Influence of prognostic nutritional index and tumor markers on survival in gastric cancer surgery patients.

PubMed

Saito, Hiroaki; Kono, Yusuke; Murakami, Yuki; Kuroda, Hirohiko; Matsunaga, Tomoyuki; Fukumoto, Yoji; Osaki, Tomohiro

2017-05-01

Blood analytes are easily used in routine clinical practice. Tumor markers (TMs) are useful in diagnosing, treating, and predicting prognosis of gastric cancer (GC). The prognostic nutritional index (PNI) was also recently found to be useful in predicting GC prognosis. The PNI and serum levels of CEA and CA19-9 of 453 patients with GC were measured to examine correlations between those levels and patients' prognoses. Of the 453 patients, 84 (18.5%) were positive for CEA and/or CA19-9 and therefore considered positive for TMs. Prognosis of patients who were TM+ was significantly worse than for those who were TM-. Mean PNI was 48.2 (range 27.7-63.6). ROC analysis indicated that 46.7 was the optimal PNI cutoff value. Prognosis of patients in the PNI Low group (<46.7) was significantly worse than in the PNI High group (≥46.7). Prognosis of patients who were both TM+ and PNI Low was significantly worse than that of patients who were either TM+ or PNI Low and those who were both TM- and PNI High . Multivariate analysis indicated that combination of TM and PNI was an independent prognostic indicator. The combination of TM and PNI offers accurate information about a patient's prognosis.

Inflammation factors in hepatoblastoma and their clinical significance as diagnostic and prognostic biomarkers.

PubMed

Guo, Fei; Ru, Qin; Zhang, Junjie; He, Shen; Yu, Jiekai; Zheng, Shu; Wang, Jiaxiang

2017-09-01

The aims of this study were to identify inflammation factors in hepatoblastoma tissue that correlated with different clinical characteristics, and to explore the probability as predictive biomarkers for diagnosis and prognosis. SELDI-TOF-MS was performed to screen protein peaks that were significantly highly expressed in tumor tissue compared with adjacent liver tissue. After removing proteins larger than 30kDa, the targeted peaks were separated by solid phase extraction and tricine-SDS-PAGE. Protein fragments produced by in-gel digestion were identified by LC-MS/MS. Immunohistochemical assays further confirmed these results. Overall survival curves were graphed by Kaplan-Meier method and multivariate analysis was performed by Cox proportional hazards regression model. Three protein peaks (m/z 12,138, m/z 13,462, and m/z 15,120) that were significantly upregulated in the tumor tissue were identified as macrophage migration inhibitory factor (MIF), chemokine (C-X-C motif) ligand 7 (CXCL7), and interleukin 25 (IL-25). These factors were closely related to clinical stage, lymph node metastasis, vascular invasion and serum AFP level. High expression of each inflammatory marker indicated poor prognosis. Multivariate analysis suggested that MIF, CXCL7, and IL-25 were prognostic factors independent of patient sex, age and tumor histological type. MIF, CXCL7, and IL-25 might be considered as effective inflammation factors for diagnosis and prognosis of hepatoblastoma and as potential novel treatment targets through inhibition of inflammatory function. Prognosis study LEVEL OF EVIDENCE: Level I. Copyright © 2017 Elsevier Inc. All rights reserved.

The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: a SEER based study.

PubMed

Wang, Haiyong; Zhang, Chenyue; Zhang, Jingze; Kong, Li; Zhu, Hui; Yu, Jinming

2017-04-18

Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2- occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P<0.01). Interestingly, for patients with two metastatic sites, those with bone and lung metastasis had best CSS in the HR+/HER2- (P<0.001) and HR+/HER2+ subgroups (P=0.009) However, for patients with three and four metastatic sites, there was no statistical difference in their CSS (all, P>0.05).

The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: a SEER based study

PubMed Central

Wang, Haiyong; Zhang, Chenyue; Zhang, Jingze; Kong, Li; Zhu, Hui; Yu, Jinming

2017-01-01

Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2− occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P<0.01). Interestingly, for patients with two metastatic sites, those with bone and lung metastasis had best CSS in the HR+/HER2- (P<0.001) and HR+/HER2+ subgroups (P=0.009) However, for patients with three and four metastatic sites, there was no statistical difference in their CSS (all, P>0.05). PMID:28038448

Postoperative fever predicts poor prognosis of gastric cancer.

PubMed

Feng, Fan; Tian, Yangzi; Yang, Xuewen; Sun, Li; Hong, Liu; Yang, Jianjun; Guo, Man; Lian, Xiao; Fan, Daiming; Zhang, Hongwei

2017-09-22

Data about prognostic value of postoperative fever in gastric cancer was lacking. Thus, the present study aims to investigate the prognostic value of postoperative fever in gastric cancer. From September 2008 to March 2015, 2938 gastric cancer patients were enrolled in the present study. Clinicopathological features were recoded. The association between postoperative fever and prognosis of gastric cancer were analyzed. There were 2294 male (78.1%) and 644 female (21.9%). Seven hundred and fifty-six patients suffered from fever. Among them, the duration of fever less than 48h occurred in 508 cases, and duration of fever over 48h occurred in 248 cases. Univariate and multivariate analysis showed that postoperative fever was an independent risk factor for prognosis of gastric cancer ( P < 0.001). For the entire cohort, duration of fever over 48h was significantly associated with decreased survival ( P < 0.001). In subgroup analysis, duration of fever over 48h was significantly associated with poor prognosis of stage I and II gastric cancer (both P < 0.001). However, postoperative fever was not associated with the prognosis of stage III gastric cancer ( P = 0.334). Considering the type of gastrectomy, postoperative fever was not associated with the prognosis of patients with proximal ( P = 0.318) and distal gastrectomy ( P = 0.806), but duration of fever over 48h was significantly associated with poor prognosis of patients with total gastrectomy ( P = 0.004). In conclusion, postoperative fever was associated with poor prognosis of gastric cancer.

High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis.

PubMed

Wikberg, Maria L; Edin, Sofia; Lundberg, Ida V; Van Guelpen, Bethany; Dahlin, Anna M; Rutegård, Jörgen; Stenling, Roger; Oberg, Ake; Palmqvist, Richard

2013-04-01

An active stroma is important for cancer cell invasion and metastasis. We investigated the expression of fibroblast activation protein (FAP) in relation to patient prognosis in colorectal cancer. Colorectal cancer specimens from 449 patients were immunohistochemically stained with a FAP antibody and evaluated in the tumor center and tumor front using a semiquantitative four-level scale. FAP was expressed by fibroblasts in 85-90 % of the tumors examined. High versus no/low expression in the tumor center was associated with poor prognosis (multivariate hazard ratio, HR = 1.72; 95 % CI 1.07-2.77, p = 0.025). FAP expression in the tumor front, though more frequent than in the tumor center, was not associated with prognosis. FAP expression in the tumor center was more common in specimens with positive microsatellite instability (MSI) screening status and in patients with high CpG island methylator phenotype (CIMP) status. However, inclusion of MSI screening status and CIMP status in the multivariate analysis strengthened the risk estimates for high FAP expression in the tumor center (HR = 1.89; 95 % CI 1.13-3.14; p = 0.014), emphasizing the role of FAP as an independent prognostic factor. Stromal FAP expression is common in colorectal cancer, and we conclude that high FAP expression in the tumor center, but not the tumor front, is an independent negative prognostic factor.

Overexpression of epithelial cell adhesion molecule protein is associated with favorable prognosis in an unselected cohort of ovarian cancer patients.

PubMed

Battista, Marco Johannes; Cotarelo, Cristina; Jakobi, Sina; Steetskamp, Joscha; Makris, Georgios; Sicking, Isabel; Weyer, Veronika; Schmidt, Marcus

2014-07-01

The aim of this study was to evaluate the prognostic influence of epithelial cell adhesion molecule (EpCAM) in an unselected cohort of ovarian cancer (OC) patients. Expression of EpCAM was determined by immunohistochemistry in an unselected cohort of 117 patients with OC. Univariable and multivariable Cox regression analyses adjusted for age, tumor stage, histological grading, histological subtype, postoperative tumor burden and completeness of chemotherapy were performed in order to determine the prognostic influence of EpCAM. The Kaplan-Meier method is used to estimate survival rates. Univariable Cox regression analysis showed that overexpression of EpCAM is associated with favorable prognosis in terms of progression-free survival (PFS) (p = 0.011) and disease-specific survival (DSS) (p = 0.003). In multivariable Cox regression analysis, overexpression of EpCAM retains its significance independent of established prognostic factors for longer PFS [hazard ratios (HR) 0.408, 95 % confidence interval (CI) 0.197-0.846, p = 0.003] but not for PFS (HR 0.666, 95 % CI 0.366-1.212, p = 0.183). Kaplan-Meier plots demonstrate an influence on 5-year PFS rates (0 vs. 27.6 %, p = 0.048) and DSS rates (11.8 vs. 54.0 %, p = 0.018). These findings support the hypothesis that the expression of EpCAM is associated with favorable prognosis in OC.

Long-term Postoperative Nutritional Status Affects Prognosis Even After Infectious Complications in Gastric Cancer.

PubMed

Kiuchi, Jun; Komatsu, Shuhei; Kosuga, Toshiyuki; Kubota, Takeshi; Okamoto, Kazuma; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Ichikawa, Daisuke; Otsuji, Eigo

2018-05-01

This study was designed to investigate the clinical impact of postoperative serum albumin level on severe postoperative complications (SPCs) and prognosis. Data for a total of 728 consecutive patients who underwent curative gastrectomy for gastric cancer between 2004 and 2013 were retrospectively analyzed. From these patients, a propensity score-matched analysis was performed based on 14 clinicopathological and surgical factors. Short-term decrease in postoperative serum albumin level was not associated with the occurrence of SPCs. Regarding long-term decrease in serum albumin level, a decrease of ≥0.5 g/dl at 3 months did not affect the long-term survival of patients without SPCs, but was related to a significantly poorer prognosis in patients with SPCs. By multivariate analysis, long-term decrease of serum albumin level was an independent prognostic factor in patients with SPCs. Long-term postoperative nutritional status as shown by a low level of albumin was related to prognosis in patients with SPCs. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Renal cell carcinoma associated with transcription factor E3 expression and Xp11.2 translocation: incidence, characteristics, and prognosis.

PubMed

Klatte, Tobias; Streubel, Berthold; Wrba, Friedrich; Remzi, Mesut; Krammer, Barbara; de Martino, Michela; Waldert, Matthias; Marberger, Michael; Susani, Martin; Haitel, Andrea

2012-05-01

We studied the characteristics and prognosis of renal cell carcinoma (RCC) associated with Xp11.2 translocation and transcription factor E3 (TFE3) expression and determined the need for genetic analysis in routine diagnostics. Of 848 consecutive cases, 75 showed microscopic features suggestive of Xp11.2 translocation RCC or occurred in patients 40 years or younger. Of these cases, 17 (23%) showed strong nuclear TFE3 immunostaining, which was associated with more advanced tumors and inverse prognosis in univariate (P = .032) but not multivariate (P = .404) analysis. With fluorescence in situ hybridization and polymerase chain reaction, only 2 cases showed alterations of the X chromosome and the ASPL-TFE3 gene fusion, respectively. In our laboratory, the predictive value of TFE3 expression for the Xp11.2 translocation was 12%. Strong nuclear TFE3 expression is associated with metastatic spread and a poor prognosis. In our laboratory, TFE3 is not diagnostic for Xp11.2 translocation RCC. Diagnosis of Xp11.2 translocation RCC may be made only genetically.

Utility of Inflammatory Marker- and Nutritional Status-based Prognostic Factors for Predicting the Prognosis of Stage IV Gastric Cancer Patients Undergoing Non-curative Surgery.

PubMed

Mimatsu, Kenji; Fukino, Nobutada; Ogasawara, Yasuo; Saino, Yoko; Oida, Takatsugu

2017-08-01

The present study aimed to compare the utility of various inflammatory marker- and nutritional status-based prognostic factors, including many previous established prognostic factors, for predicting the prognosis of stage IV gastric cancer patients undergoing non-curative surgery. A total of 33 patients with stage IV gastric cancer who had undergone palliative gastrectomy and gastrojejunostomy were included in the study. Univariate and multivariate analyses were performed to evaluate the relationships between the mGPS, PNI, NLR, PLR, the CONUT, various clinicopathological factors and cancer-specific survival (CS). Among patients who received non-curative surgery, univariate analysis of CS identified the following significant risk factors: chemotherapy, mGPS and NLR, and multivariate analysis revealed that the mGPS was independently associated with CS. The mGPS was a more useful prognostic factor than the PNI, NLR, PLR and CONUT in patients undergoing non-curative surgery for stage IV gastric cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Comparison of Survival Outcomes Among Cancer Patients Treated In and Out of Clinical Trials

PubMed Central

2014-01-01

Background Clinical trials test the efficacy of a treatment in a select patient population. We examined whether cancer clinical trial patients were similar to nontrial, “real-world” patients with respect to presenting characteristics and survival. Methods We reviewed the SWOG national clinical trials consortium database to identify candidate trials. Demographic factors, stage, and overall survival for patients in the standard arms were compared with nontrial control subjects selected from the Surveillance, Epidemiology, and End Results program. Multivariable survival analyses using Cox regression were conducted. The survival functions from aggregate data across all studies were compared separately by prognosis (≥50% vs <50% average 2-year survival). All statistical tests were two-sided. Results We analyzed 21 SWOG studies (11 good prognosis and 10 poor prognosis) comprising 5190 patients enrolled from 1987 to 2007. Trial patients were younger than nontrial patients (P < .001). In multivariable analysis, trial participation was not associated with improved overall survival for all 11 good-prognosis studies but was associated with better survival for nine of 10 poor-prognosis studies (P < .001). The impact of trial participation on overall survival endured for only 1 year. Conclusions Trial participation was associated with better survival in the first year after diagnosis, likely because of eligibility criteria that excluded higher comorbidity patients from trials. Similar survival patterns between trial and nontrial patients after the first year suggest that trial standard arm outcomes are generalizable over the long term and may improve confidence that trial treatment effects will translate to the real-world setting. Reducing eligibility criteria would improve access to clinical trials. PMID:24627276

p-Akt as a potential poor prognostic factor for gastric cancer: a systematic review and meta-analysis.

PubMed

Cao, Fang; Zhang, Cong; Han, Wei; Gao, Xiao-Jiao; Ma, Jun; Hu, Yong-Wei; Gu, Xing; Ding, Hou-Zhong; Zhu, Li-Xia; Liu, Qin

2017-08-29

To understand the relationship between p-Akt expression and the prognosis of patients with gastric cancer, we searched six databases, Pubmed, EMBASE, Cochrane Library, CNKI, Wanfang and CBM for relevant articles in order to conduct this metaanalysis. The pooled hazard ratios and corresponding 95%CI of overall survival were calculated to evaluate the prognostic value of p-Akt expression in patients with gastric cancer. With 2261 patients combined from 13 available studies, the pooled HR showed a poor prognosis in patients with gastric cancer in the univariate analysis (HR=1.88, 95%CI:1.45-2.43, P<0.00001), and the group "univariate analysis+estimate" (HR=1.41, 95%CI: 1.01-1.97, P=0.04), but not in multivariate analysis (HR=0.66, 95%CI: 0.29-1.52, P=0.33) and estimate (HR=1.13, 95%CI: 0.65-1.95, P=0.67). In conclusion, our results indicated that p-Akt was likely to be an indicator of poor prognosis in patients with gastric cancer.

The tobacco paradox in acute coronary syndrome. The prior cessation of smoking as a marker of a better short-term prognosis.

