant of resistance in solid tumors. FDG-PET/CT can identify early during chemotherapy non-responsive lesions within the whole body tumor load. This prospective multicentric proof-of-concept study explores intra-individual metabolic response (mR heterogeneity as a treatment efficacy biomarker in chemorefractory metastatic colorectal cancer (mCRC.Standardized FDG-PET/CT was performed at baseline and after the first cycle of combined sorafenib (600mg/day for 21 days, then 800mg/day and capecitabine (1700 mg/m²/day administered D1-14 every 21 days. MR assessment was categorized according to the proportion of metabolically non-responding (non-mR lesions (stable FDG uptake with SUVmax decrease <15% among all measurable lesions.Ninety-two patients were included. The median overall survival (OS and progression-free survival (PFS were 8.2 months (95% CI: 6.8-10.5 and 4.2 months (95% CI: 3.4-4.8 respectively. In the 79 assessable patients, early PET-CT showed no metabolically refractory lesion in 47%, a heterogeneous mR with at least one non-mR lesion in 32%, and a consistent non-mR or early disease progression in 21%. On exploratory analysis, patients without any non-mR lesion showed a significantly longer PFS (HR 0.34; 95% CI: 0.21-0.56, P-value <0.001 and OS (HR 0.58; 95% CI: 0.36-0.92, P-value 0.02 compared to the other patients. The proportion of non-mR lesions within the tumor load did not impact PFS/OS.The presence of at least one metabolically refractory lesion is associated with a poorer outcome in advanced mCRC patients treated with combined sorafenib-capecitabine. Early detection of treatment-induced mR heterogeneity may represent an important predictive efficacy biomarker in mCRC.ClinicalTrials.gov NCT01290926.

  9. The prevalence and prognostic significance of KRAS mutation subtypes in lung adenocarcinomas from Chinese populations

    Directory of Open Access Journals (Sweden)

    Zheng DF

    2016-02-01

    Full Text Available Difan Zheng,1,2,* Rui Wang,1,2,* Yang Zhang,1,2 Yunjian Pan,1,2 Xinghua Cheng,3 Chao Cheng,1,2 Shanbo Zheng,1,2 Hang Li,1,2 Ranxia Gong,1,2 Yuan Li,2,4 Xuxia Shen,2,4 Yihua Sun,1,2 Haiquan Chen1–3,51Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Shanghai Chest Hospital, Shanghai Jiao Tong University, 4Department of Pathology, Fudan University Shanghai Cancer Center, 5Institutes of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workBackground: We performed this retrospective study to identify the prevalence of KRAS mutation in Chinese populations and make a comprehensive investigation of the clinicopathological features of KRAS mutation in these patients.Patients and methods: Patients from 2007 to 2013 diagnosed with primary lung adenocarcinoma who received a radical resection were examined for KRAS, EGFR, HER2, BRAF mutations, and ALK, RET, and ROS1 fusions. Clinicopathological features, including sex, age, tumor–lymph node–metastasis stage, tumor differentiation, smoking status, histological subtypes, and survival information were analyzed.Result: KRAS mutation was detected in 113 of 1,368 patients. Nine different subtypes of KRAS mutation were identified in codon 12, codon 13, and codon 61. KRAS mutation was more frequently found in male patients and former/current smoker patients. Tumors with KRAS mutation had poorer differentiation. Invasive mucinous adenocarcinoma predominant and solid predominant subtypes were more frequent in KRAS mutant patients. No statistical significance was found in relapse-free survival or overall survival between patients with KRAS mutation and patients with other mutations.Conclusion: In Chinese populations, we identified KRAS mutation in 8.3% (113/1,368 of the patients with lung adenocarcinoma. KRAS mutation defines a molecular subset of

  10. Prognostic Value of Hepatocyte Growth Factor, Syndecan-1, and Osteopontin in Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

    Directory of Open Access Journals (Sweden)

    Jiri Minarik

    2012-01-01

    Full Text Available Our aim was to compare serum levels of selected biological parameters in different phases of multiple myeloma (MM and monoclonal gammopathy of undetermined significance (MGUS to determine their diagnostic and prognostic potential. A cohort of 234 individuals was assessed for serum levels of hepatocyte growth factor (HGF, syndecan-1/CD138 (SYN, and osteopontin (OPN. The patients with MM (=156 were divided into 3 groups: at the time of diagnosis (=45, in relapse/progression (=56, and in remission (=50. The analysis revealed significant differences of all three parameters in comparison of active and remission phase MM. Moreover, the parameters in active myeloma were significantly higher than in MGUS. Within the comparison of active disease (newly diagnosed and relapsing, there was no significant difference. Similar results were in remission phase MM and MGUS. There was no relationship of pretreatment levels of the parameters to therapeutic response. We conclude that serum levels of HGF, OPN, and SYN correspond to the activity of MM and might become useful in differentiation of MGUS, asymptomatic MM, and overt/symptomatic form of MM. The levels of all three parameters behave accordingly with MM activity. Pretreatment measurement without the assessment of their kinetics, however, has no relationship to therapeutic response.

  11. Prognostic Significance of a Micropapillary Pattern in Pure Mucinous Carcinoma of the Breast: Comparative Analysis with Micropapillary Carcinoma

    Science.gov (United States)

    Kim, Hyun-Jung; Park, Kyeongmee; Kim, Jung Yeon; Kang, Guhyun; Gwak, Geumhee; Park, Inseok

    2017-01-01

    Background Mucinous carcinoma of the breast is an indolent tumors with a favorable prognosis; however, micropapillary features tend to lead to aggressive behavior. Thus, mucinous carcinoma and micropapillary carcinoma exhibit contrasting biologic behaviors. Here, we review invasive mucinous carcinoma with a focus on micropapillary features and correlations with clinicopathological factors. Methods A total of 64 patients with invasive breast cancer with mucinous or micropapillary features were enrolled in the study. Of 36 pure mucinous carcinomas, 17 (47.2%) had micropapillary features and were termed mucinous carcinoma with micropapillary features (MUMPC), and 19 (52.8%) had no micropapillary features and were termed mucinous carcinoma without micropapillary features. MUMPC were compared with 15 invasive micropapillary carcinomas (IMPC) and 13 invasive ductal and micropapillary carcinomas (IDMPC). Results The clinicopathological factors of pure mucinous carcinoma and MUMPC were not significantly different. In contrast to IMPC and IDMPC, MUMPC had a low nuclear grade, lower mitotic rate, higher expression of hormone receptors, negative human epidermal growth factor receptor 2 (HER2) status, lower Ki-67 proliferating index, and less frequent lymph node metastasis (p HER2, T-stage, and lymph node metastasis were significant risk factors for overall survival; however, only T-stage remained significant in a multivariate analysis (p mucinous carcinoma does not contribute to aggressive behavior. However, further analysis of a larger series of patients is required to clarify the prognostic significance of micropapillary patterns in mucinous carcinoma of the breast. PMID:28597867

  12. Classification and Clinical Management of Variants of Uncertain Significance in High Penetrance Cancer Predisposition Genes.

    Science.gov (United States)

    Moghadasi, Setareh; Eccles, Diana M; Devilee, Peter; Vreeswijk, Maaike P G; van Asperen, Christi J

    2016-04-01

    In 2008, the International Agency for Research on Cancer (IARC) proposed a system for classifying sequence variants in highly penetrant breast and colon cancer susceptibility genes, linked to clinical actions. This system uses a multifactorial likelihood model to calculate the posterior probability that an altered DNA sequence is pathogenic. Variants between 5%-94.9% (class 3) are categorized as variants of uncertain significance (VUS). This interval is wide and might include variants with a substantial difference in pathogenicity at either end of the spectrum. We think that carriers of class 3 variants would benefit from a fine-tuning of this classification. Classification of VUS to a category with a defined clinical significance is very important because for carriers of a pathogenic mutation full surveillance and risk-reducing surgery can reduce cancer incidence. Counselees who are not carriers of a pathogenic mutation can be discharged from intensive follow-up and avoid unnecessary risk-reducing surgery. By means of examples, we show how, in selected cases, additional data can lead to reclassification of some variants to a different class with different recommendations for surveillance and therapy. To improve the clinical utility of this classification system, we suggest a pragmatic adaptation to clinical practice. © 2016 WILEY PERIODICALS, INC.

  13. Prognostic value of the seventh AJCC/UICC TNM classification of intestinal-type ethmoid adenocarcinoma: Systematic review and risk prediction model.

    Science.gov (United States)

    Fiaux-Camous, Domitille; Chevret, Sylvie; Oker, Natalie; Turri-Zanoni, Mario; Lombardi, Davide; Choussy, Olivier; Duprez, Frederic; Jorissen, Marc; de Gabory, Ludovic; Malard, Olivier; Herman, Philippe; Nicolai, Piero; Castelnuovo, Paolo; Verillaud, Benjamin

    2017-04-01

    The purpose of this study was to propose a prognostic classification of intestinal-type adenocarcinoma (ITAC) based on literature search and prognostic modeling of cohort data. We first conducted a literature search to assess the homogeneity of the reported estimates of 5-year survival and to identify the influence of T classification. We then pooled prospective data from 3 large French and Italian series to predict time to all-cause mortality. The sample was randomly split to derive and then to validate the proposed prognostic model. Literature analysis confirmed the heterogeneity in 5-year survival rates, partly explained in subsets of homogeneous T-values. The sample included 223 patients, randomly separated into a derivation (n = 141) and a validation set (n = 82). Invasion of the sphenoid lateral and/or posterior walls and dura/cerebral invasion were systematically associated with a poor survival. The incorporation of the invasion of the sphenoid lateral or posterior walls should be considered for ITAC management and prognostication. © 2017 Wiley Periodicals, Inc. Head Neck 39: 668-678, 2017. © 2017 Wiley Periodicals, Inc.

  14. Architecturally Significant Requirements Identification, Classification and Change Management for Multi-tenant Cloud-Based Systems

    DEFF Research Database (Denmark)

    Chauhan, Muhammad Aufeef; Probst, Christian W.

    2017-01-01

    requirements (such as scalability, reliability, and interoperability) are handled in the overall architecture design of a cloud-based system. It is important to distinguish tenant-specific run-time architecturally significant quality requirements and corresponding cloud-based systems’ components so that run...... identification, classification, and change management challenges. We have explored findings from systematic as well as structured reviews of the literature on quality requirements of the cloud-based systems including but not limited to security, availability, scalability, privacy, and multi-tenancy. We have...... presented a framework for requirements classification and change management focusing on distributed Platform as a Service (PaaS) and Software as a Service (SaaS) systems as well as complex software ecosystems that are built using PaaS and SaaS, such as Tools as a Service (TaaS). We have demonstrated...

  15. Prognostic significance of increased bone marrow microcirculation in newly diagnosed multiple myeloma: results of a prospective DCE-MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Merz, Maximilian; Hillengass, Jens [Department of Radiology, German Cancer Research Center, Heidelberg (Germany); University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Moehler, Thomas M.; Ritsch, Judith; Delorme, Stefan [Department of Radiology, German Cancer Research Center, Heidelberg (Germany); Baeuerle, Tobias [University of Erlangen-Nuremberg, Department of Radiology, Erlangen (Germany); Zechmann, Christian M. [Rinecker Proton Therapy, Muenchen (Germany); Wagner, Barbara; Hose, Dirk [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Jauch, Anna [University of Heidelberg, Institute of Human Genetics, Heidelberg (Germany); Kunz, Christina; Hielscher, Thomas [German Cancer Research Center, Department of Biostatistics, Heidelberg (Germany); Laue, Hendrik [Fraunhofer MEVIS, Bremen (Germany); Goldschmidt, Hartmut [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); National Center for Tumor Diseases, Heidelberg (Germany)

    2016-05-15

    Aim of this prospective study was to investigate prognostic significance of increased bone marrow microcirculation as detected by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for survival and local complications in patients with multiple myeloma (MM). We performed DCE-MRI of the lumbar spine in 131 patients with newly diagnosed MM and analysed data according to the Brix model to acquire amplitude A and exchange rate constant k{sub ep}. In 61 patients a second MRI performed after therapy was evaluated to assess changes in vertebral height and identify vertebral fractures. Correlation analysis revealed significant positive association between beta2-microglobulin as well as immunoparesis with DCE-MRI parameters A and k{sub ep}. Additionally, A was negatively correlated with haemoglobin levels and k{sub ep} was positively correlated with LDH levels. Higher baseline k{sub ep} values were associated with decreased vertebral height in a second MRI (P = 0.007) and A values were associated with new vertebral fractures in the lower lumbar spine (P = 0.03 for L4). Pre-existing lytic bone lesions or remission after therapy had no impact on the occurrence of vertebral fractures. Multivariate analysis revealed that amplitude A is an independent adverse risk factor for overall survival. DCE-MRI is a non-invasive tool with significance for systemic prognosis and vertebral complications. (orig.)

  16. Prognostic Significance of Right Heart Thrombi in Patients With Acute Symptomatic Pulmonary Embolism: Systematic Review and Meta-analysis.

    Science.gov (United States)

    Barrios, Deisy; Rosa-Salazar, Vladimir; Morillo, Raquel; Nieto, Rosa; Fernández, Sara; Zamorano, José Luis; Monreal, Manuel; Torbicki, Adam; Yusen, Roger D; Jiménez, David

    2017-02-01

    For patients diagnosed with acute pulmonary embolism (PE), the prognostic significance of concomitant right heart thrombi (RHT) lacks clarity. We performed a meta-analysis of studies that enrolled patients with acute PE to assess the prognostic value of echocardiography-detectable RHT for the primary outcome of short-term all-cause mortality and the secondary outcome of short-term PE-related mortality. Unrestricted searches were conducted of PubMed and Embase from 1980 through January 31, 2016, and used the terms "right heart thrombi," "pulmonary embolism," and "prognos.*" A random effects model was used to pool study results; Begg rank correlation method was used to evaluate for publication bias; and I2 testing was used to assess for heterogeneity. Six of 79 potentially relevant studies met the inclusion criteria (15,220 patients). Overall, 99 of 593 patients with echocardiography-detectable RHT died (16.7% [95% CI, 13.8-19.9]) compared with 639 of 14,627 without RHT (4.4% [95% CI, 4.0-4.7]). RHT had a significant association with short-term all-cause mortality in all patients (OR, 3.0 [95% CI, 2.2 to 4.1]; I2 = 20%) and with PE-related death (three cohorts, 12,955 patients; OR: 4.8 [95% CI, 2.0-11.3; I2 = 76%). Results were consistent for the prospective (two cohorts, 514 patients; OR, 4.8 [95% CI, 1.7-13.6]; I2 = 56%) and the retrospective (four cohorts, 14,706 patients; OR, 2.8 [95% CI, 2.1 to 3.8]; I2 = 0%) studies. In patients diagnosed with acute PE, concomitant RHT were significantly associated with an increased risk of death within 30 days of PE diagnosis. PROSPERO registry; No.: CRD42016033960; URL: https://www.crd.york.ac.uk/prospero/. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  17. Prognostic significance of standardized uptake value on preoperative {sup 18}F-FDG PET/CT in patients with ampullary adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hye Jin [Yonsei University College of Medicine, Division of Oncology, Department of Internal Medicine, Seoul (Korea, Republic of); Kang, Chang Moo; Lee, Woo Jung [Yonsei University College of Medicine, Division of Hepatobiliary and Pancreas, Department of Surgery, Seoul (Korea, Republic of); Jo, Kwanhyeong; Lee, Jong Doo [Yonsei University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Lee, Jae-Hoon [Yonsei University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Yonsei University College of Medicine, Department of Nuclear Medicine, Gangnam Severance Hospital, Seoul (Korea, Republic of); Ryu, Young Hoon [Yonsei University College of Medicine, Department of Nuclear Medicine, Gangnam Severance Hospital, Seoul (Korea, Republic of)

    2015-05-01

    The purpose of this study was to investigate the prognostic value of {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with ampullary adenocarcinoma (AAC) after curative surgical resection. Fifty-two patients with AAC who had undergone {sup 18}F-FDG PET/CT and subsequent curative resections were retrospectively enrolled. The maximum standardized uptake value (SUV{sub max}) and tumor to background ratio (TBR) were measured on {sup 18}F-FDG PET/CT in all patients. The prognostic significances of PET/CT parameters and clinicopathologic factors for recurrence-free survival (RFS) and overall survival (OS) were evaluated by univariate and multivariate analyses. Of the 52 patients, 19 (36.5 %) experienced tumor recurrence during the follow-up period and 18 (35.8 %) died. The 3-year RFS and OS were 62.3 and 61.5 %, respectively. Preoperative CA19-9 level, tumor differentiation, presence of lymph node metastasis, SUV{sub max}, and TBR were significant prognostic factors for both RFS and OS (p < 0.05) on univariate analyses, and patient age showed significance only for predicting RFS (p < 0.05). On multivariate analyses, SUV{sub max} and TBR were independent prognostic factors for RFS, and tumor differentiation, SUV{sub max}, and TBR were independent prognostic factors for OS. SUV{sub max} and TBR on preoperative {sup 18}F-FDG PET/CT are independent prognostic factors for predicting RFS and OS in patients with AAC; patients with high SUV{sub max} (>4.80) or TBR (>1.75) had poor survival outcomes. The role of and indications for adjuvant therapy after curative resection of AAC are still unclear. {sup 18}F-FDG uptake in the primary tumor could provide additive prognostic information for the decision-making process regarding adjuvant therapy. (orig.)

  18. Co-expression of periostin and EGFR in patients with esophageal squamous cell carcinoma and their prognostic significance

    Directory of Open Access Journals (Sweden)

    Jia W

    2016-08-01

    Full Text Available Wei Jia,1 Wei Wang,1 Chu-shu Ji,1 Jun-yang Niu,2 Ya-jing Lv,1 Hang-cheng Zhou,2 Bing Hu1 1Department of Medical Oncology, 2Department of Pathology, Anhui Provincial Hospital, Anhui Medical University, Hefei, People’s Republic of China Background: Both periostin (PN and epidermal growth factor receptor (EGFR can predict the prognosis of several carcinomas alone. However, coexpression of PN and EGFR in esophageal squamous cell carcinoma (ESCC still remains unknown. We aimed to clarify their relationship with clinicopathological factors and prognostic significance of their coexpression in ESCC. Patients and methods: In this single-center retrospective study, immunohistochemistry was performed to evaluate the expression of PN and EGFR in ESCC and paracarcinomatous tissues of 83 patients. The quantitative expression levels of PN and EGFR were examined in two ESCC and tumor-adjacent tissues. The levels of PN and EGFR expression were correlated with clinicopathological parameters by the χ2 or Kruskal–Wallis method. Spearman’s rank correlation test was performed to determine the relationship between PN and EGFR expression levels. Kaplan–Meier and Cox regression analyses were used to detect the prognostic factors of disease-free survival (DFS and overall survival (OS. Results: The high expression of PN protein in ESCC tissues was significantly associated with tumor length (P=0.044, differentiation grade (P=0.003, venous invasion (P=0.010, invasion depth (P=0.007, lymphatic metastasis (P=0.000, and tumor stage (P=0.000. The high expression of EGFR protein in ESCC tissues was only significantly related to lymphatic metastasis (P=0.000, invasion depth (P=0.022, and tumor stage (P=0.000. Kaplan–Meier analysis showed that high expression of PN was closely correlated to reduced OS (P=0.000 and DFS (P=0.000, which was consistent with EGFR expression. Cox regression analysis identified PN and EGFR as independent poor prognostic factors of OS and DFS

  19. HER family receptors expression in squamous cell carcinoma of the tongue: study of the possible prognostic and biological significance.

    Science.gov (United States)

    Del Sordo, Rachele; Angiero, Francesca; Bellezza, Guido; Cavaliere, Antonio; Mameli, Maria Grazia; Stefani, Michele; Dessy, Enrico; Sidoni, Angelo

    2010-01-01

    The squamous cell carcinoma of the tongue (SCCT) is biologically and epidemiologically distinct from other oral cavity cancers and is associated with lower overall survival rates. The role of HER family members (HER-1, HER-2/neu, HER-3 and HER-4) in the pathogenesis and progression of head and neck squamous cell carcinomas has been demonstrated but no report have focused on SCCT. This study investigated, the expression of all members of the HER family, in a series of SCCT and studied the possible prognostic value and correlation with various clinico-pathological parameters. HER-1, HER-2/neu, HER-3 and HER-4 expression was analysed by semi-quantitative immunohistochemical staining on paraffin embedded tissue specimens from 40 patients who underwent surgery for SCCT between 1996 and 2006. HER-1 was overexpressed in 26 cases (65%), HER-2/neu in two (5%), HER-3 in 19 (48%) and HER-4 in three cases (8%). No significant correlation was found between clinicopathological variables and expression of HER-1 and HER-2/neu. HER-3 overexpression was significantly related to nodal stage, age (>or=64 years) and decreased overall survival (P HER-1 and HER-2/neu when determined with stringent criteria are not useful indicators of prognosis in SCCT. Only HER-3 overexpression may help in identifying SCCT with greater malignant potential also when it is coexpressed with HER-4. Instead, as in other malignancies, HER-4 could play a protective role in SCCT.

  20. "A retrospective cohort study for prognostic significance of visual acuity for near over that for distance in anisometropic amblyopia.".

    Directory of Open Access Journals (Sweden)

    Singh Vinita

    1992-01-01

    Full Text Available A cohort of 50 anisometropic amblyopes, between the ages of 2.5 to 10 years, was studied retrospectively to assess the prognostic significance of visual acuity for near over that for distance. There is ample evidence in the literature for a significantly lower accommodative response in the anisometropic amblyopic eye. It has been proposed that the efferent accommodative dysfunction may be a fundamental and causative factor in anisometropic amblyopia. A reduced visual acuity for near over that for distance was found in 17 [34%] patients and in 11 out of these the near vision improved after an addition of +3.0D sph. When a reduced visual acuity for near, was obtained it was difficult to determine whether the visual afferent system (due to insufficient visual input, or the accommodation efferent mechanism was responsible. However an improvement in corrected near vision by addition of +3.0D sph. suggested an accommodative dysfunction. In patients with reduced visual acuity for near over that for distance, not only was the final visual outcome poor but also the onset of visual improvement in response to amblyopia therapy was delayed.

  1. Prognostic significance of focal lesions and diffuse infiltration on MRI for multiple myeloma: a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So-Yeon; Park, Hee-Jin [Sungkyunkwan University School of Medicine, Department of Radiology, Kangbuk Samsung Hospital, Seoul (Korea, Republic of); Kim, Hyun-Jung [Korea University College of Medicine, Department of Preventive Medicine, Seoul (Korea, Republic of); Shin, Yu Ri [The Catholic University of Korea, Department of Radiology, Incheon St. Mary' s Hospital, College of Medicine, Seoul (Korea, Republic of); Lee, Yun-Gyoo; Oh, Suk Joong [Sungkyunkwan University School of Medicine, Division of Hematology and Oncology, Department of Internal Medicine, Kangbuk Samsung Hospital, Seoul (Korea, Republic of)

    2017-06-15

    MRI of bone marrow of the axial skeleton is recommended for evaluation of multiple myeloma. The impact of bone marrow involvement pattern on MRI for determining progression-free survival (PFS) and overall survival (OS) is not yet clear. We performed a meta-analysis of research on the prognostic significance of MRI patterns for OS and PFS using a random effects model. Databases searched without language restriction were MEDLINE, EMBASE, and the Cochrane Library (January 1976 to April 2014). Manual searches were also conducted. Of 10,953 citations identified in the original search, 10 cohort studies for a total of 2015 patients met the inclusion criteria. Nine of the 10 included studies are from three research groups. Pooled hazard ratios were 1.80 (95 % confidence interval [CI] 1.32-2.46; P < 0.001) for OS and 2.30 (95 % CI 1.65-3.20; P < 0.001) for PFS for focal lesions on MRI; and 1.70 (95 % CI 1.30-2.21; P < 0.001) for OS and 1.74 (95 % CI 1.07-2.85; P = 0.03) for PFS for diffuse infiltration on MRI. No significant heterogeneity was observed among studies. This meta-analysis demonstrated an association between focal lesions and diffuse infiltration and poor prognosis in this population. (orig.)

  2. Prognostic significance of fluorescent in situ hybridisation in the follow-up of non-muscle-invasive bladder cancer

    National Research Council Canada - National Science Library

    Maffezzini, Massimo; Campodonico, Fabio; Capponi, Giacomo; Canepa, Giorgio; Casazza, Stefania; Bandelloni, Roberto; Tamagno, Stefania; Puntoni, Matteo

    2010-01-01

    To evaluate the potential contribution of a fluorescent in situ hybridization (FISH) as prognostic indicator of the risk of recurrence or progression in patients undergoing follow-up for non-muscle-invasive bladder cancer...

  3. Clinicopathologic and prognostic significance of human epidermal growth factor receptor in patients with gastric cancer: An updated meta-analysis.

    Science.gov (United States)

    Zhang, Zhiqiao; Tang, Hongfeng; Lin, Jixin; Hu, Yunzhao; Luo, Guanying; Luo, Zhaowen; Cheng, Canchang; Wang, Peng

    2017-03-07

    The aim of this update meta-analysis was to clarify the clinicopathologic and prognostic significance of human epidermal growth factor receptor(EGFR) expression in gastric cancer patients. Several electronic databases were searched from January 1970 to May 2016. The odds ratio (OR) was calculated to assess the association between EGFR expression and pathological parameters. The hazard ratio (HR) and 95% CI were calculated to explore the relationship between EGFR expression and overall survival. Finally 7229 patients with gastric cancer from 25 eligible studies were included in the present meta analysis. High EGFR expression was found to be significantly related with tumor differentiation (OR=1.96, 95%CI: 1.14-3.34, Z=2.43, P=0.015), lymph node metastasis (OR=2.20, 95% CI: 1.63-2.96, Z=5.17, P=0.001), and tumor stage (OR=2.13, 95% CI: 1.35-3.36, Z=3.25, P=0.001). However, high EGFR expression was not significantly associated with invasion depth (OR=2.09, 95% CI: 0.4-11.05, Z=0.87, P=0.385). The pooled HR suggested that high EGFR expression was significantly correlated with overall survival (HR=1.19, 95% CI 1.04-1.37, Z=2.44, P=0.015). The present meta-analysis demonstrated that high EGFR expression significantly predicts poor prognosis, suggesting that high EGFR expression may serve as a predictive biomarker for poor prognosis in patients with gastric cancer.

  4. Prognostic Significance of Bcl-2 and p53 Protein Expressions and Ki67 Proliferative Index in Diffuse Large B-cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Betül Bolat Küçükzeybek

    2013-09-01

    Full Text Available Objective: Diffuse large B-cell lymphoma (DLBCL is a high-grade neoplasm that has heterogeneous properties in clinical, morphological, and immunophenotypic aspects. In the present study the effects of p53, Bcl-2, and Ki67 on prognosis and their relationships with clinical parameters were examined. Materials and Methods: Thirty-five patients who had been diagnosed with nodally located DLBCL at İzmir Atatürk Training and Research Hospital between January 1999 and June 2006 were included in the study. The Ann Arbor classification system was used to determine the stage of the patients. The patients were evaluated according to age, sex, stage, B symptoms, extranodal involvement, and lactate dehydrogenase (LDH level as well as immunohistochemically. P53 protein and Bcl-2 oncoprotein expressions and Ki67 proliferation index were assessed immunohistochemically. Results: High Bcl-2 expression was found in 9 patients (25.7%, high p53 expression was found in 10 patients (28.6%, and high Ki67 was observed in 23 patients (65.7%. There was no significant correlation between p53 expression, Bcl-2 expression, or Ki67 proliferation index and age, sex, stage, B symptoms, extranodal involvement, LDH level, and overall survival (p>0.05. We did not find a relationship among p53 expression, Bcl-2 expression, Ki67 proliferation index, and prognosis (p>0.05. There was no significant relationship between overall survival and age, sex, stage, B symptoms, extranodal involvement, or LDH level (p>0.05. Our results revealed that Bcl-2 and p53 protein expressions and Ki67 proliferation index have no effect on overall survival of patients with DLBCL. Conclusion: The prognostic importance of p53 and Bcl-2 protein expressions and Ki67 proliferation index in DLBCL, which has biological and clinical heterogeneity, can be understood in a large series of studies that have subclasses and immunohistochemical markers with optimal cut-off values.

  5. Prognostic Significance of Peritoneal Metastasis in Stage IV Colorectal Cancer Patients With R0 Resection: A Multicenter, Retrospective Study.

    Science.gov (United States)

    Arakawa, Keiichi; Kawai, Kazushige; Ishihara, Soichiro; Hata, Keisuke; Nozawa, Hiroaki; Oba, Koji; Sugihara, Kenichi; Watanabe, Toshiaki

    2017-10-01

    Stage IV colorectal cancer encompasses various clinical conditions. The differences in prognosis after surgery between different metastatic organs have not been fully investigated. This study aimed to assess prognostic significance in peritoneal metastasis in R0 resected stage IV colorectal cancer. We conducted a multicenter retrospective study of patients with R0 resected stage IV colorectal cancer; they were categorized into 3 groups according to the number and location of metastatic organs, including single-organ metastasis in the peritoneum, single-organ metastasis at sites except the peritoneum, and multiple-organ metastases. This study used data accumulated by the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer. A total of 1133 patients with R0 resected stage IV colorectal cancer were registered retrospectively between 1997 and 2007 in 20 referral hospitals. Cancer-specific survival rates between the groups were measured. The median cancer-specific survival of the single-organ metastasis in the peritoneum group was considerably shorter than that of the single-organ metastasis at a site other than the peritoneum group and was almost comparable to that of the multiple-organ metastases group (3.41 years, 6.20 years, and 2.99 years). In a multivariate analysis of cancer-specific survival, peritoneal dissemination was confirmed as an independent prognostic factor of survival. The median postrecurrence survival of single-organ metastasis in the peritoneum group was considerably shorter than that of the single-organ metastasis at a site other than the peritoneum group. Approximately half of the patients who experienced recurrence of single-organ metastasis in the peritoneum experienced peritoneal recurrence. This was a retrospective, population-based study that requires a prospective design to validate its conclusions. Peritoneal metastasis of colorectal cancer frequently recurred in the peritoneum even after R0 resection. The cancer

  6. Prognostic Significance of a Micropapillary Pattern in Pure Mucinous Carcinoma of the Breast: Comparative Analysis with Micropapillary Carcinoma

    Directory of Open Access Journals (Sweden)

    Hyun-Jung Kim

    2017-07-01

    Full Text Available Background Mucinous carcinoma of the breast is an indolent tumors with a favorable prognosis; however, micropapillary features tend to lead to aggressive behavior. Thus, mucinous carcinoma and micropapillary carcinoma exhibit contrasting biologic behaviors. Here, we review invasive mucinous carcinoma with a focus on micropapillary features and correlations with clinicopathological factors. Methods A total of 64 patients with invasive breast cancer with mucinous or micropapillary features were enrolled in the study. Of 36 pure mucinous carcinomas, 17 (47.2% had micropapillary features and were termed mucinous carcinoma with micropapillary features (MUMPC, and 19 (52.8% had no micropapillary features and were termed mucinous carcinoma without micropapillary features. MUMPC were compared with 15 invasive micropapillary carcinomas (IMPC and 13 invasive ductal and micropapillary carcinomas (IDMPC. Results The clinicopathological factors of pure mucinous carcinoma and MUMPC were not significantly different. In contrast to IMPC and IDMPC, MUMPC had a low nuclear grade, lower mitotic rate, higher expression of hormone receptors, negative human epidermal growth factor receptor 2 (HER2 status, lower Ki-67 proliferating index, and less frequent lymph node metastasis (p < .05. According to univariate analyses, progesterone receptor, HER2, T-stage, and lymph node metastasis were significant risk factors for overall survival; however, only T-stage remained significant in a multivariate analysis (p < .05. Conclusions In contrast to IMPC and IDMPC, the micropapillary pattern in mucinous carcinoma does not contribute to aggressive behavior. However, further analysis of a larger series of patients is required to clarify the prognostic significance of micropapillary patterns in mucinous carcinoma of the breast.

  7. Prognostic significance of the number of postoperative intraperitoneal chemotherapy cycles for patients with advanced epithelial ovarian cancer.

    Science.gov (United States)

    Suidan, Rudy S; Zhou, Qin; Iasonos, Alexia; O'Cearbhaill, Roisin E; Chi, Dennis S; Long Roche, Kara C; Tanner, Edward J; Denesopolis, John; Barakat, Richard R; Zivanovic, Oliver

    2015-05-01

    Phase 3 trials have demonstrated a survival advantage for patients with optimally debulked epithelial ovarian cancer who received intravenous (IV) and intraperitoneal (IP) chemotherapy compared with IV therapy alone. This was despite a significant proportion of patients in the IV/IP arms not completing all 6 planned cycles. Our objective was to evaluate the prognostic significance of the number of IV/IP cycles administered. Data were analyzed for all patients with stage III to IV epithelial ovarian cancer who underwent optimal primary cytoreduction followed by 1 or more cycles of IV/IP chemotherapy from January 2005 to July 2011 at our institution. A landmark analysis was performed to associate progression-free survival (PFS) and overall survival (OS) with the number of IV/IP cycles given. We identified 201 patients; 26 (13%) received 1 to 2 cycles of IV/IP chemotherapy, 41 (20%) received 3 to 4 cycles, and 134 (67%) received 5 to 6 cycles. The 5-year PFS for patients who received 1 to 2, 3 to 4, and 5 to 6 cycles was 18%, 29%, and 17%, respectively. The 5-year OS for patients who received 1 to 2, 3 to 4, and 5 to 6 cycles was 44%, 54%, and 57%, respectively. There was no significant difference in PFS (P = 0.31) or OS (P = 0.14) between the 3 groups. The most common reason for discontinuing IV/IP therapy was treatment-related toxicity (77%). Postoperative complications were the most common reason for not initiating IV/IP therapy (42%) in patients who subsequently transitioned to it. We did not detect a significant survival difference between patients who received 1 to 2, 3 to 4, or 5 to 6 IV/IP chemotherapy cycles. Women may still derive a survival benefit if they receive fewer than 6 IV/IP cycles.

  8. The incidence and prognostic significance of cardiac arrhythmias and conduction abnormalities in patients with acute coronary syndromes and renal dysfunction.

    Science.gov (United States)

    Lisowska, Anna; Tycińska, Agnieszka; Knapp, Małgorzata; Lisowski, Piotr; Musiał, Włodzimierz J

    2011-01-01

    The incidence of cardiac arrhythmias, including atrial fibrillation (AF) in chronic kidney disease, is unknown, although AF is several times more common in patients with end-stage kidney disease than in the general population. To assess the incidence, types and management of cardiac arrhythmias and conduction abnormalities in patients with acute coronary syndromes (ACS) and renal dysfunction. We also evaluated the prognostic significance of arrhythmias in this patient group. We analysed 86 patients with renal dysfunction (GFR Cardiac arrhythmias were observed in 44 (51.1%) patients with AF being the most common (27 patients, 31.4%), predominantly in the paroxysmal form (21.4%). A total of 14 (16.3%) patients had cardiac arrhythmias requiring temporary or permanent pacing. Only 4 (4.6%) patients showed transient conduction abnormalities due to hyperkalaemia in the course of renal failure, while the remaining 10 (11.6%) patients demonstrated conduction abnormalities due to ACS. A total of 3 (3.5%) patients had other arrhythmias (atrial tachycardia, ventricular arrhythmias). During the follow-up period (mean duration: 14.3 months) 7 out of 44 patients (15.9%) with renal dysfunction and arrhythmia and 2 out of 42 patients (4.7%) without arrhythmia died (p Cardiac arrhythmias occur more often in patients with ACS if renal dysfunction is also present and are associated with poor prognosis.

  9. Prognostic significance of the total number of harvested lymph nodes for lymph node-negative gastric cancer patients.

    Science.gov (United States)

    Ji, Xin; Bu, Zhao-De; Li, Zi-Yu; Wu, Ai-Wen; Zhang, Lian-Hai; Zhang, Ji; Wu, Xiao-Jiang; Zong, Xiang-Long; Li, Shuang-Xi; Shan, Fei; Jia, Zi-Yu; Ji, Jia-Fu

    2017-08-22

    The relationship between the number of harvested lymph nodes (HLNs) and prognosis of gastric cancer patients without an involvement of lymph nodes has not been well-evaluated. The objective of this study is to further explore this issue. We collected data from 399 gastric cancer patients between November 2006 and October 2011. All of them were without metastatic lymph nodes. Survival analyses showed that statistically significant differences existed in the survival outcomes between the two groups allocated by the total number of HLNs ranging from 16 to 22. Therefore, we adopted 22 as the cut-off value of the total number of HLNs for grouping (group A: HLNs patients at the T4 stage was better in group B than in group A (76.9% vs. 58.5%; P=0.004). An analysis of multiple factors elucidated that the total number of HLNs, T stage, operation time and age were independently correlated factors of prognosis. Regarding gastric cancer patients without the involvement of lymph nodes, an HLN number ≥22 would be helpful in prolonging their overall survival, especially for those at T4 stage. The total number of HLNs was an independent prognostic factor for this population of patients.

  10. Prognostic Significance of Lymph Node Ratio in Metastatic Cutaneous Squamous Cell Carcinoma of the Head and Neck.

    Science.gov (United States)

    Tseros, Evan A; Gebski, Val; Morgan, Gary J; Veness, Michael J

    2016-05-01

    The prognostic variables in patients with metastatic cutaneous nodal squamous cell carcinoma (SCC) are well documented; however, the relationship between lymph node ratio (LNR) and outcome is not well researched. LNR represents the ratio of positive lymph nodes to total excised lymph nodes. We analyzed the correlation between LNR and outcome in patients who have undergone surgery for metastatic cutaneous nodal SCC of the head and neck. Analysis was performed on retrospectively collected data, identifying patients who underwent surgery at Westmead Hospital, Sydney. Pathology reports were reviewed to ascertain LNR. A log-rank test identified a specific LNR value to compare time to disease progression (TTDP) and overall survival (OS). Multivariate proportional hazard regression models were used to review outcome. In total, 193 males and 45 females with a median of age 68 years were identified, with a mean recorded LNR of 0.15. On multivariate analysis, an LNR cutpoint of 0.21 was a significant predictor of decreased TTDP [hazard ratio (HR) 2.34, 95 % confidence interval (CI) 4.40-0.49; p = 0.009] and OS (HR 2.75, 95 % CI 1.57-4.82; p 0.21. LNR is potentially an independent predictor of outcome in patients with metastatic cutaneous nodal SCC. The clinical relevance of this finding requires further validation.

  11. Retrospective study of the prognostic significance of neutrophil-to-lymphocyte ratio for postsurgical outcomes of patients with endometrial carcinoma.

    Science.gov (United States)

    Ding, Ling; Ding, Yi; Mao, Xiao-Hua; Zhao, Jian-Fei; Zhou, Huai-Jun

    2017-09-01

    To evaluate the significance of postoperative inflammatory system response markers in predicting the prognosis of patients with endometrial cancer undergoing surgery. The present retrospective study included patients who underwent surgical treatment for pathology-confirmed endometrial cancer between January 1, 2007, and June 30, 2013, at the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. Potential prognostic factors were investigated by Cox proportional hazards analysis and survival rates were compared using Kaplan-Meier analyses. There were 185 patients with surgically treated endometrial cancer included. Multivariate analyses demonstrated that a preoperative neutrophil-to-lymphocyte ratio (NLR) above 1.81 (P=0.010) and a postoperative NLR above 7.54 (P=0.008) were both independently associated with lower disease free survival. Elevated preoperative and postoperative NLRs were associated with higher tumor stage (P=0.021 and P=0.009, respectively), and only elevated preoperative NLR was associated with lymph node involvement (P=0.023). Preoperative and postoperative NLRs were independently associated with inflammatory system response markers and could be combined to evaluate the prognosis of patients with endometrial cancer following surgery. © 2017 International Federation of Gynecology and Obstetrics.

  12. Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zaizen, Yoshiaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Azuma, Koichi, E-mail: azuma@med.kurume-u.ac.jp [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kurata, Seiji [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Sadashima, Eiji; Hattori, Satoshi [Biostatistics Center, Kurume University, Kurume (Japan); Sasada, Tetsuro [Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume (Japan); Imamura, Yohei [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kaida, Hayato [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Kawahara, Akihiko [Department of Pathology, Kurume University School of Medicine, Kurume (Japan); Kinoshita, Takashi [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Ishibashi, Masatoshi [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Hoshino, Tomoaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan)

    2012-12-15

    Background: [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) imaging has been employed as a non-invasive diagnostic tool for malignant tumors. Total lesion glycolysis (TLG) on FDG-PET is calculated by multiplying the mean standardized uptake value (SUVmean) by the tumor volume. Unlike the maximum standardized uptake value (SUVmax), which represents the point of greatest metabolic activity within tumors, TLG has been suggested to reflect global metabolic activity in whole tumors. Methods: We retrospectively examined whether or not FDG-PET measurements, including SUVmean, SUVmax, and TLG, could predict progression-free survival (PFS) or overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving chemotherapy. Results: This study involved 81 consecutive patients with NSCLC who received chemotherapy. All of the patients underwent FDG-PET examination before treatment. SUVmean, SUVmax, and TLG on FDG-PET were significantly associated with gender, smoking status, and tumor histology. With adjustment for several other variables, Cox regression analysis showed that TLG was significantly prognostic for both PFS [hazard ratio = 2.34; 95% confidence interval, 1.18–4.64; P = 0.015] and OS (hazard ratio = 2.80; 95% confidence interval, 1.12–6.96; P = 0.003), whereas SUVmean and SUVmax had no significant association with PFS (P = 0.693 and P = 0.322, respectively) or OS (P = 0.587 and P = 0.214, respectively). Conclusions: Our findings suggest that TLG may be more useful than SUVmean and SUVmax for predicting PFS and OS in NSCLC patients receiving chemotherapy. The TLG measurement on FDG-PET imaging could be routinely recommended to advanced NSCLC patients.

  13. Mitosis trumps T stage and proposed international association for the study of lung cancer/american thoracic society/european respiratory society classification for prognostic value in resected stage 1 lung adenocarcinoma.

    Science.gov (United States)

    Duhig, Edwina Elizabeth; Dettrick, Andrew; Godbolt, David Burleigh; Pauli, John; van Zwieten, Anthony; Hansen, Aaron Richard; Yang, Ian Anthony; Fong, Kwun Meng; Clarke, Belinda Edith; Bowman, Rayleen Veronica

    2015-04-01

    We investigated whether a group of pathologists could reproducibly apply the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification for lung adenocarcinoma to a cohort of stage 1 tumors and whether this architectural classification and/or other parameters could demonstrate survival advantage. A total of 145 cases of 7 edition of tumor, node, metastasis stage 1 adenocarcinoma were retrospectively reviewed for predominant architectural pattern, including cribriform pattern, nuclear grade, mitotic index, and necrosis. The parameters were assessed for reproducibility and survival and using multivariate analysis, compared with stage, age, and sex. The majority of tumors had a mixed architecture with the acinar pattern being the most common predominant architecture. Micropapillary and cribriform architecture were the least frequent patterns. This study demonstrated that a group of five pathologists could reproducibly apply the IASLC/ATS/ERS classification. Although there were insufficient cribriform-predominant adenocarcinomas for assessment, when the percentage of all cribriform was combined with other architectures, it was associated with a worse prognosis. The majority of the parameters assessed demonstrated significance with univariate analysis but only mitotic index, as assessed by the highest count/10 high-power fields remained significant with multivariate analysis. In this study of resected stage 1 primary lung adenocarcinoma, we found mitotic index to be the only independent prognostic marker. It was more closely associated with outcome than either pathologic T stage or IASLC/ATS/ERS architecture-based classification. Further validation of concordance and reproducibility in reporting mitotic index, as well as validation of prognostic significance, needs to be undertaken in independent data sets.

  14. Effects of radiation therapy on tissue and serum concentrations of tumour associated trypsin inhibitor and their prognostic significance in rectal cancer patients

    Directory of Open Access Journals (Sweden)

    Stenman Ulf-Håkan

    2011-08-01

    Full Text Available Abstract Background We have previously demonstrated that elevated concentrations of tumour-associated trypsin inhibitor (TATI in both tumour tissue (t-TATI and in serum (s-TATI are associated with a poor prognosis in colorectal cancer patients. It was also found that s-TATI concentrations were lower in patients with rectal cancer compared to patients with colon cancer. In this study, we investigated the effects of neoadjuvant radiotherapy (RT on concentrations of t-TATI and s-TATI in patients with rectal cancer. Methods TATI was analysed in serum, normal mucosa and tumour tissue collected at various time points in 53 rectal cancer patients enrolled in a case-control study where 12 patients received surgery alone, 20 patients 5 × 5 Gy (short-term preoperative RT and 21 patients 25 × 2 Gy (long-term preoperative RT. T-TATI was analysed by immunohistochemistry and s-TATI was determined by an immunofluorometric assay. Mann-Whitney U test and Wilcoxon Z (Z test were used to assess t-TATI and s-TATI concentrations in relation to RT. Spearman's correlation (R test was used to explore the associations between t-TATI, s-TATI and clinicopathological parameters. Overall survival (OS according to high and low t-TATI and s-TATI concentrations was estimated by classification and regression tree analysis, Kaplan-Meier analysis and the log rank test. Results RT did not affect concentrations of t-TATI or s-TATI. In patients receiving short-term but not long-term RT, s-TATI concentrations were significantly higher 4 weeks post surgery than in serum drawn prior to surgery (Z = -3.366, P Conclusions The results presented here further validate the utility of t-TATI and s-TATI as prognostic biomarkers in patients with rectal cancer, independent of neoadjuvant RT.

  15. CD30 expression and prognostic significance in R-EPOCH-treated patients with diffuse large B-cell lymphoma.

    Science.gov (United States)

    Xu, Jie; Oki, Yasuhiro; Saksena, Annapurna; Desai, Parth; Lin, Pei; Tang, Guilin; Yin, C Cameron; You, M James; Thakral, Beenu; Medeiros, L Jeffrey; Li, Shaoying

    2017-02-01

    A few recent studies investigated the prognostic impact of CD30 expression in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. No study has evaluated the significance of CD30 expression in DLBCL patients treated with rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH). In a group of 97 patients with DLBCL and high-risk features who received R-EPOCH induction therapy, we studied CD30 expression by immunohistochemistry using different cutoff values (>0% and ≥20% of lymphoma cells, respectively) and correlated with prognosis. CD30 expression was detected in 24 (25%) cases using a cutoff greater than 0% and in 12 (12%) cases using a cutoff of 20% or greater. The clinicopathological features were similar between CD30+ and CD30-negative groups. A major difference was that MYC rearrangement was infrequent in the CD30+ group: 2 (9%) of 23 in CD30+ versus 25 (35%) of 72 in CD30-negative group (P=.02). CD30 expression was not associated with germinal center B-cell-like (GCB) or non-GCB type. Overall survival (OS) was not significantly different between patients with CD30+ and patients with CD30-negative DLBCL, either for all patients or for the subset of patients without MYC rearrangement, regardless of cutoff (P>.05). CD30 expression was not associated with OS in either GCB or non-GCB subtype (P>.05, > 0% cutoff). In conclusion, CD30 expression was detected in up to 25% of cases of DLBCL and was more frequent in tumors without MYC rearrangement. CD30 expression was not associated with OS in R-EPOCH-treated de novo DLBCL patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Prognostic Significance of Decreased Expression of Six Large Common Fragile Site Genes in Oropharyngeal Squamous Cell Carcinomas

    Directory of Open Access Journals (Sweden)

    Ge Gao

    2014-12-01

    Full Text Available Common fragile sites (CFSs are large regions with profound genomic instability that often span extremely large genes a number of which have been found to be important tumor suppressors. RNA sequencing previously revealed that there was a group of six large CFS genes which frequently had decreased expression in oropharyngeal squamous cell carcinomas (OPSCCs and real-time reverse transcriptase polymerase chain reaction experiments validated that these six large CFS genes (PARK2, DLG2, NBEA, CTNNA3, DMD, and FHIT had decreased expression in most of the tumor samples. In this study, we investigated whether the decreased expression of these genes has any clinical significance in OPSCCs. We analyzed the six CFS large genes in 45 OPSCC patients and found that 27 (60% of the OPSCC tumors had decreased expression of these six genes. When we correlated the expression of these six genes to each patient’s clinical records, for 11 patients who had tumor recurrence, 10 of them had decreased expression of almost all 6 genes. When we divided the patients into two groups, one group with decreased expression of the six genes and the other group with either slight changes or increased expression of the six genes, we found that there is significant difference in the incidence of tumor recurrence between these two groups by Kaplan-Meier plot analysis (P < .05. Our results demonstrated that those OPSCC tumors with decreased expression of this select group of six large CFS genes were much more likely to be associated with tumor recurrence and these genes are potential prognostic markers for predicting tumor recurrence in OPSCC.

  17. Prognostic significance of intensive local therapy to bone lesions in renal cell carcinoma patients with bone metastasis.

    Science.gov (United States)

    Fukushima, Hiroshi; Hozumi, Takahiro; Goto, Takahiro; Nihei, Keiji; Karasawa, Katsuyuki; Nakanishi, Yasukazu; Kataoka, Madoka; Tobisu, Ken-Ichi; Koga, Fumitaka

    2016-10-01

    We evaluated the prognostic roles of local therapy to bone metastasis (BM) in metastatic renal cell carcinoma (mRCC) patients with BM. This retrospective study included 71 mRCC patients with BM. Local therapy to BM included en bloc resection, curettage, and radiotherapy (RT). RT was classified into RT with biological effective dose (BED) ≥85 Gy and intensity. Local therapy to BM was given for 64 patients (90 %): en bloc resection, curettage, and RT for 16, 10, and 38 patients, respectively. Fifteen patients received RT with BED ≥85 Gy. The median overall survival (OS) was 25 months (median follow-up 16 months). For 46 patients with solitary BM, patients treated with en bloc resection, curettage, and RT with BED ≥85 Gy showed significantly better OS than those treated with RT with BED therapy (P = 0.006). Because OS was comparable among patients treated with en bloc resection, curettage, and RT with BED ≥85 Gy, these three treatment modalities were defined as "intensive local therapy". Intensive local therapy to BM was also associated with favorable OS with marginal significance (P = 0.052) in a cohort of 25 patients with multiple BM. A multivariate analysis in the whole cohort revealed that intensive local therapy to BM was independently associated with favorable OS (hazard ratio 0.23, P intensive local therapy to BM might improve OS in mRCC patients with BM including multiple BM.

  18. Possible Prognostic and Therapeutic Significance of c-Kit Expression, Mast Cell Count and Microvessel Density in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ilaria Marech

    2014-07-01

    Full Text Available Renal cell carcinoma (RCC is the most frequent renal tumor and its incidence is increasing worldwide. Tumor angiogenesis is known to play a crucial role in the etiopathogenesis of RCC and over the last few years an even deeper knowledge of its contribution in metastatic RCC development has led to the development of numerous molecular targeting agents (such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib. The above agents are principally directed against vascular endothelial growth factor receptor (VEGFR members and also against c-Kit receptor (c-KitR. The role of c-kitR inhibition on clear cell RCC (ccRCC, the main RCC subtype, is less well established. Whether c-kitR activation through its ligand, stem cell factor (SCF contributes significantly to the effects of tyrosine kinase inhibitors (TKIs treatment remains to be established. It is important to underscore that the c-KitR is expressed on mast cells (MCs and cancer cells. After an examination of the c-KitR/SCF pathway, we review here the principal studies that have evaluated c-Kit expression in RCC. Moreover, we summarize some investigations that have observed the distribution of MCs in primary renal cancer and in adjacent normal tissue with appropriate histological immunohistochemical techniques. We also focus on few studies that have evaluated the correlation between RCC proliferation, MC count and microvessel density (MVD, as hallmarks of tumor angiogenesis. Thus, the aim of this review of the literature is to clarify if c-KitR expression, MC count and MVD could have prognostic significance and the possible predictive therapeutic implications in RCC.

  19. Tumor Budding in Colorectal Carcinoma: Confirmation of Prognostic Significance and Histologic Cutoff in a Population-based Cohort.

    Science.gov (United States)

    Graham, Rondell P; Vierkant, Robert A; Tillmans, Lori S; Wang, Alice H; Laird, Peter W; Weisenberger, Daniel J; Lynch, Charles F; French, Amy J; Slager, Susan L; Raissian, Yassaman; Garcia, Joaquin J; Kerr, Sarah E; Lee, Hee Eun; Thibodeau, Stephen N; Cerhan, James R; Limburg, Paul J; Smyrk, Thomas C

    2015-10-01

    Tumor budding in colorectal carcinoma has been associated with poor outcome in multiple studies, but the absence of an established histologic cutoff for "high" tumor budding, heterogeneity in study populations, and varying methods for assessing tumor budding have hindered widespread incorporation of this parameter in clinical reports. We used an established scoring system in a population-based cohort to determine a histologic cutoff for "high" tumor budding and confirm its prognostic significance. We retrieved hematoxylin and eosin-stained sections from 553 incident colorectal carcinoma cases. Each case was previously characterized for select molecular alterations and survival data. Interobserver agreement was assessed between 2 gastrointestinal pathologists and a group of 4 general surgical pathologists. High budding (≥ 10 tumor buds in a ×20 objective field) was present in 32% of cases, low budding in 46%, and no budding in 22%. High tumor budding was associated with advanced pathologic stage (P 2 times risk of cancer-specific death (hazard ratio = 2.57 [1.27, 5.19]). After multivariate adjustment, by penalized smoothing splines, we found increasing tumor bud counts from 5 upward to be associated with an increasingly shortened cancer-specific survival. By this method, a tumor bud count of 10 corresponded to approximately 2.5 times risk of cancer-specific death. The interobserver agreement was good with weighted κ of 0.70 for 2 gastrointestinal pathologists over 121 random cases and 0.72 between all 6 pathologists for 20 random cases. Using an established method to assess budding on routine histologic stains, we have shown that a cutoff of 10 for high tumor budding is independently associated with a significantly worse prognosis. The reproducibility data provide support for the routine widespread implementation of tumor budding in clinical reports.

  20. Prognostic and diagnostic significance of tumor budding associated with β-catenin expression in submucosal invasive colorectal carcinoma.

    Science.gov (United States)

    Umemura, Ken; Takagi, Sho; Shimada, Takenobu; Masuda, Takayuki; Shiga, Hisashi; Takahashi, Shuichiro; Takahashi, Seiichi; Kinouchi, Yoshitaka; Shibuya, Daisuke; Shimosegawa, Tooru

    2013-01-01

    Endoscopic resection has become a major curative treatment for early colorectal carcinoma without lymph node metastasis. However, lymph node metastasis, a poor prognostic factor in colorectal carcinoma, occurs in about 10% of the patients with submucosal invasive colorectal carcinoma. Therefore, it is important to identify a high-risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma. This study was designed to identify the relationship between tumor budding with β-catenin expression and lymph node metastasis in submucosal invasive colorectal carcinoma. We investigated the immunohistochemistry of tumor budding in the 142 patients who underwent surgical resection for submucosal invasive colorectal carcinomas between 1984 and 1999 and the expression pattern of β-catenin in budding tumor cells. Accordingly, all the patients were followed up for at least 10 years or until death. Among the 142 patients, lymph node metastasis was detected in 14 patients (9.9%). Univariate analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was significantly associated with lymph node metastasis (P = 0.005). In contrast, tumor budding detected by hematoxylin and eosin staining was not associated with lymph node metastasis. Multivariate logistic regression analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was a significant risk factor for lymph node metastasis (odds ratio, 7.124; 95% confidence interval, 1.407-36.062). Thus, tumor budding associated with β-catenin expression is a risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma.

  1. Prognostic significance of mediastinal {sup 18}F-FDG uptake in PET/CT in advanced ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bats, Anne-Sophie; Lecuru, Fabrice [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Universite Paris Descartes, Sorbonne Paris Cite, INSERM UMR-S 747, Paris (France); Hugonnet, Florent; Faraggi, Marc [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Medecine Nucleaire, Paris (France); Huchon, Cyrille [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Bensaid, Cherazade [Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Pierquet-Ghazzar, Nadia [Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Medecine Nucleaire, Paris (France)

    2012-03-15

    To evaluate the prognostic significance of increased mediastinal {sup 18}F-FDG uptake in PET/CT for the staging of advanced ovarian cancer. We retrospectively evaluated patients managed for FIGO stage III/IV ovarian cancer between 1 January 2006 and 1 June 2009. Patients were included if they had undergone {sup 18}F-FDG PET/CT and surgery for initial staging. Exclusion criteria were age younger than 18 years, inability to undergo general anaesthesia, recurrent ovarian cancer, and borderline or nonepithelial malignancy. Whole-body PET/CT was performed after intravenous {sup 18}F-FDG injection. The location of abnormal hot spots and {sup 18}F-FDG maximal standard uptake values (SUV{sub max}) were recorded. We compared the complete cytoreduction and survival rates in groups defined based on mediastinal {sup 18}F-FDG uptake and SUV{sub max} values. Kaplan-Meier curves of overall survival and disease-free survival were compared using the log-rank test. Hazard ratios with their 95% confidence intervals were computed. Adjusted hazard ratios were obtained using a multivariate Cox model. We included 53 patients, of whom 17 (32%) had increased mediastinal {sup 18}F-FDG uptake. Complete cytoreduction was achieved in 14 (87.5%) of the 16 patients managed with primary surgery and in 21 (75%) of the 28 patients managed with interval surgery. Complete cytoreduction was achieved significantly more often among patients without increased mediastinal {sup 18}F-FDG uptake (80.6% vs. 35.3%; p = 0.001). Disease-free survival was comparable between the two groups. By univariate analysis, overall mortality was significantly higher among patients with increased mediastinal {sup 18}F-FDG uptake (hazard ratio 5.70, 95% confidence interval 1.74-18.6). The only factor significantly associated with overall survival by multivariate analysis was complete cytoreduction (adjusted hazard ratio 0.24, 95% confidence interval 0.07-0.89). Increased mediastinal {sup 18}F-FDG uptake was common in patients

  2. The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer : a population based study in the Netherlands

    NARCIS (Netherlands)

    Schaapveld, Michael; Visser, Otto; Louwman, W. J.; Willemse, Pax H. B.; de Vries, Elisabeth G. E.; van der Graaf, Winette T. A.; Otter, Renee; Coebergh, Jan Willem W.; van Leeuwen, Flora E.

    Background The impact of age and adjuvant therapy on contralateral breast cancer (CBC) risk and prognostic significance of CBC were evaluated. Patients and Methods In 45,229 surgically treated stage I-IIIA patients diagnosed in the Netherlands between 1989 and 2002 CBC risk was quantified using

  3. The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer: a population based study in the Netherlands.

    NARCIS (Netherlands)

    Schaapveld, M.; Visser, O.; Louwman, W.J.; Willemse, P.H.; Vries, EG de; Graaf, W.T.A. van der; Otter, R.; Coebergh, J.W.; Leeuwen, F.E. van

    2008-01-01

    BACKGROUND: The impact of age and adjuvant therapy on contralateral breast cancer (CBC) risk and prognostic significance of CBC were evaluated. PATIENTS AND METHODS: In 45,229 surgically treated stage I-IIIA patients diagnosed in the Netherlands between 1989 and 2002 CBC risk was quantified using

  4. The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer: A population based study in the Netherlands

    NARCIS (Netherlands)

    M. Schaapveld (Michael); O.J. Visser (Otto); W.J. Louwman; P.H.B. Willemse (Pax); E.G.E. de Vries (Elisabeth); W.T.A. van der Graaf (Winette); R. Otter (Renée); J.W.W. Coebergh (Jan Willem); F.E. van Leeuwen (Flora)

    2008-01-01

    textabstractBackground: The impact of age and adjuvant therapy on contralateral breast cancer (CBC) risk and prognostic significance of CBC were evaluated. Patients and Methods: In 45,229 surgically treated stage I-IIIA patients diagnosed in the Netherlands between 1989 and 2002 CBC risk was

  5. Determinants and prognostic significance of an intra-dialysis rise of cardiac troponin I measured by sensitive assay in hemodialysis patients

    NARCIS (Netherlands)

    Assa, Solmaz; Gansevoort, Ron T.; Westerhuis, Ralf; Kobold, Anneke C. Muller; Voors, Adriaan A.; de Jong, Paul E.; Bakker, Stephan J. L.; Franssen, Casper F. M.

    Previous studies using conventional cTnI assays reported conflicting results on the evolution of cTnI levels during hemodialysis. The determinants and prognostic significance of changes in cTnI during hemodialysis are presently unknown. The aim of this prospective study was to characterize the

  6. [THE RISK OF ACUTE RENAL LESIONS AND ITS PROGNOSTIC SIGNIFICANCE IN PATIENTS WITH CHRONIC RENAL DISEASE UNDERGOING CARDIAC SURGICAL INTERVENTION].

    Science.gov (United States)

    Iskenderov, B G; Sisina, O N; Budagovskaia, Z M

    2015-01-01

    to determine the frequency and risk factors of acute renal lesions (ARL) and their prognostic significance in patients with chronic renal disease (CRD) undergoing surgical intervention. The study included 1122 patients (586 men and 536 women) aged 32-68 (mean 62.3 ± 5.2) years who underwent correction of valvular defects, aortocoronary bypass surgery or their combination). Initial glomerular filtration rate was higher than 90 ml/min/l.73 m2 in 656 patients (group 1) and 89-60 ml/min/l/73 m2 in 470 ones (group 2). ARL were diagnosed based on the serum creatinine level using RIFLE criteria. In the early postoperative period, ARL were diagnosed in 23.9% of the patients in group I and 38.7% of those in group 2 (p < 0.001). Intra-hospital lethality in group 1 was 4.9% (14.1% in patients with ARL) and 12.1% in group 2 (18.1% iin patients with ARL). In group 2, 47.9% of the patients with ARL experienced regress of renal dysfunction during 12 months compared with 56.9% ones without ARL. The progress of CRD was documented in 11% of group 2 patients with ARL and in (4.5% without AR (p = 0.013). 5.7% of the patients in group 1 developed CRD after ARL. 4.9% of the patients in group 2 needed programmed hemodialysis. The development of ARL in patients with CRD is associated with unfvouravle cardiovascular prognosis following cardiosurgery.

  7. The Prevalence and Prognostic Significance of Frailty in Patients With Advanced Heart Failure Referred for Heart Transplantation.

    Science.gov (United States)

    Jha, Sunita R; Hannu, Malin K; Chang, Sungwon; Montgomery, Elyn; Harkess, Michelle; Wilhelm, Kay; Hayward, Christopher S; Jabbour, Andrew; Spratt, Phillip M; Newton, Phillip; Davidson, Patricia M; Macdonald, Peter S

    2016-02-01

    Frailty is a clinically recognized syndrome of decreased physiological reserve. The heightened state of vulnerability in these patients confers a greater risk of adverse outcomes after even minor stressors. Our aim was to assess the prevalence and prognostic significance of the frailty phenotype in patients referred for heart transplantation. Consecutive patients referred or on the waiting list for heart transplantation from March 2013 underwent frailty assessment. Frailty was defined as a positive response to 3 or more of the following 5 components: weak grip strength, slowed walking speed, poor appetite, physical inactivity, and exhaustion. In addition, markers of disease severity were obtained, and all patients underwent cognitive (Montreal Cognitive Assessment) and depression (Depression in Medical Illness-10) screening. One hundred twenty patients (83 men:37 women; age, 53 ± 12 years, range, 16-73 years; left ventricular ejection fraction, 27 ± 14%) underwent frailty assessment. Thirty-nine of 120 patients (33%) were assessed as frail. Frailty was associated with New York Heart Association class IV heart failure, lower body mass index, elevated intracardiac filling pressures, lower cardiac index, anemia, hypoalbuminemia, hyperbilirubinemia, cognitive impairment, and depression (all ρ < 0.05). Frailty was independent of age, sex, heart failure duration, left ventricular ejection fraction, or renal function. Frailty was an independent predictor of increased all-cause mortality: 1 year actuarial survival was 79 ± 5% in the nonfrail group compared with only 54 ± 9% for the frail group (P < 0.005). Frailty is prevalent among patients with advanced symptomatic heart failure referred for heart transplantation and is associated with increased mortality.