PubMed

Bastos-Amador, P; Almendro-Delia, M; Muñoz-Calero, B; Blanco-Ponce, E; Recio-Mayoral, A; Reina-Toral, A; Cruz-Fernandez, J M; García-Alcántara, A; Hidalgo-Urbano, R; García-Rubira, J C

2016-01-01

The tobacco paradox is a phenomenon insufficiently explained by previous studies. This study analyses the prognostic role of prior or active smoking in patients with acute coronary syndrome. We obtained data from the ARIAM registry, between 2001 and 2012. The study included 42,827 patients with acute coronary syndrome (mean age, 65±13 years; 26.4% women). The influence of smoking and that of being an ex-smoker on mortality was analysed using a multivariate analysis. The smokers were younger, were more often men, had less diabetes, hypertension and prior history of heart failure, stroke, arrhythmia and renal failure and more frequently had ST-elevation and a family history of smoking. The ex-smokers had more dyslipidaemia and history of angina, myocardial infarction, ischemic heart disease, peripheral vasculopathy and chronic bronchial disease. Smokers and ex-smokers less frequently developed cardiogenic shock (smokers 4.2%, ex-smokers 4.7% and nonsmokers 6.9%, P<.001). Hospital mortality was 7.8% for the nonsmokers, 4.9% for the ex-smokers and 3.1% for the smokers (P<.001). In the multivariate analysis, the smoker factor lost its influence in the prognosis (-0.26%, p=.52 using an inverse probability calculation; and+0.26%, P=.691 using a propensity analysis). However, the exsmoker factor showed a significant reduction in mortality in both tests (-2.4% in the inverse probability analysis, P<.001; and -1.5% in the propensity analysis, P=.005). The tobacco paradox is a finding that could be explained by other prognostic factors. Smoking cessation prior to hospitalization for acute coronary syndrome is associated with a better prognosis. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

The Surgical Apgar Score Predicts Not Only Short-Term Complications But Also Long-Term Prognosis After Esophagectomy.

PubMed

Nakagawa, Akio; Nakamura, Tetsu; Oshikiri, Taro; Hasegawa, Hiroshi; Yamamoto, Masashi; Kanaji, Shingo; Matsuda, Yoshiko; Yamashita, Kimihiro; Matsuda, Takeru; Sumi, Yasuo; Suzuki, Satoshi; Kakeji, Yoshihiro

2017-12-01

The surgical Apgar score (SAS) quantifies three intraoperative factors and predicts postoperative complications, but few reports describe its usefulness in esophagectomy, and no studies to date show its correlation with long-term prognosis after esophagectomy. This study investigated 400 cases in which esophagectomy was performed on esophageal malignant tumors at the authors' hospital from January 2007 to January 2017. In this study, SAS was defined as the sum of the scores of three parameters, namely, estimated blood loss, lowest mean arterial pressure, and lowest heart rate, with values extracted from medical records. Postoperative complications classified as Clavien-Dindo grade 3 or higher were also extracted. The study retrospectively compared the relationship of SAS to postoperative complications and survival. Univariate analysis showed that postoperative complications were significantly associated with hypertension (p = 0.017), thoracotomy (p = 0.012), and SAS ≤ 5 (p < 0.0001), and multivariate analysis showed that hypertension (p = 0.049) and SAS ≤ 5 (p < 0.0001) were significant predictive factors for complications. In the prognostic analysis, log-rank analysis showed that patients with an SAS ≤ 5 had a significantly poorer prognosis than those with a SAS > 5 (p = 0.043), especially for complications classified as clinical stage 2 or higher (p = 0.027). In the multivariate analysis, SAS ≤ 5 was identified as a significantly poor prognostic factor for complications classified as clinical stage 2 or higher (p = 0.029). In this study, SAS was useful not only for predicting short-term complications, but also as a long-term prognostic factor after esophagectomy.

Anemia and Long-Term Renal Prognosis in Patients with Post-Renal Acute Kidney Injury of Nonmalignant Cause.

PubMed

Sasaki, Sho; Kawarazaki, Hiroo; Hasegawa, Takeshi; Shima, Hideaki; Naganuma, Toshihide; Shibagaki, Yugo

2017-01-01

The renal prognosis of post-renal acute kidney injury (PoR-AKI) has not been verified so far. The objective of this study was to assess the association of baseline anemia with long-term renal prognosis in patients with PoR-AKI. We performed a multicenter retrospective cohort study. Consecutive adult patients from December 2006 to February 2010, who met the requirements as mentioned in the definition of PoR-AKI, were included. Patients without data on baseline renal function and at 6 months after PoR-AKI were excluded. We set baseline hemoglobin (Hb) level (g/dl) as the main exposure to be tested. The main outcome measure was long-term renal prognosis as determined by the difference between proximate estimated glomerular filtration rate (eGFR) at 6 months after diagnosis of PoR-AKI and baseline eGFR prior to the occurrence of the present PoR-AKI (ΔeGFR after 6 months) using the general linear model. We included 136 patients with PoR-AKI. The most frequent cause of PoR-AKI was malignancy, accounting for 39.0% (n = 53) of cases. Multivariate analysis adjusted for possible confounders showed that ΔeGFR after 6 months significantly changed by -4.28 ml/min/1.73 m2 for every 1 g/dl lower Hb at diagnosis (95% CI 1.86-6.69, p < 0.01). An additional multivariate analysis that was stratified by the presence or absence of malignancy as the cause of PoR-AKI yielded the same significant result only in the stratum of the nonmalignant cause of PoR-AKI. Patients with a nonmalignant cause of PoR-AKI who have baseline anemia may have poor long-term renal prognosis. In these cases, close observation of renal function after renal recovery may be required. © 2016 S. Karger AG, Basel.

[Effect of Complicated Hemophagocytic Syndrome on Clinical Prognosis of Patients with Non-Hodgkin's Lymphoma and Analysis of Its Affecting Factors].

PubMed

Lin, Jun-Fang; Zeng, Zhi-Yong; Yang, A-Peng; Zheng, Ling; Chen, Jun-Min

2017-08-01

To investigate the effect of complicatal hemophagocytic syndrome on clinical prognosis of patients with non-Hodgkin's lymphoma (NHL) and analyze its factors affecting prognosis. Ninety cases of NHL were selected and divided into 2 groups: 61 cases of NHL without hemophagocytic syndrome as group A and 29 cases of NHL with hemophagocytic syndrame as group B. The survival analysis of Kaplan-Meter method and the Cox regression model were used for univariate and multivariate analyses of related factors. The patients in group B were more likely to start with fever, moreover, the hemophagocytes could be found in bone marrow samples of 89.66% (26/29) patients; the levels of total bilirubin, triglycerides, serum ferritin, serum soluble CD25, DNA copies of epstein-barr virus (EBV) and lactate dehydrogenase level in the group B were significantly higher than those in the group A(P<0.05). And the patients in group B had worse physical state, later disease stage, worse disease status and lower overall prognosis as compared with patients in the group A. The complicased hemophagocytic syndrome, incomplete improvemant of deseases state after treatment and EBV infection were the independent risk factors for the poor prognosis of patients with NHL. The complicated hemophagocytic syndrome can increase the severity of NHL, there fore significantly influences the clinical prognosis of patients, while the complicated hemophagocytic syndrome, poor therapatic efficacy for patients and EBV infection are independent risk factors affecting the prognosis of NHL patients.

Prediction of Therapeutic Effect of Chemotherapy for NSCLC Using Dual-Input Perfusion CT Analysis: Comparison among Bevacizumab Treatment, Two-Agent Platinum-based Therapy without Bevacizumab, and Other Non-Bevacizumab Treatment Groups.

PubMed

Yabuuchi, Hidetake; Kawanami, Satoshi; Iwama, Eiji; Okamoto, Isamu; Kamitani, Takeshi; Sagiyama, Koji; Yamasaki, Yuzo; Honda, Hiroshi

2018-02-01

Purpose To determine whether dual-input perfusion computed tomography (CT) can predict therapeutic response and prognosis in patients who underwent chemotherapy for non-small cell lung cancer (NSCLC). Materials and Methods The institutional review board approved this study and informed consent was obtained. Sixty-six patients with stage III or IV NSCLC (42 men, 24 women; mean age, 63.4 years) who underwent chemotherapy were enrolled. Patients were separated into three groups: those who received chemotherapy with bevacizumab (BV) (n = 20), those who received two-agent platinum-based therapy without BV (n = 25), and those who received other non-BV treatment (n = 21). Before treatment, pulmonary artery perfusion (PAP) and bronchial artery perfusion (BAP) of the tumors were calculated. Predictors of tumor reduction after two courses of chemotherapy and prognosis were identified by using univariate and multivariate analyses. Covariates included were age, sex, patient's performance status, baseline maximum diameter of the tumor, clinical stage, pretreatment PAP, and pretreatment BAP. For multivariate analyses, multiple linear regression analysis for tumor reduction rate and Cox proportional hazards model for prognosis were performed, respectively. Results Pretreatment BAP was independently correlated with tumor reduction rate after two courses of chemotherapy in the BV treatment group (P = .006). Pretreatment BAP was significantly associated with a highly cumulative risk of death (P = .006) and disease progression after chemotherapy (P = .015) in the BV treatment group. Pretreatment PAP and clinical parameters were not significant predictors of therapeutic effect or prognosis in three treatment groups. Conclusion Pretreatment BAP derived from dual-input perfusion CT seems to be a promising tool to help predict responses to chemotherapy with BV in patients with NSCLC. © RSNA, 2017.

CD44 Gene Polymorphisms in Breast Cancer Risk and Prognosis: A Study in North Indian Population

PubMed Central

Tulsyan, Sonam; Agarwal, Gaurav; Lal, Punita; Agrawal, Sushma; Mittal, Rama Devi; Mittal, Balraj

2013-01-01

Background Cell surface biomarker CD44 plays an important role in breast cancer cell growth, differentiation, invasion, angiogenesis and tumour metastasis. Therefore, we aimed to investigate the role of CD44 gene polymorphisms in breast cancer risk and prognosis in North Indian population. Materials & Methods A total of 258 breast cancer patients and 241 healthy controls were included in the case-control study for risk prediction. According to RECIST, 114 patients who received neo-adjuvant chemotherapy were recruited for the evaluation of breast cancer prognosis. We examined the association of tagging SNP (rs353639) of Hapmap Gujrati Indians in Houston (GIH population) in CD44 gene along with a significant reported SNP (rs13347) in Chinese population by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. In-silico analysis for prediction of functional effects was done using F-SNP and FAST-SNP. Results No significant association of both the genetic variants of the CD44 gene polymorphisms was found with breast cancer risk. On performing univariate analysis with clinicopathological characteristics and treatment response, we found significant association of genotype (CT+TT) of rs13347 polymorphism with earlier age of onset (P = 0.029, OR = 0.037). However, significance was lost in multivariate analysis. For rs353639 polymorphism, significant association was seen with clinical tumour size, both at the genotypic (AC+CC) (P = 0.039, OR = 3.02) as well as the allelic (C) (P = 0.042, OR = 2.87) levels. On performing multivariate analysis, increased significance of variant genotype (P = 0.017, OR = 4.29) and allele (P = 0.025, OR = 3.34) of rs353639 was found with clinical tumour size. In-silico analysis using F-SNP, showed altered transcriptional regulation for rs353639 polymorphism. Conclusions These findings suggest that CD44 rs353639 genetic variants may have significant effect in breast cancer prognosis. However, both the polymorphisms- rs13347 and rs353639 had no effect on breast cancer susceptibility. PMID:23940692

Multivariate analysis of prognostic factors for idiopathic sudden sensorineural hearing loss treated with adjuvant hyperbaric oxygen therapy.

PubMed

Xie, Shaobing; Qiang, Qingfen; Mei, Lingyun; He, Chufeng; Feng, Yong; Sun, Hong; Wu, Xuewen

2018-01-01

The objective of this study is to evaluate possible prognostic factors of idiopathic sudden sensorineural hearing loss (ISSNHL) treated with adjuvant hyperbaric oxygen therapy (HBOT) using univariate and multivariate analyses. From January 2008 to October 2016, records of 178 ISSNHL patients treated with auxiliary hyperbaric oxygen therapy were reviewed to assess hearing recovery and evaluate associated prognostic factors (gender, age, localization, initial hearing threshold, presence of tinnitus, vertigo, ear fullness, hypertension, diabetes, onset of HBOT, number of HBOT, and audiogram), by using univariate and multivariate analyses. The overall recovery rate was 37.1%, including complete recovery (19.7%) and partial recovery (17.4%). According to multivariate analysis, later onset of HBOT and higher initial hearing threshold were associated with a poor prognosis in ISSNHL patients treated with HBOT. HBOT is a safe and beneficial adjuvant therapy for ISSNHL patients. 20 sessions of HBOT is possibly enough to show its therapeutic effect. Earlier HBOT onset and lower initial hearing threshold is associated with favorable hearing recovery.

Role of hepatic resection for patients with carcinoid heart disease.

PubMed

Bernheim, Alain M; Connolly, Heidi M; Rubin, Joseph; Møller, Jacob E; Scott, Christopher G; Nagorney, David M; Pellikka, Patricia A

2008-02-01

To evaluate the effects of resection of hepatic carcinoid metastases on progression and prognosis of carcinoid heart disease. From our database of 265 consecutive patients diagnosed as having carcinoid heart disease from January 1, 1980, through December 31, 2005, we calculated survival from first diagnosis of cardiac involvement. Hepatic resection during follow-up was entered as a time-dependent covariable in a multivariable analysis. In patients with serial echocardiograms more than 1 year apart without intervening cardiac surgery, a previously validated cardiac severity score was calculated. A score increase that exceeded 25% was considered relevant progression. Hepatic resection was performed in 31 patients (12%) during follow-up. Five-year survival was significantly higher in these patients (86.5%; 95% confidence interval [CI], 73.5%-100.0%) than in patients without hepatic resection (29.0%; 95% CI, 23.3%-36.1%; univariable hazard ratio for hepatic resection, 0.25; 95% CI 0.12-0.53; P<.001). Hepatic resection remained strongly associated with improved prognosis in multivariable analysis (hazard ratio, 0.31; 95% CI, 0.14-0.66; P=.003). Among 77 patients (29%) with serial echocardiograms, 10 (13%) underwent hepatic resection during follow-up; resection was independently associated with decreased risk of cardiac progression (odds ratio, 0.29; 95% CI, 0.06-0.75; P=.03). Despite the limitations of this retrospective nonrandomized study, our data suggest that patients with carcinoid heart disease who undergo hepatic resection have decreased cardiac progression and improved prognosis. Eligible patients should be considered for hepatic surgery.

[Sinonasal adenocarcinomas: our experience].

PubMed

Llorente, José Luis; Núñez, Faustino; Rodrigo, Juan Pablo; Fernández León, Ramón; Alvarez, César; Hermsen, Mario; Suárez, Carlos

2008-05-01

Sinonasal adenocarcinoma is a rare epithelial cancer of the nasal cavities and paranasal sinuses and exposure to sawdust particles is a strong aetiological factor. Seventy-nine patients (78 men and 1 woman) operated on between 1986 and 2002 were studied. In 62 patients (78.5 %) there was a history of exposure to wood dust. The clinical factors presenting statistical significance in the multivariate analysis with prognosis were: the exclusive invasion of the middle concha (as good prognosis), recurrence and invasion of the dura mater (as bad prognosis). The actuarial survival rate was 36 % at 5 years falling to 28 % at 10 years. Exposure to wood dust, even over a short period of time, must be considered as a high risk factor for the development of a sinonasal adenocarcinoma. This tumour must be ruled out in all patients suffering any type of sinonasal pathology.

Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy.