  8. Prognostic significance of TRAIL death receptors in Middle Eastern colorectal carcinomas and their correlation to oncogenic KRAS alterations

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    Hussain Azhar R

    2010-07-01

    Full Text Available Abstract Background Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL is a member of the tumour necrosis factor cytokine family that induces apoptosis upon binding to its death domain containing receptors, TRAIL receptor 1 (DR4 and TRAIL receptor 2 (DR5. Expression of TRAIL receptors is higher in colorectal carcinoma (CRC as compared to normal colorectal mucosa and targeted therapy with TRAIL leads to preferential killing of tumor cells sparing normal cells. Methods We investigated the expression of TRAIL and its receptors in a tissue microarray cohort of 448 Middle Eastern CRC. We also studied the correlation between TRAIL receptors and various clinico-pathological features including key molecular alterations and overall survival. Results CRC subset with TRAIL-R1 expression was associated with a less aggressive phenotype characterized by early stage (p = 0.0251 and a histology subtype of adenocarcinomas (p = 0.0355. Similarly CRC subset with TRAIL-R2 expression was associated with a well-differentiated tumors (p KIP1 and KRAS4A isoforms was significantly higher in CRC subset with TRAIL-R1 and TRAIL-R2 expression; TRAIL-R1 expression was also associated with cleaved caspase-3(p = 0.0011. Interestingly, TRAIL-R2 expression was associated with a microsatellite stable (MS--S/L phenotype (p = 0.0003 and with absence of KRAS mutations (p = 0.0481. Conclusion TRAIL-R1 expression was an independent prognostic marker for better survival in all CRC samples and even in the CRC group that received adjuvant therapy. The biological effects of TRAIL in CRC models, its enhancement of chemosensitivity towards standard chemotherapeutic agents and the effect of endogenous TRAIL receptor levels on survival make TRAIL an extremely attractive therapeutic target.

  9. Prognostic significance of FTO genotype in the development of obesity in Japanese: the J-SHIPP study.

    Science.gov (United States)

    Tabara, Y; Osawa, H; Guo, H; Kawamoto, R; Onuma, H; Shimizu, I; Takara, Y; Nishida, W; Yamamoto, M; Makino, H; Kohara, K; Miki, T

    2009-11-01

    Susceptibility of fat mass and obesity-associated (FTO) gene polymorphisms to obesity has been reported in various populations. Polymorphisms in the melanocortin 4 receptor (MC4R) gene were recently explored as another susceptible locus. However, prognostic significance of these genetic variations has not been fully elucidated. Here, we investigated the involvement of FTO rs9939609 and MC4R rs17782313 polymorphisms in the development of obesity. Association with type 2 diabetes mellitus (T2DM) was also investigated. We analyzed 2806 community-dwelling middle-aged to elderly subjects (61+/-14 years). Clinical parameters were obtained from the subjects' personal health records, evaluated at their annual medical check-up. FTO genotype was significantly associated with current body mass index (BMI; TT 23.2+/-3.2, TA 23.7+/-3.2, AA 24.4+/-3.2 kg m(-2), P=2.5 x 10(-6)) and frequency of obesity (26.6, 32.0, 43.0% respectively, P=2.0 x 10(-4)). Age- and sex-adjusted odds ratio for obesity was 1.30 (P=0.004) in TA and 2.07 (P=0.002) in AA genotype. During the 9.4 years comprising the follow-up period, 214 new cases of obesity were diagnosed among 1718 subjects whose retrospective data were available. A allele frequency of the FTO genotype was significantly higher in subjects who developed obesity (22.2, 15.8%, P=0.001), Age-, sex- and initial BMI-adjusted odds ratio for the development of obesity was 1.46 (95% confidence interval, 1.04-2.04) (P=0.031). However, association studies and meta-analysis of T2DM did not actively support the involvement of FTO genotype. No significant differences were observed between the MC4R genotype and BMI (P=0.015), and the frequency of obesity (P=0.284). FTO genotype is an independent risk factor for future development of obesity.

  10. Prognostic Significance of Immunoreactive Neutrophil Elastase in Human Breast Cancer: Long-Term Follow-Up Results in 313 Patients

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    Miwa Akizuki

    2007-03-01

    Full Text Available OBJECTIVE: We have measured the concentration of immunoreactive neutrophil elastase (ir-NE in the tumor extracts of 313 primary human breast cancers. Sufficient time has elapsed, and we are now ready to analyze its prognostic value in human breast cancer. METHODS: ir-NE concentration in tumor extracts was determined with an enzyme-linked immunosorbent assay that enables a rapid measurement of both free-form ir-NE and the α1-protease inhibitor-complexed form of ir-NE. We analyzed the prognostic value of this enzyme in human breast cancer in univariate and multivariate analyses. RESULTS: Patients with breast cancer tissue containing a high concentration of ir-NE had poor survival compared to those with a low concentration of ir-NE at the cutoff point of 9.0 µg/100 mg protein (P = .0012, which had been previously determined in another group of 49 patients. Multivariate stepwise analysis selected lymph node status (P= .0004; relative risk = 1.46 and ir-NE concentration (P= .0013; relative risk = 1.43 as independent prognostic factors for recurrence. CONCLUSIONS: Tumor ir-NE concentration is an independent prognostic factor in patients with breast cancer who undergo curative surgery. This enzyme may play an active role in tumor progression that leads to metastasis in human breast cancer.

  11. Serum alpha fetoprotein surge after the initiation of chemotherapy for non-seminomatous testicular cancer has an adverse prognostic significance

    NARCIS (Netherlands)

    de Wit, R; Collette, L; Sylvester, R; de Mulder, PHM; Sleijfer, DT; Huinink, WWT; Kaye, SB; van Oosterom, AT; Boven, E; Stoter, G

    1998-01-01

    It has been recognized that the tumour markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) may show a transient elevation after the initiation of chemotherapy in non-seminomatous testicular cancer. We investigated the prognostic importance of these so-called marker surges in a

  12. Prognostic significance of the combined expression of neutral endopeptidase and dipeptidyl peptidase IV in intrahepatic cholangiocarcinoma patients after surgery resection

    Directory of Open Access Journals (Sweden)

    Zhu JY

    2014-02-01

    Full Text Available Jianyong Zhu,1,* XiaoDong Guo,2,* Baoan Qiu,1 Zhiyan Li,2 Nianxin Xia,1 Yingxiang Yang,1 Peng Liu1 1Department of Hepatobiliary Surgery, Navy General Hospital, PLA, Beijing, People's Republic of China; 2302 Hospital of PLA, Beijing, People's Republic of China *These authors contributed equally to this work Aim: The aim of this study was to investigate the relationship between the expression of neutral endopeptidase (NEP and dipeptidyl peptidase IV (DPP IV proteins, and the clinical significance of the two proteins in patients with intrahepatic cholangiocarcinomas (IHCC. Methods: Expression patterns and subcellular localizations of NEP and DPP IV proteins in 186 primary IHCC and 60 noncancerous liver tissue specimens were detected by immunohistochemistry. Results: Both the expression of NEP and DPP IV proteins in IHCC tissues were significantly higher than those in noncancerous liver tissues (both P<0.001. Of 186 patients with IHCC, 128 (68.82% highly expressed both NEP and DPP IV proteins. In addition, the coexpression of NEP and DPP IV proteins was significantly associated with advanced tumor stage (P=0.009, positive lymph node metastasis (P=0.016 and distant metastasis (P=0.013, and the presence of recurrence (P=0.027. Moreover, Kaplan–Meier analysis showed that IHCC patients with high NEP expression, high DPP IV expression, and combined overexpression of NEP and DPP IV proteins all had poorer overall survival and early recurrence after surgery. Furthermore, Cox analysis suggested that NEP expression, DPP IV expression, and combined expression of NEP and DPP IV proteins were all independent prognostic markers for overall survival and recurrence-free survival in patients with IHCC. Conclusion: Our data suggest, for the first time, that both the expression of NEP and DPP IV proteins may be upregulated in human IHCC tissues and the combined expression of NEP and DPP IV proteins may play important roles in progression and prognosis of patients

  13. Prognostic significance of metabolic tumor volume measured by {sup 18}F FDG PET/CT in operable primary breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jahae; Yoo, Su Woong; Kang, Sae Ryung; Cho, Sang Geon; Oh, Jong Ryool; Chong, Ari; Min, Jung Joon; Bom, Hee Seung; Yoon, Jung Han; Song, Ho Chun [Chonnam National Univ. Medical School and Hospital, Gwangju (Korea, Republic of)

    2012-12-15

    We investigated whether PET indices measured by {sup 18}F fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) can predict prognosis in patients with operable primary breast cancer. We reviewed 53 patients with operable primary breast cancer who underwent pretreatment FDG PET/CT. PET indices, maximum standardized uptake value (SUV) and metabolic tumor volume (MTV), were measured in the primary breast tumor (P), metastatic lymph nodes (N) and total tumor (T). The cox proportional hazards model was used with age, tumor size, clinical lymph node status, method od of surgery, presence or absence of neoadjuvant chemo therapy, histological type, histological grade, hormone grade, hormone receptors and HER2 status to predict disease free survival (DFS) and overall survival (OS). Median follow up period was 50 months (range, 17 73 months), during which 17 patients had recurrent disease and nine of whom died. The univariate analysis showed that high SUV of N (N{sup SUV,} =0.011), MTV of N (N{sup MTV,} =0.011) and MTV of T (T{sup MTV,} =0.045) as well as high histological grade (=0.008), negative estrogen ( =0.045) and negative progesterone ( =0.029) receptor status were associated with shorter DFS. High N{sup SUV(}=0.035) and N{sup MTV(} =0.035) and T{sup MTV(}=0.035)as well as high histological grade (=0.012) and negative estrogen receptor status ( =0.009)were associated with shorted OS. N{sup SUV,} N{sup MTVa}nd T{sup MTw}ere found to be significantly associated with high histological grade ( =0.005). However, those failed to be statistically significant prognostic factors on multivariate analysis PET indices seem to be useful in the preoperative evaluation of prognosis in patients with operable primary breast cancer, N{sup SUV,} N{sup MTVa}nd T{sup MTVm}ight be considerable factors associated with patient outcome in operable breast cancer.

  14. Prognostic significance of NPM1 mutations in the absence of FLT3-internal tandem duplication in older patients with acute myeloid leukemia: a SWOG and UK National Cancer Research Institute/Medical Research Council report.

    Science.gov (United States)

    Ostronoff, Fabiana; Othus, Megan; Lazenby, Michelle; Estey, Elihu; Appelbaum, Frederick R; Evans, Anna; Godwin, John; Gilkes, Amanda; Kopecky, Kenneth J; Burnett, Alan; List, Alan F; Fang, Min; Oehler, Vivian G; Petersdorf, Stephen H; Pogosova-Agadjanyan, Era L; Radich, Jerald P; Willman, Cheryl L; Meshinchi, Soheil; Stirewalt, Derek L

    2015-04-01

    Younger patients with acute myeloid leukemia (AML) harboring NPM1 mutations without FLT3-internal tandem duplications (ITDs; NPM1-positive/FLT3-ITD-negative genotype) are classified as better risk; however, it remains uncertain whether this favorable classification can be applied to older patients with AML with this genotype. Therefore, we examined the impact of age on the prognostic significance of NPM1-positive/FLT3-ITD-negative status in older patients with AML. Patients with AML age ≥ 55 years treated with intensive chemotherapy as part of Southwest Oncology Group (SWOG) and UK National Cancer Research Institute/Medical Research Council (NCRI/MRC) trials were evaluated. A comprehensive analysis first examined 156 patients treated in SWOG trials. Validation analyses then examined 1,258 patients treated in MRC/NCRI trials. Univariable and multivariable analyses were used to determine the impact of age on the prognostic significance of NPM1 mutations, FLT3-ITDs, and the NPM1-positive/FLT3-ITD-negative genotype. Patients with AML age 55 to 65 years with NPM1-positive/FLT3-ITD-negative genotype treated in SWOG trials had a significantly improved 2-year overall survival (OS) as compared with those without this genotype (70% v 32%; P 65 years with this genotype (70% v 27%; P 65 years was marginal (27% v 16%; P = .33). In multivariable analysis, NPM1-positive/FLT3-ITD-negative genotype remained independently associated with an improved OS in patients age 55 to 65 years (P = .002) but not in those age > 65 years (P = .82). These results were confirmed in validation analyses examining the NCRI/MRC patients. NPM1-positive/FLT3-ITD-negative genotype remains a relatively favorable prognostic factor for patients with AML age 55 to 65 years but not in those age > 65 years. © 2015 by American Society of Clinical Oncology.

  15. Prognostic Significance of NPM1 Mutations in the Absence of FLT3–Internal Tandem Duplication in Older Patients With Acute Myeloid Leukemia: A SWOG and UK National Cancer Research Institute/Medical Research Council Report

    Science.gov (United States)

    Ostronoff, Fabiana; Othus, Megan; Lazenby, Michelle; Estey, Elihu; Appelbaum, Frederick R.; Evans, Anna; Godwin, John; Gilkes, Amanda; Kopecky, Kenneth J.; Burnett, Alan; List, Alan F.; Fang, Min; Oehler, Vivian G.; Petersdorf, Stephen H.; Pogosova-Agadjanyan, Era L.; Radich, Jerald P.; Willman, Cheryl L.; Meshinchi, Soheil; Stirewalt, Derek L.

    2015-01-01

    Purpose Younger patients with acute myeloid leukemia (AML) harboring NPM1 mutations without FLT3–internal tandem duplications (ITDs; NPM1-positive/FLT3-ITD–negative genotype) are classified as better risk; however, it remains uncertain whether this favorable classification can be applied to older patients with AML with this genotype. Therefore, we examined the impact of age on the prognostic significance of NPM1-positive/FLT3-ITD–negative status in older patients with AML. Patients and Methods Patients with AML age ≥ 55 years treated with intensive chemotherapy as part of Southwest Oncology Gorup (SWOG) and UK National Cancer Research Institute/Medical Research Council (NCRI/MRC) trials were evaluated. A comprehensive analysis first examined 156 patients treated in SWOG trials. Validation analyses then examined 1,258 patients treated in MRC/NCRI trials. Univariable and multivariable analyses were used to determine the impact of age on the prognostic significance of NPM1 mutations, FLT3-ITDs, and the NPM1-positive/FLT3-ITD–negative genotype. Results Patients with AML age 55 to 65 years with NPM1-positive/FLT3-ITD–negative genotype treated in SWOG trials had a significantly improved 2-year overall survival (OS) as compared with those without this genotype (70% v 32%; P 65 years with this genotype (70% v 27%; P 65 years was marginal (27% v 16%; P = .33). In multivariable analysis, NPM1-positive/FLT3-ITD–negative genotype remained independently associated with an improved OS in patients age 55 to 65 years (P = .002) but not in those age > 65 years (P = .82). These results were confirmed in validation analyses examining the NCRI/MRC patients. Conclusion NPM1-positive/FLT3-ITD–negative genotype remains a relatively favorable prognostic factor for patients with AML age 55 to 65 years but not in those age > 65 years. PMID:25713434

  16. Prognostic Significance of the Lymphoblastic Leukemia-Derived Sequence 1 (LYL1 Gene Expression in Egyptian Patients with Acute Myeloid Leukemia

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    Nadia El Menshawy

    2014-06-01

    Full Text Available OBJECTIVE: Aberrant activation of transcription factor genes is the most frequent target of genetic alteration in lymphoid malignancies. The lymphoblastic leukemia-derived sequence 1 (LYL1 gene, which encodes a basic helix-loop helix, was first identified with human T-cell acute leukemia. Recent studies suggest its involvement in myeloid malignancies. We aimed to study the expression percent of oncogene LYL1 in primary and secondary high-risk myeloid leukemia and the impact on prognostic significance in those patients. METHODS: Using quantitative real-time polymerase chain reaction for detection of LYL1 oncogenes, our study was carried out on 39 myeloid leukemia patients including de novo cases, myelodysplastic syndrome (MDS with transformation, and chronic myelogenous leukemia (CML in accelerated and blast crisis, in addition to 10 healthy individuals as the reference control. RESULTS: LYL1 expression was increased at least 2 times compared to the controls. The highest expression of this transcription factor was observed in the MDS cases transformed to acute leukemia at 7.3±3.1, p=0.0011. LYL1 expression was found in 68.2%, 75%, and 77.8% of cases of acute myeloid leukemia, CML crisis, and MDS, respectively. Significant correlation of LYL1 overexpression with some subtypes of French-American-British classification was found. There was, for the first time, significant correlation between the blood count at diagnosis and LYL1 expression (p=0.023, 0.002, and 0.031 for white blood cells, hemoglobin, and platelets, respectively. The rate of complete remission was lower with very high levels of LYL1 expression and the risk of relapse increased with higher levels of LYL1 expression, suggesting an unfavorable prognosis for cases with enhanced expression. CONCLUSION: Overexpression of LYL1 is highly associated with acute myeloid leukemia and shows more expression in MDS with unfavorable prognosis in response to induction chemotherapy. These

  17. Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas

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    Mukherjee Abir L

    2006-10-01

    Full Text Available Abstract Background Fascin is an actin bundling protein with roles in the formation of cell protrusions and motility of mesenchymal and neuronal cells. Fascin is normally low or absent from epithelia, but is upregulated in several epithelial neoplasms where it may contribute to an invasive phenotype. Here, we report on the prevalence and potential clinical significance of fascin expression in relation to the progression of colorectal adenocarcinoma and to tumor cell proliferation as measured by Ki67 index. Methods Conventional tissue sections of 107 colorectal adenomas and 35 adenocarcinomas were analyzed by immunohistochemistry for fascin and Ki67 expression. Fascin expression and Ki67 proliferation index were also investigated by use of a tissue microarray containing cores from a further 158 colorectal adenocarcinomas and 15 adenomas linked to a CCF, IRB-approved database with a mean of 38 months of clinical follow-up. Survival analysis was carried out by the Kaplan-Meier and Cox regression methods. Results Fascin was not expressed by the normal colonic epithelium. In conventional sections, 16% of adenomas and 26% of adenocarcinomas showed fascin expression in greater than 10% of the tumor cells. In the clinically-annotated tumors, fascin immunoreactivity was more common in tumors located in the proximal colon (p = 0.009, but was not associated with age, gender, or TNM stage. Patients with stage III/IV adenocarcinomas (n = 62 with strong fascin immunoreactivity had a worse prognosis than patients with low or absent fascin, (3-year overall survival of 11% versus 43% for fascin-negative patients; p = 0.023. In adenomas, fascin and Ki67 tended to be inversely correlated at the cellular level; this trend was less apparent in adenocarcinomas. Conclusion Fascin is upregulated in a proportion of adenomas, where its expression is often focal. Strong and diffuse expression was seen in a subset of advanced colorectal adenocarcinomas that correlated with

  18. Unrecognized non-Q-wave myocardial infarction: prevalence and prognostic significance in patients with suspected coronary disease.

    Directory of Open Access Journals (Sweden)

    Han W Kim

    2009-04-01

    Full Text Available Unrecognized myocardial infarction (UMI is known to constitute a substantial portion of potentially lethal coronary heart disease. However, the diagnosis of UMI is based on the appearance of incidental Q-waves on 12-lead electrocardiography. Thus, the syndrome of non-Q-wave UMI has not been investigated. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR can identify MI, even when small, subendocardial, or without associated Q-waves. The aim of this study was to investigate the prevalence and prognosis associated with non-Q-wave UMI identified by DE-CMR.We conducted a prospective study of 185 patients with suspected coronary disease and without history of clinical myocardial infarction who were scheduled for invasive coronary angiography. Q-wave UMI was determined by electrocardiography (Minnesota Code. Non-Q-wave UMI was identified by DE-CMR in the absence of electrocardiographic Q-waves. Patients were followed to determine the prognostic significance of non-Q-wave UMI. The primary endpoint was all-cause mortality. The prevalence of non-Q-wave UMI was 27% (50/185, compared with 8% (15/185 for Q-wave UMI. Patients with non-Q-wave UMI were older, were more likely to have diabetes, and had higher Framingham risk than those without MI, but were similar to those with Q-wave UMI. Infarct size in non-Q-wave UMI was modest (8%+/-7% of left ventricular mass, and left ventricular ejection fraction (LVEF by cine-CMR was usually preserved (52%+/-18%. The prevalence of non-Q-wave UMI increased with the extent and severity of coronary disease on angiography (p<0.0001 for both. Over 2.2 y (interquartile range 1.8-2.7, 16 deaths occurred: 13 in non-Q-wave UMI patients (26%, one in Q-wave UMI (7%, and two in patients without MI (2%. Multivariable analysis including New York Heart Association class and LVEF demonstrated that non-Q-wave UMI was an independent predictor of all-cause mortality (hazard ratio [HR] 11.4, 95% confidence interval [CI] 2

  19. Prognostic value of clinical and Doppler echocardiographic findings in children and adolescents with significant rheumatic valvular disease

    OpenAIRE

    Fátima Derlene da Rocha Araújo; Eugênio Marcos Andrade Goulart; Zilda Maria Alves Meira

    2012-01-01

    Introduction: The diagnosis of acute rheumatic fever (RF) is based on clinical findings. However, during the chronic phase of the disease, the clinical approach is not sufficient for the follow-up of the patients and the Doppler echocardiography is a tool for the diagnosis of cardiac involvement. Prognostic variables that influence long-term outcomes are not well known. Methods: 462 patients with RF according to Jones criteria were studied, and followed-up from the initial attack to 13.6 ...

  20. An abnormal nonhyperdiploid karyotype is a significant adverse prognostic factor for multiple myeloma in the bortezomib era.

    Science.gov (United States)

    Tan, Daryl; Teoh, Gerrard; Lau, L C; Lim, Alvin; Lim, T H; Yap, K C; Premalatha, P; Lao, Z T; Wee, Nelson; Choo, Christine; Wee, H C; Su, S; Lee, Y S; Lee, L H; Hwang, William; Goh, Y T

    2010-10-01

    Multiple myeloma is clinically heterogeneous and risk stratification is vital for prognostication and informing treatment decisions. As bortezomib is able to overcome several high-risk features of myeloma, the validity of conventional risk-stratification and prognostication systems needs to be reevaluated. We study the survival data of 261 previously untreated myeloma patients managed at our institution, where bortezomib became available from 2004 for the treatment of relapse disease. Patient and disease characteristics, and survival data were evaluated overall, and with respect to bortezomib exposure. Overall, the international staging system (ISS), metaphase karyotyping and interphase fluorescence in situ hybridization (FISH) were discerning of survival outcomes, where the median for the entire cohort was 5.2 years. However, when stratified by bortezomib exposure, only metaphase karyotyping was still discriminating of long-term prognosis. The presence of an abnormal nonhyperdiploid karyotype overrides all other clinical and laboratory parameters in predicting for a worse outcome on multivariate analysis (median survival 2.6 years, P = 0.001), suggesting that bortezomib used at relapse is better able to overcome adverse risk related to high tumor burden (as measured by the ISS) than adverse cytogenetics on conventional karyotyping. Metaphase karyotyping provides additional prognostic information on tumor kinetics where the presence of a normal diploid karyotype in the absence of any high-risk FISH markers correlated with superior survival and could act as a surrogate for lower plasma cell proliferation. © 2010 Wiley-Liss, Inc.

  1. Plasminogen activator inhibitor type 1 is the most significant of the usual tissue prognostic factors in node-negative breast ductal adenocarcinoma independent of urokinase-type plasminogen activator.

    Science.gov (United States)

    Descotes, Françoise; Riche, Benjamin; Saez, Simone; De Laroche, Guy; Datchary, Jean; Roy, Pascal; André, Jean; Bobin, Jean Yves

    2008-04-01

    The aim of the present investigation was to evaluate the prognostic significance of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) tissue contents in primary breast adenocarcinoma. Patients from 3 medical centers were included between 1994 and 2001. Biologic factors in tumor extracts were all assayed in the same laboratory. PAI-1 and uPA were treated as continuous or dichotomized variables. Metastasis-free survival analyses were performed using the Cox model and the classification algorithm and regression tree (CART) in the whole population and in the subsets of node-negative (pN0) or positive (pN+) cases. Kaplan curves of metastasis-free survival were designed for different groups in relation to uPA/PAI-1 combinations. Urokinase-type plasminogen activator tumor level appears related to the anatomic degree of extension; conversely, PAI-1 tumor content is independent of tumor size and nodal extension. In univariate analysis, adjusted on usual prognostic factors, the metastasis risk increased with PAI-1 level in all patients (HR [hazard ratio], 3.1; P < .001), in pN0 (HR, 4.3; P < .001), and pN+ patients (HR, 2.3; P = .019). It increased also with uPA in all patients (HR, 2.6; P = 0.006). In multivariate analysis, when both variables were included, PAI-1 remained significant in all patients (HR, 2.4; P = .002) and pN0 patients (HR, 3.2; P = .003) but not uPA. CART analyses confirmed that the best partitioning factor was PAI-1. There was no evidence for any additional impact of uPA. PAI-1 is an independent prognostic factor in particular in pN0 breast ductal carcinoma.

  2. Prognostic significance of tympanosclerotic plaques localization and their morphological and histological characteristics for the outcome of surgical treatment

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    Milojević Milanko

    2012-01-01

    Full Text Available Background/Aim. Tympanosclerosis is a sequela of inflammation of the middle ear usually causing conductive hearing loss. The aim of the study was to determine the significance of tympanosclerotic plaques localization in the middle ear and their morphological and histological characteristics for surgical treatment outcome. Methods. This retrospective study included a total of 73 patients operated on for tympanosclerosis in the Clinic for Otorhinolaryngology, Military Medical Academy (MMA in a period 1996-2010. The results of surgical treatment as well as the last audiometry findings were analyzed. considering follow-up periods of 6 months to 8 years. The patients were divided into 4 groups according to tympanosclerotic plaques localization in the middle ear and the classification suggested by Wieling and Kerr. The patients were also divided based on intraoperatively noticed morphological characteristics of tympanosclerotic plaques, while the third division was done as per histological findings. Surgical success was assessed using the suggestions of the Japan Otological Society. Results. The analyzed results showed the surgical success especially in the group II according to Wieling and Kerr, while histological findings had no impact on the outcome of the surgery. Conclusion. Surgical treatment has good results especially in patients with the mobile stapes. Results are satisfactory in other localizations, while various morphological and histological characteristics do not have impact on the surgery outcome.

  3. Prognostic significance of ankle-brachial index, brachial-ankle pulse wave velocity, flow-mediated dilation, and nitroglycerin-mediated dilation in end-stage renal disease.

    Science.gov (United States)

    Morimoto, Satoshi; Yurugi, Takatomi; Aota, Yasuko; Sakuma, Takao; Jo, Fusakazu; Nishikawa, Mitsushige; Iwasaka, Toshiji; Maki, Kei

    2009-01-01

    Identifying patients at high risk of cardiovascular disease is important in managing patients undergoing hemodialysis. We evaluated a series of prognostic values: flow-mediated dilation (FMD) and nitrogen-mediated dilation (NMD), an index of endothelium-dependent and endothelium-independent function, respectively, ankle-brachial index (ABI), and brachial-ankle pulse wave velocity (baPWV) in patients undergoing chronic hemodialysis. A cohort of 199 patients was studied. At entry, these values were examined and the prognostic significances were investigated. In estimating the significance of baPWV, patients with ABI hemodialysis patients by means of ABI and baPWV but not FMD or NMD provides complementary information in identifying a high-risk population in these patients.

  4. Prognostic significance of multiple-detector computed tomography in conjunction with TIMI risk score for patients with non-ST elevation acute coronary syndrome.

    Science.gov (United States)

    Noda, Mayumi; Takagi, Atsushi; Kuwatsuru, Ryohei; Mitsuhashi, Norio; Kasanuki, Hiroshi

    2008-05-01

    Risk stratification among patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) has been made by clinical scoring. Recently, multiple-detector computed tomography (MDCT) appeared to provide noninvasive coronary angiography (CAG). To clarify the prognostic significance of MDCT, we aimed to evaluate the clinical utility of MDCT in the early management and in predicting the long-term prognosis of NSTE-ACS with low to intermediate risk. Among 84 consecutive patients with NSTEACS, risk stratification using a TIMI risk score was done. A total of 48 patients were categorized as low to intermediate risk. Multiple-detector CT was performed in 30 patients using 16-slice MDCT. MDCT detected coronary stenoses in 18 patients. Compared to invasive CAG, MDCT successfully depicted the coronary stenosis (P TIMI risk score appeared to demonstrate prognostic significance in patients with NSTE-ACS.

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

    Science.gov (United States)

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

    2014-07-01

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

  6. Prognostic significance of complex karyotype and monosomal karyotype in adult patients with acute lymphoblastic leukemia treated with risk-adapted protocols.

    Science.gov (United States)

    Motlló, Cristina; Ribera, Josep-María; Morgades, Mireia; Granada, Isabel; Montesinos, Pau; González-Campos, José; Fernández-Abellán, Pascual; Tormo, Mar; Bethencourt, Concepción; Brunet, Salut; Hernández-Rivas, Jesús-María; Moreno, María-José; Sarrà, Josep; Del Potro, Eloy; Barba, Pere; Bernal, Teresa; Grande, Carlos; Grau, Javier; Cervera, José; Feliu, Evarist

    2014-12-15

    The karyotype is a predictor of outcomes in adults with acute lymphoblastic leukemia (ALL). The unfavorable prognostic significance of complex karyotype (CK) has been reported, whereas the prognostic relevance of monosomal karyotype (MK) has not been consistently evaluated. We aimed to assess the prognostic value of CK and MK in adults with ALL treated with risk-adapted protocols of the Spanish PETHEMA Group. The karyotypes of 881 adult ALL patients treated according to the protocols of the PETHEMA Group between 1993 and 2012 were centrally reviewed. CK and MK were assessed according to Moorman's criteria, and Breem's criteria, respectively. Specific analyses according to the risk groups and to the presence of t(9:22) were performed. Of 364 evaluable patients 33 (9.2%) had CK, and 68 of 535 evaluable patients (12.8%) had MK. Complete remission rate, remission duration, and overall survival were not significantly different according to the presence of CK or MK in the whole series, according to the B or T lineage, in the high-risk group, or in patients with t(9;22), regardless of imatinib treatment, and in patients who received chemotherapy alone or chemotherapy followed by stem cell transplantation Our study shows that CK and MK were not associated with a worse prognosis in adult patients with ALL treated with risk-adapted or subtype-oriented protocols. In patients with Ph+ ALL, MK did not have an impact on prognosis irrespective of imatinib treatment. © 2014 American Cancer Society.

  7. International germ cell consensus classification : A prognostic factor-erased staging system for metastatic germ cell cancers

    NARCIS (Netherlands)

    Mead, GM; Stenning, SP; Cook, P; Fossa, SD; Horwich, A; Kaye, SB; Oliver, RTD; deMulder, PHM; deWit, R; Stoter, G; Sylvester, RJ; Bajorin, DF; Bosl, GJ; Mazumdar, M; Nichols, CR; Amato, R; Pizzocaro, G; Droz, JP; Kramar, A; Daugaard, G; CortesFunes, H; PazAres, L; Levi, JA; Colls, BM; Harvey, VJ; Coppin, C

    Purpose: Cisplatin-containing chemotherapy has dramatically improved the outlook for patients with metastatic germ cell tumors (GCT), and overall cure rates now exceed 80%. To make appropriate risk-based decisions about therapy and to facilitate collaborative trials, a simple prognostic factor-based

  8. Intensity and Pattern of Enhancement on CESM: Prognostic Significance and its Relation to Expression of Podoplanin in Tumor Stroma - A Preliminary Report.

    Science.gov (United States)

    Luczynska, Elzbieta; Niemiec, Joanna; Heinze, Sylwia; Adamczyk, Agnieszka; Ambicka, Aleksandra; Marcyniuk, Paulina; Rudnicki, Wojciech; Mitus, Jerzy W; Dyczek, Sonia; Rys, Janusz; Sas-Korczynska, Beata

    2018-02-01

    It is possible that the degree of enhancement on contrast-enhanced spectral mammography (CESM), a new diagnostic method, might provide prognostic information for breast cancer patients. Therefore, in a group of 82 breast cancer patients, we analyzed the prognostic significance of degree and pattern of enhancement on CESM as well as its relation to: (a) breast cancer immunophenotype (based on ER/PR/HER2 status) (b) podoplanin expression in cancer stroma (lymphatic vessel density plus podoplanin-positivity of cancer-associated fibroblasts), and (c) other histological parameters. For each tumor the intensity of enhancement on CESM was qualitatively assessed as strong or weak/medium, while the pattern - as homogenous and heterogenous. Herein we report, for the first time, that strong and heterogenous enhancement on CESM was related to unfavorable disease-free survival of breast cancer patients (p=0.005). Moreover, the strong enhancement was more frequent in large and node-positive tumors (pT>1, pN>0) (p=0.002), as well as in carcinomas with podoplanin-sparse stroma (p=0.008). Intensity and pattern of enhancement on CESM might provide (together with the results of other diagnostic imaging methods) not only the confirmation of presence or absence of tumor, but also prognostic information. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Lack of prognostic significance of BCL2 and p53 protein overexpression in elderly patients with diffuse large B-cell non-Hodgkin's lymphoma : Results from a population-based non-Hodgkin's lymphoma registry

    NARCIS (Netherlands)

    Maartense, E.; Kramer, M.H.H.; Le Cessie, S.; Kluin-Nelemans, J. C.; Kluin, P.M.; Snijder, S.; Noordijk, E.M.

    The prognostic significance of age was studied in 372 patients with diffuse large B-cell non-Hodgkin's lymphoma, in relation to the prognostic factors of overexpressed BCL2 and p53 oncoprotein. Overexpression of BCL2 and p53 oncoprotein was defined when more than 50% of the tumor cells showed

  10. Prognostic Significance of Diffuse Large B-Cell Lymphoma Cell of Origin Determined by Digital Gene Expression in Formalin-Fixed Paraffin-Embedded Tissue Biopsies

    Science.gov (United States)

    Scott, David W.; Mottok, Anja; Ennishi, Daisuke; Wright, George W.; Farinha, Pedro; Ben-Neriah, Susana; Kridel, Robert; Barry, Garrett S.; Hother, Christoffer; Abrisqueta, Pau; Boyle, Merrill; Meissner, Barbara; Telenius, Adele; Savage, Kerry J.; Sehn, Laurie H.; Slack, Graham W.; Steidl, Christian; Staudt, Louis M.; Connors, Joseph M.; Rimsza, Lisa M.; Gascoyne, Randy D.

    2015-01-01

    Purpose To evaluate the prognostic impact of cell-of-origin (COO) subgroups, assigned using the recently described gene expression–based Lymph2Cx assay in comparison with International Prognostic Index (IPI) score and MYC/BCL2 coexpression status (dual expressers). Patients and Methods Reproducibility of COO assignment using the Lymph2Cx assay was tested employing repeated sampling within tumor biopsies and changes in reagent lots. The assay was then applied to pretreatment formalin-fixed paraffin-embedded tissue (FFPET) biopsies from 344 patients with de novo diffuse large B-cell lymphoma (DLBCL) uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the British Columbia Cancer Agency. MYC and BCL2 protein expression was assessed using immunohistochemistry on tissue microarrays. Results The Lymph2Cx assay provided concordant COO calls in 96% of 49 repeatedly sampled tumor biopsies and in 100% of 83 FFPET biopsies tested across reagent lots. Critically, no frank misclassification (activated B-cell–like DLBCL to germinal center B-cell–like DLBCL or vice versa) was observed. Patients with activated B-cell–like DLBCL had significantly inferior outcomes compared with patients with germinal center B-cell–like DLBCL (log-rank P survival, disease-specific survival, and overall survival). In pairwise multivariable analyses, COO was associated with outcomes independent of IPI score and MYC/BCL2 immunohistochemistry. The prognostic significance of COO was particularly evident in patients with intermediate IPI scores and the non–MYC-positive/BCL2-positive subgroup (log-rank P < .001 for time to progression). Conclusion Assignment of DLBCL COO by the Lymph2Cx assay using FFPET biopsies identifies patient groups with significantly different outcomes after R-CHOP, independent of IPI score and MYC/BCL2 dual expression. PMID:26240231

  11. Classification

    Science.gov (United States)

    Clary, Renee; Wandersee, James

    2013-01-01

    In this article, Renee Clary and James Wandersee describe the beginnings of "Classification," which lies at the very heart of science and depends upon pattern recognition. Clary and Wandersee approach patterns by first telling the story of the "Linnaean classification system," introduced by Carl Linnacus (1707-1778), who is…

  12. Prognostic significance of peripheral monocytic myeloid-derived suppressor cells and monocytes in patients newly diagnosed with diffuse large b-cell lymphoma

    OpenAIRE

    Wu, Chongyang; Wu, Xiangyang; Zhang, Xiaoni; Chai, Ye; Guo, Qi; Li, Lijuan; Yue, Lingling; Bai, Jun; Wang, Zhiping; Zhang, Liansheng

    2015-01-01

    Objective: The revised International Prognostic Index (R-IPI) aids in predicting the prognosis of patients with diffuse large B cell lymphoma (DLBCL), but R-IPI yields no significant differences in assessing different subtypes of DLBCL. It is necessary to identify patients with a high-risk of DLBCL and alternative therapy should be delivered as early as possible. Methods: In total, 144 patients newly diagnosed with DLBCL including 63 GCB-DLBCL and 81 non-GCB-DLBCL and 30 healthy controls were...

  13. Prevalence of myocardial fibrosis patterns in patients with systolic dysfunction: prognostic significance for the prediction of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy.

    Science.gov (United States)

    Almehmadi, Fahad; Joncas, Sebastien Xavier; Nevis, Immaculate; Zahrani, Mohammad; Bokhari, Mahmoud; Stirrat, John; Fine, Nowell M; Yee, Raymond; White, James A

    2014-07-01

    Late gadolinium enhancement-cardiac magnetic resonance is increasingly performed in patients with systolic dysfunction. Numerous patterns of fibrosis are commonly reported among this population. However, the relative prevalence and prognostic significance of these findings remains uncertain. Three hundred eighteen consecutive patients referred for late gadolinium enhancement-cardiac magnetic resonance and a left ventricular ejection fraction 35% (40% versus 6%; P=0.005). Patients with systolic dysfunction frequently demonstrate multiple patterns of myocardial fibrosis. Of these, a midwall striae pattern of fibrosis is the strongest independent predictor of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy. © 2014 American Heart Association, Inc.

  14. Multiplex Approach in Classification, Diagnosis, and Prognostication in Acute Myeloid Leukemia: An Experience from Tertiary Cancer Center in South India.

    Science.gov (United States)

    Khera, Rachna; Ahmed, Faiq; Mundada, Manasi Chetan; Devi, Sandhya G; Murthy, Sudha S; Lavanya, Nambaru; Rajappa, Senthil J; Mallavarapu, Krishna Mohan; Santa, A

    2017-01-01

    Acute myeloid leukemia (AML) is a heterogeneous group of disorders classified as per FAB subtypes and more recently by WHO by underlying genetic abnormalities. This study aims to analyze the morphology, immunophenotype, cytogenetic and molecular abnormalities in around 200 patients of AML diagnosed over a period of 7 years at our institute and to determine relative frequency of various subtypes (based on FAB and WHO classification). An attempt to characterize the associations between hematological parameters, immunophenotype and these subtypes was also made. All cases diagnosed as AML on morphology, cytochemistry and/or immunophenotyping and tested for recurrent genetic abnormalities during period of Jan 2008-July 2014 were included in the study. Age of presentation was younger in our AML patients as compared to western literature. Amongst FAB and WHO subtypes, M2 and t (15;17) PML-RARA were the most common groups respectively. As expected, CD33, CD13, were the most commonly expressed markers followed by HLA-DR, CD117, CD34 and CD14. Aberrant expression was seen in 62(41.6%) cases, most common was CD7 (15.4%), followed by CD56 (14.8%), CD19 (6.7%) and CD2 (4.7%). Significant associations between immunophenotypic markers and FAB subtypes as well as WHO subtypes were established. This is a hospital based study, giving a detailed account of frequencies of AML subtypes, hematological parameters and immunophenotypic markers in AML patients at our institute. Being a large and one of its kind study to establish significant associations between various haematological and immunophenotypic parameters with respective AML subtypes and genetic abnormalities, it might prove to be very useful in Indian setup where facilities for cytogenetic analysis are not available in many laboratories.

  15. Significance of FAB subclassification of “acute myeloid leukemia, NOS” in the 2008 WHO classification: analysis of 5848 newly diagnosed patients

    Science.gov (United States)

    Othus, Megan; Burnett, Alan K.; Löwenberg, Bob; Kantarjian, Hagop M.; Ossenkoppele, Gert J.; Hills, Robert K.; van Montfort, Kees G. M.; Ravandi, Farhad; Evans, Anna; Pierce, Sherry R.; Appelbaum, Frederick R.; Estey, Elihu H.

    2013-01-01

    The World Health Organization (WHO) classifies acute myeloid leukemia (AML) via genetic, immunophenotypic, biological, and clinical features. Still, “AML, not otherwise specified (NOS)” is further subdivided based on morphologic criteria similar to those of the French-American-British (FAB) classification. We analyzed the relevance of this practice in patients with newly diagnosed “AML, NOS” with available FAB information undergoing curative-intent therapy in trials of 3 cooperative study groups (Dutch-Belgian Cooperative Trial Group for Hematology/Oncology [HOVON], UK Medical Research Council/National Cancer Research Institute [MRC/NCRI], and the US cooperative group Southwest Oncology Group [SWOG]) or at MD Anderson Cancer Center. Ignoring information on NPM1 and CEBPA, 5848 patients met criteria for “AML, NOS.” After multivariate adjustment, FAB M0 was independently associated with significantly lower likelihood of achieving complete remission and inferior relapse-free and overall survival as compared with FAB M1, M2, M4, M5, and M6, with inconclusive data regarding M7. However, restricting attention to known NPM1neg patients, FAB M0 was no longer associated with worse outcomes; restricting attention to patients known to be NPM1neg/CEPBAneg (ie, honoring the provisional entities of “AML with mutated NPM1” and “AML with mutated CEBPA”) did not affect this result. In conclusion, in the 2008 WHO classification scheme, FAB subclassification does not provide prognostic information for “AML, NOS” cases if data on NPM1 and CEBPA mutations are available. PMID:23325837

  16. Diagnostic and prognostic significance of transient ischemic dilation (TID) in myocardial perfusion imaging: A systematic review and meta-analysis.

    Science.gov (United States)

    Alama, Mohamed; Labos, Christopher; Emery, Handel; Iwanochko, Robert M; Freeman, Michael; Husain, Mansoor; Lee, Douglas S

    2017-09-25

    Transient ischemic dilatation (TID) of the left ventricle is a potential marker of high risk obstructive coronary artery disease on stress myocardial perfusion imaging (MPI). There is, however, interstudy variation in the diagnostic performance of TID for identification of severe and extensive coronary disease anatomy, and varied prognostic implications in the published literature. We searched MEDLINE, EMBASE, and COCHRANE databases for studies where TID was compared with invasive or CT coronary angiography for evaluation of coronary artery stenosis. Two reviewers independently evaluated and abstracted data from each study. A bivariate random effects model was used to derive pooled sensitivities and specificities, in order to account for correlation between TID in MPI and anatomic disease severity. A total of 525 articles were reviewed, of which 51 met inclusion criteria. Thirty-one studies contributed to the analysis, representing a total of 2037 patients in the diagnostic meta-analysis and 9003 patients in the review of prognosis. The ratio above which TID was deemed present ranged from 1.13 to 1.38. Pooled sensitivity was 44% (95% CI 30%-60%) and specificity was 88% (95% CI 83%-92%) for the detection of extensive or severe anatomic coronary artery disease. Analysis of outcome data demonstrated increased cardiac event rates in patients with TID and an abnormal MPI. In otherwise normal perfusion, TID is an indicator of poor prognosis in patients with diabetes and/or a history of coronary disease. Among patients undergoing MPI, the presence of TID is specific for the detection of extensive or severe coronary artery disease.

  17. A pilot study of the prognostic significance of metabolic tumor size measurements in PET/CT imaging of lymphomas

    Science.gov (United States)

    Kallergi, Maria; Botsivali, Maria; Politis, Nikolaos; Menychtas, Dimitrios; Georgakopoulos, Alexandros; Chatziioannou, Sofia

    2015-03-01

    This study explores changes in metabolic tumor volume, metabolic tumor diameter, and maximum standardized uptake value (SUVmax), for earlier and more accurate identification of lymphomas' response to treatment using 18F- FDG PET/CT. Pre- and post-treatment PET/CT studies of 20 patients with Hodgkin disease (HL) and 7 patients with non- Hodgkin lymphoma (NHL) were retrospectively selected for this study. The diameter and volume of the metabolic tumor was determined by an in-house developed adaptive local thresholding technique based on a 50% threshold of the maximum pixel value within a region. Statistical analysis aimed at exploring associations between metabolic size measurements and SUVmax and the ability of the three biomarkers to predict the patients' response to treatment as defined by the four classes in the European Organization for Research and Treatment of Cancer (EORTC) guidelines. Results indicated moderate correlations between % change in metabolic tumor volume and % change in metabolic tumor maximum diameter (R=0.51) and between % change in maximum diameter and % change in SUVmax (R=0.52). The correlation between % change in tumor volume and % change in SUVmax was weak (R=0.24). The % change in metabolic tumor size, either volume or diameter, was a "very strong" predictor of response to treatment (R=0.89), stronger than SUVmax (R=0.63). In conclusion, metabolic tumor volume could have important prognostic value, possibly higher than maximum metabolic diameter or SUVmax that are currently the standard of practice. Volume measurements, however, should be based on robust and standardized segmentation methodologies to avoid variability. In addition, SUV-peak or lean body mass corrected SUV-peak may be a better PET biomarker than SUVmax when SUV-volume combinations are considered.

  18. [Prognostic significance of leukocyte count in the venous blood in the acute stage of cerebral aneurism rupture].

    Science.gov (United States)

    Kalinkin, A A; Petrikov, S S; Khamidova, L T; Krylov, V V

    To determine a prognostic role of leukocyte count in the venous blood in the acute stage of cerebral aneurysm (CA) rupture. Fifty-one patients with CA rupture, aged from 20 to 65 years, hospitalized in the first 72 h over the period from 01.10.12 to 01.02.16 were examined. The severity of disease and anatomical form of hemorrhage was corresponded to III-IV degree on the W. Hunt - R. Hess scale and Fisher scale. All patients underwent surgery. Outcomes after open and endovascular surgeries were similar. Normal leukocyte number in the venous blood at admission was identified in 12 (24%) of patients (on average 7.3±1.4·109/L), leukocytosis in 39 (76%) (14.3±3.1·109/L) (pLeukocyte number in the acute stage of CA rupture was correlated with the frequency and severity of the vessel spasm. In 28 (55%) of patients with ischemic lesions of the brain matter, mean leukocyte number in the first 72 h after hemorrhage was higher by 2-24% (3±4.8·109/L) compared to patients without ischemia (11.9±2.5·109/L) (p=0.06). The level of leukocytes in survivors was lower by 3 - 28% (122±3.4·109/L) compared to patients with fatal outcome and patients with severe neurological deficit after the surgery (14.5±3.9·109/L) (p>0.05). The increase in leukocyte number in the venous blood in the first 72 h after CA rupture ≥10,1·109/L is a reliable risk factor of marked vessel spasm. The level of leukocytes in patients with cerebral ischemia and poor prognosis in the first 72h after aneurysmal hemorrhage was higher by 2-28% compared to survivors without neurological impairment or mild neurological deficit.

  19. Prognostic and diagnostic significance of copeptin in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from the ACE 2 study.

    Science.gov (United States)

    Winther, Jacob A; Brynildsen, Jon; Høiseth, Arne Didrik; Strand, Heidi; Følling, Ivar; Christensen, Geir; Nygård, Ståle; Røsjø, Helge; Omland, Torbjørn

    2017-11-03

    Copeptin is a novel biomarker that predicts mortality in lower respiratory tract infections and heart failure (HF), but the diagnostic value of copeptin in acute dyspnea and the prognostic significance of copeptin in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is not clear. We determined copeptin and NT-proBNP concentrations at hospital admission in 314 patients with acute dyspnea who were categorized by diagnosis. Survival was registered after a median follow-up of 816 days, and the prognostic and diagnostic properties of copeptin and NT-proBNP were analyzed in acute HF (n = 143) and AECOPD (n = 84) separately. The median concentration of copeptin at admission was lower in AECOPD compared to acute HF (8.8 [5.2-19.7] vs. 22.2 [10.2-47.9]) pmol/L, p copeptin (ROC-AUC 0.85 [0.81-0.89] vs. 0.71 [0.66-0.77], p copeptin concentrations predicted mortality in AECOPD (HR per log (ln) unit 1.72 [95% CI 1.21-2.45], p = 0.003) and acute HF (1.61 [1.25-2.09], p copeptin reclassified a significant proportion of patients into a more accurate risk strata in AECOPD (NRI 0.60 [0.19-1.02], p = 0.004) and acute HF (0.39 [0.06-0.71], p = 0.020). Copeptin is a strong prognostic marker in both AECOPD and acute HF, while NT-proBNP concentrations predict mortality only in patients with acute HF. NT-proBNP levels are superior to copeptin levels to diagnose acute HF in patients with acute dyspnea.

  20. Clinical Significance and Prognostic Value of CA72-4 Compared with CEA and CA19-9 in Patients with Gastric Cancer

    Directory of Open Access Journals (Sweden)

    M. Ychou

    2000-01-01

    Full Text Available Carcinoembryonic antigen (CEA and CA 19-9 are both widely used in the follow up of patients with gastrointestinal cancer. More recently another tumor marker, named CA 72-4 has been identified and characterized using two different monoclonal antibodies B72.3 and CC49. Several reports evaluated CA 72-4 as a serum tumor marker for gastric cancer and compared its clinical utility with that of CEA or CA 19-9; few reports concerned its prognostic value. In the present study, CA 72-4 is evaluated and compared with CEA and CA 19-9 in various populations of patients with gastric cancer and benign disease; for 52 patients with gastric adenocarcinoma and 57 patients without neoplastic disease CEA, CA 19-9 and CA 72-4 were evaluated before treatment. Sensitivity of the tumor markers CA 72-4, CA 19-9 and CEA at the recommended cut-off level in all 52 patients were 58%, 50% the sensitivity increased to 75%. of these markers, for non metastatic patients, multivariate analyses indicated that none of the markers were significant, when adjusted for gender and age (which were indicators of poor prognosis; patients with abnormal values of CA72-4 tended to have shorter survival than patients with normal values (p < 0.07. In the metastatic population, only high values of CA19-9 (p < 0.02 and gender (women (p < 0.03 were indicators of poor prognosis in univariate analysis; multivariate analysis revealed that both CA72-4 (p = 0.034 and CA19-9 p = 0.009, adjusted for gender were independent prognostic factors. However, CA72-4 lost significance (p = 0.41 when adjusted for CA19-9 and gender, indicating that CA19-9 provides more prognostic information than CA72-4.

  1. Prognostic Performance and Reproducibility of the 1973 and 2004/2016 World Health Organization Grading Classification Systems in Non-muscle-invasive Bladder Cancer: A European Association of Urology Non-muscle Invasive Bladder Cancer Guidelines Panel Systematic Review.

    Science.gov (United States)

    Soukup, Viktor; Čapoun, Otakar; Cohen, Daniel; Hernández, Virginia; Babjuk, Marek; Burger, Max; Compérat, Eva; Gontero, Paolo; Lam, Thomas; MacLennan, Steven; Mostafid, A Hugh; Palou, Joan; van Rhijn, Bas W G; Rouprêt, Morgan; Shariat, Shahrokh F; Sylvester, Richard; Yuan, Yuhong; Zigeuner, Richard

    2017-11-01

    Tumour grade is an important prognostic indicator in non-muscle-invasive bladder cancer (NMIBC). Histopathological classifications are limited by interobserver variability (reproducibility), which may have prognostic implications. European Association of Urology NMIBC guidelines suggest concurrent use of both 1973 and 2004/2016 World Health Organization (WHO) classifications. To compare the prognostic performance and reproducibility of the 1973 and 2004/2016 WHO grading systems for NMIBC. A systematic literature search was undertaken incorporating Medline, Embase, and the Cochrane Library. Studies were critically appraised for risk of bias (QUIPS). For prognosis, the primary outcome was progression to muscle-invasive or metastatic disease. Secondary outcomes were disease recurrence, and overall and cancer-specific survival. For reproducibility, the primary outcome was interobserver variability between pathologists. Secondary outcome was intraobserver variability (repeatability) by the same pathologist. Of 3593 articles identified, 20 were included in the prognostic review; three were eligible for the reproducibility review. Increasing tumour grade in both classifications was associated with higher disease progression and recurrence rates. Progression rates in grade 1 patients were similar to those in low-grade patients; progression rates in grade 3 patients were higher than those in high-grade patients. Survival data were limited. Reproducibility of the 2004/2016 system was marginally better than that of the 1973 system. Two studies on repeatability showed conflicting results. Most studies had a moderate to high risk of bias. Current grading classifications in NMIBC are suboptimal. The 1973 system identifies more aggressive tumours. Intra- and interobserver variability was slightly less in the 2004/2016 classification. We could not confirm that the 2004/2016 classification outperforms the 1973 classification in prediction of recurrence and progression. This article

  2. Prognostic and predictive significance of thymidylate synthase protein expression in non-small cell lung cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Liu, Qingyun; Yu, Zubin; Xiang, Ying; Wu, Na; Wu, Long; Xu, Bin; Wang, Liang; Yang, Ping; Li, Yafei; Bai, Li

    2015-01-01

    It remains controversial whether thymidylate synthase (TS) protein expression is associated with survival for patients with non-small cell lung cancer (NSCLC). To evaluate prognostic and predictive significance of tumor TS protein level in NSCLC. Electronic searches were performed for relevant studies in PubMed, EMBASE, Web of Science, and Chinese Biomedical Literature Database. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled for meta-analysis. Subgroup and sensitivity analyses were performed. Publication bias was evaluated by funnel plot and Begg's test. Twenty-four studies, including 2280 patients, were eligible. This analysis showed that patients with low TS expression had statistically significantly longer OS and PFS than those with high TS (HR=0.51 and HR=0.49, respectively). Based on TS-targeted drug use status, TS expression was significantly associated with OS in pemetrexed (HR=0.42) and 5-Fluorouracil subgroups (HR=0.34), but not in no TS-targeted drug subgroup. There were similar results for PFS analyses. Sensitivity analysis indicated that the results were robust. Begg's test did not reveal any publication bias. Low TS protein expression is a favorable predictive factor for better OS/PFS in NSCLC patients treated with TS-targeted drugs. Prognostic value of TS protein expression needs further validation.

  3. Prognostic significance of pretherapeutic and therapeutic factors in patients with advanced cancer of the uterine cervix treated with radical radiotherapy alone

    Energy Technology Data Exchange (ETDEWEB)

    Karolewski, K.; Korzeniowski, S.; Urbanski, K.; Kojs, Z. [Centre of Oncology, Maia Sklodowska-Curie Memorial Inst., Krakow (Poland); Sokolowski, A. [Dept. of Statistics, Cracow Univ. of Economics (Poland)

    1999-11-01

    The prognostic importance of various pretherapeutic and therapeutic factors was analysed in a group of 413 cervical cancer patients with stage IIB (183 pts) and IIIB (230 pts) treated with radical radiotherapy, which consisted of external irradiation and intracavitary brachytherapy. Univariate analysis of pretherapeutic factors revealed the prognostic significance of patient age, history of abortion, stage, haemoglobin and hematocrit levels. Five-year overall survival rate in stage IIB patients was 51% in stage IIIB 40% and the respective rates for local control at each stage were 61%, and 46%. Univariate analysis of therapeutic factors showed that survival and local control rates increased with the dose, but a significant difference was found only in the case of a paracentral (point A) dose. In a multivariate analysis only patient age, abortions, and clinical stage appeared to have a significant and independent impact on survival. Linear regression analysis results indicated that prolongation of treatment time between 33 and 108 days caused a loss of local control of 0.36% per day. (orig.)

  4. Prognostic significance of repeat biopsy in lupus nephritis: Histopathologic worsening and a short time between biopsies is associated with significantly increased risk for end stage renal disease and death.

    Science.gov (United States)

    Arriens, Cristina; Chen, Sixia; Karp, David R; Saxena, Ramesh; Sambandam, Kamalanathan; Chakravarty, Eliza; James, Judith A; Merrill, Joan T

    2017-12-01

    histopathology had died compared to 2 (3.2%) of non-worsening patients. Biopsy worsening was associated with a significantly greater 15-year risk of ESRD (Hazard Ratio 4.2, p=0.0001) and death (Hazard Ratio 4.3, p=0.022), adjusting for age, gender, race, biopsy class, and treatment. Time between first and second biopsies was 5years in 28. Over a 15-year period, those with biopsies (presumably enriched for patients with early clinical signs of progression) had a significantly greater risk of ESRD (Hazard Ratio 13.7, pbiopsy class, and treatment. A repeat renal biopsy demonstrating worsening pathology increases the risk of ESRD and death more than four-fold compared to non-worsening patients. Given known potential mismatch between biopsy and clinical data, repeat biopsies may add important information and justify changes in treatment not considered on clinical grounds. Earlier detection of poor prognostic signs in those without early clinical deterioration might improve outcomes in enough patients to reconsider cost effectiveness of routine repeat biopsy. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Classification

    DEFF Research Database (Denmark)

    Hjørland, Birger

    2017-01-01

    This article presents and discusses definitions of the term “classification” and the related concepts “Concept/conceptualization,”“categorization,” “ordering,” “taxonomy” and “typology.” It further presents and discusses theories of classification including the influences of Aristotle...... and Wittgenstein. It presents different views on forming classes, including logical division, numerical taxonomy, historical classification, hermeneutical and pragmatic/critical views. Finally, issues related to artificial versus natural classification and taxonomic monism versus taxonomic pluralism are briefly...

  6. Prognostic significance of genetic polymorphisms in disease progression and survival in prostate cancer after androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Tsung-Yi Huang

    2015-06-01

    Full Text Available It is believed that androgens and their receptors regulate normal prostate growth and mediate prostate cancer development. Androgen deprivation therapy is the most commonly used treatment for advanced prostate cancer. Although the therapy is initially effective, progression of the disease to castration-resistant prostate cancer is almost inevitable, leading to treatment failure. Despite the existence of current clinical parameters, new biomarkers are urgently needed to improve the prognosis. Some molecules and DNA-based genetic biomarkers are under investigation as potential prognostic factors. The advancement in molecular cytogenetic research, such as genome-wide association for single-nucleotide polymorphisms, has made possible the detection of genetic mutations. In this study, a literature search from August 1985 to April 2013 was performed through the PubMed database using the keywords “genetic polymorphisms”, “prostate cancer” and “androgen deprivation therapy”. The results revealed that several genome-wide association studies (such as rs16901979, rs7931342, HSD17B4, rs6162 in the CYP17A1, rs4243229 and rs7201637 in the HSD17B2, rs1062577 in the ESR1, SLCO1B3, SLCO2B1, rs2939244 in the ARRDC3, rs9508016 in the FLT1, rs6504145 in the SKAP1, rs7830611 in the FBXO32, rs9508016 in the FLT1, rs12529 in the AKR1C3, rs16934641 in the BNC2, rs3763763 in the TACC2, rs2051778 in the ALPK1, and rs3763763 in the TACC2, AR, ESR1, and ESR2 and single-nucleotide polymorphisms in important pathways (such as androgen signal, biosynthesis, metabolism, androgen receptor binding site, response element, androgen receptor CAG repeat polymorphism length, and estrogen receptor-binding sites involved in prostate cancer occurrence and mechanism could serve as candidate biomarkers for the early detection of castration-resistant prostate cancer after androgen deprivation therapy. Additional investigations are required to decipher precisely the gene

  7. Prognostic significance and gene expression profiles of p53 mutations in microsatellite-stable stage III colorectal adenocarcinomas.

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    Venkat R Katkoori

    Full Text Available Although the prognostic value of p53 abnormalities in Stage III microsatellite stable (MSS colorectal cancers (CRCs is known, the gene expression profiles specific to the p53 status in the MSS background are not known. Therefore, the current investigation has focused on identification and validation of the gene expression profiles associated with p53 mutant phenotypes in MSS Stage III CRCs. Genomic DNA extracted from 135 formalin-fixed paraffin-embedded tissues, was analyzed for microsatellite instability (MSI and p53 mutations. Further, mRNA samples extracted from five p53-mutant and five p53-wild-type MSS-CRC snap-frozen tissues were profiled for differential gene expression by Affymetrix Human Genome U133 Plus 2.0 arrays. Differentially expressed genes were further validated by the high-throughput quantitative nuclease protection assay (qNPA, and confirmed by quantitative real-time polymerase chain reaction (qRT-PCR and by immunohistochemistry (IHC. Survival rates were estimated by Kaplan-Meier and Cox regression analyses. A higher incidence of p53 mutations was found in MSS (58% than in MSI (30% phenotypes. Both univariate (log-rank, P = 0.025 and multivariate (hazard ratio, 2.52; 95% confidence interval, 1.25-5.08 analyses have demonstrated that patients with MSS-p53 mutant phenotypes had poor CRC-specific survival when compared to MSS-p53 wild-type phenotypes. Gene expression analyses identified 84 differentially expressed genes. Of 49 down-regulated genes, LPAR6, PDLIM3, and PLAT, and, of 35 up-regulated genes, TRIM29, FUT3, IQGAP3, and SLC6A8 were confirmed by qNPA, qRT-PCR, and IHC platforms. p53 mutations are associated with poor survival of patients with Stage III MSS CRCs and p53-mutant and wild-type phenotypes have distinct gene expression profiles that might be helpful in identifying aggressive subsets.