PubMed

Umemoto, Yuichiroh; Okano, Shinji; Matsumoto, Yoshihiro; Nakagawara, Hidekazu; Matono, Rumi; Yoshiya, Shohei; Yamashita, Yo-Ichi; Yoshizumi, Tomoharu; Ikegami, Toru; Soejima, Yuji; Harada, Mamoru; Aishima, Shinichi; Oda, Yoshinao; Shirabe, Ken; Maehara, Yoshihiko

2015-01-01

Hepatocellular carcinoma (HCC) is one of the most common solid tumors worldwide. Surgery is potentially curative, but high recurrence rates worsen patient prognosis. The interaction between the proteins programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) is an important immune checkpoint. The significance of PD-L1 expression and human leukocyte antigen class I (HLA class I), recognized by CD8 T cells, in the prognosis of patients with HCC remains to be determined. We assessed the levels of PD-L1 and HLA class I expression on HCC samples from 80 patients who had undergone hepatectomy at our institution, and evaluated the correlations between PD-L1 and HLA class I expression and patient prognosis. High HLA class I expression was correlated with significantly better recurrence-free survival (RFS), but not overall survival (OS). Multivariate analysis showed that high HLA class I expression was an independent predictor of improved RFS. Low expression of PD-L1 on HCC tended to predict better OS, but the difference was not statistically significant. PD-L1 expression on HCC correlated with the number of CD163-positive macrophages and HLA class I expression with CD3-positive cell infiltration. Univariable and multivariable analyses showed that combined PD-L1 low/HLA class I high expression on HCCs was prognostic for improved OS and RFS. PD-L1 status may be a good predictor of prognosis in HCC patients with high HLA class I expression. Novel therapies targeting the PD-L1/PD-1 pathway may improve the prognosis of patients with HCC.

Influence of hospital type on survival in stage IV colorectal cancer.

PubMed

Hoshino, Nobuaki; Hasegawa, Suguru; Hida, Koya; Kawada, Kenji; Okamura, Ryosuke; Hamada, Madoka; Munemoto, Yoshinori; Sakai, Yoshiharu; Watanabe, Masahiko

2016-08-01

Hospital factors along with various patient and surgeon factors are considered to affect the prognosis of colorectal cancer. Hospital volume is well known, but little is known regarding other hospital factors. We reviewed data on 853 patients with stage IV colorectal cancer who underwent elective palliative primary tumor resection between January 2006 and December 2007. To detect the hospital factors that could influence the prognosis of incurable colorectal cancer, the relationships between patient/hospital factors and overall survival were analyzed. Among hospital factors, hospital type (Group A: university hospital or cancer center; Group B: community hospital), hospital volume, and number of colorectal surgeons were examined. In univariate analysis, Group A hospitals showed significantly better prognosis than Group B hospitals (p = 0.034), while hospital volume and number of colorectal surgeons were not associated with overall survival. After adjustment for patient factors in multivariate analysis, hospital type was significantly associated with overall survival (hazard ratio: 1.31; 95 % confidence interval: 1.05-1.63; p = 0.016). However, there was no significant difference in short-term outcomes between hospital types. Hospital type was identified as a hospital factor that possibly affects the prognosis of stage IV colorectal cancer patients.

Pontin Acts as a Potential Biomarker for Poor Clinical Outcome and Promotes Tumor Invasion in Hilar Cholangiocarcinoma.

PubMed

Sun, Qi; Li, Fanni; Yu, Songyang; Zhang, Xiang; Shi, Feiyu; She, Junjun

2018-01-01

Hilar cholangiocarcinoma (HC) is a devastating malignancy that carries a poor overall prognosis. As a member of the AAA+ superfamily, Pontin becomes highly expressed in several malignant tumors, which contributes to tumor progression and influences tumor prognosis. In our research, Pontin expression in tumor specimens resected from 86 HC patients was detected by immunohistochemistry. Interestingly, high expression of Pontin was significantly associated with lymph node metastasis ( p = 0.011) and tumor node metastasis (TNM) stage ( p = 0.005). The Kaplan-Meier overall survival rate and multivariate analyses were performed to evaluate the prognosis of patients with HC. Patients with high Pontin expression had significantly poorer overall survival outcomes. Multivariate analyses found that Pontin was an independent prognostic factor ( p = 0.001). Moreover, bioinformatics analysis confirmed the increase in Pontin mRNA expression levels in cholangiocarcinoma tissues. In addition, in vitro experiments showed that Pontin expression was inhibited at the mRNA as well as protein levels after transfection with Pontin siRNA in human cholangiocarcinoma cell lines. Moreover, significant suppression of cell invasion was observed after the downregulation of Pontin. Taken together, the present study suggested that Pontin could act as a potential prognostic predictor, which might be a new valuable molecular candidate for the prevention and treatment of HC.

Significance of serum CA125 and TPS antigen levels for determination of overall survival after three chemotherapy courses in ovarian cancer patients during long-term follow-up.

PubMed

van Dalen, A; Favier, J; Hallensleben, E; Burges, A; Stieber, P; de Bruijn, H W A; Fink, D; Ferrero, A; McGing, P; Harlozinska, A; Kainz, Ch; Markowska, J; Molina, R; Sturgeon, C; Bowman, A; Einarsson, R; Goike, H

2009-01-01

To evaluate the prognostic significance for overall survival rate for the marker combination TPS and CA125 in ovarian cancer patients after three chemotherapy courses during long-term clinical follow-up. The overall survival of 212 (out of 213) ovarian cancer patients (FIGO Stages I-IV) was analyzed in a prospective multicenter study during a 10-year clinical follow-up by univariate and multivariate analysis. In patients with ovarian cancer FIGO Stage I (34 patients) or FIGO Stage II (30 patients) disease, the univariate and multivariate analysis of the 10-year overall survival data showed that CA125 and TPS serum levels were not independent prognostic factors. In the FIGO Stage III group (112 patients), the 10-year overall survival was 15.2%; while in the FIGO Stage IV group (36 patients) a 10-year overall survival of 5.6% was seen. Here, the tumor markers CA125 and TPS levels were significant prognostic factors in both univariate and multivariate analysis (p < 0.0001). In a combined FIGO Stage III + FIGO Stage IV group (60 patients with optimal debulking surgery), multivariate analysis demonstrated that CA125 and TPS levels were independent prognostic factors. For patients in this combined FIGO Stage III + IV group having both markers below respective discrimination level, 35.3% survived for more than ten years, as opposed to patients having one marker above the discrimination level where the 10-year survival was reduced to 10% of the patients. For patients showing both markers above the respective discrimination level, none of the patients survived for the 10-year follow-up time. In FIGO III and IV ovarian cancer patients, only patients with CA 125 and TPS markers below the discrimination level after three chemotherapy courses indicated a favorable prognosis. Patients with an elevated level of CA 125 or TPS or both markers after three chemotherapy courses showed unfavorable prognosis.

Decompressive craniectomy in severe traumatic brain injury: prognostic factors and complications

PubMed Central

Grille, Pedro; Tommasino, Nicolas

2015-01-01

Objective To analyze the clinical characteristics, complications and factors associated with the prognosis of severe traumatic brain injury among patients who undergo a decompressive craniectomy. Methods Retrospective study of patients seen in an intensive care unit with severe traumatic brain injury in whom a decompressive craniectomy was performed between the years 2003 and 2012. Patients were followed until their discharge from the intensive care unit. Their clinical-tomographic characteristics, complications, and factors associated with prognosis (univariate and multivariate analysis) were analyzed. Results A total of 64 patients were studied. Primary and lateral decompressive craniectomies were performed for the majority of patients. A high incidence of complications was found (78% neurological and 52% nonneurological). A total of 42 patients (66%) presented poor outcomes, and 22 (34%) had good neurological outcomes. Of the patients who survived, 61% had good neurological outcomes. In the univariate analysis, the factors significantly associated with poor neurological outcome were postdecompressive craniectomy intracranial hypertension, greater severity and worse neurological state at admission. In the multivariate analysis, only postcraniectomy intracranial hypertension was significantly associated with a poor outcome. Conclusion This study involved a very severe and difficult to manage group of patients with high morbimortality. Intracranial hypertension was a main factor of poor outcome in this population. PMID:26340150

Effect of epidermal growth factor receptor gene polymorphisms on prognosis in glioma patients

PubMed Central

Li, Jingjie; Yan, Mengdan; Xie, Zhilan; Zhu, Yuanyuan; Chen, Chao; Jin, Tianbo

2016-01-01

Previous studies suggested that single nucleotide polymorphisms (SNPs) in epidermal growth factor receptor (EGFR) are associated with risk of glioma. However, the associations between these SNPs and glioma patient prognosis have not yet been fully investigated. Therefore, the present study was aimed to evaluate the effects of EGFR polymorphisms on the glioma patient prognosis. We retrospectively evaluated 269 glioma patients and investigated associations between EGFR SNPs and patient prognosis using Cox proportional hazard models and Kaplan-Meier curves. Univariate analysis revealed that age, gross-total resection and chemotherapy were associated with the prognosis of glioma patients (p < 0.05). In addition, four EGFR SNPs (rs11506105, rs3752651, rs1468727 and rs845552) correlated with overall survival (OS) (Log-rank p = 0.011, 0.020, 0.008, and 0.009, respectively) and progression-free survival PFS (Log-rank p = 0.026, 0.024, 0.019 and 0.009, respectively). Multivariate analysis indicated that the rs11506105 G/G genotype, the rs3752651 and rs1468727 C/C genotype and the rs845552 A/A genotype correlated inversely with OS and PFS. In addition, OS among patients with the rs730437 C/C genotype (p = 0.030) was significantly lower OS than among patients with A/A genotype. These data suggest that five EGFR SNPs (rs11506105, rs3752651, rs1468727, rs845552 and rs730437) correlated with glioma patient prognosis, and should be furthered validated in studies of ethnically diverse patients. PMID:27437777

Reduced miR-300 expression predicts poor prognosis in patients with laryngeal squamous cell carcinoma.

PubMed

He, F-Y; Liu, H-J; Guo, Q; Sheng, J-L

2017-02-01

miR-300 has been demonstrated to play an important role in the progression of several tumors, but its role in tumorigenesis of laryngeal squamous cell carcinoma (LSCC) is still unclear. The purpose of this study was to explore miR-300 expression in LSCC patients and analyze its association with clinicopathological factors and prognosis. In the present study, we measured the expression level of miR-300 in LSCC tissues by RT-PCR. Associations between miRNA-300 expressions and various clinicopathological characteristics were analyzed. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. The univariate and multivariate analysis were performed using the Cox proportional hazard analysis. miR-300 expression was significantly increased in LSCC tissues compared with that in adjacent non-cancerous tissues (p < 0.01). In addition, lymph node metastasis (p = 0.004) and TNM stage (p = 0.001) were obvious influence factors for the expression of miR-300. More importantly, Kaplan-Meier analysis showed that LSCC patients with low miR-300 expression tended to have shorter overall survival (p < 0.001). Finally, multivariate analysis revealed that miR-300 expression was an independent prognostic factor for LSCC patients. Our results pointed to miR-300 as a powerful prognostic marker in LSCC and as a novel target for tumor-suppressive therapy.

Impact of the branched-chain amino acid to tyrosine ratio and branched-chain amino acid granule therapy in patients with hepatocellular carcinoma: A propensity score analysis.

PubMed

Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Kiriyama, Seiki; Tanikawa, Makoto; Hisanaga, Yasuhiro; Kanamori, Akira; Kitabatake, Shusuke; Yama, Tsuyoki

2015-09-01

It has been reported that the branched-chain amino acid (BCAA) to tyrosine ratio (BTR) is a useful indicator of liver function and BCAA therapy is associated with a decreased incidence of hepatocellular carcinoma (HCC). However, there has not been sufficient research on the relationship between BTR and the effects of BCAA therapy after initial treatment of HCC. We investigated the impact of BTR and BCAA therapy on survival in patients with HCC. A total of 315 patients with HCC who were treated (n = 66) or not treated (n = 249) with BCAA were enrolled; of these, 66 were selected from each group using propensity score matching. Survival from liver-related mortality was analyzed. In patients who did not receive BCAA therapy (n = 249), multivariate analysis for factors associated with survival indicated that low BTR (≤ 4.4) was independently associated with poor prognosis in patients with HCC (hazard ratio, 1.880; 95% confidence interval, 1.125-3.143; P = 0.016). In addition, among patients selected by propensity score matching (n = 132), multivariate analysis indicated that BCAA therapy was independently associated with good prognosis in patients with HCC (hazard ratio, 0.524; 95% confidence interval, 0.282-0.973; P = 0.041). BTR was not significantly associated with survival. Intervention involving BCAA therapy improved survival in patients with HCC versus untreated controls, regardless of BTR. In addition, low BTR was associated with poor prognosis in patients who did not receive BCAA therapy. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Inactivation of Hippo Pathway Is Significantly Associated with Poor Prognosis in Hepatocellular Carcinoma.

PubMed

Sohn, Bo Hwa; Shim, Jae-Jun; Kim, Sang-Bae; Jang, Kyu Yun; Kim, Soo Mi; Kim, Ji Hoon; Hwang, Jun Eul; Jang, Hee-Jin; Lee, Hyun-Sung; Kim, Sang-Cheol; Jeong, Woojin; Kim, Sung Soo; Park, Eun Sung; Heo, Jeonghoon; Kim, Yoon Jun; Kim, Dae-Ghon; Leem, Sun-Hee; Kaseb, Ahmed; Hassan, Manal M; Cha, Minse; Chu, In-Sun; Johnson, Randy L; Park, Yun-Yong; Lee, Ju-Seog

2016-03-01

The Hippo pathway is a tumor suppressor in the liver. However, the clinical significance of Hippo pathway inactivation in HCC is not clearly defined. We analyzed genomic data from human and mouse tissues to determine clinical relevance of Hippo pathway inactivation in HCC. We analyzed gene expression data from Mst1/2(-/-) and Sav1(-/-) mice and identified a 610-gene expression signature reflecting Hippo pathway inactivation in the liver [silence of Hippo (SOH) signature]. By integrating gene expression data from mouse models with those from human HCC tissues, we developed a prediction model that could identify HCC patients with an inactivated Hippo pathway and used it to test its significance in HCC patients, via univariate and multivariate Cox analyses. HCC patients (National Cancer Institute cohort, n = 113) with the SOH signature had a significantly poorer prognosis than those without the SOH signature [P < 0.001 for overall survival (OS)]. The significant association of the signature with poor prognosis was further validated in the Korean (n = 100, P = 0.006 for OS) and Fudan University cohorts (n = 242, P = 0.001 for OS). On multivariate analysis, the signature was an independent predictor of recurrence-free survival (HR, 1.6; 95% confidence interval, 1.12-2.28: P = 0.008). We also demonstrated significant concordance between the SOH HCC subtype and the hepatic stem cell HCC subtype that had been identified in a previous study (P < 0.001). Inactivation of the Hippo pathway in HCC is significantly associated with poor prognosis. ©2015 American Association for Cancer Research.