  8. Prognostic significance of aortic valve gradient in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

    Science.gov (United States)

    Witberg, Guy; Finkelstein, Arik; Barbash, Issi; Assali, Abid; Shapira, Yaron; Segev, Amit; Halkin, Amir; Fefer, Paul; Ben-Shoshan, Jeremy; Konigstein, Maayan; Sagie, Alexander; Guetta, Victor; Kornowski, Ran; Barsheshet, Alon

    2017-05-22

    To evaluate the effect of baseline aortic valve gradient (AVG) both as a continuous and a categorical variable on mortality in patients undergoing transcatheter aortic valve replacement (TAVR), focusing on the high-gradient severe aortic stenosis (AS) patients. Identifying new predictors of mortality in the TAVR population can help refine risk stratification and improve the patient selection process for this procedure. So far, AVG has mainly been studied as a categorical variable and there is a paucity of data on its prognostic value as a continuous variable, especially in patients with high AVG AS, who constitute the majority of patients referred for TAVR. We analyzed data on 1,224 consecutive symptomatic severe AS patients, who underwent TAVR at 3 centers. The relation between pre-TAVR AVG and mortality was evaluated among all patients and in patients with high AVGs (mean AVG ≥40 mm Hg) using the Cox proportional hazard model adjusting for multiple variables. During a mean follow-up of 1.8 years, baseline AVG was inversely associated with mortality in the entire cohort and in patients with high AVG AS. By multivariable analysis, patients with mean AVG 40-60 mm Hg and >60 mm Hg had a respective 38% (P = 0.010) and 61% (P 40 mm Hg) and very high AVG AS (mean AVG >60 mm Hg) yielded similar results (HR = 0.88, P = 0.031, and HR = 0.80, P = 0.019, per 10 mm Hg increase in AVG, respectively). Using peak AVGs and an analysis restricted to patients without reduced ejection fraction yielded consistent results. Baseline AVGs show an inverse association with mortality post-TAVR. These results were consistent also in patients with high-gradient AS, suggesting that AVG can be used to identify patients most likely to benefit from TAVR. © 2017 Wiley Periodicals, Inc.

  9. Prognostic significance of stress myocardial ECG-gated perfusion imaging in asymptomatic patients with diabetic chronic kidney disease on initiation of haemodialysis

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    Momose, Mitsuru; Kondo, Chisato; Kobayashi, Hideki; Kusakabe, Kiyoko [Tokyo Women' s Medical University, School of Medicine, Department of Radiology, Shinjuku-ku, Tokyo (Japan); Babazono, Tetsuya [Tokyo Women' s Medical University, School of Medicine, Diabetes Centre, Shinjuku-ku, Tokyo (Japan); Nakajima, Takatomo [Tokyo Women' s Medical University, School of Medicine, Department of Cardiology, Shinjuku-ku, Tokyo (Japan)

    2009-08-15

    Diabetic patients with chronic kidney disease (CKD) frequently develop cardiac events within several years of the initiation of haemodialysis. The present study assesses the prognostic significance of stress myocardial ECG-gated perfusion imaging (MPI) in patients with diabetic CKD requiring haemodialysis. Fifty-five asymptomatic patients with diabetic stage V CKD and no history of heart disease scheduled to start haemodialysis were enrolled in this study (56{+-}11 years old; 49 with type 2 diabetes mellitus). All patients underwent {sup 201}Tl stress ECG-gated MPI 1 month before or after the initiation of haemodialysis to assess myocardial involvement. We evaluated SPECT images using 17-segment defect scores graded on a 5-point scale, summed stress score (SSS) and summed difference scores (SDS). The patients were followed up for at least 2 years (42{+-}15 months) to determine coronary intervention (CI) and heart failure (HF) as soft events and acute myocardial infarction (AMI) and all causes of deaths as hard events. The frequencies of myocardial ischaemia, resting perfusion defects, low ejection fraction and left ventricular (LV) dilatation were 24,20,29 and 49%, respectively. Ten events (18%) developed during the follow-up period including four CI, one HF, one AMI and four sudden deaths. Multivariate Cox analysis selected SDS (p=0.0011) and haemoglobin A{sub 1c} (HbA{sub 1c}) (p=0.0076) as independent prognostic indicators for all events. Myocardial ischaemia, in addition to glycaemic control, is a strong prognostic marker for asymptomatic patients with diabetic CKD who are scheduled to start haemodialysis. Stress MPI is highly recommended for the management and therapeutic stratification of such patients. (orig.)

  10. Prognostic significance of blood pressure measured in the office, at home and during ambulatory monitoring in older patients in general practice.

    Science.gov (United States)

    Fagard, R H; Van Den Broeke, C; De Cort, P

    2005-10-01

    The purpose of the study was to assess the prognostic significance of out-of-the-office blood pressure (BP) measurement in older patients in general practice, and to compare the results for BP measured in the office, at home and during 24-h ambulatory monitoring. All registerd patients who were 60 years or older were eligible for the study, except when bedridden, demented or admitted in a home for sick elderly people, or when they had suffered a myocardial infarction or stroke. After baseline measurements in 1990-1993, incidence of major cardiovascular events (cardiovascular death, myocardial infarction and stroke) was ascertained in 2002-2003 and related to the BPs by use of multivariate Cox regression analysis. Age of the 391 patients averaged 71+/-9 years; 40% were men. During median follow-up of 10.9 years, 86 patients (22%) suffered a cardiovascular event. The adjusted relative hazard rate, associated with a 1 s.d. increment in systolic BP was 1.13 for office BP (NS), and, respectively, 1.32, 1.33 and 1.42, for home, daytime and night time BP (Poffice BPs was independent of office BP. The prognostic value of home BP was equal to (systolic) or even better (diastolic) than that of daytime BP. Night time BP predicted cardiovascular events independent of all other BPs. Prognosis of white-coat hypertension was similar to that of true normotension, but better than in sustained hypertension. In conclusion, the prognostic value of home BP is better than that of office BP in older patients in primary care, and is at least equal to that of daytime ambulatory BP. The prognosis of patients with white-coat hypertension is similar to that of true normotensives.

  11. Tumor Necrosis Adds Prognostically Significant Information to Grade in Clear Cell Renal Cell Carcinoma: A Study of 842 Consecutive Cases From a Single Institution.

    Science.gov (United States)

    Khor, Li-Yan; Dhakal, Hari P; Jia, Xuefei; Reynolds, Jordan P; McKenney, Jesse K; Rini, Brian I; Magi-Galluzzi, Cristina; Przybycin, Christopher G

    2016-09-01

    Tumor necrosis has been shown to be an independent predictor of adverse outcome in renal cell carcinoma. A modification of the International Society of Urological Pathology (ISUP) grading system for renal cell carcinomas has recently been proposed, which incorporates the presence of tumor necrosis into grade. The investigators proposing this system found that necrosis added significant prognostic information to ISUP grade. We attempted to describe our experience with the effect of tumor necrosis in relationship to nuclear grade by reviewing the slides from a large consecutive series of localized clear cell renal cell carcinomas from our institution and obtaining long-term clinical follow-up information (overall survival). Of the 842 clear cell renal cell carcinomas reviewed, 265 (31.5%) were ISUP grade 1 or 2, 437 (51.9%) were ISUP grade 3, and 140 (16.6%) were ISUP grade 4. Tumor necrosis was present in 177 (21%) cases. Five hundred and forty-seven (64.9%) cases were stage pT1, 83 (9.9%) were stage pT2, 193 (22.9%) were stage pT3a, and 19 (2.3%) were pT3b or higher. Median follow-up was 73.2 months (range 0.12 to 273.6), and 310 (36.8%) patients died. On univariable analysis, there was no significant difference in outcome for tumors of ISUP grades 1 to 3. After adjustment for age, tumor stage, and tumor size, ISUP grade 4 and necrosis were significant predictors of overall survival on multivariable analysis. When the recently proposed modified grading system incorporating tumor necrosis was applied to our data, there was no significant difference in overall survival between patients with modified grade 1 tumors and those with modified grade 2 tumors (P=0.31); however, there was a statistically significant difference between patients with modified grade 1 or 2 tumors and those with modified grade 3 tumors (P=0.04),and a substantial difference in outcome between those with modified grade 3 and modified grade 4 tumors (Pnecrosis and could be divided into 3

  12. Prognostic classifications of lymph node involvement in lung cancer and current International Association for the Study of Lung Cancer descriptive classification in zones.

    Science.gov (United States)

    Riquet, Marc; Arame, Alex; Foucault, Christophe; Le Pimpec Barthes, Françoise

    2010-09-01

    The lymphatic drainage of solid organ tumors crosses through the lymph nodes (LNs) whose tumoral involvement may still be considered as local disease. Concerning lung cancer, LN involvement may be intrapulmonary (N1), and mediastinal and/or extra-thoracic. More than 30 years ago, mediastinal involved LNs were all considered as N2, and outside the scope of surgery. In 1978, Naruke presented an original article entitled 'Lymph node mapping and curability at various levels of metastasis in resected lung cancer', demonstrating that N2 was not a contraindication to surgery in all patients. The map permitted to localize the favorable N2 on the lung cancer ipsilateral side of the mediastinum. Several maps ensued aiming to discriminate between right and left involvement (1983), and to distinguish N2 (ipsilateral) and N3 (contralateral) mediastinal LN involvement (1983, 1986). The last map (1997 regional LN classification) was recently replaced by a descriptive classification in anatomical zones. This new LN map of the TNM classification for lung cancer is a step toward using anatomical view points which might be the best way to better understand lung cancer lymphatic spread. Nowadays, the LNs are easily identified by current radiological imaging, and their resectability may be anticipated. Each LN chain may be removed by en-bloc lymphadenectomy performed during radical lung resection, a safe procedure which seems to be more oncological based than sampling, and which avoids the source of discrepancies pointed out during the labeling of LN stations by surgeons.

  13. Prognostic significance of bcl-2 expression in stage III breast cancer patients who had received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy

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    Kim Dong-Wan

    2007-04-01

    Full Text Available Abstract Background Bcl-2 is positively regulated by hormonal receptor pathways in breast cancer. A study was conducted to assess the prognostic significances of clinico-pathologic variables and of ER, PR, p53, c-erbB2, bcl-2, or Ki-67 as markers of relapse in breast cancer patients who had received the identical adjuvant therapy at a single institution. Methods A cohort of 151 curatively resected stage III breast cancer patients (M:F = 3:148, median age 46 years who had 4 or more positive lymph nodes and received doxorubicin and cyclophosphamide followed by paclitaxel (AC/T as adjuvant chemotherapy was analyzed for clinico-pathologic characteristics including disease-free survival (DFS and overall survival (OS. Patients with positive ER and/or PR expression received 5 years of tamoxifen following AC/T. The protein expressions of biomarkers were assessed immunohistochemically. Results The median follow-up duration was 36 months, and 37 patients (24.5% experienced a recurrence. Univariate analyses indicated that the tumor size (P = 0.038 and the number of involved lymph nodes (P P = 0.013, bcl-2 positivity (P = 0.002 and low p53 expression (P = 0.032 were found to be significantly associated with a prolonged DFS. Furthermore, multivariate analysis identified 10 or more involved lymph nodes (HR 7.366; P P = 0.030, and c-erbB2 over-expression (HR 3.535; P = 0.001 as independent indicators of poorer DFS. In addition, bcl-2 expression was found to be significantly correlated with the expressions of ER and PR, and inversely correlated with the expressions of p53, c-erbB2 and Ki-67. Patients with bcl-2 expression had a significantly longer DFS than those without, even in the ER (+ subgroup. Moreover, OS was significantly affected by ER, bcl-2 and c-erbB2. Conclusion Bcl-2 is an independent prognostic factor of DFS in curatively resected stage III breast cancer patients and appears to be a useful prognostic factor in combination with c-erbB2 and the

  14. [Practical significance of sonographic type IIa of dysplastic hip joint according to Graf's classifications].

    Science.gov (United States)

    Peled, Eli; Fishkin, Michael; Eidelman, Mark; Katzman, Alexander; Bialik, Victor

    2004-06-01

    Hip joint assessment in newborns and neonates is currently performed with ultrasonography due to the high degree of sensitivity and specificity of this technology as compared to the usual radiography. Measuring the alpha and beta angles is indicative in assessing the hip joint. The alpha angle represents the bony acetabular components and the beta angle represents the cartilaginous roof. According to Graf's classifications, type IIa is subdivided into two subgroups; type IIa- and IIa+. This study examined the need for following-up on these hip joints in newborn and neonate. The study population included the newborns and neonates born in our facility between the period 1/1/1999 to 1/4/2002. We routinely screened 10,432 newborns both clinically and ultrasonographically. This included a total of 20,862 hip joints, of which 915 were pathological according to Graf's classifications. Type IIa was diagnosed in 232 newborns and a total of 330 hip joints. The follow-up examinations were performed at 6 and 12 weeks of age, and at six months of age. Each follow-up visit included clinical and sonographic evaluation and alpha angle measuring. The incidence of type IIa was 1.6% of all hips and 36.9% of the pathological hip joints. These joints were divided into two subgroups. Group A included 254 hip joints among 156 newborns, 116 girls [74.3%] and 40 boys [25.6%]. Group A members had bilateral or unilateral type IIa hip joints. In the latter case, the other joint was type I-normal. Group B included 76 hip joints among 76 newborns, 72 girls [94.5%] and four boys [5.5%]. Group B members had one type IIa hip joint and a second more severely graded hip joint. Follow-up only was required in 88% of the type IIa hip joints and 12% were treated using Pavlik's method. Surprisingly, all the joints with unilateral type IIa hips developed into normal or type I by six months of age without treatment, independent of the alpha angle value, and the pathology on the opposite side.

  15. Pro-atrial natriuretic peptide (pro-ANP) level in patients with severe sepsis and septic shock: prognostic and diagnostic significance.

    Science.gov (United States)

    Lipinska-Gediga, M; Mierzchala, M; Durek, G

    2012-06-01

    To establish the prognostic and discriminative value of the pro-atrial natriuretic peptide (pro-ANP) level in patients with severe sepsis or septic shock. An observational and prospective study was conducted on 50 critically ill patients with severe sepsis or septic shock. Measurements of the level of procalcitonin (PCT) and mid-regional pro-ANP were determined in the serum of patients with commercially available immunoluminometric tests. The median pro-ANP level was significantly higher in non-survivors than in survivors (P ANP levels were observed in patients with severe sepsis and septic shock. There was a strong correlation between the PCT and pro-ANP levels on admission in non-survivors and in septic shock patients (r = 0.56, P = 0.007 and r = 0.43, P = 0.02, respectively). pro-ANP evaluated in severe sepsis and septic shock patients is a valuable prognostic biomarker, but, in contrast to PCT, which is routinely used as a diagnostic marker of severe sepsis and septic shock, it does not possess diagnostic and discriminative value.

  16. Lack of prognostic significance of p16 and p27 after radical prostatectomy in hormone-naïve prostate cancer

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    Vlachostergios Panagiotis J

    2012-01-01

    Full Text Available Abstract Background Loss of normal cell cycle control is an early event in the evolution of cancer. The expression of cyclin-dependent kinase (CDK inhibitors p16 and p27 has been previously associated with progression of prostate cancer (PC. 70 patients diagnosed with early stage PCwere treated with radical prostatectomy (RP at our institution and their tumor specimens were immunohistochemically evaluated for expression of p16 and p27. Available clinical data of time to PSA recurrence were correlated with the examined parameters and combined with pre-operative PSA level, Gleason score and pathological TNM (pT stage assessment. Results Nuclear overexpression of p16 was not associated with time to biochemical failure (BF (p = 0.572. Same was the case for nuclear p27 overexpression (p = 1.000. Also, no significant correlations were found between either p16 or p27, and pre-operative PSA level, pT stage and Gleason grade. pT stage emerged as the only independent prognostic factor for biochemical recurrence (p = 0.01. Conclusions These data question previously reported data supporting the prognostic relevance of both p16 and p27 proteins in early PC.

  17. Preoperative PET/CT standardized FDG uptake values of pelvic lymph nodes as a significant prognostic factor in patients with endometrial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hyun Hoon; Kim, Hee Seung; Kim, Jae Weon; Park, Noh-Hyun [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Cheon, Gi Jeong [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Song, Yong Sang [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Seoul National University, WCU Biomodulation Major, Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul (Korea, Republic of)

    2014-09-15

    Using integrated PET/CT, we evaluated the prognostic relevance of preoperative pelvic lymph node (LN) {sup 18}F-FDG uptake in endometrioid endometrial cancer. We retrospectively reviewed patients with pathologically proven endometrial cancer who underwent preoperative {sup 18}F-FDG PET/CT scans to evaluate the prognostic significance of PET/CT parameters and other clinicopathological variables. We used Cox proportional hazards regression to examine the relationship between recurrence and the maximum standardized uptake value (SUV{sub max}) in pelvic LNs (SUV{sub LN}) on FDG PET/CT. Clinical data, treatment modalities and results were reviewed in 70 eligible patients. The median postsurgical follow-up was 29 months (range 6 to 95 months). Receiver-operating characteristic analysis identified the significant SUV{sub LN} cut-off value as 15. The SUV{sub LN} correlated with FIGO stage (P < 0.001), LN metastasis (P < 0.001), lymphovascular space invasion (P < 0.001), SUV{sub tumour} (P = 0.001), metastatic LN size (P = 0.004), primary tumour size (P = 0.012), tumour grade (P = 0.015) and depth of tumour invasion (P = 0.035). Regression analysis showed a statistically significant association between recurrence and SUV{sub LN} (P = 0.002). Recurrence differed significantly (P < 0.001) between patients with SUV{sub LN} >15 and those with SUV{sub LN} ≤15. Preoperative pelvic LN FDG uptake exhibited a strong significant association with recurrence of endometrioid endometrial cancer. (orig.)

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

    Science.gov (United States)

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

    2016-01-01

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

  19. Prognostic significance of ASXL1, JAK2V617F mutations and JAK2V617F allele burden in Philadelphia-negative myeloproliferative neoplasms

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    Yonal-Hindilerden I

    2015-06-01

    Full Text Available Ipek Yonal-Hindilerden, Aynur Daglar-Aday, Basak Akadam-Teker, Ceylan Yilmaz, Meliha Nalcaci, Akif Selim Yavuz, Deniz SarginDivision of Hematology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Fatih-Istanbul, Turkey Background: Despite insights into the genetic basis of Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs, a significant proportion of essential thrombocythemia (ET and primary myelofibrosis (PMF patients present with no known MPN disease alleles. There were no previous studies investigating the impact of ASXL1 mutations in Ph-negative MPNs in Turkey. In the current study, we investigated the prognostic significance of ASXL1 mutations in Turkish MPN patients. We also aimed to determine the prognostic significance of JAK2V617F allele burden and the relationship of JAK2V617F mutation with ASXL1 mutations in Ph-negative MPNs. Methods: About 184 patients from a single center diagnosed with Ph-negative MPNs were screened for ASXL1, JAK2V617F mutations, and JAK2V617F allele burden: 107 ET and 77 PMF. Results: A total of 29 ASXL1 mutations were detected in 24.7% of PMF and 8.4% of ET patients. ASXL1-mutated ET patients showed a trend toward an increase in the incidence of cerebrovascular events and higher total leukocyte counts. ASXL1-mutation in PMF was associated with older age and a higher prevalence of bleeding complications. In univariate analysis, overall survival (OS was significantly reduced in ASXL1-mutated PMF patients. In multivariate analysis, Dynamic International Prognostic Scoring System-plus high-risk category and ASXL1 mutation status were independently associated with shorter survival in PMF. In PMF, mutational status and allele burden of JAK2V617F showed no difference in terms of OS and leukemia-free survival. Conclusion: We conclude that ASXL1 mutations are molecular predictors of short OS in PMF. Keywords: Philadelphia-negative myeloproliferative neoplasms (Ph

  20. Prognostic Significance of Monocytes and Monocytic Myeloid-Derived Suppressor Cells in Diffuse Large B-Cell Lymphoma Treated with R-CHOP

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    Chongyang Wu

    2016-07-01

    Full Text Available Background/Aims: To evaluate the prognostic significance of monocytes and monocytic myeloid-derived suppressor cells (M-MDSCs for patients with diffuse large B-cell lymphoma (DLBCL under R-CHOP chemotherapy. Methods: Flow cytometry (FCM was applied to measure M-MDSCs (CD14+ HLA-DRlow/− M-MDSCs. Results: Analysis of 144 patients with DLBCL under R-CHOP treatment showed that the 5-year overall survival rate was 61.09% (95% CI: 43.72%-72.56% and the average survival time of patients with monocytes (% ≥ 8% was shorter than those with monocytes (% 2 (P = 0.0397, meanwhile, there was no significant difference in survival of patients with monocytes (% ≥ 8% compared to patients with monocytes (% Conclusion: Our results indicated that monocytes (% and M-MDSCs combined with R-IPI may be a simple and efficient immunological index to evaluate prognosis.

  1. Prognostic significance of standardized uptake value and metabolic tumour volume on {sup 18}F-FDG PET/CT in oropharyngeal squamous cell carcinoma

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    Kim, Ji Won; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl [University of Ulsan College of Medicine, Department of Otolaryngology, Asan Medical Centre, Seoul (Korea, Republic of); Oh, Jungsu S.; Kim, Jae Seung [University of Ulsan College of Medicine, Department of Nuclear Medicine, Asan Medical Centre, Seoul (Korea, Republic of); Kim, Sang Yoon [University of Ulsan College of Medicine, Department of Otolaryngology, Asan Medical Centre, Seoul (Korea, Republic of); Biomedical Research Institute, Korea Institute of Science and Technology, Seoul (Korea, Republic of)

    2015-08-15

    Standardized uptake value (SUV) and metabolic tumour volume (MTV) measured by {sup 18}F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers. However, their prognostic significance in oropharyngeal squamous cell carcinoma (OPSCC) has been investigated in only a few studies and with small cohorts. In the present study we evaluated the ability of SUV, MTV, and total lesion glycolysis (TLG) measured on pretreatment {sup 18}F-FDG PET/CT to predict recurrence and survival outcomes in OPSCC. The study included 221 patients with OPSCC who underwent pretreatment {sup 18}F-FDG PET/CT imaging and received definitive treatment at our tertiary referral centre. The PET imaging parameters SUV{sub max}, SUV{sub peak}, MTV and TLG were measured in primary tumours with focal {sup 18}F-FDG uptake. Clinical and imaging variables significantly associated with overall survival (OS) and disease-free survival (DFS) were identified by univariate and multivariate analyses using the Cox proportional hazards model. Overall 5-year OS and DFS rates were 72.0 % and 79.5 %, respectively, during a median follow-up of 61 months (range 18 - 122 months). The cut-off values of tumour SUV{sub max}, SUV{sub peak}, MTV and TLG for prediction of DFS were 7.55, 6.80, 11.06 mL and 78.56 g, respectively. Univariate analyses showed that age >60 years, advanced tumour stage, and high tumour SUV{sub max}, SUV{sub peak}, MTV and TLG were significantly associated with decreased OS and DFS (P < 0.05 each). Age, tumour SUV{sub max} and MTV remained independent variables for OS and DFS (P < 0.05 each) in the multivariate analyses. SUV{sub max} and MTV measured on pretreatment {sup 18}F-FDG PET/CT may be useful in predicting the clinical outcomes in OPSCC patients. This study investigated the clinical prognostic value of imaging parameters from pretreatment {sup 18}F-FDG PET/CT in 221 patients who underwent definitive treatment for oropharyngeal squamous cell carcinoma. High maximum standardized

  2. Age and associated fibrocystic changes are prognostically significant in patients with small node-negative (T1a,bN0) invasive breast cancer.

    Science.gov (United States)

    Durak, Merih Guray; Gonzalez-Angulo, Ana M; Hanrahan, Emer O; Broglio, Kristine R; Valero, Vicente; Hortobagyi, Gabriel N; Hunt, Kelly K; Sahin, Aysegul A

    2011-01-01

    Some patients with small (≤1.0 cm) node-negative (T1a,bN0) invasive breast cancer (IBC) who undergo only local therapy experience recurrences. There is limited information on prognostic factors in these patients. We sought to identify prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in patients with T1a,bN0 IBC. Histologic sections from 273 T1a,bN0 IBC patients treated at M. D. Anderson Cancer Center (MDACC) between 1980 and 1999 were reviewed. Microscopic tumor size; multifocality; histologic type, grade of tumor; presence, type, grade of associated ductal carcinoma in situ (DCIS); presence of fibrocystic changes (FCC) with/without atypia; and lymphovascular invasion were identified. The Kaplan-Meier method was used to evaluate DFS and OS. Median patient age was 58 years, median follow-up period was 10.8 years, and median tumor size was 0.8 cm. Multifocal disease was identified in 26% of cases. At 10 years, the DFS and OS rates were 91% and 88%, respectively. Twenty-one percent of patients had extensive (>50%), and 30% had grade 3 DCIS. Nonproliferative FCC and proliferative FCC with/without atypia were present in 80%, 36%, and 38% of patients, respectively. In univariate analysis, age at diagnosis (p < 0.0001), grade (p = 0.015), and percent (p = 0.046) of DCIS were significantly associated with DFS; presence of FCC was associated with longer DFS and OS. In multivariable models, age and presence of FCC remained significantly associated with survival. Age at diagnosis and associated FCC are significant factors in predicting recurrence in patients with T1a,bN0 IBC. Adjuvant systemic therapy should be discussed with and considered for young patients with T1a,bN0 IBC. © 2011 Wiley Periodicals, Inc.

  3. NY-BR-1 Antigen Expression and anti-NY-BR-1 IgG in Egyptian Breast Cancer Patients: Clinicopathological and Prognostic Significance.

    Science.gov (United States)

    Abu El-Nazar, Salma Y; Ghazy, Amany A; Ghoneim, Hossam E; Zoheir, Malak; Ahmed, Ahmed S; Sorour, Sally S; Abouelella, Amira M

    2015-01-01

    Breast cancer is the most common gynecological malignancy in the world. In Egypt, it ranks the first among female malignancies with incidence of 37.7%. Over the last decades, the integration of prognostic and predictive markers in treatment decisions has led to more individualized and optimized therapy. NY-BR-1 antigen has been shown to be frequently expressed in breast cancers. The study aimed to assess the tissue expression of NY-BR-1 antigen and serum IgG antibody to this antigen in Egyptian breast cancer females. The study was conducted on 60 females (10 healthy, 10 having benign breast lesions, 40 with malignant breast cancer). NY-BR-1 Ag expression was evaluated by immunohistochemistry and anti-NY-BR-1 IgG was assessed by ELISA. Results revealed a significant difference in NY-BR-1 Ag expression between benign and malignant breast cancer patients. There was a significant correlation between NY-BR-1 antigen expression and estrogen receptor's status (P = 0.019), stage of the disease (P = 0.008), menopausal status (P = 0.008), lymph node involvement (P = 0.022) and anti-NY-BR-1 IgG (P = 0.032) among the studied individuals. In addition, there was a statistically significant increase in anti-NY-BR-1 IgG O.D. results among malignant breast cancer group. It is correlated with tumor type (P 1) and progesterone receptor status (P = 0.038). In conclusion, our work may represent a step towards identification of a new prognostic marker specific for breast cancer.

  4. Prognostic significance of primary Gleason pattern in Japanese men with Gleason score 7 prostate cancer treated with radical prostatectomy.

    Science.gov (United States)

    Miyake, Hideaki; Muramaki, Mototsugu; Furukawa, Junya; Tanaka, Hirokazu; Inoue, Taka-aki; Fujisawa, Masato

    2013-11-01

    To evaluate the significance of the primary Gleason pattern in patients with Gleason score (GS) 7 prostate cancer treated with radical prostatectomy. This study included 959 consecutive Japanese men who underwent radical prostatectomy without neoadjuvant therapies and were subsequently diagnosed as having GS 7 prostate cancer based on the modified International Society of Urological Pathology (ISUP) 2005 Gleason grading system. Of these 959 patients, 666 (69.4%) and 293 (30.6%) had GS 3+4 and GS 4+3 tumors, respectively. There were significant differences in the prostate-specific antigen (PSA) level, biopsy GS, pathologic T stage, lymphatic invasion, microvenous invasion, and perineural invasion between these 2 groups. During the mean observation of 48.9 months, biochemical recurrence occurred in 211 patients (22.0%), and there was a significant difference in the biochemical recurrence-free survival between patients with GS 3+4 tumors and those with GS 4+3 tumors. Of several factors examined, biochemical recurrence-free survival was significantly associated with the PSA level, biopsy Gleason score, capsular penetration, seminal vesicle invasion, surgical margin status, lymphatic invasion, microvenous invasion, perineural invasion, and primary Gleason pattern, among which the PSA level, capsular penetration, seminal vesicle invasion, and surgical margin status, but not primary Gleason pattern, appeared to be independent predictors of biochemical recurrence. Despite the lack of an independent significance, primary Gleason pattern based on the modified ISUP 2005 Gleason grading system is shown to be significantly associated with the biochemical outcome of Japanese men with GS 7 prostate cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. FLT3 Mutation as a Significant Prognostic Marker in de novo Acute Myeloid Leukemia Patients: Incidence, Distribution and Association with Cytogenetic Findings in a Study from South India

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    Santhi Sarojam

    2014-10-01

    Full Text Available Background: Fms-like tyrosine kinase 3 is a tyrosine kinase receptor that plays an important role in proliferation and differentiation of hematopoietic stem cells. Internal tandem duplication and tyrosine kinase domain mutation are the two most common types of fms-like tyrosine kinase 3 mutations frequently reported in acute myeloid leukemia associated with pathogenesis of this disease. The present study investigates the prevalence and distribution pattern in different acute myeloid leukemia sub- and cytogenetic groups, the association with clinical parameters and the prognostic importance of these mutations in acute myeloid leukemia patients from South India. Methods:Mutation analysis was performed in 276 de novo acute myeloid leukemia patients by polymerase chain reaction restriction fragment length polymorphism using specific restriction enzymes followed by sequencing to confirm the mutations. Kaplan-Meier survival analysis was performed to detect the prognosis. Results: Fms-like tyrosine kinase 3 internal tandem duplication mutations were observed in 20%, tyrosine kinase domain mutation in 4% and dual mutations in 0.3% of the analyzed cases. The internal tandem duplication mutations ranged from 15-107 nucleotides with the majority at the juxta membrane domain of the receptor. Three types of tyrosine kinase domain point mutations were identified: D835Y, D835H and D835V. We observed a significant association between fms-like tyrosine kinase 3 mutations and increased WBC and LDH counts (P<0.001 and blast percentage but not with age, gender and FAB subtypes. A significant association with normal karyotype was observed for the mutants (P=0.002. Survival analysis revealed that the fms-like tyrosine kinase 3 gene mutation was a negative prognostic marker for acute myeloid leukemia patients. The risk stratified analysis showed the mutation to be a risk factor for the intermediate karyotype group, especially for those with normal cytogenetics

  6. Prognostic significance of stress myocardial gated SPECT among Japanese patients referred for coronary angiography: A study of data from the J-ACCESS database

    Energy Technology Data Exchange (ETDEWEB)

    Momose, Mitsuru [Tokyo Women' s Medical University, Department of Radiology, Tokyo (Japan); Nakajima, Kenichi [Kanazawa University Hospital, Department of Nuclear Medicine, Kanazawa (Japan); Nishimura, Tsunehiko [Kyoto Prefectural University of Medicine, Department of Radiology, Graduate School of Medical Science, Kyoto (Japan)

    2009-08-15

    The J-ACCESS [Japanese investigation of prognosis based on gated single photon emission computed tomography (SPECT)] study found that quantitative gated myocardial SPECT (QGS) is valuable for predicting the prognosis of Japanese patients with known or suspected ischaemic heart disease. The present study evaluates the incremental prognostic value of myocardial perfusion imaging (MPI) with QGS among patients referred for coronary angiography (CAG). Among 4,031 Japanese patients registered at 117 hospitals for the J-ACCESS study, we selected 1,011 who underwent CAG within 3 months before or after MPI with QGS. Summed stress, rest and difference scores (SSS, SRS and SDS) were generated from myocardial perfusion images using a 20-segment scoring system. Myocardial ischaemia was judged visually. End-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) were determined by QGS. Numbers of diseased (> 75% stenosis) coronary vessels (CDV) were assessed by CAG. All patients were followed up for 3 years to determine cardiac events (CE) including cardiac death, non-fatal myocardial infarction and severe heart failure. Univariate and multivariate analyses of prognostic ability included age, cardiac risk factors (hypertension, hyperlipidaemia, diabetes mellitus and prior myocardial infarction), angiographic findings and the QGS parameters as independent variables. Cardiac events occurred more frequently with increasing numbers of coronary vessel lesions (p=0.0016). Cox univariate analysis revealed that diabetes, CDV, SSS, SDS, EDV, ESV and EF were significant predictors (Wald {chi}{sup 2}=5.99, 12.9, 8.39, 9.11, 35.5, 42.1 and 31.1, respectively), whereas multivariate analysis selected only ESV and SDS as significant predictors (Wald {chi}{sup 2}=36.4, 8.4; p = 0.0038, p < 0.001). MPI with QGS, especially with gated functional data, has incremental prognostic value in addition to angiographic findings. MPI with QGS findings predominantly contribute to the

  7. Clinical significance of pretreatment serum levels of VEGF and its receptors, IL- 8, and their prognostic value in type I and II endometrial cancer patients.

    Directory of Open Access Journals (Sweden)

    Beata Kotowicz

    Full Text Available The study aimed to assess the usefulness of the determination of cytokines: IL-8, VEGF and its soluble receptors: VEGF-R1, VEGF-R2 in patients with endometrial cancer (EC.The study group consisted of 118 patients with EC subjected to surgical treatment. Before the treatment we determined the serum levels of cytokines IL-8, and VEGF as well as VEGFR1 and VEGFR2 receptors. For comparison, the concentration of CA 125 was also measured. VEGFR1 and CA 125 were determined in the COBAS e601 system using Roche Diagnostics kits, while IL-8, VEGF and VEGFR2 were measured by ELISA assay using R&D Systems kits.The concentrations of IL-8, VEGF, VEGFR1 and CA 125 allowed to distinguish patients for the control group. The highest diagnostic sensitivity has been shown for the concentrations of VEGF (AUC = 0.904 and IL-8 (AUC = 0.818. Among all studied parameters only CA125 concentrations increased with the clinical stage; being significantly higher in patients in FIGO III-IV, than FIGO I-IB. In patients at the FIGO stage I-IB, complementary determinations of CA 125 and VEGF resulted in the largest increase of diagnostic sensitivity. Patients with metastases to the para-aortic lymph nodes had significantly higher levels of VEGF compared to subjects without such lesions. The concentrations of IL-8 were an independent prognostic factor in the assessment of overall survival in patients with type I endometrial cancer, while the concentrations of VEGFR2 in those with type II.In patients with endometrial cancer, the clinical usefulness of IL-8 and VEGFR2 measurements as the potential prognostic factors has been demonstrated. In type I, the concentrations of IL-8 determined before treatment can be helpful in predicting overall survival. In patients qualified to type II EC, the concentrations of VEGFR2 have the value of an independent prognostic factor for overall survival, this requires research on larger groups of patients. The increased levels of VEGF may be useful

  8. Prognostic significance of social network, social support and loneliness for course of major depressive disorder in adulthood and old age

    NARCIS (Netherlands)

    van den Brink, R H S; Schutter, N; Hanssen, D. J. C.; Elzinga, B. M.; Rabeling-Keus, I M; Stek, M L; Comijs, H C; Penninx, B W J H; Oude Voshaar, R C

    2017-01-01

    AIMS: Poor recovery from depressive disorder has been shown to be related to low perceived social support and loneliness, but not to social network size or frequency of social interactions. Some studies suggest that the significance of social relationships for depression course may be greater in

  9. Prognostic Value of Gai′s Plaque Score and Agatston Coronary Artery Calcium Score for Functionally Significant Coronary Artery Stenosis

    Directory of Open Access Journals (Sweden)

    Chuang Zhang

    2016-01-01

    Conclusions: Both CACS in a single artery and Gai's plaque score demonstrated a good capacity to assess functionally significant coronary artery stenosis when compared to the gold standard FFR. However, Gai's plaque score was more predictive of FFR <0.80. Gai's score can be easily calculated in daily clinical practice and could be used when considering revascularization.

  10. Prognostic significance of axillary dissection in breast cancer patients with micrometastases or isolated tumor cells in sentinel nodes

    DEFF Research Database (Denmark)

    Tvedskov, Tove Filtenborg; Jensen, Maj-Britt; Ejlertsen, Bent

    2015-01-01

    . In this nationwide study, we found a low risk of AR on 1.58 % and we did not find a significantly increased risk of AR if ALND was omitted in patients with micrometastases or ITC in sentinel nodes. Furthermore, no significant difference in overall survival was seen between patients with and without ALND when......We estimated the impact of axillary lymph node dissection (ALND) on the risk of axillary recurrence (AR) and overall survival (OS) in breast cancer patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes. We used the Danish Breast Cancer Cooperative Group (DBCG) database...... to identify patients with micrometastases or ITC in sentinel nodes following surgery for primary breast cancer between 2002 and 2008. A Cox proportional hazard regression model was developed to assess the hazard ratios (HR) for AR and OS between patients with and without ALND. We identified 2074 patients...

  11. Thrombocytosis portends adverse prognostic significance in patients with stage II colorectal carcinoma [v2; ref status: indexed, http://f1000r.es/4k6

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    Tianhua Guo

    2014-10-01

    Full Text Available Thrombocytosis portends adverse prognostic significance in many types of cancers including ovarian and lung carcinoma. In this study, we determined the prevalence and prognostic significance of thrombocytosis (defined as platelet count in excess of 400 × 103/μl in patients with colorectal cancer. We performed a retrospective analysis of 310 consecutive patients diagnosed at our Institution between 2004 and 2013. The patients (48.7% male and 51.3% female had a mean age of 69.9 years (+/- 12.7 years at diagnosis. Thrombocytosis was found in a total of 25 patients, with a higher incidence in those with stage III and IV disease (14.4% of patients. Although the mean platelet count increased with the depth of tumor invasion (pT, its values remained within normal limits in the whole patient cohort. No patient with stage I cancer (n=57 had elevated platelet count at diagnosis. By contrast, five of the 78 patients (6.4% with stage II cancer showed thrombocytosis, and four of these patients showed early recurrence and/or metastatic disease, resulting in shortened survival (they died within one year after surgery. The incidence of thrombocytosis increased to 12.2% and 20.6%, respectively, in patients with stage III and IV disease. The overall survival rate of patients with thrombocytosis was lower than those without thrombocytosis in the stage II and III disease groups, but this difference disappeared in patients with stage IV cancer who did poorly regardless of their platelet count. We concluded that thrombocytosis at diagnosis indicates adverse clinical outcome in colorectal cancer patients with stage II or III disease. This observation is especially intriguing in stage II patients because the clinical management of these patients is controversial. If our data are confirmed in larger studies, stage II colon cancer patients with thrombocytosis may be considered for adjuvant chemotherapy.

  12. Prognostic significance of interleukin-8 and CD163-positive cell-infiltration in tumor tissues in patients with oral squamous cell carcinoma.

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    Yohei Fujita

    Full Text Available PURPOSE: We investigated whether serum interleukin (IL-8 reflects the tumor microenvironment and has prognostic value in patients with oral squamous cell carcinoma (OSCC. EXPERIMENTAL DESIGN: Fifty OSCC patients who received radical resection of their tumor(s were enrolled. Preoperative sera were measured for IL-8 by ELISA. Expression of IL-8 and the infiltration of immune cells in tumor tissues were analyzed by an immunohistochemical staining of surgical specimens. RESULTS: We found that disease-free survival (DFS was significantly longer in the Stage I/II OSCC patients with low serum IL-8 levels compared to those with high levels (p = 0.001. The tumor expression of IL-8, i.e., IL-8(T and the density of CD163-positive cells in the tumor invasive front, i.e., CD163(IF were correlated with the serum IL-8 level (p = 0.033 and p = 0.038, respectively, and they were associated with poor clinical outcome (p = 0.007 and p = 0.002, respectively, in DFS in all patients. A multivariate analysis revealed that N status, IL-8(T and CD163(IF significantly affected the DFS of the patients. Further analysis suggested that combination of N status with serum IL-8, IL-8(T or CD163(IF may be a new criterion for discriminating between OSCC patients at high and low risk for tumor relapse. Interestingly, the in vitro experiments demonstrated that IL-8 enhanced generation of CD163-positive M2 macrophages from peripheral blood monocytes, and that the cells produced IL-10. CONCLUSIONS: These findings indicate that IL-8 may be involved in poor clinical outcomes via generation of CD163-positive M2 macrophages, and that these factors in addition to N status may have prognostic value in patients with resectable OSCSS.

  13. Prognostic factors for patients with brain metastasis from gynecological cancer: a significance of treatment-free interval of more than 6 months.

    Science.gov (United States)

    Takeshita, Sho; Todo, Yukiharu; Furuta, Yu; Okamoto, Kazuhira; Minobe, Shinichiro; Yamashiro, Katsushige; Kato, Hidenori

    2017-07-01

    Treatment-free interval has been confirmed as a significant prognostic factor in recurrent gynecological cancers. However, treatment-free interval has not been evaluated in previous studies investigating brain metastasis from gynecological malignancies. The aim of the study was to establish a predictive model of survival period after brain metastasis from gynecological cancer. Of a total of 2848 patients with gynecological cancer, patients with brain metastasis were included in the study. Data at the time of brain metastasis diagnosis, which included primary origin, presence of extracranial metastasis, the Eastern Cooperative Oncology Group (ECOG) performance status, the number of brain metastases, brain-metastasis free-interval, treatment-free interval and treatment for brain metastasis were collected. Survival data were analyzed using Kaplan-Meier methods and Cox proportional hazards models. Incidences of brain metastasis were 1.7% (47/2848). Median survival period after diagnosis of brain metastasis was 20 weeks (4-5 months). The 6-, 12- and 24-month survival rates after brain metastasis were 44.0%, 22.0% and 16.5%, respectively. Cox regression analysis showed that extracranial metastasis (hazard ratio [HR], 5.2; 95% confidence interval [CI]: 1.04-26.3), ECOG performance status of 3-4 (HR, 3.1; 95% CI: 1.20-7.91), treatment-free interval of cancer treatment for brain metastasis (HR, 3.6; 95% CI: 1.34-9.41) were significantly and independently related to poor survival. Treatment-free interval should be assessed in a future study to verify prognostic predictors of brain metastasis from gynecological cancer.

  14. The prognostic significance of celiac lymph node metastasis in patients with locally advanced esophageal squamous cell carcinoma receiving curative concurrent chemoradiotherapy.

    Science.gov (United States)

    Chen, Yen-Hao; Lu, Hung-I; Wang, Yu-Ming; Lo, Chien-Ming; Chou, Shang-Yu; Huang, Cheng-Hua; Shih, Li-Hsueh; Chen, Su-Wei; Li, Shau-Hsuan

    2017-11-10

    To evaluate the clinical outcomes of celiac lymph node (LN) metastasis in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving curative concurrent chemoradiotherapy (CCRT). A total of 375 stage III ESCC patients were identified, including 51 patients with celiac LN metastasis and 324 patients without celiac LN metastasis. Among these 324 patients without celiac LN metastasis, 51 were matched with the 51 patients with celiac LN metastasis using the propensity score matching method. Overall, the celiac LN metastasis group had worse progression-free survival (PFS) and overall survival (OS) than the non-celiac LN metastasis group and the matched non-celiac LN metastasis group. For the ESCC patients with celiac LN metastasis, lower third ESCC was significantly associated with superior PFS and OS. For patients with upper/middle third ESCC, the celiac LN metastasis group had worse PFS and OS than the non-celiac LN metastasis group and the matched non-celiac LN metastasis group. For patients with lower third ESCC, there were no significant differences in PFS and OS between these groups. Our study suggests celiac LN metastasis is a poor prognostic factor for locally advanced ESCC patients receiving curative CCRT. Among these ESCC patients with celiac LN metastasis, tumor location is a strongly prognostic factor, indicating patients with lower third ESCC have better PFS and OS than those with upper/middle third ESCC. The 6 th American Joint Committee on Cancer staging system seems more favorable than 7 th edition in the definition of celiac LNs for those patients.

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

    Science.gov (United States)

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

    2017-09-01

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

  16. Hemodialysis-Induced Regional Left Ventricular Systolic Dysfunction: Prevalence, Patient and Dialysis Treatment-Related Factors, and Prognostic Significance

    Science.gov (United States)

    Assa, Solmaz; Hummel, Yoran M.; Voors, Adriaan A.; Kuipers, Johanna; Westerhuis, Ralf; de Jong, Paul E.

    2012-01-01

    Summary Background and objectives The hemodialysis procedure may acutely induce regional left ventricular systolic dysfunction. This study evaluated the prevalence, time course, and associated patient- and dialysis-related factors of this entity and its association with outcome. Design, setting, participants, & measurements Hemodialysis patients (105) on a three times per week dialysis schedule were studied between March of 2009 and March of 2010. Echocardiography was performed before dialysis, at 60 and 180 minutes intradialysis, and at 30 minutes postdialysis. Hemodialysis-induced regional left ventricular systolic dysfunction was defined as an increase in wall motion score in more than or equal to two segments. Results Hemodialysis-induced regional left ventricular systolic dysfunction occurred in 29 (27%) patients; 17 patients developed regional left ventricular systolic dysfunction 60 minutes after onset of dialysis. Patients with hemodialysis-induced left ventricular systolic dysfunction were more often male, had higher left ventricular mass index, and had worse predialysis left ventricular systolic function (left ventricular ejection fraction). The course of blood volume, BP, heart rate, electrolytes, and acid–base parameters during dialysis did not differ significantly between the two groups. Patients with hemodialysis-induced regional left ventricular systolic dysfunction had a significantly higher mortality after correction for age, sex, dialysis vintage, diabetes, cardiovascular history, ultrafiltration volume, left ventricular mass index, and predialysis wall motion score index. Conclusions Hemodialysis induces regional wall motion abnormalities in a significant proportion of patients, and these changes are independently associated with increased mortality. Hemodialysis-induced regional left ventricular systolic dysfunction occurs early during hemodialysis and is not related to changes in blood volume, electrolytes, and acid–base parameters. PMID

  17. Diagnostic and Prognostic Significance of Lipid Profiles in Holstein Dairy Cattle with Displaced Abomasum: Before and After Surgical Operation

    Directory of Open Access Journals (Sweden)

    Arafat Khalphallah

    2016-01-01

    Full Text Available The study aimed to describe the pattern of changes in clinical findings and lipid metabolism profiles in dairy cattle with displacement of the abomasum (DA from day 0 until day 30 after operation. The study was conducted on DA cattle (n= 25 belonged to dairy farms in Hokkaido area, Japan. Cows were examined and sampled at days 0 (operation, 7 and 30. They were clinically and biochemically examined to estimate BCS and many serum biochemical constituents such as lecithin:cholesterol acyltransferase (LCAT and apolipoprotein B-100 (apoB-100, β-hydroxybutyric acid (BHBA, non-esterified fatty acids (NEFAs and aspartate amino transferase (AST. Based on blood BHBA at day 0, DA cows were classified into three categories; DA only (<1.2 mmol/l, DA with subclinical ketosis (DA SCK (1.2-2.4 mmol/l and DA with clinical ketosis (DA CK (≥2.5 mmol/l. The changes in the pattern of serum biochemical constituents throughout this study indicated recovery of diseased cows and significant effect of surgical operation. Serum biochemical constituents returned to their physiological values indicating that these cows were restoring their normal physiological status. This was reflected through a significant (P<0.05 elevation of LCAT, apoB-100, and cholesterol and a significant (P<0.05 reduction in AST, NEFAs and BHBA (Not in DA group, in all DA groups particularly at day 30 when their values compared with those at day 0. The current study also recorded no remarkable changes (P>0.05 between the diseased groups except for NEFA and BHBA (at day 0 between DA group and the other two groups at any of the three sampling days.

  18. Analysis of postoperative morbidity and mortality following surgery for gastric cancer. Surgeon volume as the most significant prognostic factor

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    Maciej Ciesielski

    2017-09-01

    Full Text Available Introduction : Surgical resection is the only potentially curative modality for gastric cancer and it is associated with substantial morbidity and mortality. Aim: To determine risk factors for postoperative morbidity and mortality following major surgery for gastric cancer. Material and methods : Between 1.08.2006 and 30.11.2014 in the Department of Oncological Surgery of Gdynia Oncology Centre 162 patients underwent gastric resection for adenocarcinoma. All procedures were performed by 13 surgeons. Five of them performed at least two gastrectomies per year (n = 106. The remaining 56 resections were done by eight surgeons with annual volume lower than two. Perioperative mortality was defined as every in-hospital death and death within 30 days after surgery. Causes of perioperative deaths were the matter of in-depth analysis. Results: Overall morbidity was 23.5%, including 4.3% rate of proximal anastomosis leak. Mortality rate was 4.3%. Morbidity and mortality were not dependent on: age, gender, body mass index, tumour location, extent of surgery, splenectomy performance, or pTNM stage. The rates of morbidity (50% vs. 21.3% and mortality (16.7% vs. 3.3% were significantly higher in cases of tumour infiltration to adjacent organs (pT4b. Perioperative morbidity and mortality were 37.5% and 8.9% for surgeons performing less than two gastrectomies per year and 16% and 0.9% for surgeons performing more than two resections annually. The differences were statistically significant (p = 0.002, p = 0.003. Conclusions : Annual surgeon case load and adjacent organ infiltration (pT4b were significant risk factors for morbidity and mortality following major surgery for gastric cancer. The most common complications leading to perioperative death were cardiac failure and proximal anastomosis leak.

  19. Prognostic significance of STAT3 and phosphorylated STAT3 in human soft tissue tumors - a clinicopathological analysis

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    Nair Asha S

    2011-05-01

    Full Text Available Abstract Background Signal transducer and activator of transcription 3 (STAT3 is a key signaling molecule and a central cytoplasmic transcription factor, implicated in the regulation of growth. Its aberrant activation has been demonstrated to correlate with many types of human malignancy. However, whether constitutive STAT3 signaling plays a key role in the survival and growth of soft-tissue tumors is still unclear and hence needs to be elucidated further. In our study we examined the expression levels of STAT3 and pSTAT3 in different grades of soft tissue tumors and correlated with its clinicopathological characteristics. Methods Expression levels of STAT3 and pSTAT3 in soft tissue tumors were studied using Immunohistochemistry, Western blotting and Reverse transcriptase- PCR and correlated with its clinicopathological characteristics using Chi squared or Fisher's exact test and by logistic regression analysis. Statistical analysis was done using Intercooled Stata software (Intercooled Stata 8.2 version. Results Of the 82 soft tissue tumor samples, fifty four (65.8% showed immunoreactivity for STAT3 and twenty eight (34.1% for pSTAT3. Expression of STAT3 and pSTAT3 was significantly associated with tumor grade (P Conclusion These findings suggest that constitutive activation of STAT3 is an important factor related to carcinogenesis of human soft tissue tumors and is significantly associated with its clinicopathological parameters which may possibly have potential diagnostic implications.

  20. Gene expression programs of human smooth muscle cells: tissue-specific differentiation and prognostic significance in breast cancers.

    Directory of Open Access Journals (Sweden)

    Jen-Tsan Chi

    2007-09-01

    Full Text Available Smooth muscle is present in a wide variety of anatomical locations, such as blood vessels, various visceral organs, and hair follicles. Contraction of smooth muscle is central to functions as diverse as peristalsis, urination, respiration, and the maintenance of vascular tone. Despite the varied physiological roles of smooth muscle cells (SMCs, we possess only a limited knowledge of the heterogeneity underlying their functional and anatomic specializations. As a step toward understanding the intrinsic differences between SMCs from different anatomical locations, we used DNA microarrays to profile global gene expression patterns in 36 SMC samples from various tissues after propagation under defined conditions in cell culture. Significant variations were found between the cells isolated from blood vessels, bronchi, and visceral organs. Furthermore, pervasive differences were noted within the visceral organ subgroups that appear to reflect the distinct molecular pathways essential for organogenesis as well as those involved in organ-specific contractile and physiological properties. Finally, we sought to understand how this diversity may contribute to SMC-involving pathology. We found that a gene expression signature of the responses of vascular SMCs to serum exposure is associated with a significantly poorer prognosis in human cancers, potentially linking vascular injury response to tumor progression.

  1. The incidence of MYB gene breaks in adenoid cystic carcinoma of the salivary glands and its prognostic significance.

    Science.gov (United States)

    Broz, Martin; Steiner, Petr; Salzman, Richard; Hauer, Lukas; Starek, Ivo

    2016-09-01

    To detect MYB gene breaks in adenoid cystic carcinoma (ACC) of the salivary glands and its correlation with prognosis and selected clinical parameters MYB gene break was detected by FISH assay in 23 adenoid cystic carcinomas using formalin-fixed paraffin-embedded blocks. The Kaplan-Meier survival analysis was used to estimate prognosis. Fifteen of 23 evaluated tumours were MYB positive and 8 MYB negative. The 10-year cumulative survival, respectively disease free interval, was 60.0%, respectively 59.3%, in MYB positive patients and 88.5%, respectively 80.0%, in MYB negative patients (long rank test, P=0.23). There were no significant differences in age, gender, perineural invasion, the presence of hematogenic or nodal metastases or degree of histopathological grading between MYB positive and MYB negative patients. A tendency to differences in the survival of patients with ACC, depending on their MYB status. MYB negative patients were predisposed to better prognosis.

  2. A prognostic model for development of significant liver fibrosis in HIV-hepatitis C co-infection.

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    Nasheed Moqueet

    Full Text Available Liver fibrosis progresses rapidly in HIV-Hepatitis C virus (HCV co-infected individuals partially due to heightened inflammation. Immune markers targeting stages of fibrogenesis could aid in prognosis of fibrosis.A case-cohort study was nested in the prospective Canadian Co-infection Cohort (n = 1119. HCV RNA positive individuals without fibrosis, end-stage liver disease or chronic Hepatitis B at baseline (n = 679 were eligible. A random subcohort (n = 236 was selected from those eligible. Pro-fibrogenic markers and Interferon Lambda (IFNL rs8099917 genotype were measured from first available sample in all fibrosis cases (APRI ≥ 1.5 during follow-up and the subcohort. We used Cox proportional hazards and compared Model 1 (selected clinical predictors only to Model 2 (Model 1 plus selected markers for predicting 3-year risk of liver fibrosis using weighted Harrell's C and Net Reclassification Improvement indices.113 individuals developed significant liver fibrosis over 1300 person-years (8.63 per 100 person-years 95% CI: 7.08, 10.60. Model 1 (age, sex, current alcohol use, HIV RNA, baseline APRI, HCV genotype was nested in model 2, which also included IFNL genotype and IL-8, sICAM-1, RANTES, hsCRP, and sCD14. The C indexes (95% CI for model 1 vs. model 2 were 0.720 (0.649, 0.791 and 0.756 (0.688, 0.825, respectively. Model 2 classified risk more appropriately (overall net reclassification improvement, p<0.05.Including IFNL genotype and inflammatory markers IL-8, sICAM-1, RANTES, hs-CRP, and sCD14 enabled better prediction of the 3-year risk of significant liver fibrosis over clinical predictors alone. Whether this modest improvement in prediction justifies their additional cost requires further cost-benefit analyses.

  3. The prognostic significance of cardiac structure and function in atrial fibrillation: the ENGAGE AF-TIMI 48 Echocardiographic Substudy

    Science.gov (United States)

    Gupta, Deepak K; Giugliano, Robert P; Ruff, Christian T; Claggett, Brian; Murphy, Sabina; Antman, Elliott; Mercuri, Michele F.; Braunwald, Eugene; Solomon, Scott D

    2016-01-01

    Background Atrial fibrillation (AF) is associated with increased risk for thromboembolism and death; however, the relationships between cardiac structure and function and adverse outcomes among individuals with AF are incompletely understood. Methods The ENGAGE AF –TIMI 48 study tested the once-daily oral factor Xa inhibitor edoxaban in comparison to warfarin for the prevention of stroke (ischemic or hemorrhagic) or systemic embolism in 21,105 subjects with nonvalvular AF and increased risk for thromboembolic events (CHADS2 ≥ 2). In a prospective substudy of 971 subjects who underwent transthoracic echocardiography at baseline, we used Cox proportional hazards models to evaluate the associations between cardiac structure and function and the risks for death and thromboembolism (ischemic stroke, TIA, or systemic embolism). Results Over a median follow up of 2.5 years, 89 (9.2%) deaths and 48 (4.9%) incident thromboembolic events occurred in 971 subjects. In models adjusted for CHADS2 score, aspirin use, and randomized treatment, larger LV end diastolic volume index (HR: 1.49 [95%CI: 1.16,1.91] per 1 SD [12.9 ml/m2]) and higher LV filling pressures measured by E/′e (HR: 1.32 [95%CI: 1.08,1.61] per 1 SD [4.6]) were independently associated with increased risks for death. E/e′ > 13 significantly improved prediction of death beyond clinical factors alone. No features of cardiac structure and function were independently associated with thromboembolism in this population. Findings were similar when adjusted for CHA2DS2-VASc in place of CHADS2. Conclusions In a contemporary population of patients with atrial fibrillation at increased risk for thromboembolic events, larger LV size and higher filling pressures were significantly associated with increased risk for death, but neither left atrial nor left ventricular measures were associated with thromboembolic risk. LV size and filling pressures may help identify AF patients at increased risk of death. PMID:27106009

  4. Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction

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    Carlos Alberto Scrideli

    2001-09-01

    Full Text Available CONTEXT: The CDR-3 region of heavy-chain immunoglobulin has been used as a clonal marker in the study of minimal residual disease in children with acute lymphoblastic leukemia. Southern blot and polymerase chain reaction studies have demonstrated the occurrence of bi/oligoclonality in a variable number of cases of B-lineage acute lymphoblastic leukemia, a fact that may strongly interfere with the detection of minimal residual disease. Oligoclonality has also been associated with a poorer prognosis and a higher chance of relapse. OBJECTIVES: To correlate bi/oligoclonality, detected by polymerase chain reaction in Brazilian children with B-lineage acute lymphoblastic leukemia with a chance of relapse, with immunophenotype, risk group, and disease-free survival. DESIGN: Prospective study of patients’ outcome. SETTING: Pediatric Oncology Unit of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. PARTICIPANTS: 47 children with acute lymphoblastic leukemia DIAGNOSTIC TEST: Polymerase chain reaction using consensus primers for the CDR-3 region of heavy chain immunoglobulin (FR3A, LJH and VLJH for the detection of clonality. RESULTS: Bi/oligoclonality was detected in 15 patients (31.9%. There was no significant difference between the groups with monoclonality and biclonality in terms of the occurrence of a relapse (28.1% versus 26.1%, presence of CALLA+ (81.2% versus 80% or risk group (62.5% versus 60%. Disease-free survival was similar in both groups, with no significant difference (p: 0.7695. CONCLUSIONS: We conclude that bi/oligoclonality was not associated with the factors investigated in the present study and that its detection in 31.9% of the patients may be important for the study and monitoring of minimal residual disease.

  5. Atypical Squamous Cells of Undetermined Significance: Bethesda Classification and Association with Human Papillomavirus

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    Ana Cristina Macêdo Barcelos; Márcia Antoniazi Michelin; Sheila Jorge Adad; Eddie Fernando Candido Murta

    2011-01-01

    Introduction. To analyze patients with atypical squamous cells of undetermined significance (ASCUS) through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking. Methods. 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, A...

  6. A STUDY ON CLINICAL AND PROGNOSTIC SIGNIFICANCE OF GAMMA-GLUTAMYL TRANSFERASE IN PATIENTS WITH ACUTE STROKE

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    Shriram Ganesh R. T

    2017-07-01

    Full Text Available BACKGROUND Stroke is one of the major health problems in many countries. There is supporting evidence suggesting that Gamma-Glutamyl Transferase (GGT enzyme has an active involvement in atherosclerosis through its oxidative and inflammatory mechanisms. With this background, we conducted a study among acute stroke patients with an aim and objective to evaluate the relationship between stroke and serum GGT levels and to assess the severity of various types of stroke in relation to the levels of serum GGT enzyme. MATERIALS AND METHODS A total of 50 acute stroke patients and 50 normal individuals as controls participated in the study. Stroke patients were advised for routine haematological investigations, serum GGT estimation and plain CT of brain. RESULTS Out of the 50 acute stroke patients who participated in our study, 32 patients had elevated levels of serum GGT and 3 patients had drastically elevated levels of GGT (>100 IU/L. A statistically significant relationship was found between ischaemic stroke and GGT with a p-value of 0.0418. CONCLUSION Gamma-glutamyl transferase estimation in acute stroke patients may serve as a reliable and feasible clinical test for the physician to initially stratify patient risk and provide prompt therapy.

  7. Management, Diagnostic and Prognostic Significance of Acetylcholinesterase as a Biomarker of the Toxic Effects of Pesticides in People Occupationally Exposed

    Science.gov (United States)

    Lutovac, Mitar; Popova, Olga V.; Jovanovic, Zoran; Berisa, Hatidza; Kristina, Radoman; Ketin, Sonja; Bojic, Marko

    2017-01-01

    AIM: The paper presents research on the most common causes of exposure that leads to disorders of cholinesterase activity, as well as an overview of the results of cholinesterase activity with the poisoned people. MATERIAL AND METHODS: In a group of 35 acute poisoned patients by organophosphate compounds has led to inhibition of AchE. A total number of examined workers are 175 in the chemical industry and agricultural production in the area of Rasina District-Serbia. RESULTS: The results showed that among workers who are constantly exposed to pesticides, acetylcholinesterase is within the reference value. Having examined the medical records of these workers, it is noted that, at 72%, there is a slight fall of AchE activity, each year. The workers who had been exposed to pesticides at the time of testing had acetylcholinesterase regarding reference value, but 52% of them had a few years ago significantly reduced the value of the activity of acetylcholinesterase, which was treated and then transferred to other jobs. The 48% of these workers had acetylcholinesterase regarding benchmarks or were transferred to other jobs, for a variety of other health problems. CONCLUSION: Using each pesticide should only deal with people who are well versed in the way of its use, as well as the way of protecting them from poisoning.

  8. Prognostic Significance of Blood Transfusion in Newly Diagnosed Multiple Myeloma Patients without Autologous Hematopoietic Stem Cell Transplantation

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    Liping Fan

    2017-01-01

    Full Text Available The aim of this study was to evaluate whether blood transfusions affect overall survival (OS and progression-free survival (PFS in newly diagnosed multiple myeloma (MM patients without hematopoietic stem cell transplantation. A total of 181 patients were enrolled and divided into two groups: 68 patients in the transfused group and 113 patients in the nontransfused group. Statistical analyses showed that there were significant differences in ECOG scoring, Ig isotype, platelet (Plt counts, hemoglobin (Hb level, serum creatinine (Scr level, and β2-microglobulin (β2-MG level between the two groups. Univariate analyses showed that higher International Staging System staging, Plt counts < 100 × 109/L, Scr level ≥ 177 μmol/L, serum β2-MG ≥ 5.5 μmol/L, serum calcium (Ca ≥ 2.75 mmol/L, and thalidomide use were associated with both OS and PFS in MM patients. Age ≥ 60 was associated with OS and Ig isotype was associated with PFS in MM patients. Moreover, blood transfusion was associated with PFS but not OS in MM patients. Multivariate analyses showed that blood transfusion was not an independent factor for PFS in MM patients. Our preliminary results suggested that newly diagnosed MM patients may benefit from a liberal blood transfusion strategy, since blood transfusion is not an independent impact factor for survival.

  9. Prognostic significance of miR-23b in combination with P-gp, MRP and LRP/MVP expression in non-small cell lung cancer.