Declined Preoperative Aspartate Aminotransferase to Neutrophil Ratio Index Predicts Poor Prognosis in Patients with Intrahepatic Cholangiocarcinoma after Hepatectomy

PubMed Central

Liu, Lingyun; Wang, Wei; Zhang, Yi; Long, Jianting; Zhang, Zhaohui; Li, Qiao; Chen, Bin; Li, Shaoqiang; Hua, Yunpeng; Shen, Shunli; Peng, Baogang

2018-01-01

Purpose Various inflammation-based prognostic biomarkers such as the platelet to lymphocyte ratio and neutrophil to lymphocyte ratio, are related to poor survival in patients with intrahepatic cholangiocarcinoma (ICC). This study aims to investigate the prognostic value of the aspartate aminotransferase to neutrophil ratio index (ANRI) in ICC after hepatic resection. Materials and Methods Data of 184 patients with ICC after hepatectomy were retrospectively reviewed. The cut-off value of ANRIwas determined by a receiver operating characteristic curve. Preoperative ANRI and clinicopathological variables were analyzed. The predictive value of preoperative ANRI for prognosis of ICC was identified by univariate and multivariate analyses. Results The optimal cut-off value of ANRI was 6.7. ANRI was associated with tumor size, tumor recurrence, white blood cell, neutrophil count, aspartate aminotransferase, and alanine transaminase. Univariate analysis showed that ANRI, sex, tumor number, tumor size, tumor differentiation, lymph node metastasis, resection margin, clinical TNM stage, neutrophil count, and carcinoembryonic antigen were markedly correlated with overall survival (OS) and disease-free survival (DFS) in patients with ICC. Multivariable analyses revealed that ANRI, a tumor size > 6 cm, poor tumor differentiation, and an R1 resection margin were independent prognostic factors for both OS and DFS. Additionally, preoperative ANRI also had a significant value to predict prognosis in various subgroups of ICC, including serum hepatitis B surface antigen‒negative and preoperative elevated carbohydrate antigen 19-9 patients. Conclusion Preoperative declined ANRI is a noninvasive, simple, and effective predictor of poor prognosis in patients with ICC after hepatectomy. PMID:28602056

Chemokine-like factor-like MARVEL transmembrane domain-containing 3 expression is associated with a favorable prognosis in esophageal squamous cell carcinoma.

PubMed

Han, Tianci; Shu, Tianci; Dong, Siyuan; Li, Peiwen; Li, Weinan; Liu, Dali; Qi, Ruiqun; Zhang, Shuguang; Zhang, Lin

2017-05-01

Decreased expression of human chemokine-like factor-like MARVEL transmembrane domain-containing 3 (CMTM3) has been identified in a number of human tumors and tumor cell lines, including gastric and testicular cancer, and PC3, CAL27 and Tca-83 cell lines. However, the association between CMTM3 expression and the clinicopathological features and prognosis of esophageal squamous cell carcinoma (ESCC) patients remains unclear. The aim of the present study was to investigate the correlation between CMTM3 expression and clinicopathological parameters and prognosis in ESCC. CMTM3 mRNA and protein expression was analyzed in ESCC and paired non-tumor tissues by quantitative real-time polymerase chain reaction, western blotting and immunohistochemical analysis. The Kaplan-Meier method was used to plot survival curves and the Cox proportional hazards regression model was also used for univariate and multivariate survival analysis. The results revealed that CMTM3 mRNA and protein expression levels were lower in 82.5% (30/40) and 75% (30/40) of ESCC tissues, respectively, when compared with matched non-tumor tissues. Statistical analysis demonstrated that CMTM3 expression was significantly correlated with lymph node metastasis (P=0.002) and clinical stage (P<0.001) in ESCC tissues. Furthermore, the survival time of ESCC patients exhibiting low CMTM3 expression was significantly shorter than that of ESCC patients exhibiting high CMTM3 expression (P=0.01). In addition, Kaplan-Meier survival analysis revealed that the overall survival time of patients exhibiting low CMTM3 expression was significantly decreased compared with patients exhibiting high CMTM3 expression (P=0.010). Cox multivariate analysis indicated that CMTM3 protein expression was an independent prognostic predictor for ESCC after resection. This study indicated that CMTM3 expression is significantly decreased in ESCC tissues and CMTM3 protein expression in resected tumors may present an effective prognostic biomarker.

Demographic and lifestyle factors and survival among patients with esophageal and gastric cancer: The Biobank Japan Project.

PubMed

Okada, Emiko; Ukawa, Shigekazu; Nakamura, Koshi; Hirata, Makoto; Nagai, Akiko; Matsuda, Koichi; Ninomiya, Toshiharu; Kiyohara, Yutaka; Muto, Kaori; Kamatani, Yoichiro; Yamagata, Zentaro; Kubo, Michiaki; Nakamura, Yusuke; Tamakoshi, Akiko

2017-03-01

Several studies have evaluated associations between the characteristics of patients with esophageal and gastric cancer and survival, but these associations remain unclear. We described the distribution of demographic and lifestyle factors among patients with esophageal and gastric cancer in Japan, and investigated their potential effects on survival. Between 2003 and 2007, 24- to 95-year-old Japanese patients with esophageal and gastric cancer were enrolled in the BioBank Japan Project. The analysis included 365 patients with esophageal squamous cell carcinoma (ESCC) and 1574 patients with gastric cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using medical institution-stratified Cox proportional hazards models. During follow-up, 213 patients with ESCC (median follow-up, 4.4 years) and 603 patients with gastric cancer (median follow-up, 6.1 years) died. Among patients with ESCC, the mortality risk was higher in ever drinkers versus never drinkers (multivariable HR = 2.37, 95% CI: 1.24, 4.53). Among patients with gastric cancer, the mortality risk was higher in underweight patients versus patients of normal weight (multivariable HR = 1.66, 95% CI: 1.34, 2.05). Compared to patients with gastric cancer with no physical exercise habit, those who exercised ≥3 times/week had a lower mortality risk (multivariate HR = 0.75, 95% CI = 0.61, 0.93). However, lack of stage in many cases was a limitation. Among patients with ESCC, alcohol drinkers have a poor prognosis. Patients with gastric cancer who are underweight also have a poor prognosis, whereas patients with physical exercise habits have a good prognosis. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Prognostic significance of postoperative pneumonia after curative resection for patients with gastric cancer.

PubMed

Tu, Ru-Hong; Lin, Jian-Xian; Li, Ping; Xie, Jian-Wei; Wang, Jia-Bin; Lu, Jun; Chen, Qi-Yue; Cao, Long-Long; Lin, Mi; Zheng, Chao-Hui; Huang, Chang-Ming

2017-12-01

Few studies have been designed to investigate the incidence of postoperative pneumonia after radical gastrectomy and its effect on prognosis of these patients. Incidences of postoperative pneumonia after radical gastrectomy in our department between January 1996 and December 2014 were summarized. Their effects on prognosis were retrospectively analyzed using survival curves and Cox regression. A total of 5237 patients were included in this study, 767 (14.4%) of them had complications, including 383 cases of postoperative pneumonia (7.2%). The 5-year overall and disease-specific survival of patients with postoperative pneumonia were both lower than those without this complication (P < 0.001). Stratified analysis demonstrated that this difference existed in all Stage I, II, and III patients (log-rank, P < 0.05). Multivariate analysis revealed that age, neoadjuvant chemotherapy, tumor size, tumor stage, and postoperative pneumonia were independent risk factors for disease-specific survival. Postoperative pneumonia after radical gastrectomy is an independent risk factor for prognosis of gastric cancer patients, especially in stage III. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Decreased expression of class III β-tubulin is associated with unfavourable prognosis in patients with malignant melanoma.

PubMed

Shimizu, Akira; Kaira, Kyoichi; Yasuda, Masahito; Asao, Takayuki; Ishikawa, Osamu

2016-02-01

Class III β-tubulin (TUBB3) has been recognized as being associated with resistance to taxane-based regimens in several cancers. However, little is known about the clinicopathological significance of TUBB3 expression in patients with cutaneous malignant melanoma. The aim of this study was to examine the prognostic significance of TUBB3 expression in cutaneous malignant melanoma. A total of 106 patients with surgically resected cutaneous malignant melanoma were assessed. Tumour sections were immunohistochemically stained for TUBB3, Ki-67 and microvessel density with CD34. TUBB3 was highly expressed in 80% (85/106) of patients. No statistically significant relationship was observed between the high expression of TUBB3 and any variables. On univariate analysis, ulceration, disease stage, TUBB3 and CD34 revealed a significant relationship with overall survival and progression-free survival. Multivariate analysis confirmed that a low TUBB3 expression was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The decreased expression of TUBB3 could be a significant marker for predicting unfavourable prognosis in patients with cutaneous malignant melanoma.

Upregulated SOX9 expression indicates worse prognosis in solid tumors: a systematic review and meta-analysis

PubMed Central

Ruan, Haihua; Hu, Shuangyan; Zhang, Hongyu; Du, Gang; Li, Xiaoting; Li, Xiaobo; Li, Xichuan

2017-01-01

It was recently reported that increased SOX9 expression drives tumor growth and promotes cancer invasion during human tumorigenicity and metastasis. However, the prognostic value of SOX9 for the survival of patients with solid tumors remains controversial. The present meta-analysis was thus performed to highlight the link between dysregulated SOX9 expression and prognosis in cancer patients. A systematic literature search was conducted using the electronic databases PubMed, Web of Science and Embase to identify eligible studies. A random-effects meta-analytical model was employed to correlate SOX9 expression with overall survival (OS), disease-free survival (DFS) and clinicopathological features. In total, 17 studies with 3307 patients were eligible for the final analysis. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) suggested that high SOX9 expression has an unfavourable impact on OS (HR = 1.66, 95% CI 1.36–2.02, P < 0.001) and DFS (HR = 3.54, 95% CI 2.29–5.47, P = 0.008) in multivariate analysis. Additionally, the pooled odds ratios (ORs) indicated that SOX9 over-expression is associated with large tumor size, lymph node metastasis, distant metastasis and a higher clinical stage. Overall, these results indicated that SOX9 over-expression in patients with solid tumors might be related to poor prognosis and could serve as a potential predictive marker of poor clinicopathological prognosis factor. PMID:29348895

Fasting blood glucose is a novel prognostic indicator for extranodal natural killer/T-cell lymphoma, nasal type

PubMed Central

Cai, Q; Luo, X; Liang, Y; Rao, H; Fang, X; Jiang, W; Lin, T; Lin, T; Huang, H

2013-01-01

Background: Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is an aggressive disease with poor prognosis, requiring risk stratification. However, the prognosis of ENKTL is not fully defined and needs supplementation. We hypothesised that fasting blood glucose (FBG) may be a new prognostic factor for ENKTL. Methods: We retrospectively analysed 130 patients newly diagnosed with ENKTL. Results: Both univariate analysis and multivariate analysis revealed that FBG >100 mg dl−1 was associated with a poor outcome. Patients with FBG >100 mg dl−1 at diagnosis had more adverse clinical features, achieved lower complete remission rates (P=0.003) and had worse overall survival (P<0.001) and progression-free survival (P<0.001) compared with low-FBG patients. Measurement of FBG was helpful in differentiating between low-risk patients using the International Prognostic Index (IPI) and Prognosis Index for peripheral T-cell lymphoma (PIT) scoring and patients in a different category using the Korean Prognostic Index (KPI) scores with different survival outcomes (P<0.05). Conclusion: Our data suggest that measuring FBG levels at diagnosis is a novel, independent predictor of prognosis in ENKTL and helps to distinguish low-risk patients with poor survival, and this holds true in patients considered low-risk by IPI, PIT and KPI. PMID:23299534

OPLS statistical model versus linear regression to assess sonographic predictors of stroke prognosis.

PubMed

Vajargah, Kianoush Fathi; Sadeghi-Bazargani, Homayoun; Mehdizadeh-Esfanjani, Robab; Savadi-Oskouei, Daryoush; Farhoudi, Mehdi

2012-01-01

The objective of the present study was to assess the comparable applicability of orthogonal projections to latent structures (OPLS) statistical model vs traditional linear regression in order to investigate the role of trans cranial doppler (TCD) sonography in predicting ischemic stroke prognosis. The study was conducted on 116 ischemic stroke patients admitted to a specialty neurology ward. The Unified Neurological Stroke Scale was used once for clinical evaluation on the first week of admission and again six months later. All data was primarily analyzed using simple linear regression and later considered for multivariate analysis using PLS/OPLS models through the SIMCA P+12 statistical software package. The linear regression analysis results used for the identification of TCD predictors of stroke prognosis were confirmed through the OPLS modeling technique. Moreover, in comparison to linear regression, the OPLS model appeared to have higher sensitivity in detecting the predictors of ischemic stroke prognosis and detected several more predictors. Applying the OPLS model made it possible to use both single TCD measures/indicators and arbitrarily dichotomized measures of TCD single vessel involvement as well as the overall TCD result. In conclusion, the authors recommend PLS/OPLS methods as complementary rather than alternative to the available classical regression models such as linear regression.

Community-acquired pneumonia in the elderly: A multivariate analysis of risk and prognostic factors.

PubMed

Riquelme, R; Torres, A; El-Ebiary, M; de la Bellacasa, J P; Estruch, R; Mensa, J; Fernández-Solá, J; Hernández, C; Rodriguez-Roisin, R

1996-11-01

To assess the risk and prognostic factors of community-acquired pneumonia occurring in the elderly (over age 65 yr) requiring hospitalization, two studies, case-control and cohort, were performed over an 8-mo period in a 1,000-bed university teaching hospital. We studied 101 patients with pneumonia (cases), age 78.5 +/- 7.9 yr (mean +/- SD). Each case was matched for sex, age (+/- 5 yr), and date of admission (+/- 2 d) with a control subject, without pneumonia during the preceding 3 yr, arriving at the emergency room. Etiologic diagnosis was obtained in 43 of 101 (42%) cases. The main microbial agents causing pneumonia were: Streptococcus pneumoniae (19 of 43, 44%), and Chlamydia pneumoniae (9 of 43, 21%). Gram-negative bacilli were uncommon (2 of 43, 5%). The multivariate analysis demonstrated that large-volume aspiration, and low serum albumin (< 30 mg/dl) were independent risk factors associated with the development of pneumonia. Crude mortality rate was 26% (26 of 101), while pneumonia-related mortality was 20% (20 of 101). The attributable mortality was 23% (odds ratio [OR]: 11.3; 95% confidence interval [CI]: 3.25 to 60.23; p < 0.0001). The multivariate analysis showed that patients had a worse prognosis if they were previously bedridden, had prior swallowing disorders, body temperature on admission was less than 37 degrees C, respiratory frequency was greater than 30/min or had three or more affected lobes on chest radiograph. Age by itself was not a significant factor related to prognosis. Among the significant risk factors, only nutritional status is probably amenable to medical intervention. The prognostic factors found in this study may help to identify, upon admission, those subjects at higher risk and who may require special observation.

Prognostic value of MLH1 promoter methylation in male patients with esophageal squamous cell carcinoma.

PubMed

Wu, Dongping; Chen, Xiaoying; Xu, Yan; Wang, Haiyong; Yu, Guangmao; Jiang, Luping; Hong, Qingxiao; Duan, Shiwei

2017-04-01

The DNA mismatch repair (MMR) gene MutL homolog 1 ( MLH1 ) is critical for the maintenance of genomic integrity. Methylation of the MLH1 gene promoter was identified as a prognostic marker for numerous types of cancer including glioblastoma, colorectal, ovarian and gastric cancer. The present study aimed to determine whether MLH1 promoter methylation was associated with survival in male patients with esophageal squamous cell carcinoma (ESCC). Formalin-fixed, paraffin-embedded ESCC tissues were collected from 87 male patients. MLH1 promoter methylation was assessed using the methylation-specific polymerase chain reaction approach. Kaplan-Meier survival curves and log-rank tests were used to evaluate the association between MLH1 promoter methylation and overall survival (OS) in patients with ESCC. Cox regression analysis was used to obtain crude and multivariate hazard ratios (HR), and 95% confidence intervals (CI). The present study revealed that MLH1 promoter methylation was observed in 53/87 (60.9%) of male patients with ESCC. Kaplan-Meier survival analysis demonstrated that MLH1 promoter hypermethylation was significantly associated with poorer prognosis in patients with ESCC (P=0.048). Multivariate survival analysis revealed that MLH1 promoter hypermethylation was an independent predictor of poor OS in male patients with ESCC (HR=1.716; 95% CI=1.008-2.921). Therefore, MLH1 promoter hypermethylation may be a predictor of prognosis in male patients with ESCC.

Robust tumor morphometry in multispectral fluorescence microscopy

NASA Astrophysics Data System (ADS)

Tabesh, Ali; Vengrenyuk, Yevgen; Teverovskiy, Mikhail; Khan, Faisal M.; Sapir, Marina; Powell, Douglas; Mesa-Tejada, Ricardo; Donovan, Michael J.; Fernandez, Gerardo

2009-02-01

Morphological and architectural characteristics of primary tissue compartments, such as epithelial nuclei (EN) and cytoplasm, provide important cues for cancer diagnosis, prognosis, and therapeutic response prediction. We propose two feature sets for the robust quantification of these characteristics in multiplex immunofluorescence (IF) microscopy images of prostate biopsy specimens. To enable feature extraction, EN and cytoplasm regions were first segmented from the IF images. Then, feature sets consisting of the characteristics of the minimum spanning tree (MST) connecting the EN and the fractal dimension (FD) of gland boundaries were obtained from the segmented compartments. We demonstrated the utility of the proposed features in prostate cancer recurrence prediction on a multi-institution cohort of 1027 patients. Univariate analysis revealed that both FD and one of the MST features were highly effective for predicting cancer recurrence (p <= 0.0001). In multivariate analysis, an MST feature was selected for a model incorporating clinical and image features. The model achieved a concordance index (CI) of 0.73 on the validation set, which was significantly higher than the CI of 0.69 for the standard multivariate model based solely on clinical features currently used in clinical practice (p < 0.0001). The contributions of this work are twofold. First, it is the first demonstration of the utility of the proposed features in morphometric analysis of IF images. Second, this is the largest scale study of the efficacy and robustness of the proposed features in prostate cancer prognosis.

Elevated red cell distribution width contributes to a poor prognosis in patients with esophageal carcinoma.

PubMed

Wan, Guo-Xing; Chen, Ping; Cai, Xiao-Jun; Li, Lin-Jun; Yu, Xiong-Jie; Pan, Dong-Feng; Wang, Xian-He; Wang, Xuan-Bin; Cao, Feng-Jun

2016-01-15

The red cell distribution width (RDW) has also been reported to reliably reflect the inflammation and nutrition status and predict the prognosis across several types of cancer, however, the prognostic value of RDW in esophageal carcinoma has seldom been studied. A retrospective study was performed to assess the prognostic value of RDW in patients with esophageal carcinoma by the Kaplan-Meier analysis and multivariate Cox regression proportional hazard model. All enrolled patients were divided into high RDW group (≧15%) and low RDW group (<15%) according to the detected RDW values. Clinical and laboratory data from a total of 179 patients with esophageal carcinoma were retrieved. With a median follow-up of 21months, the high RDW group exhibited a shorter disease-free survival (DFS) (p<0.001) and an unfavorable overall survival (OS) (p<0.001) in the univariate analysis. The multivariate analysis revealed that elevated RDW at diagnosis was an independent prognostic factor for shorter PFS (p=0.043, HR=1.907, 95% CI=1.020-3.565) and poor OS (p=0.042, HR=1.895, 95% CI=1.023-3.508) after adjustment with other cancer-related prognostic factors. The present study suggests that elevated preoperative RDW(≧15%) at the diagnosis may independently predict poorer disease-free and overall survival among patients with esophageal carcinoma. Copyright © 2015 Elsevier B.V. All rights reserved.

Can the new RCP R0/R1 classification predict the clinical outcome in ductal adenocarcinoma of the pancreatic head?

PubMed

Janot, M S; Kersting, S; Belyaev, O; Matuschek, A; Chromik, A M; Suelberg, D; Uhl, W; Tannapfel, A; Bergmann, U

2012-08-01

According to the International Union Against Cancer (UICC), R1 is defined as the microscopic presence of tumor cells at the surface of the resection margin (RM). In contrast, the Royal College of Pathologists (RCP) suggested to declare R1 already when tumor cells are found within 1 mm of the RM. The aim of this study was to determine the significance of the RM concerning the prognosis of pancreatic ductal adenocarcinoma (PDAC). From 2007 to 2009, 62 patients underwent a curative operation for PDAC of the pancreatic head. The relevance of R status on cumulative overall survival (OS) was assessed on univariate and multivariate analysis for both the classic R classification (UICC) and the suggestion of the RCP. Following the UICC criteria, a positive RM was detected in 8 %. Along with grading and lymph node ratio, R status revealed a significant impact on OS on univariate and multivariate analysis. Applying the suggestion of the RCP, R1 rate rose to 26 % resulting in no significant impact on OS in univariate analysis. Our study has shown that the RCP suggestion for R status has no impact on the prognosis of PDAC. In contrast, our data confirmed the UICC R classification of RM as well as N category, grading, and lymph node ratio as significant prognostic factors.

Chest wall recurrence after mastectomy does not always portend a dismal outcome.

PubMed

Chagpar, Anees; Meric-Bernstam, Funda; Hunt, Kelly K; Ross, Merrick I; Cristofanilli, Massimo; Singletary, S Eva; Buchholz, Thomas A; Ames, Frederick C; Marcy, Sylvie; Babiera, Gildy V; Feig, Barry W; Hortobagyi, Gabriel N; Kuerer, Henry M

2003-07-01

Chest wall recurrence (CWR) after mastectomy often forecasts a grim prognosis. Predictors of outcome after CWR, however, are not clear. From 1988 to 1998, 130 patients with isolated CWRs were seen at our center. Clinicopathologic factors were studied by univariate and multivariate analyses for distant metastasis-free survival after CWR. The median post-CWR follow-up was 37 months. Initial nodal status was the strongest predictor of outcome by univariate analysis. Other significant factors included initial T4 disease, primary lymphovascular invasion, treatment of the primary tumor with neoadjuvant therapy or radiation, time to CWR >24 months, and treatment for CWR (surgery, radiation, or multimodality therapy). Multivariate analysis also found initial nodal status to have the greatest effect; time to CWR and use of radiation for CWR were also independent predictors. Three groups of patients were identified. Low risk was defined by initial node-negative disease, time to CWR >24 months, and radiation for CWR; intermediate risk had one or two favorable features; and high risk had none. The median distant metastasis-free survival after CWR was significantly different among these groups (P <.0001). Patients with CWR are a heterogeneous population. Patients with initial node-negative disease who develop CWR after 24 months have an optimistic prognosis, especially if they are treated with radiation.

Pattern of spread and prognosis in lower limb-onset ALS

PubMed Central

TURNER, MARTIN R.; BROCKINGTON, ALICE; SCABER, JAKUB; HOLLINGER, HANNAH; MARSDEN, RACHAEL; SHAW, PAMELA J.; TALBOT, KEVIN

2011-01-01

Our objective was to establish the pattern of spread in lower limb-onset ALS (contra- versus ipsi-lateral) and its contribution to prognosis within a multivariate model. Pattern of spread was established in 109 sporadic ALS patients with lower limb-onset, prospectively recorded in Oxford and Sheffield tertiary clinics from 2001 to 2008. Survival analysis was by univariate Kaplan-Meier log-rank and multivariate Cox proportional hazards. Variables studied were time to next limb progression, site of next progression, age at symptom onset, gender, diagnostic latency and use of riluzole. Initial progression was either to the contralateral leg (76%) or ipsilateral arm (24%). Factors independently affecting survival were time to next limb progression, age at symptom onset, and diagnostic latency. Time to progression as a prognostic factor was independent of initial direction of spread. In a regression analysis of the deceased, overall survival from symptom onset approximated to two years plus the time interval for initial spread. In conclusion, rate of progression in lower limb-onset ALS is not influenced by whether initial spread is to the contralateral limb or ipsilateral arm. The time interval to this initial spread is a powerful factor in predicting overall survival, and could be used to facilitate decision-making and effective care planning. PMID:20001488

Downregulation of SASH1 correlates with poor prognosis in cervical cancer.

PubMed

Xie, J; Zhang, W; Zhang, J; Lv, Q-Y; Luan, Y-F

2017-10-01

The aim of this study was to analyze the association of SASH1 expression with clinicopathological features and prognosis in patients suffering cervical cancer. The expressions of SASH1 mRNA and protein in cervical cancer tissues and matched normal cervical tissues were detected by Real-time PCR and Immunohistochemistry. Based on the above findings, the association among SASH1 expression and clinicopathological features was analyzed. Overall survival was evaluated using the Kaplan-Meier method. The variables were used in univariate and multivariate analysis by the Cox proportional hazards model. The results demonstrated that both SASH1 mRNA and proteins were downregulated in cervical cancer tissues compared with those in matched normal tissues (both p < 0.05). Also, decreased SASH1 expression in cervical cancer was found to be significantly associated with high FIGO Stage (p = 0.001), lymph nodes metastasis (p = 0.003) and differentiation (p = 0.018). Furthermore, Kaplan-Meier analysis demonstrated that low SASH1 expression level was associated with poorer overall survival (p < 0.01). Univariate and multivariate analyses indicated that status of SASH1 was an independent prognostic factor for patients with cervical cancer. These findings suggested that SASH1 can be useful as a new prognostic marker and therapeutic target in cervical cancer patients.

Grave prognosis on spontaneous intracerebral haemorrhage: GP on STAGE score.

PubMed

Poungvarin, Niphon; Suwanwela, Nijasri C; Venketasubramanian, Narayanaswamy; Wong, Lawrence K S; Navarro, Jose C; Bitanga, Ester; Yoon, Byung Woo; Chang, Hui M; Alam, Sardar M

2006-11-01

Spontaneous intracerebral haemorrhage (ICH) is more common in Asia than in western countries, and has a high mortality rate. A simple prognostic score for predicting grave prognosis of ICH is lacking. Our objective was to develop a simple and reliable score for most physicians. ICH patients from seven Asian countries were enrolled between May 2000 and April 2002 for a prospective study. Clinical features such as headache and vomiting, vascular risk factors, Glasgow coma scale (GCS), body temperature (BT), blood pressure on arrival, location and size of haematoma, intraventricular haemorrhage (IVH), hydrocephalus, need for surgical treatment, medical treatment, length of hospital stay and other complications were analyzed to determine the outcome using a modified Rankin scale (MRS). Grave prognosis (defined as MRS of 5-6) was judged on the discharge date. 995 patients, mean age 59.5 +/- 14.3 years were analyzed, after exclusion of incomplete data in 87 patients. 402 patients (40.4%) were in the grave prognosis group (MRS 5-6). Univariable analysis and then multivariable analysis showed only four statistically significant predictors for grave outcome of ICH. They were fever (BT > or = 37.8 degrees c), low GCS, large haematoma and IVH. The grave prognosis on spontaneous intracerebral haemorrhage (GP on STAGE) score was derived from these four factors using a multiple logistic model. A simple and pragmatic prognostic score for ICH outcome has been developed with high sensitivity (82%) and specificity (82%). Furthermore, it can be administered by most general practitioners. Validation in other populations is now required.

Decreased expression of the ATM gene linked to poor prognosis for gastric cancer of different nationalities in Xinjiang.

PubMed

Han, Mei; Ma, Lanying; Qu, Yanli; Tang, Yong

2017-08-01

To explore the clinicopathological significance of ATM gene in the occurrence and prognosis of gastric cancer (GC) from different nationalities in Xinjiang. The expression of ATM in 385 patients with GC (including 98 Uygurs, 231 Hans and 56 Kazaks) and its corresponding adjacent tissues were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry assay to, analyze its correlations with clinicopathological features and prognosis of GC. The ATM expression in GC tissues was significantly decreased when compared to that in adjacent normal tissues of Uygur, Han and Kazak patients in Xinjiang, while Uygurs and Kazaks were much lower than Hans in the ATM expression of GC tissues (all P<0.05). Kaplan-Meier analysis showed that Uygur and Kazak patients with ATM-negative tumors had a markedly lower survival rate than patients in Hans (P=0.028), and GC patients with ATM negative expression presented more unfavorable overall survival rate than those with positive expression among the three different nationalities (all P<0.05). Multivariate Cox regression analysis revealed that nationality, ATM expression, TNM staging, depth of invasion, and lymph node metastasis were independent factors affecting the prognosis of GC patients in Xinjiang (all P<0.05). ATM was downregulated in GC patients in Xinjiang, especially for Uygurs and Kazaks, which suggested ATM to be an independent indicator of prognosis for GC therapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

[FAP Expression and Its Association with the Prognosis of Gastric Stromal Tumors].

PubMed

Tang, Su-Min; Shen, Chao-Yong; Yin, Yuan; Yin, Xiao-Nan; Cai, Zhao-Lun; Chen, Zhi-Xin; Zhang, Bo

2017-03-01

To determine the association of FAP expression with the prognosis of gastric stromal tumors (GSTs). Paraffin-embedded GSTs samples were collected from January 2010 to December 2013 in the department of pathology of our hospital. FAP expression was examined by immunohistochemistry staining. Its correlations with clinical pathological characteristics and prognosis of GSTs were analyzed. A total of 98 cases were included in this study. FAP was expressed in the cytoplasm of GSTs cells, with a positive rate of 42.9%. No FAP expression was found in normal gastric tissues. No differences of FAP expression were found in patients with different gender, age and tumor mitotic counts ( P >0.05). Tumor diameter and risk classification were associated with FAP expression ( P <0.05). Higher levels of FAP expression were found in larger and higher risk tumors. No significant correlations between FAP expression and routine immunohistochemical markers were found. Log-rank univariate survival analysis showed that mitotic counts, tumor size, postoperative IM and FAP expression were associated with recurrence free survival of GSTs patients with intermediate-high risks ( P <0.05). Cox multivariate survival analysis showed that mitotic counts, tumor size, postoperative IM and FAP were independent predictors for the prognosis of GSTs patients with intermediate-high risks ( P <0.05). FAP is expressed in the cytoplasm of gastric GIST cells, but not in normal gastric tissues. FAP is a predictor for the prognosis of GSTs patients with intermediate-high risks.

[An evaluation of clinical characteristics and prognosis of brain-stem infarction in diabetics].

PubMed

Lu, Zheng-qi; Li, Hai-yan; Hu, Xue-qiang; Zhang, Bing-jun

2011-01-01

To analyze the relationship between diabetics and the onset, clinical outcomes and prognosis of brainstem infarction, and to evaluate the impact of diabetes on brainstem infarction. Compare 172 cases of acute brainstem infarction in patients with or without diabetes. Analyze the associated risk factors of patients with brain-stem infarction in diabetics by multi-variate logistic regression analysis. Compare the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin scale (mRS) Score, pathogenetic condition and the outcome of the two groups in different times. The systolic blood pressure (SBP), TG, LDL-C, apolipoprotein B (Apo B), glutamyl transpeptidase (γ-GT), fibrinogen (Fb), fasting blood glucose (FPG) and glycosylated hemoglobin(HbA1c)in diabetic group were higher than those in non-diabetic group, which was statistically significant (P < 0.05). From multi-variate logistic regression analysis, γ-GT, Apo B and FPG were the risk predictors of diabetes with brainstem infarction(OR = 1.017, 4.667 and 3.173, respectively), while HDL-C was protective (OR = 0.288). HbA1c was a risk predictor of severity for acute brainstem infarction (OR = 1.299), while Apo A was beneficial (OR = 0.212). Compared with brain-stem infarction in non-diabetic group, NIHSS score and intensive care therapy of diabetic groups on the admission had no statistically significance, while the NIHSS score on discharge and the outcome at 6 months' of follow-up were statistically significant. Diabetes is closely associated with brainstem infarction. Brainstem infarction with diabetes cause more rapid progression, poorer prognosis, higher rates of mortality as well as disability and higher recurrence rate of cerebral infarction.

Different pathological features and prognosis in gastric cancer patients coming from high-risk and low-risk areas of Italy.