    Science.gov (United States)

    Janikova, M; Zizkova, V; Skarda, J; Kharaishvili, G; Radova, L; Kolar, Z

    2016-01-01

    Recently, miR-23b has emerged as a promising new cancer biomarker but its role in lung cancer has not been established yet. Patients still do not respond well to available treatments, probably due to expression of multidrug resistance (MDR) proteins, such as P-gp, MRP and LRP/MVP. The aim of this study was to determine the role of miR-23b in non-small cell lung cancer (NSCLC) and its relationship to the patient outcome together with MDR transporter proteins. We immunohistochemically evaluated expression of P-gp, MRP and LRP/MVP and quantified the relative levels of miR-23b in 62 NSCLC patients´ samples. The prognostic significance of miR-23b and MDR proteins was tested by Kaplan-Meier and Cox-regression analysis. Our results showed that miR-23b is mostly downregulated in NSCLC samples (57/62) and that its upregulation in tumors is connected with longer progression-free survival (PFS; P = 0.065) and overall survival (OS; P = 0.048). The Cox proportional hazard model revealed that the risk of death or relapse in NSCLC patients with miR-23b downregulation increases together with LRP/MVP expression and both risks decrease with miR-23b upregulation (HRPFS = 4.342, PPFS = 0.022; HROS = 4.408, POS = 0.015). Our findings indicate that miR-23b, especially in combination with LRP/MVP expression, might serve as a suitable prognostic biomarker for NSCLC patients.

  10. Prognostic significance of the complex "Visceral Adiposity Index" vs. simple anthropometric measures: Tehran lipid and glucose study.

    Science.gov (United States)

    Mohammadreza, Bozorgmanesh; Farzad, Hadaegh; Davoud, Khalili; Fereidoun Prof, Azizi Fereidoun

    2012-03-07

    Visceral adiposity index (VAI) has recently been suggested to be used as a surrogate of visceral adiposity. We examined if VAI could improve predictive performances for CVD of the Framingham's general CVD algorithm (a multivariate model incorporating established CVD risk factors). We compared the predictive abilities of the VAI with those of simple anthropometric measures i.e. BMI, waist-to-height ratio (WHtR) or waist-to-hip ratio (WHpR). In a nine-year population-based follow-up, 6,407 (2,778 men) participants, free of CVD at baseline, aged≥30 years were eligible for the current analysis. The risk of CVD was estimated by incorporating VAI, BMI, WHpR, and WHtR, one at a time, into multivariate accelerated failure time models. We documented 534 CVD events with the annual incidence rate (95%CIs) being 7.3 (6.4-8.3) among women and 13.0 (11.7-14.6) among men. Risk of future CVD increased with increasing levels of VAI among both men and women. VAI was associated with multivariate-adjusted increased risk of incident CVD among women. However, the magnitude of risk conferred by VAI was not significantly higher than those conferred by BMI, WHpR, or WHtR. Among men, after adjustment for established CVD risk factors, VAI was no longer associated with increased risk of CVD. VAI failed to add to the predictive ability of the Framingham general CVD algorithm. Using VAI instead of simple anthropometric measures may lead to loss of much information needed for predicting incident CVD.

  11. The Prognostic Significance of CD44V6, CDH11, and β-Catenin Expression in Patients with Osteosarcoma

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    Zhouming Deng

    2013-01-01

    Full Text Available This study aimed to examine the expression of and the relationship between CD44V6, CDH11, and β-catenin. The expression of these cell adhesion molecules was detected in 90 osteosarcoma and 20 osteochondroma specimens using immunohistochemistry. Associations between these parameters and clinicopathological data were also examined. The expression rates of CD44V6, CDH11, and β-catenin were 25.0% (5/20, 70.0% (14/20, and 20.0% (4/20 in osteochondroma specimens, respectively. Compared to osteochondromas, the proportions of expression of CD44V6 and β-catenin in osteosarcoma specimens increased to 65.6% (59/90 and 60.0% (54/90, respectively. However, the expression rate of CDH11 in osteosarcomas was reduced to 40.0% (36/90. The expression of these markers was significantly associated with metastasis and overall survival (P<0.05. Survival analysis revealed that patients with increased expression of CD44V6 and β-catenin as well as decreased expression of CDH11 were correlated with a shorter survival time. Multivariate analysis indicated that clinical stage, metastasis status, and the expression of CD44V6, CDH11, and β-catenin were found to be associated with overall survival. Further, the expression of β-catenin and that of CD44V6 were positively correlated with each other. Thus, our results indicated abnormal expression of CD44V6, CDH11, and β-catenin in osteosarcomas and osteochondromas, which may provide important indicators for further research.

  12. Prognostic significance of cellular vascular endothelial growth factor (VEGF expression in the course of chronic myeloid leukaemia

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    Vidović Ana

    2009-01-01

    Full Text Available Introduction. Increased angiogenesis in bone marrow is one of the characteristics of chronic myeloid leukaemia (CML, a clonal myeloproliferative disorder that expresses a chimeric bcr/abl protein. Vascular endothelial growth factor (VEGF is one of the most potent and a specific regulator of angiogenesis which principally targets endothelial cells and regulates several of their functions, including mitogenesis, permeability and migration. The impact of elevated VEGF expression on the course of chronic myeloid leukaemia is unknown. Objective. The aim of this study was the follow-up of VEGF expression during the course of CML. Methods. We studied VEGF expression of 85 CML patients (median age 50 years, range 16-75 years. At the commencement of the study, 29 patients were in chronic phase (CP, 25 in an accelerated phase (AP, and 31 in the blast crisis (BC. The temporal expression (percentage positivity per 1000 analysed cells VEGF proteins over the course of CML were studied using the immunohistochemical technique utilizing relevant monoclonal antibodies. It was correlated with the laboratory (Hb, WBC and platelet counts, and the percentage of blasts and clinical parameters (organomegaly, duration of CP, AP, and BC of disease progression. Results. The expression of VEGF protein was most pronounced in AP (ANOVA, p=0.033. The level of VEGF expression correlated inversely with the degree of splenomegaly (Pearson, r=-0.400, p=0.011. High expression of VEGF correlated with a shorter overall survival (log rank, p=0.042. Conclusion. Immunohistochemically confirmed significance of the expression of VEGF in dependence of the CML stage could be of clinical importance in deciding on the timing therapy. These data suggest that VEGF plays a role in the biology of CML and that VEGF inhibitors should be investigated in CML.

  13. Hematologic, clinical, and cytogenetic analysis in 109 patients with primary myelodysplastic syndrome. Prognostic significance of morphology and chromosome findings.

    Science.gov (United States)

    Parlier, V; van Melle, G; Beris, P; Schmidt, P M; Tobler, A; Haller, E; Bellomo, M J

    1994-12-01

    One hundred and nine patients with primary myelodysplastic syndrome (MDS) were classified according to the French-American-British (FAB) criteria: 27 refractory anemia (RA, 25%), 26 RA with ringed sideroblasts (RARS, 24%), 16 RA with excess of blasts (RAEB, 15%), 10 RAEB in transformation (RAEB-t, 9%), 25 chronic myelomonocytic leukemia (CMMoL, 23%), and five unclassifiable MDS (4%). Forty-three were women and 66 were men (sex ratio 2:3). Age ranged from 30-92 years (mean 69 years) with nine patients aged less than 50 years (8%). A cytogenetic result was obtained in all cases. At initial study, a chromosome defect was observed in 56% of patients. Rates of abnormality depended on FAB subtype: 52% in RA, 100% in RA 5q-, 50% in RARS, 56% in RAEB, 70% in RAEB-t and 44% in CMMoL. The most frequent single defects were del(5q), -7/del(7q), del(20q), Y loss, and +8. Except for the 5q- syndrome entity, specific chromosome defects were not associated with particular FAB subtypes. Bone marrow (BM) insufficiency (22%) and leukemic transformation (21%) were the most important causes of death. The rate of leukemic transformation increased with the number of dysplastic BM cell lineages and was also associated with karyotype complexity and the proportion of abnormal/normal metaphases. The longest median survivals were observed in RARS (142 months) and RA/RA5q- (91 months) types. Median survivals decreased with increasing Bournemouth score values. Patients with three abnormal cell lineages had a median survival shorter than those with one or two abnormal lineages. Similarly, patients with complex defects had shorter survival than those with single or double defects or a normal karyotype. There was no statistically significant difference between survival of NN (normal), AN (abnormal/normal), and AA patients or between survival of patients with del(5q), -7/del(7q), +8 or del(20q).

  14. PREVALENCE AND PROGNOSTIC SIGNIFICANCE OF APPARENT TREATMENT RESISTANT HYPERTENSION IN CHRONIC KIDNEY DISEASE: A REPORT FROM THE CRIC STUDY

    Science.gov (United States)

    Thomas, George; Xie, Dawei; Chen, Hsiang-Yu; Anderson, Amanda H.; Appel, Lawrence; Bodana, Shirisha; Brecklin, Carolyn S.; Drawz, Paul; Flack, John M.; Miller, Edgar R.; Steigerwalt, Susan P.; Townsend, Raymond R.; Weir, Matthew R.; Wright, Jackson T.; Rahman, Mahboob

    2015-01-01

    The association between apparent treatment resistant hypertension (ATRH) and clinical outcomes is not well studied in chronic kidney disease (CKD). We analyzed data on 3367 hypertensive participants in the Chronic Renal Insufficiency Cohort (CRIC) to determine prevalence, associations, and clinical outcomes of ATRH in non-dialysis CKD patients. ATRH was defined as blood pressure (BP) ≥140/90 mm Hg on ≥3 antihypertensives, or use of ≥4 antihypertensives with BP at goal at baseline visit. Prevalence of ATRH was 40.4%. Older age, male gender, black race, diabetes, and higher BMI were independently associated with higher odds of having ATRH. Participants with ATRH had a higher risk of clinical events compared to participants without ATRH - composite of myocardial infarction (MI), stroke, peripheral arterial disease (PAD), congestive heart failure (CHF), and all-cause mortality HR [95% CI]: (1.38 [1.22,1.56]); renal events (1.28 [1.11, 1.46]); CHF (1.66 [1.38, 2.00]); and all-cause mortality (1.24 [1.06,1.45]). The subset of participants with ATRH and BP at goal on ≥ 4 medications also had higher risk for composite of MI, stroke, PAD, CHF, and all-cause mortality HR [95% CI] (1.30 [1.12, 1.51]) and CHF (1.59 [1.28, 1.99]) compared to those without ATRH. ATRH was associated with significantly higher risk for CHF and renal events only among those with eGFR ≥30 ml/min/1.73 m2. Our findings show that ATRH is common and associated with high risk of adverse outcomes in a cohort of patients with CKD. This underscores the need for early identification and management of patients with ATRH and CKD. PMID:26711738

  15. Patient-specific metrics of invasiveness reveal significant prognostic benefit of resection in a predictable subset of gliomas.

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    Anne L Baldock

    Full Text Available Malignant gliomas are incurable, primary brain neoplasms noted for their potential to extensively invade brain parenchyma. Current methods of clinical imaging do not elucidate the full extent of brain invasion, making it difficult to predict which, if any, patients are likely to benefit from gross total resection. Our goal was to apply a mathematical modeling approach to estimate the overall tumor invasiveness on a patient-by-patient basis and determine whether gross total resection would improve survival in patients with relatively less invasive gliomas.In 243 patients presenting with contrast-enhancing gliomas, estimates of the relative invasiveness of each patient's tumor, in terms of the ratio of net proliferation rate of the glioma cells to their net dispersal rate, were derived by applying a patient-specific mathematical model to routine pretreatment MR imaging. The effect of varying degrees of extent of resection on overall survival was assessed for cohorts of patients grouped by tumor invasiveness.We demonstrate that patients with more diffuse tumors showed no survival benefit (P = 0.532 from gross total resection over subtotal/biopsy, while those with nodular (less diffuse tumors showed a significant benefit (P = 0.00142 with a striking median survival benefit of over eight months compared to sub-totally resected tumors in the same cohort (an 80% improvement in survival time for GTR only seen for nodular tumors.These results suggest that our patient-specific, model-based estimates of tumor invasiveness have clinical utility in surgical decision making. Quantification of relative invasiveness assessed from routinely obtained pre-operative imaging provides a practical predictor of the benefit of gross total resection.

  16. Pharmacology of Ultrasonic Vocalizations in adult Rats: Significance, Call Classification and Neural Substrate.

    Science.gov (United States)

    Brudzynski, Stefan M

    2015-01-01

    Pharmacological studies of emotional arousal and initiation of emotional states in rats measured by their ultrasonic vocalizations are reviewed. It is postulated that emission of vocalizations is an inseparable feature of emotional states and it evolved from mother-infant interaction. Positive emotional states are associated with emission of 50 kHz vocalizations that could be induced by rewarding situations and dopaminergic activation of the nucleus accumbens and are mediated by D1, D2, and partially D3 dopamine receptors. Three biologically significant subtypes of 50 kHz vocalizations have been identified, all expressing positive emotional states: (1) flat calls without frequency modulation that serve as contact calls during social interactions; (2) frequencymodulated calls without trills that signal rewarding and significantly motivated situation; and (3) frequency-modulated calls with trills or trills themselves that are emitted in highly emotional situations associated with intensive affective state. Negative emotional states are associated with emission of 22 kHz vocalizations that could be induced by aversive situations, muscarinic cholinergic activation of limbic areas of medial diencephalon and forebrain, and are mediated by M2 muscarinic receptors. Two biologically significant subtypes of 22 kHz vocalizations have been identified, both expressing negative emotional sates: (1) long calls that serve as alarm calls and signal external danger; and (2) short calls that express a state of discomfort without external danger. The positive and negative states with emission of vocalizations are initiated by two ascending reticular activating subsystems: the mesolimbic dopaminergic subsystem as a specific positive arousal system, and the mesolimbic cholinergic subsystem as a specific negative arousal system.

  17. Prognostic significance of social network, social support and loneliness for course of major depressive disorder in adulthood and old age.

    Science.gov (United States)

    van den Brink, R H S; Schutter, N; Hanssen, D J C; Elzinga, B M; Rabeling-Keus, I M; Stek, M L; Comijs, H C; Penninx, B W J H; Oude Voshaar, R C

    2017-02-10

    Poor recovery from depressive disorder has been shown to be related to low perceived social support and loneliness, but not to social network size or frequency of social interactions. Some studies suggest that the significance of social relationships for depression course may be greater in younger than in older patients, and may differ between men and women. None of the studies examined to what extent the different aspects of social relationships have unique or overlapping predictive values for depression course. It is the aim of the present study to examine the differential predictive values of social network characteristics, social support and loneliness for the course of depressive disorder, and to test whether these predictive associations are modified by gender or age. Two naturalistic cohort studies with the same design and overlapping instruments were combined to obtain a study sample of 1474 patients with a major depressive disorder, of whom 1181 (80.1%) could be studied over a 2-year period. Social relational variables were assessed at baseline. Two aspects of depression course were studied: remission at 2-year follow-up and change in depression severity over the follow-up period. By means of logistic regression and random coefficient analysis, the individual and combined predictive values of the different social relational variables for depression course were studied, controlling for potential confounders and checking for effect modification by age (below 60 v. 60 years or older) and gender. Multiple aspects of the social network, social support and loneliness were related to depression course, independent of potential confounders - including depression severity - but when combined, their predictive values were found to overlap to a large extent. Only the social network characteristic of living in a larger household, the social support characteristic of few negative experiences with the support from a partner or close friend, and limited feelings of

  18. Prognostic significance of Ki67 proliferation index, HIF1 alpha index and microvascular density in patients with non-small cell lung cancer brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Berghoff, A.S. [Medical University of Vienna, Institute of Neurology, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Ilhan-Mutlu, A.; Preusser, M. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Woehrer, A.; Hainfellner, J.A. [Medical University of Vienna, Institute of Neurology, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Hackl, M. [Austrian National Cancer Registry, Statistics Austria, Vienna (Austria); Widhalm, G. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Neurosurgery, Vienna (Austria); Dieckmann, K. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Radiotherapy, Vienna (Austria); Melchardt, T. [Paracelsus Medical University Hospital Salzburg, Third Medical Department, Salzburg (Austria); Dome, B. [Medical University of Vienna, Department of Surgery, Vienna (Austria); Heinzl, H. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Center for Medical Statistics, Informatics, and Intelligent Systems, Vienna (Austria); Birner, P. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Institute of Clinical Pathology, Vienna (Austria)

    2014-07-15

    Survival upon diagnosis of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) is highly variable and established prognostic scores do not include tissue-based parameters. Patients who underwent neurosurgical resection as first-line therapy for newly diagnosed NSCLC BM were included. Microvascular density (MVD), Ki67 tumor cell proliferation index and hypoxia-inducible factor 1 alpha (HIF-1 alpha) index were determined by immunohistochemistry. NSCLC BM specimens from 230 patients (151 male, 79 female; median age 56 years; 199 nonsquamous histology) and 53/230 (23.0 %) matched primary tumor samples were available. Adjuvant whole-brain radiation therapy (WBRT) was given to 153/230 (66.5 %) patients after neurosurgical resection. MVD and HIF-1 alpha indices were significantly higher in BM than in matched primary tumors. In patients treated with adjuvant WBRT, low BM HIF-1 alpha expression was associated with favorable overall survival (OS), while among patients not treated with adjuvant WBRT, BM HIF-1 alpha expression did not correlate with OS. Low diagnosis-specific graded prognostic assessment score (DS-GPA), low Ki67 index, high MVD, low HIF-1 alpha index and administration of adjuvant WBRT were independently associated with favorable OS. Incorporation of tissue-based parameters into the commonly used DS-GPA allowed refined discrimination of prognostic subgroups. Ki67 index, MVD and HIF-1 alpha index have promising prognostic value in BM and should be validated in further studies. (orig.) [German] Die Ueberlebensprognose von Patienten mit zerebralen Metastasen eines nicht-kleinzelligen Lungenkarzinoms (NSCLC) ist sehr variabel. Bisher werden gewebsbasierte Parameter nicht in die prognostische Beurteilung inkludiert. Neurochirurgische Resektate zerebraler NSCLC-Metastasen wurden in dieser Studie untersucht. Die Gefaessdichte (''microvascular density'', MVD), der Ki67-Proliferationsindex sowie der HIF-1α-Index wurden mittels

  19. A transfer learning approach for classification of clinical significant prostate cancers from mpMRI scans

    Science.gov (United States)

    Chen, Quan; Xu, Xiang; Hu, Shiliang; Li, Xiao; Zou, Qing; Li, Yunpeng

    2017-03-01

    Deep learning has shown a great potential in computer aided diagnosis. However, in many applications, large dataset is not available. This makes the training of a sophisticated deep learning neural network (DNN) difficult. In this study, we demonstrated that with transfer learning, we can quickly retrain start-of-the-art DNN models with limited data provided by the prostateX challenge. The training data consists of 330 lesions, only 78 were clinical significant. Efforts were made to balance the data during training. We used ImageNet pre-trained inceptionV3 and Vgg-16 model and obtained AUC of 0.81 and 0.83 respectively on the prostateX test data, good for a 4th place finish. We noticed that models trained for different prostate zone has different sensitivity. Applying scaling factors before merging the result improves the AUC for the final result.

  20. Atypical Squamous Cells of Undetermined Significance: Bethesda Classification and Association with Human Papillomavirus

    Science.gov (United States)

    Barcelos, Ana Cristina Macêdo; Michelin, Márcia Antoniazi; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

    2011-01-01

    Introduction. To analyze patients with atypical squamous cells of undetermined significance (ASCUS) through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking. Methods. 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV) were performed. Results. Upon review, ASCUS was diagnosis in 70/103 (67.9%), being 38 (54.2%) reactive ASCUS and 32 (45.71%) neoplastic ASCUS; 62 (88.5%) ASC-US and 8 (11.41%) ASC-H. ASCUS (Regione Protocol), respectively 1-5: 15 (21.4%), 19 (27.1%), 3 (27.1%), 16 (22.8%), and 1 (1.4%). A higher number of cases of cervical intraepithelial neoplasia (CIN) II/III in the biopsies of patients with ASC-H compared to ASC-US (P = .0021). High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P = .031). Conclusions. ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN. PMID:21760701

  1. Prognostic Significance of Digital Rectal Examination and Prostate Specific Antigen in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Arm.

    Science.gov (United States)

    Halpern, Joshua A; Shoag, Jonathan E; Mittal, Sameer; Oromendia, Clara; Ballman, Karla V; Hershman, Dawn L; Wright, Jason D; Shih, Ya-Chen Tina; Nguyen, Paul L; Hu, Jim C

    2017-02-01

    The absence of definitive data or explicit guidelines regarding the use of digital rectal examination for prostate cancer screening may lead to confusion for physicians and patients alike. We evaluated the prognostic value of abnormal digital rectal examination and prostate specific antigen following the widespread dissemination of prostate specific antigen testing in the U.S. Collectively, men comprising the screening arm of the PLCO cancer screening trial who underwent digital rectal examination screening (35,350) were followed for 314,033 person-years. Adjusted analyses with competing risks regression were performed to assess the association of suspicious (nodularity, induration, asymmetry) digital rectal examination and abnormal prostate specific antigen (4 ng/ml or greater) with the detection of clinically significant prostate cancer, prostate cancer specific mortality and overall mortality. Among all screening encounters with a suspicious digital rectal examination only 15.4% had a concurrently abnormal prostate specific antigen (McNemar's test p digital rectal examination and abnormal prostate specific antigen were associated with a greater risk of clinically significant prostate cancer (HR 2.21, 95% CI 1.99-2.44 vs HR 5.48, 95% CI 5.05-5.96, p digital rectal examination and abnormal prostate specific antigen on routine screening were independently associated with clinically significant prostate cancer and prostate cancer specific mortality. However, additional research is needed to optimize screening protocols. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Prognostic Factors in Hodgkin's Disease

    DEFF Research Database (Denmark)

    Specht

    1996-01-01

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

  3. Classification of Non-Small Cell Lung Cancer Using Significance Analysis of Microarray-Gene Set Reduction Algorithm

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2016-01-01

    Full Text Available Among non-small cell lung cancer (NSCLC, adenocarcinoma (AC, and squamous cell carcinoma (SCC are two major histology subtypes, accounting for roughly 40% and 30% of all lung cancer cases, respectively. Since AC and SCC differ in their cell of origin, location within the lung, and growth pattern, they are considered as distinct diseases. Gene expression signatures have been demonstrated to be an effective tool for distinguishing AC and SCC. Gene set analysis is regarded as irrelevant to the identification of gene expression signatures. Nevertheless, we found that one specific gene set analysis method, significance analysis of microarray-gene set reduction (SAMGSR, can be adopted directly to select relevant features and to construct gene expression signatures. In this study, we applied SAMGSR to a NSCLC gene expression dataset. When compared with several novel feature selection algorithms, for example, LASSO, SAMGSR has equivalent or better performance in terms of predictive ability and model parsimony. Therefore, SAMGSR is a feature selection algorithm, indeed. Additionally, we applied SAMGSR to AC and SCC subtypes separately to discriminate their respective stages, that is, stage II versus stage I. Few overlaps between these two resulting gene signatures illustrate that AC and SCC are technically distinct diseases. Therefore, stratified analyses on subtypes are recommended when diagnostic or prognostic signatures of these two NSCLC subtypes are constructed.

  4. Synchronization of cortisol circadian rhythm by the pineal hormone melatonin in untreatable metastatic solid tumor patients and its possible prognostic significance on tumor progression.

    Science.gov (United States)

    Brivio, Fernando; Fumagalli, Luca; Fumagalli, Gabriele; Pescia, Simonetta; Brivio, Rinaldo; Di Fede, Giuseppe; Rovelli, Franco; Lissoni, Paolo

    2010-01-01

    Cancer progression has been associated with neuroendocrine alterations involved in the control of the circadian rhythms, particularly those of cortisol. Moreover, the evidence of an altered cortisol rhythm may predict a poor prognosis in cancer patients. Finally, cancer progression has been proven to be associated with alterations in the pineal gland, which plays a fundamental role in the control of circadian biological rhythms. On this basis, a study was planned to evaluate the effects of a chronic treatment with the pineal hormone melatonin (MLT) in advanced cancer patients with altered cortisol circadian rhythm. The study included 14 untreatable metastatic cancer patients showing alterations of cortisol rhythm. They were treated by MLT at 20 mg/day orally, in the evening, for 3 consecutive months. a normalization of cortisol rhythm was achieved in 4/14 (29%) patients. Moreover, stable disease (SD) was obtained in 6/14 (43%) patients under MLT therapy, whereas the other 8 patients had progressive disease (PD). Finally, the percentage of cortisol rhythm normalization achieved in patients with SD was significantly higher than that observed in patients with PD. These results show that MLT may normalize cortisol rhythm in advanced cancer patients and this effect appears to be associated with SD, thus confirming the negative prognostic significance of cortisol rhythm alterations in cancer.

  5. Outcome Analysis of First-line Somatostatin Analog Treatment in Metastatic Pulmonary Neuroendocrine Tumors and Prognostic Significance of (18)FDG-PET/CT.

    Science.gov (United States)

    Bongiovanni, Alberto; Recine, Federica; Riva, Nada; Foca, Flavia; Liverani, Chiara; Mercatali, Laura; Nicolini, Silvia; Pieri, Federica; Amadori, Dino; Ibrahim, Toni

    2017-07-01

    Pulmonary carcinoids (PCs) are classed according to the World Health Organization 2004 classification as typical or atypical carcinoids. Owing to their rarity, no dedicated clinical trials with somatostatin analogs (SSAs) have been carried out on primary PCs. From January 2007 to December 2015, 30 patients with metastatic PCs underwent first-line SSA treatment (20 with octreotide long-acting repeatable 30 mg and 10 with lanreotide 120 mg every 28 days). Eight (23.3%) patients had typical carcinoids and 23 (76.7%) had atypical carcinoids. The median age was 65.5 years (range, 47-82 years). All patients (23 males and 7 females) were Gallium-68-DOTA-TOC-positron emission tomography/computed tomography (PET/CT)-positive (29 patients) or octreoscan-positive (1 patient). Of the 20 patients who performed fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)FDG-PET/CT), 14 (70.0%) were positive and 6 negative (30.0%). The median treatment duration was 10 months (range, 2-59 months). One patient achieved a partial response (3.3%), and 26 (86.6%) showed stable disease. One patient interrupted SSA treatment owing to symptomatic cholelithiasis. Five-year survival was 53.0% (95% confidence interval [CI], 15.0%-80.0%). The median progression-free survival (mPFS) was 11.1 months (95% CI, 7.0-15.0 months). Negative (18)FDG-PET/CT patients had an mPFS of 15.2 months (95% CI, 7.6 months to not reached) compared with 7.0 months (95% CI, 4.0-10.1 months) for (18)FDG-PET/CT-positive patients. No differences in mPFS were found in relation to TTF1-value, histologic subtype, and presence of extrahepatic metastases. SSAs showed antitumor activity in terms of disease control rate and PFS and proved safe, even in patients with poor Eastern Cooperative Oncology Group status. (18)FDG-PET/CT would appear to be a prognostic factor. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Differential expression and prognostic significance of GLUT1 according to histologic type of non-small-cell lung cancer and its association with volume-dependent parameters.

    Science.gov (United States)

    Koh, Young Wha; Lee, Su Jin; Park, Seong Yong

    2017-02-01

    We evaluated glucose transporter type 1 (GLUT1) and carbonic anhydrase IX (CAIX) expression, together with volume-based18F-fluorodeoxyglucose positron emission tomography (FDG-PET) parameters, in non-small cell lung cancer (NSCLC) patients, and examined the prognostic significance of those parameters according to its histologic subtype. A total of 269 patients, who underwent surgical resection for NSCLC, were reviewed retrospectively. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values were measured by preoperative 18F-fluorodeoxyglucose positron emission tomography computed tomography. GLUT1 and CAIX expression was evaluated using immunohistochemical method. The mean MTV and TLG values were 30.0±57.1 and 165.4±361.3, respectively, and were significantly higher in patients with squamous cell carcinoma than with adenocarcinoma (p=0.047 for MTV; p=0.042 for TLG). GLUT1 expression was identified in 99% of squamous cell carcinoma and 50% of adenocarcinoma patients. MTV and TLG values were significantly higher in GLUT1-positive than GLUT-negative adenocarcinomas; however, CAIX expression did not show this pattern. GLUT1-positive adenocarcinoma patients had a lower OS than GLUT1-negative patients (plung adenocarcinoma patients (hazard ratio=2.574, p=0.016). GLUT1 expression was associated with micropapillary/solid histology, lymphovascular invasion, and advanced pTNM stage. MTV and TLG values, and GLUT1 expression, significantly differed between patients with squamous cell carcinoma and adenocarcinoma. High GLUT1 expression levels were significantly associated with MTV and TLG values and adverse clinical outcomes in patients with adenocarcinoma. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Requirements Specifications for Prognostics: An Overview

    Data.gov (United States)

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

  8. On Applying the Prognostic Performance Metrics

    Data.gov (United States)

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

  9. Metrics for Offline Evaluation of Prognostic Performance

    Data.gov (United States)

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

  10. Prognostic Significance of Tumor Response as Assessed by Sequential {sup 18}F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography During Concurrent Chemoradiation Therapy for Cervical Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Dongryul [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Jeong Eun [Department of Radiation Oncology, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Huh, Seung Jae, E-mail: sj5201.huh@samsung.com [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, Won [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Nam, Heerim [Department of Radiation Oncology, Kangbuk Samsung Hospital, Seoul (Korea, Republic of); Choi, Joon Young; Kim, Byung-Tae [Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2013-11-01

    Purpose: To investigate the prognostic role of metabolic response by the use of serial sets of positron emission tomography/computed tomography (PET/CT) in patients with cervical cancer who were treated with concurrent chemoradiation therapy (CCRT). Methods and Materials: A total of 60 patients who were treated with CCRT between February 2009 and December 2010 were analyzed. Three sequential PET/CT images were acquired for each patient: pre-CCRT, during-CCRT at 4 weeks of CCRT, and 1 month post-CCRT PET/CT. Metabolic responses were assessed qualitatively. The percentage changes in the maximum values of standardized uptake value (ΔSUV{sub max}%) from the PET/CT images acquired pre-CCRT and during-CCRT were calculated. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether ΔSUV{sub max}% could predict complete response (CR) on the post-CCRT PET/CT and to identify the best cutoff value. Prognostic factors of progression-free survival (PFS) were analyzed. Results: During-CCRT PET/CT showed that 8 patients (13%) had CR, and the other 52 patients (87%) had partial response (PR). On the post-CCRT PET/CT, 43 patients (73%) had CR, 12 patients (20%) had PR, and 4 patients (7%) had progressive disease. The average SUV{sub max} in primary tumors was 16.3 (range, 6.4-53.0) on the pre-CCRT PET/CT images and 5.3 (range, 0-19.4) on the during-CCRT PET/CT images. According to ROC curve analysis, ΔSUV{sub max}% could predict CR response on post-CCRT PET/CT (P<.001, cutoff value of 59.7%). In all patients, the PFS rate was 71.9% at 2 years. Multivariate analysis showed that ΔSUV{sub max}% ≥60% (P=.045) and CR response on the post-CCRT PET/CT (P=.012) were statistically significant predictors of PFS. Conclusion: Metabolic responses on the during-CCRT images at 4 weeks of treatment and 1-month post-CCRT PET/CT images may predict treatment outcomes in patients with cervical cancer. ΔSUV{sub max}% ≥60% at 4 weeks of CCRT may predict CR response

  11. Preoperative PET/CT FDG standardized uptake value of pelvic lymph nodes as a significant prognostic factor in patients with uterine cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hyun Hoon [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of); Cheon, Gi Jeong; Kang, Keon Wook [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kim, Jae Weon; Park, Noh-Hyun [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul (Korea, Republic of); Song, Yong Sang [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul (Korea, Republic of); Seoul National University, WCU Biomodulation Major, Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul (Korea, Republic of)

    2014-04-15

    Using integrated PET/CT, we evaluated the prognostic relevance in uterine cervical cancer of preoperative pelvic lymph node (LN) [{sup 18}F]FDG uptake. Patients with FIGO stage IB to IIA uterine cervical cancer were imaged with FDG PET/CT before radical surgery. We used Cox proportional hazards regression to examine the relationship between recurrence and the FDG maximum standardized uptake value (SUV{sub max}) in the pelvic LN (SUV{sub LN}) on PET/CT. Clinical data, treatment modalities, and results in 130 eligible patients were reviewed. The median postsurgical follow-up was 34 months (range 6 to 109 months). Receiver operating characteristic analysis identified SUV{sub LN} 2.36 as the most significant cut-off value for predicting recurrence. SUV{sub LN} was correlated with SUV{sub tumour} (P = 0.002), primary tumour size (P = 0.004), and parametrial invasion (P = 0.013). Univariate analyses showed significant associations between recurrence and SUV{sub LN} (P = 0.001), SUV{sub tumour} (P = 0.007), pelvic LN metastasis (P = 0.002), parametrial invasion (P < 0.001), primary tumour size (P = 0.007), suspected LN metastasis on MRI (P = 0.024), and FIGO stage (P = 0.026). Multivariate analysis identified SUV{sub LN} (P = 0.013, hazard ratio, HR, 4.447, 95 % confidence interval, CI, 1.379 - 14.343) and parametrial invasion (P = 0.013, HR 6.728, 95 % CI 1.497 - 30.235) as independent risk factors for recurrence. Patients with SUV{sub LN} ≥2.36 and SUV{sub LN} <2.36 differed significantly in terms of recurrence (HR 15.20, P < 0.001). Preoperative pelvic LN FDG uptake showed a strong significant association with uterine cervical cancer recurrence. (orig.)