PubMed

Marrelli, Daniele; Pedrazzani, Corrado; Corso, Giovanni; Neri, Alessandro; Di Martino, Marianna; Pinto, Enrico; Roviello, Franco

2009-07-01

To compare clinicopathological features and long-term outcome in gastric cancer patients coming from high-risk and low-risk areas of Italy. Better survival rates have been reported from countries with higher incidence of gastric cancer. Data regarding 829 patients coming from Tuscany (group A) and 143 patients coming from Southern Italy (group B) were analyzed. Mean follow-up time was 56 +/- 57 months; it was 85 +/- 63 months in surviving patients or not tumor-related deaths. Prognostic factors were investigated by multivariate analysis with Cox proportional hazard model after verifying the assumption of proportionality of the risk associated with covariates. Lauren diffuse-mixed histotype, younger age, extended lymphadenectomy, and advanced stages were more common in group B. Gastric cancer-related 10-year survival probability was 48% in group A versus 29% in group B (log-rank test: P < 0.001). By multivariate analysis, geographic area was confirmed as a significant prognostic factor (hazard ratio for group B vs. group A: 1.52, 95% confidence interval: 1.12-2.06, P = 0.006). The influence of this factor on long-term survival was independent from other clinical, surgical, and pathologic factors, and was notable in neoplasms involving the serosa (10-year survival probability: 15% in group A vs. 3% in group B, log-rank test: P = 0.005). Patients coming from low-risk area of Italy showed distinct pathologic features, more advanced stage, and worse prognosis when compared with patients coming from high-risk area. These findings may be indicative of different tumor biology, and may contribute to partly explain worldwide geographic variability in prognosis reported in different series.

Shorter survival in adolescent and young adult patients, compared to adult patients, with stage IV colorectal cancer in Japan.

PubMed

Shida, Dai; Ahiko, Yuka; Tanabe, Taro; Yoshida, Takefumi; Tsukamoto, Shunsuke; Ochiai, Hiroki; Takashima, Atsuo; Boku, Narikazu; Kanemitsu, Yukihide

2018-03-27

The incidence of colorectal cancer in adolescent and young adult patients is increasing. However, survival and clinical features of young patients, especially those with stage IV disease, relative to adult patients remain unclear. This retrospective single-institution cohort study was conducted at a tertiary care cancer center. Subjects were 861 consecutive patients who were diagnosed with stage IV colorectal cancer at the age of 15 to 74 years and who were referred to the division of surgery or gastrointestinal oncology at the National Cancer Center Hospital from 1999 to 2013. Overall survival (OS) was investigated and clinicopathological variables were analyzed for prognostic significance. Of these, 66 (8%) were adolescent and young adult patients and 795 (92%) were adult patients. Median survival time was 13.6 months in adolescent and young adult patients and 22.4 months in adult patients, and 5-year OS rates were 17.3% and 20.3%, respectively, indicating significant worse prognosis of adolescent and young adult patients (p = 0.042). However, age itself was not an independent factor associated with prognosis by multivariate analysis. When compared with adult patients, adolescent and young adult patients consisted of higher proportion of the patients who did not undergo resection of primary tumor, which was an independent factor associated with poor prognosis in multivariate analysis. In patients who did not undergo resection (n = 349), OS of adolescent and young adult patients were significantly worse (p = 0.033). Prognoses were worse in adolescent and young adult patients with stage IV colorectal cancer compared to adult patients in Japan, due to a higher proportion of patients who did not undergo resection with more advanced and severe disease, but not due to age itself.

Ethnicity and association with disease manifestations and mortality in Behçet's disease.

PubMed

Savey, Lea; Resche-Rigon, Mathieu; Wechsler, Bertrand; Comarmond, Cloé; Piette, Jean Charles; Cacoub, Patrice; Saadoun, David

2014-03-27

Behçet's disease (BD) significantly increases morbidity and mortality. BD mainly affects young adults with a peculiar geographical distribution. It has been suggested that BD varies in its phenotypic expression in different ethnic groups. We investigated potential ethnicity-related differences relative to phenotype and prognosis of BD patients in a French multiethnic country. We included 769 consecutive patients fulfilling the international criteria of classification for BD, in the 3 largest ethnic groups of our cohort [European (n = 369), North African (n = 350) and sub Saharan African (n = 50)]. Factors that affect prognosis were assessed by multivariate analysis. 535 (69.6%) patients were male and the median (IQR) age at diagnosis was of 30.9 (24.9-37.2) years. Sub Saharan African BD patients had a higher frequency of CNS involvement (48% vs 32.3% vs 29.5%, p = 0 .035), a higher rate of death (12% vs 6% vs 3.5%, p = 0.029) and a lower frequency of HLA B51 allele (29.4% vs 49.2% vs 55.8%, p = 0.009) compared to those from North Africa and Europe, respectively. Multivariate analysis showed that male gender (HR: 5.01, CI: 1.51-16.65), cardiovascular involvement (HR: 2.24, CI: 1.15-4.36), and sub Saharan African origin (HR 2.62 (0.98-6.97) were independently associated with mortality. The 15-year mortality rate was of 19%, 9% and 6% in sub Saharan African, North African and European BD patients, respectively (p = 0.015). We reported ethnicity-related differences with respect to phenotype of BD. Sub Saharan Africans patients exhibited a worse prognosis.

Ethnicity and association with disease manifestations and mortality in Behçet’s disease

PubMed Central

2014-01-01

Background Behçet’s disease (BD) significantly increases morbidity and mortality. BD mainly affects young adults with a peculiar geographical distribution. It has been suggested that BD varies in its phenotypic expression in different ethnic groups. Methods We investigated potential ethnicity-related differences relative to phenotype and prognosis of BD patients in a French multiethnic country. We included 769 consecutive patients fulfilling the international criteria of classification for BD, in the 3 largest ethnic groups of our cohort [European (n = 369), North African (n = 350) and sub Saharan African (n = 50)]. Factors that affect prognosis were assessed by multivariate analysis. Results 535 (69.6%) patients were male and the median (IQR) age at diagnosis was of 30.9 (24.9-37.2) years. Sub Saharan African BD patients had a higher frequency of CNS involvement (48% vs 32.3% vs 29.5%, p = 0 .035), a higher rate of death (12% vs 6% vs 3.5%, p = 0.029) and a lower frequency of HLA B51 allele (29.4% vs 49.2% vs 55.8%, p = 0.009) compared to those from North Africa and Europe, respectively. Multivariate analysis showed that male gender (HR: 5.01, CI: 1.51-16.65), cardiovascular involvement (HR: 2.24, CI: 1.15-4.36), and sub Saharan African origin (HR 2.62 (0.98-6.97) were independently associated with mortality. The 15-year mortality rate was of 19%, 9% and 6% in sub Saharan African, North African and European BD patients, respectively (p = 0.015). Conclusion We reported ethnicity-related differences with respect to phenotype of BD. Sub Saharan Africans patients exhibited a worse prognosis. PMID:24674137

BICD1 expression, as a potential biomarker for prognosis and predicting response to therapy in patients with glioblastomas

PubMed Central

Huang, Shang-Pen; Chang, Yu-Chan; Low, Qie Hua; Wu, Alexander T.H.; Chen, Chi-Long; Lin, Yuan-Feng; Hsiao, Michael

2017-01-01

There is variation in the survival and therapeutic outcome of patients with glioblastomas (GBMs). Therapy resistance is an important challenge in the treatment of GBM patients. The aim of this study was to identify Temozolomide (TMZ) related genes and confirm their clinical relevance. The TMZ-related genes were discovered by analysis of the gene-expression profiling in our cell-based microarray. Their clinical relevance was verified by in silico meta-analysis of the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) datasets. Our results demonstrated that BICD1 expression could predict both prognosis and response to therapy in GBM patients. First, high BICD1 expression was correlated with poor prognosis in the TCGA GBM cohort (n=523) and in the CGGA glioma cohort (n=220). Second, high BICD1 expression predicted poor outcome in patients with TMZ treatment (n=301) and radiation therapy (n=405). Third, multivariable Cox regression analysis confirmed BICD1 expression as an independent factor affecting the prognosis and therapeutic response of TMZ and radiation in GBM patients. Additionally, age, MGMT and BICD1 expression were combinedly utilized to stratify GBM patients into more distinct risk groups, which may provide better outcome assessment. Finally, we observed a strong correlation between BICD1 expression and epithelial-mesenchymal transition (EMT) in GBMs, and proposed a possible mechanism of BICD1-associated survival or therapeutic resistance in GBMs accordingly. In conclusion, our study suggests that high BICD1 expression may result in worse prognosis and could be a predictor of poor response to TMZ and radiation therapies in GBM patients. PMID:29371945

Clinical outcome of patients with heart failure and preserved left ventricular function.

PubMed

Gotsman, Israel; Zwas, Donna; Planer, David; Azaz-Livshits, Tanya; Admon, Dan; Lotan, Chaim; Keren, Andre

2008-11-01

Patients with heart failure have a poor prognosis. However, it has been presumed that patients with heart failure and preserved left ventricular function (LVF) may have a more benign prognosis. We evaluated the clinical outcome of patients with heart failure and preserved LVF compared with patients with reduced function and the factors affecting prognosis. We prospectively evaluated 289 consecutive patients hospitalized with a definite clinical diagnosis of heart failure based on typical symptoms and signs. They were divided into 2 subsets based on echocardiographic LVF. Patients were followed clinically for a period of 1 year. Echocardiography showed that more than one third (36%) of the patients had preserved systolic LVF. These patients were more likely to be older and female and have less ischemic heart disease. The survival at 1 year in this group was poor and not significantly different from patients with reduced LVF (75% vs 71%, respectively). The adjusted survival by Cox regression analysis was not significantly different (P=.25). However, patients with preserved LVF had fewer rehospitalizations for heart failure (25% vs 35%, P<.05). Predictors of mortality in the whole group by multivariate analysis were age, diabetes, chronic renal failure, atrial fibrillation, residence in a nursing home, and serum sodium < or = 135 mEq/L. The prognosis of patients with clinical heart failure with or without preserved LVF is poor. Better treatment modalities are needed in both subsets.

LDHB and FABP4 are Associated With Progression and Poor Prognosis of Pancreatic Ductal Adenocarcinomas.

PubMed

Luo, Yuan; Yang, Zhulin; Li, Daiqiang; Liu, Ziru; Yang, Leping; Zou, Qiong; Yuan, Yuan

Pancreatic ductal adenocarcinoma (PDAC) is a fast-growth tumor with poor prognosis. The molecular events involving in the abnormal energy metabolism have been reported without being fully identified. This study investigated the expression of FABP4 and LDHB, 2 metabolism-associated molecules, in malignant and benign lesions of pancreas by immunohistochemical staining, and analyzed their clinical and pathologic significances. The results showed that FABP4 and LDHB protein were overexpressed in PDAC tumors compared with peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (P<0.01). The percentage of patients with FABP4 and LDHB protein overexpression was significantly higher in PDAC patients with lymph node metastasis, invasion, and tumour, node, metastasis stage III/IV disease than in patients without lymph node metastasis and invasion, and having tumour, node, metastasis stage I/II stage disease (P<0.05 or P<0.01). Benign pancreatic lesions with positive FABP4 and LDHB protein expression exhibited dysplasia or intraepithelial neoplasia I and III grade. Kaplan-Meier survival analysis showed that positive FABP4 and LDHB protein expression were associated with worse survival in PDAC patients (P<0.05 or P<0.001). Cox multivariate analysis revealed that positive FABP4 and LDHB protein expression were independent poor prognosis factors in PDAC patients. In conclusion, positive FABP4 and LDHB protein expression are associated with the progression and poor prognosis in patients with PDAC.

[Comparison of the prognostic value of the seventh and eighth edition of The AJCC Esophageal Cancer Staging System for the patients with stage Ⅱ and Ⅲesophageal squamous cell carcinoma].

PubMed

Zhong, H; Ma, R; Gong, L; Chen, C G; Tang, P; Ren, P; Jiang, H J; Yu, Z T

2017-12-01

Objective: To compare and evaluate the prognostic value of the 7(th) and 8(th) edition of The AJCC Esophageal Cancer Staging System for patients with stage Ⅱ and Ⅲ esophageal squamous cell carcinoma. Methods: The clinical data of 328 esophageal cancer patients who received operation at Department of Esophageal Cancer, Tianjin Tumour Hospital from January 2006 to December 2010 were restrospectively analyzed. There were 63 female and 265 male patients. The mean age was 65 (range: 33 to 87) years. Univariate and multivariate analysis were performed to identify the prognosis factors. Results: The five years overall survival rates among patients with stage Ⅱ and Ⅲ were both significantly different (χ(2)=87.035, 84.730, all P =0.000) according to the 7(th) and 8(th) editions of the TNM staging systems. The five years overall survival rate among patients with stage ⅡB and ⅢA were significantly different (39.6% vs 23.4%, P =0.001) according to the 7(th) edition of the esophageal cancer staging systems.According to the 8(th) edition of the esophageal cancer staging system, the 5 years survival rate of patients with stage ⅡA and ⅡB, ⅢB and Ⅳ was statistically significant (58.5% vs . 35.5%, P =0.040; 18.9% vs . 0, P =0.000). In multivariate analysis, tumor size, T staging, N staging and tumor differentiation ( HR =1.592, 95% CI: 1.185 to 2.139, P =0.002; HR =1.519, 95% CI: 1.236 to 1.867, P =0.000; HR =1.647, 95% CI: 1.448 to 1.874, P =0.000; HR =1.404, 95% CI: 1.059 to 1.861, P =0.018) were the main independent prognosis factors affecting the prognosis of esophageal squamous cell carcinoma patients. Conclusions: Both the 7(th) and the 8(th) editions of TNM staging systems are able to reflect the clinical prognosis of patients receiving radical resection of esophageal cancer, and the factors of tumor size, differentiaton, invasion depth and lymph node metastases are the independent predictors of prognosis. The 8(th) edition provides a more detailed and more reasonable for the staging of stage Ⅱ and Ⅲ for esophageal cancer patients than the 7(th) edition, and it is more accurate for the prognosis of patients with esophageal cancer after surgery.

Ulex europeus agglutinin-I binding as a potential prognostic marker in ovarian cancer.

PubMed

Blonski, Katharina; Milde-Langosch, Karin; Bamberger, Ana-Maria; Osterholz, Tina; Utler, Christian; Berger, Jürgen; Löning, Thomas; Schumacher, Udo

2007-01-01

Ovarian cancer represents the malignant tumour of the female genital tract with the worst prognosis, mainly caused by early intraperitoneal spread. Cell-to-cell and cell-to-matrix interactions play a functionally important role in this spread and are both mediated by the cell membrane. Changes in the glycosylation of the cell membrane, as detected by lectin histochemistry, are sometimes associated with a poor prognosis. The expression of lectin binding of 164 ovarian cancer patients was analysed and the staining results were correlated with the clinical data of the patients. The univariate and multivariate statistical analysis revealed an independent prognostic significance for Ulex europeus agglutinin-I (UEA-I) binding. These findings indicate that UEA-I binding can serve as a prognostic factor in ovarian cancer.

PubMed Central

Bouchard, E; Daignault, D; Bélanger, D; Couture, Y

1994-01-01

A retrospective study on 159 cesareans on dairy cows referred between 1985 and 1989 to the veterinary teaching hospital is reported. The objective of the study was to evaluate the probability and the factors associated with survival and subsequent calving. The risk of dying for the cows was 24% following surgery. The risk of dying differed if the cow had an emphysematous, dead, or live calf; it was 63%, 21%, and 14%, respectively. Of all the cows returned to the farm and for which there was a breeding recorded, 64% calved again. But only 28% of all the cows returned home and, therefore, only 17% of all the referred cases calved again. We used multivariate analysis to obtain a predictive model on prognosis following surgery. The prognosis was only influenced by the calf condition at admission. PMID:9132287

Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein evaluates liver function and predicts prognosis in liver cirrhosis.

PubMed

Xu, Wen Ping; Wang, Ze Rui; Zou, Xia; Zhao, Chen; Wang, Rui; Shi, Pei Mei; Yuan, Zong Li; Yang, Fang; Zeng, Xin; Wang, Pei Qin; Sultan, Sakhawat; Zhang, Yan; Xie, Wei Fen

2018-04-01

Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA + -M2BP) is a novel glycobiomarker for evaluating liver fibrosis, but less is known about its role in liver cirrhosis (LC). This study aimed to investigate the utility of WFA + -M2BP in evaluating liver function and predicting prognosis of cirrhotic patients. We retrospectively included 197 patients with LC between 2013 and 2016. Serum WFA + -M2BP and various biochemical parameters were measured in all patients. With a median follow-up of 23 months, liver-related complications and deaths of 160 patients were recorded. The accuracy of WFA + -M2BP in evaluating liver function, predicting decompensation and mortality were measured by the receiver operating characteristic (ROC) curve, logistic and Cox's regression analyses, respectively. WFA + -M2BP levels increased with elevated Child-Pugh classification, especially in patients with hepatitis B virus (HBV) infection. ROC analysis confirmed the high reliability of WFA + -M2BP for the assessment of liver function using Child-Pugh classification. WFA + -M2BP was also significantly positively correlated with the model for end-stage liver disease (MELD) score. Multivariate logistic regression analysis indicated WFA + -M2BP as an independent predictor of clinical decompensation for compensated patients (odds ratio 11.958, 95% confidence interval [CI] 1.876-76.226, P = 0.009), and multivariate Cox's regression analysis verified WFA + -M2BP as an independent risk factor for liver-related death in patients with HBV infection (hazards ratio 10.596, 95% CI 1.356-82.820, P = 0.024). Serum WFA + -M2BP is a reliable predictor of liver function and prognosis in LC and could be incorporated into clinical surveillance strategies for LC patients, especially those with HBV infection. © 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Distinct Characteristics of Small Cell Lung Cancer Correlate With Central or Peripheral Origin: Subtyping Based on Location and Expression of Transcription Factor TTF-1.

PubMed

Miyauchi, Eisaku; Motoi, Noriko; Ono, Hiroshi; Ninomiya, Hironori; Ohyanagi, Fumiyoshi; Nishio, Makoto; Okumura, Sakae; Ichinose, Masakazu; Ishikawa, Yuichi

2015-12-01

Small-cell lung carcinoma (SCLC) is a type of lung cancer with neuroendocrine differentiation and a poor prognosis that is widely believed to arise in the central lung. Thyroid transcription factor-1 (TTF-1) is a peripheral marker of lung adenocarcinoma that is also highly expressed in SCLC. In this study, we examined whether SCLC is really a central-type tumor and the relationship between tumor location, TTF-1 expression and prognosis of SCLC.Ninety six SCLCs, diagnosed from biopsies or surgical materials, for which detailed computed tomography (CT) images were available, were collected consecutively from Japanese patients between 2004 and 2011. We examined the location of the primary tumor (central or peripheral) using thin-sliced CT, a TTF-1 immunohistochemical expression, and clinicopathology including prognosis.Of the 96 SCLCs, 74% (71/96) were of the peripheral type and found to have a significantly worse prognosis than central-type tumors. TTF-1 immunoreactivity was identified in 79 tumors (82%), 78% of which (62/79) were of the peripheral type and 22% of which were central. TTF-1 expression was significantly correlated with peripheral location (P = 0.030). Multivariate analysis revealed that high TNM stages and the peripheral location were independent markers for poor survival.The majority of SCLCs were of the peripheral type. The peripheral-type SCLC expressed TTF-1 more frequently and had a poorer prognosis than central-type tumors did. Further analysis on original sites of SCLC, using molecular methodology, or based on another ethnicity, should be warranted.

Serum surfactant protein D predicts the outcome of patients with idiopathic pulmonary fibrosis treated with pirfenidone.

PubMed

Ikeda, Kimiyuki; Shiratori, Masanori; Chiba, Hirofumi; Nishikiori, Hirotaka; Yokoo, Keiki; Saito, Atsushi; Hasegawa, Yoshihiro; Kuronuma, Koji; Otsuka, Mitsuo; Yamada, Gen; Takahashi, Hiroki

2017-10-01

Idiopathic pulmonary fibrosis (IPF) is a fatal pulmonary disease with poor prognosis. Pirfenidone, the first antifibrotic drug, suppresses the decline in forced vital capacity (FVC) and improves prognosis in some, but not all, patients with IPF; therefore, an indicator for identifying improved outcomes in pirfenidone therapy is desirable. This study aims to clarify whether baseline parameters can be predictors of disease progression and prognosis in patients with IPF treated with pirfenidone. We retrospectively investigated patients with IPF who started treatment with pirfenidone between December 2008 and November 2014 at the Sapporo Medical University Hospital. Patients treated with pirfenidone for ≥6 months were enrolled in this study and were observed until November 2015. We investigated the association of clinical characteristics, pulmonary function test results, and blood examination results at the start of pirfenidone with the outcome of patients. Sixty patients were included in this study. In multivariate logistic regression analysis, % predicted FVC and serum surfactant protein (SP)-D levels were predictors of a ≥10% decline in FVC in the initial 12 months. In the Cox proportional hazards model, these two factors predicted progression-free survival. Pack-years, % predicted diffusing capacity for carbon monoxide, and SP-D levels predicted overall survival. The serum SP-D level was a predictor of disease progression and prognosis in patients with IPF treated with pirfenidone. In addition, this analysis describes the relative usefulness of other clinical parameters at baseline in estimating the prognosis of patients with IPF who are candidates for pirfenidone therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prognostic Impact of Tumor Mutation Burden in Patients With Completely Resected Non-Small Cell Lung Cancer: Brief Report.

PubMed

Owada-Ozaki, Yuki; Muto, Satoshi; Takagi, Hironori; Inoue, Takuya; Watanabe, Yuzuru; Fukuhara, Mitsuro; Yamaura, Takumi; Okabe, Naoyuki; Matsumura, Yuki; Hasegawa, Takeo; Ohsugi, Jun; Hoshino, Mika; Shio, Yutaka; Nanamiya, Hideaki; Imai, Jun-Ichi; Isogai, Takao; Watanabe, Shinya; Suzuki, Hiroyuki

2018-04-12

Tumor mutation burden (TMB) is thought to be associated with the amount of neoantigen in the tumor and to have an important role in predicting the effect of immune checkpoint inhibitors. However, the relevance of TMB to prognosis is not yet fully understood. In this study, we investigated the clinical significance of TMB in patients with NSCLC and examined the relationship between TMB and prognosis. We calculated TMB within individual tumors by whole-exome sequencing analysis using next-generation sequencing. We included that there were 90 patients with NSCLC who underwent surgery in the Hospital of Fukushima Medical University from 2013 to 2016. No patients received chemotherapy or immunotherapy before surgery. We assessed the correlation between TMB and prognosis. TMB greater than 62 was associated with worse overall survival (OS) of patients with NSCLC (hazard ratio [HR] = 6.633, p = 0.0003). Multivariate analysis showed poor prognosis with high TMB (HR = 12.31, p = 0.019). In patients with stage I NSCLC, higher TMB was associated with worse prognosis for both OS (HR = 7.582, p = 0.0018) and disease-free survival (HR = 6.07, p = 0.0072). High TMB in NSCLC is a poor prognostic factor. If high TMB is a predictor of the efficacy of immune checkpoint inhibitors, postoperative adjuvant therapy with immune checkpoint inhibitors may contribute to improvement of recurrence and OS. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

FAS ligand expression in inflammatory infiltrate lymphoid cells as a prognostic marker in oral squamous cell carcinoma.

PubMed

Peterle, G T; Santos, M; Mendes, S O; Carvalho-Neto, P B; Maia, L L; Stur, E; Agostini, L P; Silva, C V M; Trivilin, L O; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

2015-09-22

Currently, the most important prognostic factor in oral squamous cell carcinoma (OSCC) is the presence of regional lymph node metastases, which correlates with a 50% reduction in life expectancy. We have previously observed that expression of hypoxia genes in the tumor inflammatory infiltrate is statistically related to prognosis in OSCC. FAS and FASL expression levels in OSCC have previously been related to patient survival. The present study analyzed the relationship between FASL expression in the inflammatory infiltrate lymphoid cells and clinical variables, tumor histology, and prognosis of OSCC. Strong FASL expression was significantly associated with lymph node metastases (P = 0.035) and disease-specific death (P = 0.014), but multivariate analysis did not confirm FASL expression as an independent death risk factor (OR = 2.78, 95%CI = 0.81-9.55). Disease-free and disease-specific survival were significantly correlated with FASL expression (P = 0.016 and P = 0.005, respectively). Multivariate analysis revealed that strong FASL expression is an independent marker for earlier disease relapse and disease-specific death, with approximately 2.5-fold increased risk compared with weak expression (HR = 2.24, 95%CI = 1.08-4.65 and HR = 2.49, 95%CI = 1.04-5.99, respectively). Our results suggest a potential role for this expression profile as a tumor prognostic marker in OSCC patients.

The proliferation marker Ki67, but not neuroendocrine expression, is an independent factor in the prediction of prognosis of primary prostate cancer patients

PubMed Central

Pascale, Mariarosa; Aversa, Cinzia; Barbazza, Renzo; Marongiu, Barbara; Siracusano, Salvatore; Stoffel, Flavio; Sulfaro, Sando; Roggero, Enrico; Stanta, Giorgio

2016-01-01

Abstract Background Neuroendocrine markers, which could indicate for aggressive variants of prostate cancer and Ki67 (a well-known marker in oncology for defining tumor proliferation), have already been associated with clinical outcome in prostate cancer. The aim of this study was to investigate the prognostic value of those markers in primary prostate cancer patients. Patients and methods NSE (neuron specific enolase), ChrA (chromogranin A), Syp (Synaptophysin) and Ki67 staining were performed by immunohistochemistry. Then, the prognostic impact of their expression on overall survival was investigated in 166 primary prostate cancer patients by univariate and multivariate analyses. Results NSE, ChrA, Syp and Ki67 were positive in 50, 45, 54 and 146 out of 166 patients, respectively. In Kaplan-Meier analysis only diffuse NSE staining (negative vs diffuse, p = 0.004) and Ki67 (≤ 10% vs > 10%, p < 0.0001) were significantly associated with overall survival. Ki67 expression, but not NSE, resulted as an independent prognostic factor for overall survival in multivariate analysis. Conclusions A prognostic model incorporating Ki67 expression with clinical-pathological covariates could provide additional prognostic information. Ki67 may thus improve prediction of prostate cancer outcome based on standard clinical-pathological parameters improving prognosis and management of prostate cancer patients. PMID:27679548

[Factors associated with the timely treatment of women with breast cancer supported by a non-governmental organization in Bogotá, Colombia].

PubMed

Sánchez, Guillermo; Niño, Carlos Gustavo; Estupiñán, Carolina

2015-01-01

The prognosis for a woman with breast cancer is related to the time that elapses before diagnosis and integral treatment. Colombian women face barriers that determine effective access to the health system. To establish the determinants of timely treatment for breast cancer in a group of women supported by a non-governmental organization in Bogotá. An observational analytical study was carried out on 136 women with breast cancer supported by the non-governmental organization. The cut-off point for timely treatment was defined as 90 days, calculated as the time between the appearance of symptoms and the initiation of treatment. Predictors of timely treatment were explored by means of multivariate analysis. Although 96% of the women had health insurance only 26.4% received timely treatment, and 36 of them reported being denied medical services. Of these women, 23% took legal action to gain access to their healthcare rights. Significant associations were established by multivariate analysis for timely treatment among women belonging to socioeconomic strata IV and V (OR=3.39), as well as those with higher education (OR=2.72). According to the international literature, the prognosis for women with breast cancer improves when they are able to access opportune treatment. In this group of women socioeconomic factors appeared to determine effective access to treatment, revealing the existence of inequalities that may be socially determined.

Comorbid renal tubular damage and hypoalbuminemia exacerbate cardiac prognosis in patients with chronic heart failure.

PubMed

Otaki, Yoichiro; Watanabe, Tetsu; Takahashi, Hiroki; Funayama, Akira; Kinoshita, Daisuke; Yokoyama, Miyuki; Takahashi, Tetsuya; Nishiyama, Satoshi; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Kubota, Isao

2016-02-01

Renal tubular damage (RTD) and hypoalbuminemia are risks for poor prognosis in patients with chronic heart failure (CHF). Renal tubules play a pivotal role in amino acid and albumin reabsorption, which maintain serum albumin levels. The aims of the present study were to (1) examine the association of RTD with hypoalbuminemia, and (2) assess the prognostic importance of comorbid RTD and hypoalbuminemia in patients with CHF. We measured N-acetyl-β-D-glucosamidase (NAG) levels and the urinary β2-microglobulin to creatinine ratio (UBCR) in 456 patients with CHF. RTD was defined as UBCR ≥ 300 μg/g or NAG ≥ 14.2 U/g. There were moderate correlations between RTD markers and serum albumin (NAG, r = -0.428, P < 0.0001; UBCR, r = -0.399, P < 0.0001). Multivariate logistic analysis showed that RTD was significantly related to hypoalbuminemia in patients with CHF. There were 134 cardiac events during a median period of 808 days. The comorbidity of RTD and hypoalbuminemia was increased with advancing New York Heart Association functional class. Multivariate Cox proportional hazard regression analysis showed that the presence of RTD and hypoalbuminemia was associated with cardiac events. The net reclassification index was significantly improved by adding RTD and hypoalbuminemia to the basic risk factors. Comorbid RTD and hypoalbuminemia are frequently observed and increase the risk for extremely poor outcome in patients with CHF.

Expression of miR-146a-5p in patients with intracranial aneurysms and its association with prognosis.

PubMed

Zhang, H-L; Li, L; Cheng, C-J; Sun, X-C

2018-02-01

The study aims to detect the association of miR-146a-5p with intracranial aneurysms (IAs). The expression of miR-146a-5p was compared from plasma samples between 72 patients with intracranial aneurysms (IAs) and 40 healthy volunteers by quantitative Real-time polymerase chain reaction (qRT-PCR). Statistical analysis was performed to analyze the relationship between miR-146a-5p expression and clinical data and overall survival (OS) time of IAs patients. Univariate and multivariate Cox proportional hazards have also been performed. Notably, higher miR-146a-5p expression was found in plasma samples from 72 patients with intracranial aneurysms (IAs) compared with 40 healthy controls. Higher miR-146a-5p expression was significantly associated with rupture and Hunt-Hess level in IAs patients. Kaplan-Meier survival analysis verified that higher miR-146a-5p expression predicted a shorter overall survival (OS) compared with lower miR-146a-5p expression in IAs patients. Univariate and multivariate Cox proportional hazards demonstrated that higher miR-146a-5p expression, rupture, and Hunt-Hess were independent risk factors of OS in patients with intracranial aneurysms (IAs). MiR-146a-5p expression may serve as a biomarker for predicting prognosis in patients with IAs.

Usefulness of BCOR gene mutation as a prognostic factor in acute myeloid leukemia with intermediate cytogenetic prognosis.