  12. New risk markers may change the HeartScore risk classification significantly in one-fifth of the population

    DEFF Research Database (Denmark)

    Olsen, M H; Hansen, T W; Christensen, M K

    2008-01-01

    The study aim was to determine whether urine albumin/creatinine ratio (UACR), high-sensitivity C-reactive protein (hsCRP) or N-terminal pro-brain natriuretic peptide (Nt-proBNP) added to risk prediction based on HeartScore and history of diabetes or cardiovascular disease. A Danish population......CRP in subjects with low-moderate risk and UACR and Nt-proBNP in subjects with known diabetes of cardiovascular disease changed HeartScore risk classification significantly in 19% of the population....... sample of 2460 individuals was divided in three groups: 472 subjects receiving cardiovascular medication or having history of diabetes, prior myocardial infarction or stroke, 559 high-risk subjects with a 10-year risk of cardiovascular death above 5% as estimated by HeartScore, and 1429 low-moderate risk...

  13. Profiling of microRNAs in tumor interstitial fluid of breast tumors - a novel resource to identify biomarkers for prognostic classification and detection of cancer.

    Science.gov (United States)

    Halvorsen, Ann Rita; Helland, Åslaug; Gromov, Pavel; Wielenga, Vera Timmermans; Talman, Maj-Lis Møller; Brunner, Nils; Sandhu, Vandana; Børresen-Dale, Anne-Lise; Gromova, Irina; Haakensen, Vilde D

    2017-02-01

    It has been hypothesized based on accumulated data that a class of small noncoding RNAs, termed microRNAs, are key factors in intercellular communication. Here, microRNAs present in interstitial breast tumor fluids have been analyzed to identify relevant markers for a diagnosis of breast cancer and to elucidate the cross-talk that exists among cells in a tumor microenvironment. Matched tumor interstitial fluid samples (TIF, n = 60), normal interstitial fluid samples (NIF, n = 51), corresponding tumor tissue specimens (n = 54), and serum samples (n = 27) were collected from patients with breast cancer, and detectable microRNAs were analyzed and compared. In addition, serum data from 32 patients with breast cancer and 22 healthy controls were obtained for a validation study. To identify potential serum biomarkers of breast cancer, first the microRNA profiles of TIF and NIF samples were compared. A total of 266 microRNAs were present at higher level in the TIF samples as compared to normal counterparts. Sixty-one of these microRNAs were present in > 75% of the serum samples and were subsequently tested in a validation set. Seven of the 61 microRNAs were associated with poor survival, while 23 were associated with the presence of immune cells and adipocytes. To our knowledge, these data demonstrate for the first time that profiling of microRNAs in TIF can identify novel biomarkers for the prognostic classification and detection of breast cancer. In addition, the present findings demonstrate that microRNAs may represent the cross-talk that occurs between tumor cells and their surrounding stroma. © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  14. Prognostic Impact of Serum Heavy/Light Chain Pairs in Patients With Monoclonal Gammopathy of Undetermined Significance and Smoldering Myeloma: Long-Term Results From a Single Institution.

    Science.gov (United States)

    Magnano, Laura; Fernández de Larrea, Carlos; Elena, Montserrat; Cibeira, María Teresa; Tovar, Natalia; Aróstegui, Juan I; Pedrosa, Fabiola; Rosiñol, Laura; Filella, Xavier; Yagüe, Jordi; Bladé, Joan

    2016-06-01

    Asymptomatic monoclonal gammopathies, such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM), are clinical conditions that usually precede symptomatic multiple myeloma. Therefore, risk stratification is crucial owing to the heterogeneous progression rate among these patients. In previous years, suppression of the uninvolved chain of specific heavy/light chain (HLC) pairs in serum has been identified as a new risk factor in MGUS. The aim of the present study was to investigate the prognostic effect of involved and uninvolved HLC pairs and HLC ratios on progression in a series of patients with MGUS and SMM. All specific serum HLC pairs were measured in 114 patients diagnosed with SMM (n = 27) and MGUS (n = 87) from 1983 to 2003. Also, the HLC ratios were calculated. Progression to symptomatic multiple myeloma was observed in 13 patients (8 with SMM and 5 with MGUS). The risk of progression was 6 times greater in those with SMM (P = .001) and 4 times greater for those with the IgA isotype (P = .01). The suppression of any IgM isotypes (IgMκ or IgMλ) in patients with IgA or IgG gammopathy or any IgA isotypes (IgAκ or IgAλ) in patients with IgG or IgM gammopathy was associated with a shorter time to progression to symptomatic gammopathy (P = .001 and P = .03, respectively). On multivariate analysis, the evolving pattern and suppression of any IgM HLC pair remained significant. HLC ratios could be a valuable tool in the risk stratification of patients with SMM and MGUS, especially patients with IgG isotypes. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. The natural history of left ventricular geometry in the community: clinical correlates and prognostic significance of change in LV geometric pattern.

    Science.gov (United States)

    Lieb, Wolfgang; Gona, Philimon; Larson, Martin G; Aragam, Jayashri; Zile, Michael R; Cheng, Susan; Benjamin, Emelia J; Vasan, Ramachandran S

    2014-09-01

    This study sought to evaluate pattern and clinical correlates of change in left ventricular (LV) geometry over a 4-year period in the community; it also assessed whether the pattern of change in LV geometry over 4 years predicts incident cardiovascular disease (CVD), including myocardial infarction, heart failure, and cardiovascular death, during an additional subsequent follow-up period. It is unclear how LV geometric patterns change over time and whether changes in LV geometry have prognostic significance. This study evaluated 4,492 observations (2,604 unique Framingham Heart Study participants attending consecutive examinations) to categorize LV geometry at baseline and after 4 years. Four groups were defined on the basis of the sex-specific distributions of left ventricular mass (LVM) and relative wall thickness (RWT) (normal: LVM and RWT geometry or concentric remodeling progressed infrequently (4% to 8%) to eccentric or concentric hypertrophy. Change from eccentric to concentric hypertrophy was uncommon (8%). Among participants with concentric hypertrophy, 19% developed eccentric hypertrophy within the 4-year period. Among participants with abnormal LV geometry at baseline, a significant proportion (29% to 53%) reverted to normal geometry within 4 years. Higher blood pressure, greater body mass index (BMI), advancing age, and male sex were key correlates of developing an abnormal geometry. Development of an abnormal LV geometric pattern over 4 years was associated with increased CVD risk (140 events) during a subsequent median follow-up of 12 years (adjusted-hazards ratio: 1.59; 95% confidence interval: 1.04 to 2.43). The longitudinal observations in the community suggest that dynamic changes in LV geometric pattern over time are common. Higher blood pressure and greater BMI are modifiable factors associated with the development of abnormal LV geometry, and such progression portends an adverse prognosis. Copyright © 2014 American College of Cardiology

  16. Prediction of outcome after moderate and severe traumatic brain injury: External validation of the International Mission on Prognosis and Analysis of Clinical Trials (IMPACT) and Corticoid Randomisation after Significant Head injury (CRASH) prognostic models

    NARCIS (Netherlands)

    B. Roozenbeek (Bob); H.F. Lingsma (Hester); F.E. Lecky (Fiona); J. Lu (Juan); J. Weir (James); I. Butcher (Isabella); G.S. McHugh (Gillian); G.D. Murray (Gordon); P. Perel (Pablo); A.I.R. Maas (Andrew); E.W. Steyerberg (Ewout)

    2012-01-01

    textabstractObjective: The International Mission on Prognosis and Analysis of Clinical Trials and Corticoid Randomisation After Significant Head injury prognostic models predict outcome after traumatic brain injury but have not been compared in large datasets. The objective of this is study is to

  17. The Prognostic Significance of Serum Glucose Levels After the Onset of Ventricular Arrhythmia on In-Hospital Mortality of Patients with Acute Coronary Syndrome

    Science.gov (United States)

    Nicolaou, Vassilios N.; Papadakis, John E.; Chrysohoou, Christina; Panagiotakos, Demosthenes B.; Krinos, Xenofon; Skoufas, Panagiotis D.; Stefanadis, Christodoulos

    2008-01-01

    BACKGROUND: Several studies have illustrated the role played by serum glucose levels in cardiovascular morbidity and mortality in general and, more particularly, after an acute coronary event. AIM: The aim of this study was to evaluate the impact of serum potassium and glucose levels on in-hospital mortality in patients with ischemic heart disease, who exhibited severe ventricular arrhythmia. METHODS: We enrolled 162 consecutive patients who were referred to our institution for an acute coronary event and presented with sustained ventricular tachycardia or ventricular fibrillation during the first 24 hours of hospitalization. Serum potassium and glucose levels were measured in all patients at the onset of tachycardia and after 2, 4, 6, 12, 36, 48 hours. RESULTS: During hospitalization, 23 out of 162 patients died (61% males). Serum glucose levels at the onset of the arrhythmia, as well as after 2, 12, 36 and 48 hours, were higher in the deceased (onset: 228.8 ± 108 vs. 158 ± 68 mg/dl, p = 0.0001, 2 h: 182 ± 109 vs. 149 ± 59 mg/dl, p = 0.03, 12 h: 155.5 ± 72 vs. 128 ± 48 mg/dl, p = 0.025, 36 h: 163.8 ± 63 vs.116 ± 42 mg/dl, p = 0.002, and 48 h: 138 ± 64 vs. 122 ± 42 mg/dl, p = 0.05, respectively), even after adjustment for age, sex, diabetes, left ventricular ejection fraction, type of acute coronary syndrome and site of infarction and medication intake. There was no difference in serum potassium levels between the deceased and survivors. CONCLUSION: Serum glucose levels at the onset of arrhythmia and 2, 36 and 48 hours later seem to have prognostic significance for in-hospital mortality in patients hospitalized for an acute coronary event, who exhibit severe ventricular arrhythmia. PMID:18548170

  18. Prognostic significance of a systemic inflammatory response in patients receiving first-line palliative chemotherapy for recurred or metastatic gastric cancer

    Directory of Open Access Journals (Sweden)

    Hwang Jun-Eul

    2011-11-01

    Full Text Available Abstract Background There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor prognosis in patients with advanced cancers. We evaluated the relationships between clinical status, laboratory factors and progression free survival (PFS, and overall survival (OS in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy. Methods We reviewed 402 patients with advanced gastric adenocarcinoma who received first-line palliative chemotherapy from June 2004 and December 2009. Various chemotherapy regimens were used. Eastern Cooperative Oncology Group performance status (ECOG PS, C-reactive protein (CRP, albumin, Glasgow prognostic score (GPS, and clinical factors were recorded immediately prior to first-line chemotherapy. Patients with both an elevated CRP (>1.0 mg/dL and hypoalbuminemia ( Results According to multivariate analysis, the factors independently associated with PFS were ECOG PS (HR 1.37, 95% CI 1.02-1.84, P = 0.035, bone metastasis (HR 1.74, 95% CI 1.14-2.65, P = 0.009, and CRP elevation (HR 1.64, 95% CI 1.28-2.09, P = 0.001. The factors independently associated with OS were ECOG PS (HR 1.33, 95% CI 1.01-1.76, P = 0.037, bone metastasis (HR 1.61, 95% CI 1.08-2.39, P = 0.017, and GPS ≥ 1 (HR 1.76, 95% CI 1.41-2.19, P = 0.001. Conclusions The results of this study showed that the presence of a systemic inflammatory response as evidenced by the CRP, GPS was significantly associated with shorter PFS and OS in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy. Bone metastasis and GPS were very useful indicator for survival in patients with recurrent or metastatic gastric cancer receiving palliative chemotherapy.

  19. Prognostic significance of serum uric acid in outpatients with chronic heart failure is complex and related to body mass index: data from the IN-CHF Registry.

    Science.gov (United States)

    Baldasseroni, S; Urso, R; Maggioni, A P; Orso, F; Fabbri, G; Marchionni, N; Tavazzi, L

    2012-05-01

    In the field of cardiovascular diseases, elevated levels of serum uric acid (UA) reflect a marked activation of the xanthine oxidase pathway with increase in free radicals production; it is often associated with an inflammatory state, oxygen consumption and endothelial dysfunction. All these associations have been also confirmed in heart failure (HF) but the pathophysiological role of UA in this setting is not well understood. The aim of this study was to evaluate the prognostic role of UA in outpatients enrolled in the Italian Registry of Congestive Heart Failure (IN-CHF). All patients met the European Society of Cardiology (ESC) criteria for diagnosis of HF. We considered patients with complete clinical data and UA level available at the baseline and at 1-year follow-up. The study population was composed of 877 patients aged 63 ± 12 years. One-year mortality was 10.8% and dead patients had a higher level of UA than survivors (7.1 mg dl⁻¹ vs 6.6 mg dl⁻¹, p < 0.0207). In multivariable full model of analysis, UA did not result in an independent predictor of death in overall population, but only in patients with low body mass index (BMI) (≤22 kg m⁻²) (hazard ratio (HR): 2.38, 95% confidence interval (CI) 1.36-4.18). In this subgroup, a statistically significant gradual relationship between UA and survival was detected starting from values higher than 8 mg dl⁻¹. Elevated level of UA is not an independent predictor of mortality in chronic HF, but it markedly worsens outcome if associated with low level of BMI. This association is likely an indicator of chronic inflammatory and catabolic state. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Prevalence and Prognostic Significance of Hyponatremia in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Data from the Akershus Cardiac Examination (ACE 2 Study.

    Directory of Open Access Journals (Sweden)

    Jacob A Winther

    Full Text Available Hyponatremia is prevalent and associated with mortality in patients with heart failure (HF. The prevalence and prognostic implications of hyponatremia in acute exacerbation of chronic obstructive pulmonary (AECOPD have not been established.We included 313 unselected patients with acute dyspnea who were categorized by etiology of dyspnea according to established guidelines (derivation cohort. Serum Na+ was determined on hospital admission and corrected for hyperglycemia, and hyponatremia was defined as [Na+]<137 mmol/L. Survival was ascertained after a median follow-up of 816 days and outcome was analyzed in acute HF (n = 143 and AECOPD (n = 83 separately. Results were confirmed in an independent AECOPD validation cohort (n = 99.In the derivation cohort, median serum Na+ was lower in AECOPD vs. acute HF (138.5 [135.9-140.5] vs. 139.2 [136.7-141.3] mmol/L, p = 0.02, while prevalence of hyponatremia (27% [22/83] vs. 20% [29/143], p = 0.28 and mortality rate (42% [35/83] vs. 46% [66/143], p = 0.56 were similar. By univariate Cox regression analysis, hyponatremia was associated with increased mortality in acute HF (HR 1.85 [95% CI 1.08, 3.16], p = 0.02, but not in AECOPD (HR 1.00 [0.47, 2.15], p = 1.00. Analogous to the results of the derivation cohort, hyponatremia was prevalent also in the AECOPD validation cohort (25% [25/99], but not associated with mortality. The diverging effect of hyponatremia on outcome between AECOPD and acute HF was statistically significant (p = 0.04.Hyponatremia is prevalent in patients with acute HF and AECOPD, but is associated with mortality in patients with acute HF only.

  1. Prognostic significance of 5-fluorouracil metabolism-relating enzymes and enhanced chemosensitivity to 5-fluorouracil by 5-chloro 2,4-dihydroxy-pyridine in urothelial carcinoma

    Directory of Open Access Journals (Sweden)

    Ide Hiroki

    2012-09-01

    Full Text Available Abstract Background Recently, S-1, a novel 5-fluorouracil (5-FU-based agent containing the strong dihydropyrimidine dehydrogenase (DPD inhibitor, 5-chloro-2,4-dihydropyrimidine (CDHP has been clinically used to treat various non-urothelial carcinomas (UC. High levels of thymidylate synthase (TS, the target enzyme of 5-FU and DPD which degrades the majority of 5-FU, are associated with poor prognosis in some cancers. However, only a few reports have dealt with this in UC. The aim of this study was to investigate the clinical significance of TS and DPD in upper tract urothelial carcinoma (UTUC and evaluate the role of TS and DPD on the sensitivity of 5-FU in UC cell lines and the anti-tumor effect of S-1 in UC xenograft model. Methods Firstly, we evaluated the immunohistochemical expression of TS and DPD in 176 patients with UTUC to determine their prognostic significance. Secondly, the levels of TS and DPD in UC cell lines were measured by ELISA and real-time PCR. Furthermore, the association between their levels and the sensitivity to 5-FU was examined using the small interfering RNA (siRNA specific for TS and DPD. Thirdly, the anti-tumor effect of S-1 was evaluated in UC xenograft model. Results Immunohistochemical evaluation of TS and DPD in UTUC human samples revealed that TS expression was significantly associated with stage, grade, and lymphovascular invasion and DPD expression was significantly associated with grade. Multivariate analysis revealed that high TS expression was an independent predictor of disease-specific survival in them. In in vitro study using UC cell lines, high levels of TS and DPD were associated with low response to 5-FU and these associations were confirmed with siRNA specific for TS and DPD. In in vivo study using UC xenograft model, S-1 treatment dramatically inhibited tumor growth compared to controls, tegafur, or UFT in UC tumor with a high level of DPD. Conclusions TS plays an important role in the prognosis of

  2. Deletion in HSP110 T17: correlation with wild-type HSP110 expression and prognostic significance in microsatellite-unstable advanced gastric cancers.

    Science.gov (United States)

    Kim, Kyung-Ju; Lee, Tae Hun; Kim, Jung Ho; Cho, Nam-Yun; Kim, Woo Ho; Kang, Gyeong Hoon

    2017-09-01

    Deletion of the HSP110 T17 mononucleotide repeat has recently been identified as a prognostic marker that is correlated with wild-type HSP110 (HSP110wt) expression in microsatellite instability-high (MSI-H) colorectal cancers. The aim of this study was to assess the correlation between deletion of the HSP110 T17 repeat and expression of HSP110wt using DNA testing and immunohistochemistry and to determine the prognostic implications of HSP110 T17 deletion in MSI-H advanced gastric cancers (GCs). The status of HSP110wt expression was evaluated by immunohistochemistry using an HSP110wt-specific antibody in 142 MSI-H advanced GCs. The size of the HSP110 T17 repeat deletion was analyzed in 96 MSI-H advanced GCs; deletions were divided into small (0-2base pairs) and large deletions (3-5base pairs). Low and high expressions of HSP110wt were detected in 38 (26.8%) and 104 (73.2%) of the 142 cases, respectively. The HSP110 T17 deletion was observed in 45 (46.9%) of the 96 MSI-H GC samples. Tumors with high expression of HSP110wt showed a tendency to have small or no deletion of HSP110 T17. In Kaplan-Meier survival analysis, tumors with a large HSP110 T17 deletion were associated with favorable overall survival and disease-free survival compared with those with small/no deletion of HSP110 T17. However, HSP110 T17 deletion size was not an independent prognostic factor in multivariate analysis. In summary, deletion of the HSP110 T17 repeat was frequently observed in MSI-H GCs, and HSP110 T17 deletion size was inversely correlated with HSP110wt expression status. Large HSP110 T17 was not a prognostic indicator in MSI-H GCs. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Prognostic significance of bone invasion for oral cavity squamous cell carcinoma considered T1/T2 by American joint committee on cancer size criteria.

    Science.gov (United States)

    Fried, David; Mullins, Brandon; Weissler, Mark; Shores, Carol; Zanation, Adam; Hackman, Trevor; Shockley, William; Hayes, Neil; Chera, Bhishamjit S

    2014-06-01

    It is unclear whether bone invasion in small oral cavity squamous cell carcinomas (OCSCC) results in worse prognosis. Two hundred fifty-four patients with OCSCC were identified and divided into 3 cohorts: (1) ≤4 cm with no bone invasion; (2) ≤4 cm with bone invasion; and (3) ≥4 cm or other factors (eg, skin invasion, deep muscle invasion) that would qualify for American Joint Committee on Cancer (AJCC) T4 classification aside from bone invasion. Depth of bone invasion (none, cortical, or medullary) was also recorded. Cohorts 1 and 2 had similar outcomes. Cohort 3 had lower rates of regional control (p = .04), disease-specific survival (DSS; p < .01), and overall survival (OS; p < .01). On multivariate analysis, margin status and medullary bone invasion were associated with worse outcomes. Bone invasion does not seem to significantly influence outcomes in patients with small primary tumors treated with surgery/radiation. Medullary bone invasion seems to result in reduced rates of control and survival. © 2013 Wiley Periodicals, Inc.

  4. Clinical and prognostic significance of aberrant T-cell marker expression in 225 cases of de novo diffuse large B-cell lymphoma and 276 cases of other B-cell lymphomas

    Science.gov (United States)

    Tsuyama, Naoko; Ennishi, Daisuke; Yokoyama, Masahiro; Baba, Satoko; Asaka, Reimi; Mishima, Yuko; Terui, Yasuhito; Hatake, Kiyohiko; Takeuchi, Kengo

    2017-01-01

    Expression of T-cell markers, generally investigated for immunophenotyping of T-cell lymphomas, is also observed in several types of B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). We previously reported that CD5 expression in DLBCL is an inferior prognostic factor in the era of rituximab. However, data regarding the frequencies, histological relevance, and prognostic importance of T-cell markers other than CD5 are currently unavailable. In the present study, we comprehensively evaluated the expression of T-cell markers (CD2, CD3, CD4, CD5, CD7, and CD8) in 501 B-cell lymphomas, including 225 DLBCLs, by flow cytometry and subsequent immunohistochemistry. T-cell markers other than CD5, such as CD2, CD4, CD7, and CD8, were expressed in 27 (5%) patients, and notably, all of these cases were classified as large B-cell lymphoma subtypes: 25 DLBCLs and 2 intravascular large B-cell lymphomas. CD5 and other T-cell markers were expressed in 15% (31/225) and 10% (25/225) of DLBCL cases, respectively. Five of them co-expressed CD5 and other T-cell markers. Retrospectively analyzing the prognostic relevance of T-cell markers in 169 patients with primary DLBCL treated with rituximab-based chemotherapy, we showed that only CD5 was a strong predictor of poor survival. This study provides information about the occurrence of T-cell markers other than CD5 in B-cell lymphomas, their frequent histological subtypes, and their prognostic significance in DLBCL. CD5 was reconfirmed as a negative prognostic marker in DLBCL patients receiving rituximab-inclusive chemotherapy, whereas T-cell markers other than CD5 were found to have no impact on clinicopathological and survival analyses. PMID:28380441

  5. Derivation and Validation of a Novel Prognostic Scale (Modified-Stroke Subtype, Oxfordshire Community Stroke Project Classification, Age, and Prestroke Modified Rankin) to Predict Early Mortality in Acute Stroke.

    Science.gov (United States)

    Abdul-Rahim, Azmil H; Quinn, Terence J; Alder, Sarah; Clark, Allan B; Musgrave, Stanley D; Langhorne, Peter; Potter, John F; Myint, Phyo Kyaw

    2016-01-01

    The stroke subtype, Oxfordshire Community Stroke Project classification, age, and prestroke modified Rankin (SOAR) score is a prognostic scale proposed for early mortality prediction after acute stroke. We aimed to evaluate whether including a measure of initial stroke severity (National Institutes of Health Stroke Scale and modified-SOAR [mSOAR] scores) would improve the prognostic accuracy. Using Anglia Stroke and Heart Clinical Network data, 2008 to 2011, we assessed the performance of SOAR and mSOAR against in-hospital mortality using area under the receiver operating curve statistics. We externally validated the prognostic utility of SOAR and mSOAR using an independent cohort data set from Glasgow. We described calibration using Hosmer-Lemeshow goodness-of-fit test. A total of 1002 patients were included in the derivation cohort, and 105 (10.5%) died as inpatients. The area under the receiver operating curves for outcome of early mortality derived from the SOAR and mSOAR scores were 0.79 (95% confidence interval, 0.75-0.84) and 0.83 (95% confidence interval, 0.79-0.86), respectively (P=0.001). The external validation data set contained 1012 patients with stroke; of which, 121 (12.0%) patients died within 90 days. The mSOAR scores identified the risk of early mortality ranging from 3% to 42%. External validation of mSOAR score yielded an area under the receiver operating curve of 0.84 (95% confidence interval, 0.82-0.88) for outcome of early mortality. Calibration was good (P=0.70 for the Hosmer-Lemeshow test). Adding National Institutes of Health Stroke Scale data to create a modified-SOAR score improved prognostic utility in both derivation and validation data sets. The mSOAR may have clinical utility by using easily available data to predict mortality. © 2015 American Heart Association, Inc.

  6. Autonomic nervous system dynamics for mood and emotional-state recognition significant advances in data acquisition, signal processing and classification

    CERN Document Server

    Valenza, Gaetano

    2014-01-01

    This monograph reports on advances in the measurement and study of autonomic nervous system (ANS) dynamics as a source of reliable and effective markers for mood state recognition and assessment of emotional responses. Its primary impact will be in affective computing and the application of emotion-recognition systems. Applicative studies of biosignals such as: electrocardiograms; electrodermal responses; respiration activity; gaze points; and pupil-size variation are covered in detail, and experimental results explain how to characterize the elicited affective levels and mood states pragmatically and accurately using the information thus extracted from the ANS. Nonlinear signal processing techniques play a crucial role in understanding the ANS physiology underlying superficially noticeable changes and provide important quantifiers of cardiovascular control dynamics. These have prognostic value in both healthy subjects and patients with mood disorders. Moreover, Autonomic Nervous System Dynamics for Mood and ...

  7. Tumor cell concentration and tumor burden in relation to histopathologic subtype and other prognostic factors in early stage Hodgkin's disease. The Danish National Hodgkin Study Group

    DEFF Research Database (Denmark)

    Specht, L.; Lauritzen, A.F.; Nordentoft, A.M.

    1990-01-01

    . Initial biopsy material was classified according to the Rye histopathologic classification, the grading and subclassification proposed by the British National Lymphoma Investigation (BNLI), and tumor cell concentration in sections. Tumor cell concentration as a prognostic factor turned out to be better...... than the other classifications. However, if macroscopic tumor burden was taken into account both tumor cell concentration and the other histopathologic classification systems lost their prognostic significance. Significantly, however, a combination of macroscopic tumor burden and tumor cell...... concentration, yielding an estimate of the total tumor cell burden, was even better than the macroscopic tumor burden as a prognostic factor. In conclusion, a simple tumor cell concentration count seems to be the most useful form of histopathologic subtyping for prognostic purposes in early stage Hodgkin...

  8. Prognostic significance of urokinase plasminogen activator receptor and its cleaved forms in blood from patients with non-small cell lung cancer

    DEFF Research Database (Denmark)

    Almasi, Charlotte Elberling; Høyer-Hansen, Gunilla; Christensen, Ib Jarle

    2009-01-01

    in lung tumour extracts. Here we analyse uPAR forms in blood from patients with non-small cell lung cancer (NSCLC). Preoperatively sampled plasma/serum from 32 patients with NSCLC was analysed. Three time-resolved fluoroimmunoassays (TR-FIAs) measuring intact uPAR(I-III) (TR-FIA 1), uPAR(I-III) + u......Urokinase plasminogen activator (uPA) cleaves its three-domain cell surface receptor, uPAR, liberating domain I [uPAR(I)] and leaving the cleaved uPAR(II-III) on the cell surface. Both intact and cleaved uPAR can be shed from the cell surface. uPAR(I) was previously shown to be a prognostic factor...

  9. Stereological estimates of nuclear volume and other quantitative variables in supratentorial brain tumors. Practical technique and use in prognostic evaluation

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Braendgaard, H; Chistiansen, A O

    1991-01-01

    the practical technique. The continuous variables were correlated with the subjective, qualitative WHO classification of brain tumors, and the prognostic value of the parameters was assessed. Well differentiated astrocytomas (n = 14) had smaller estimates of the volume-weighted mean nuclear volume and mean...... was significantly increased in glioblastomas (2p = 0.01). Three-dimensional, shape-independent estimates of macroscopical tumor volume were not different in anaplastic astrocytomas and glioblastomas (2p = 0.39). Histological type of tumor and mitotic index were of significant prognostic value (2p = 8.2.10(-6) and 2...... techniques in the prognostic evaluation of primary brain tumors....

  10. Prognostic significance of high GFI1 expression in AML of normal karyotype and its association with a FLT3-ITD signature.

    Science.gov (United States)

    Volpe, Giacomo; Walton, David S; Grainger, David E; Ward, Carl; Cauchy, Pierre; Blakemore, Daniel; Coleman, Daniel J L; Cockerill, Peter N; Garcia, Paloma; Frampton, Jon

    2017-09-11

    Growth Factor Independence 1 (GFI1) is a transcriptional repressor that plays a critical role during both myeloid and lymphoid haematopoietic lineage commitment. Several studies have demonstrated the involvement of GFI1 in haematological malignancies and have suggested that low expression of GFI1 is a negative indicator of disease progression for both myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). In this study, we have stratified AML patients into those defined as having a normal karyotype (CN-AML). Unlike the overall pattern in AML, those patients with CN-AML have a poorer survival rate when GFI1 expression is high. In this group, high GFI1 expression is paralleled by higher FLT3 expression, and, even when the FLT3 gene is not mutated, exhibit a FLT3-ITD signature of gene expression. Knock-down of GFI1 expression in the human AML Fujioka cell line led to a decrease in the level of FLT3 RNA and protein and to the down regulation of FLT3-ITD signature genes, thus linking two major prognostic indicators for AML.

  11. Prognostic factors in lupus nephritis

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Starklint, Henrik; Halberg, Poul

    2006-01-01

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

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

    Science.gov (United States)

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

    2005-01-01

    No ideal and generally accepted prognostic factors and scoring systems exist to determine the prognosis of peritonitis associated with colonic perforation. This study was designed to investigate prognostic factors and evaluate the various scoring systems to allow identification of high-risk patients. Between 1996 and 2003, excluding iatrogenic and trauma cases, 26 consecutive patients underwent emergency operations for colorectal perforation and were selected for this retrospective study. Several clinical factors were analyzed as possible predictive factors, and APACHE II, SOFA, MPI, and MOF scores were calculated. The overall mortality was 26.9%. Compared with the survivors, non-survivors were found more frequently in Hinchey's stage III-IV, a l