PubMed

Terada, Kazuki; Yamaguchi, Hiroki; Ueki, Toshimitsu; Usuki, Kensuke; Kobayashi, Yutaka; Tajika, Kenji; Gomi, Seiji; Kurosawa, Saiko; Saito, Riho; Furuta, Yutaka; Miyadera, Keiki; Tokura, Taichiro; Marumo, Atushi; Omori, Ikuko; Sakaguchi, Masahiro; Fujiwara, Yusuke; Yui, Shunsuke; Ryotokuji, Takeshi; Arai, Kunihito; Kitano, Tomoaki; Wakita, Satoshi; Fukuda, Takahiro; Inokuchi, Koiti

2018-04-16

BCOR gene is a transcription regulatory factor that plays an essential role in normal hematopoiesis. The wider introduction of next-generation sequencing technology has led to reports in recent years of mutations in the BCOR gene in acute myeloid leukemia (AML), but the related clinical characteristics and prognosis are not sufficiently understood. We investigated the clinical characteristics and prognosis of 377 de novo AML cases with BCOR or BCORL1 mutation. BCOR or BCORL1 gene mutations were found in 28 cases (7.4%). Among cases aged 65 years or below that were also FLT3-ITD-negative and in the intermediate cytogenetic prognosis group, BCOR or BCORL1 gene mutations were observed in 11% of cases (12 of 111 cases), and this group had significantly lower 5-year overall survival (OS) (13.6% vs. 55.0%, P=0.0021) and relapse-free survival (RFS) (14.3% vs. 44.5%, P=0.0168) compared to cases without BCOR or BCORL1 gene mutations. Multivariate analysis demonstrated that BCOR mutations were an independent unfavorable prognostic factor (P=0.0038, P=0.0463) for both OS and RFS. In cases of AML that are FLT3-ITD-negative, aged 65 years or below, and in the intermediate cytogenetic prognosis group, which are considered to have relatively favorable prognosis, BCOR gene mutations appear to be an important prognostic factor. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Evaluation of clinical, laboratory and morphologic prognostic factors in colon cancer

PubMed Central

Grande, Michele; Milito, Giovanni; Attinà, Grazia Maria; Cadeddu, Federica; Muzi, Marco Gallinella; Nigro, Casimiro; Rulli, Francesco; Farinon, Attilio Maria

2008-01-01

Background The long-term prognosis of patients with colon cancer is dependent on many factors. To investigate the influence of a series of clinical, laboratory and morphological variables on prognosis of colon carcinoma we conducted a retrospective analysis of our data. Methods Ninety-two patients with colon cancer, who underwent surgical resection between January 1999 and December 2001, were analyzed. On survival analysis, demographics, clinical, laboratory and pathomorphological parameters were tested for their potential prognostic value. Furthermore, univariate and multivariate analysis of the above mentioned data were performed considering the depth of tumour invasion into the bowel wall as independent variable. Results On survival analysis we found that depth of tumour invasion (P < 0.001; F-ratio 2.11), type of operation (P < 0.001; F-ratio 3.51) and CT scanning (P < 0.001; F-ratio 5.21) were predictors of survival. Considering the degree of mural invasion as independent variable, on univariate analysis, we observed that mucorrhea, anismus, hematocrit, WBC count, fibrinogen value and CT scanning were significantly related to the degree of mural invasion of the cancer. On the multivariate analysis, fibrinogen value was the most statistically significant variable (P < 0.001) with the highest F-ratio (F-ratio 5.86). Finally, in the present study, the tumour site was significantly related neither to the survival nor to the mural invasion of the tumour. Conclusion The various clinical, laboratory and patho-morphological parameters showed different prognostic value for colon carcinoma. In the future, preoperative prognostic markers will probably gain relevance in order to make a proper choice between surgery, chemotherapy and radiotherapy. Nevertheless, current data do not provide sufficient evidence for preoperative stratification of high and low risk patients. Further assessments in prospective large studies are warranted. PMID:18778464

Does buccal cancer have worse prognosis than other oral cavity cancers?

PubMed

Camilon, P Ryan; Stokes, William A; Fuller, Colin W; Nguyen, Shaun A; Lentsch, Eric J

2014-06-01

To determine whether buccal squamous cell carcinoma has worse overall survival (OS) and disease-specific survival (DSS) than cancers in the rest of the oral cavity. Retrospective analysis of a large population database. We began with a Kaplan-Meier analysis of OS and DSS for buccal versus nonbuccal tumors with unmatched data, followed by an analysis of cases matched for race, age at diagnosis, stage at diagnosis, and treatment modality. This was supported by a univariate Cox regression comparing buccal cancer to nonbuccal cancer, followed by a multivariate Cox regression that included all significant variables studied. With unmatched data, buccal cancer had significantly lesser OS and DSS values than cancers in the rest of the oral cavity (P < .001). After case matching, the differences between OS and DSS for buccal cancer versus nonbuccal oral cancer were no longer significant. Univariate Cox regression models with respect to OS and DSS showed a significant difference between buccal cancer and nonbuccal cancer. However, with multivariate analysis, buccal hazard ratios for OS and DSS were not significant. With the largest series of buccal carcinoma to date, our study concludes that the OS and DSS of buccal cancer are similar to those of cancers in other oral cavity sites once age at diagnosis, tumor stage, treatment, and race are taken into consideration. The previously perceived poor prognosis of buccal carcinoma may be due to variations in tumor presentation, such as later stage and older patient age. 2b. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Prevalence and prognosis of ventricular tachycardia/ventricular fibrillation in patients with post-infarction left ventricular aneurysm: Analysis of 575 cases.

PubMed

Ning, Xiaohui; Ye, Xuerui; Si, Yanhua; Yang, Zihe; Zhao, Yunzi; Sun, Qi; Chen, Ruohan; Tang, Min; Chen, Keping; Zhang, Xiaoli; Zhang, Shu

2018-03-21

We investigated the prevalence of ventricular tachycardia/ventricular fibrillation (VT/VF) in Post-infarction left ventricular aneurysm (PI-LVA) patients and analyze clinical outcomes in patients presenting with VT/VF. 575 PI-LVA patients were enrolled and investigated by logistic regression analysis. Patients with VT/VF were followed up, the composite primary endpoint was cardiac death and appropriate ICD/external shocks. The incidence of sustained VT/VF was 11%. Logistical regression analysis showed male gender, enlarged LV end diastolic diameter (LVEDD) and higher NYHA class were correlated with VT/VF development. During follow up of 46 ± 15 months, 19 out of 62(31%) patients reached study end point. Multivariate Cox regression analysis revealed that enlarged LVEDD and moderate/severe mitral regurgitation (MR) were independently predictive of clinical outcome. Male gender, enlarged LVEDD and higher NYHA class associated with risk of sustained VT/VF in PI-LVA patients. Among VT/VF positive patients, enlarged LVEDD and moderate/severe MR independently predicted poor clinical prognosis. Copyright © 2018. Published by Elsevier Inc.

Effect of hypertension on preoperative neutrophil-lymphocyte ratio evaluation of prognosis of renal cell carcinoma.

PubMed

Sun, Jia; Ning, Hao; Sun, Jintang; Qu, Xun

2016-05-01

As an indicator of inflammatory reaction of immune system, the neutrophil-lymphocyte ratio (NLR) is a significantly independent prognostic factor of renal cell carcinoma (RCC). However, the NLR was not added in any well-established prognostic models. Many physiologic factors were also associated with NLR, such as hypertension. As such, we evaluated the effect of hypertension on NLR evaluation of prognosis of RCC. Hematological parameters and clinicopathological data during diagnosis were retrospectively recorded for 401 patients with RCC between the years 1999 and 2009. The standardized cutoff-finder algorithm was used to find the suitable NLR cutoff value for recurrence. The Log-rank test and Kaplan-Meier method were used to compare and estimate the recurrence-free survival. Univariate and multivariate Cox regression analyses were used to evaluate the association between NLR and clinicopathologic outcomes. In the analysis of total subjects, recurrence-free survival was significantly worse among patients with a preoperative NLR (>3.139 [21.9%] vs.≤3.139 [78.1%]; P<0.001). High NLR value was associated with high pathological TNM stage (P = 0.009, 0.018, 0.001, respectively). In the normotensive subgroup, recurrence-free survival was also significantly worse among patients with a preoperative NLR (>3.139 [22.6%] vs.≤3.139 [77.4%]; P<0.001). However, in the subgroup with hypertension, the difference of recurrence-free survival was not significant between patients with preoperative NLR (>3.139 [21.2%] vs.≤3.139 [78.8%]; P = 0.093). Moreover, multivariate analysis identified increased NLR as a poor prognosis index for recurrence-free survival in total group (hazard ratio [HR] = 2.27; 95% CI: 1.50-3.44; P<0.001) and normotensive subgroup (HR = 2.97; 95% CI: 1.74-5.07; P<0.001), but not in hypertensive subgroup (HR = 1.25; 95% CI: 0.59-2.65; P = 0.566). Hypertension is a disturbance factor in the evaluation of prognosis of RCC by preoperative NLR. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognosis Biomarkers of Severe Sepsis and Septic Shock by 1H NMR Urine Metabolomics in the Intensive Care Unit

PubMed Central

Modesto-Alapont, Vicente; Gonzalez-Marrachelli, Vannina; Vento-Rehues, Rosa; Jorda-Miñana, Angela; Blanquer-Olivas, Jose; Monleon, Daniel

2015-01-01

Early diagnosis and patient stratification may improve sepsis outcome by a timely start of the proper specific treatment. We aimed to identify metabolomic biomarkers of sepsis in urine by 1H-NMR spectroscopy to assess the severity and to predict outcomes. Urine samples were collected from 64 patients with severe sepsis or septic shock in the ICU for a 1H NMR spectra acquisition. A supervised analysis was performed on the processed spectra, and a predictive model for prognosis (30-days mortality/survival) of sepsis was constructed using partial least-squares discriminant analysis (PLS-DA). In addition, we compared the prediction power of metabolomics data respect the Sequential Organ Failure Assessment (SOFA) score. Supervised multivariate analysis afforded a good predictive model to distinguish the patient groups and detect specific metabolic patterns. Negative prognosis patients presented higher values of ethanol, glucose and hippurate, and on the contrary, lower levels of methionine, glutamine, arginine and phenylalanine. These metabolites could be part of a composite biopattern of the human metabolic response to sepsis shock and its mortality in ICU patients. The internal cross-validation showed robustness of the metabolic predictive model obtained and a better predictive ability in comparison with SOFA values. Our results indicate that NMR metabolic profiling might be helpful for determining the metabolomic phenotype of worst-prognosis septic patients in an early stage. A predictive model for the evolution of septic patients using these metabolites was able to classify cases with more sensitivity and specificity than the well-established organ dysfunction score SOFA. PMID:26565633

BMI and breast cancer prognosis benefit: mammography screening reveals differences between normal weight and overweight women.

PubMed

Crispo, Anna; Grimaldi, Maria; D'Aiuto, Massimiliano; Rinaldo, Massimo; Capasso, Immacolata; Amore, Alfonso; D'Aiuto, Giuseppe; Giudice, Aldo; Ciliberto, Gennaro; Montella, Maurizio

2015-02-01

Few studies are available on the potential impact of body weight on breast cancer prognosis in screen-detected patients. Moreover, it is not known whether body mass index (BMI) could have a different prognostic impact in screen-detected versus symptomatic breast cancer patients. To investigate these unsolved issues, we carried out a retrospective study evaluating the effect of BMI on breast cancer prognosis in screen-detected vs symptomatic breast cancer patients. We conducted a follow-up study on 448 women diagnosed with incident, histologically-confirmed breast cancer. Patients were categorized according to their BMI as normal weight, overweight and obese. Disease free survival (DFS), overall survival (OS), and BMI curves were compared according to mode of cancer detection. Among screen-detected patients, higher BMI was associated with a significant lower DFS, whereas no significant difference was observed among symptomatic patients. OS showed similar results. In the multivariate analysis adjusting for age, education, tumor size, nodal status, estrogen receptor (ER), progesterone receptor (PR) and menopausal status, the risk for high level of BMI among screen-detected patients did not reach the statistical significance for either recurrence or survival. Our study highlights the potential impact of high bodyweight in breast cancer prognosis, the findings confirm that obesity plays a role in women breast cancer prognosis independently from diagnosis mode. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structural Technology Evaluation and Analysis Program (STEAP). Delivery Order 0037: Prognosis-Based Control Reconfiguration for an Aircraft with Faulty Actuator to Enable Performance in a Degraded State

DTIC Science & Technology

2010-12-01

computers in 1953. HIL motion simulators were also built for the dynamic testing of vehicle com- ponents (e.g. suspensions, bodies ) with hydraulic or...complex, comprehensive mechanical systems can be simulated in real-time by parallel computers; examples include multi- body sys- tems, brake systems...hard constraints in a multivariable control framework. And the third aspect is the ability to perform online optimization. These aspects results in

Insulin-like growth factor II messenger RNA-binding protein-3 is an independent prognostic factor in uterine leiomyosarcoma.

PubMed

Yasutake, Nobuko; Ohishi, Yoshihiro; Taguchi, Kenichi; Hiraki, Yuka; Oya, Masafumi; Oshiro, Yumi; Mine, Mari; Iwasaki, Takeshi; Yamamoto, Hidetaka; Kohashi, Kenichi; Sonoda, Kenzo; Kato, Kiyoko; Oda, Yoshinao

2018-04-01

The aim of this study was to identify the prognostic factors of uterine leiomyosarcoma (ULMS). We reviewed 60 cases of surgically resected ULMSs and investigated conventional clinicopathological factors, together with the expression of insulin-like growth factor II messenger RNA-binding protein-3 (IMP3), hormone receptors and cell cycle regulatory markers by immunohistochemistry. Mediator complex subunit 12 (MED12) mutation analysis was also performed. Univariate analyses revealed that advanced stage (P < 0.0001), older age (P = 0.0244) and IMP3 expression (P = 0.0011) were significant predictors of a poor outcome. Multivariate analysis revealed advanced stage (P < 0.0001) and IMP3 (P = 0.0373) as independent predictors of a poor prognosis. Expressions of cell cycle markers and hormone receptors, and MED12 mutations (12% in ULMSs) were not identified as prognostic markers in this study. IMP3 expression in ULMS could be a marker of a poor prognosis. © 2017 John Wiley & Sons Ltd.

Evolution of noninvasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C.

PubMed

Vergniol, Julien; Boursier, Jérôme; Coutzac, Clélia; Bertrais, Sandrine; Foucher, Juliette; Angel, Camille; Chermak, Faiza; Hubert, Isabelle Fouchard; Merrouche, Wassil; Oberti, Frédéric; de Lédinghen, Victor; Calès, Paul

2014-07-01

No data are available about the prediction of long-term survival using repeated noninvasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis 4 (FIB-4) evolution in CHC. CHC patients with two LSM (1,000-1,500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline (bLSM) and follow-up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow-up-baseline results)/duration. Date and cause of death were recorded during follow-up that started the day of fLSM. In all, 1,025 patients were included. Median follow-up after fLSM was 38.0 months (interquartile range [IQR]: 27.7-46.1) during which 35 patients died (14 liver-related death) and seven had liver transplantation. Prognostic accuracy (Harrell C-index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 (P ≥ 0.24), whereas FIB-4 provided more accurate prognostic models than APRI (P = 0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and sustained virological response (SVR). Prognosis was excellent in patients having bLSM <7 kPa, SVR, or no increase (<1 kPa/year) in 7-14 kPa bLSM. Prognosis was significantly impaired in patients with an increase (≥ 1 kPa/year) in 7-14 kPa bLSM, or decrease (≤ 0 kPa/year) in ≥ 14 kPa bLSM (P = 0.949 between these two groups). Patients with an increase (>0 kPa/year) in ≥ 14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significantly different prognosis. Three-year evolution of noninvasive tests of liver fibrosis has a strong prognostic value in CHC patients. These tests should be repeated to monitor patients and predict their outcome. © 2014 by the American Association for the Study of Liver Diseases.

Adverse effect of splenectomy on recurrence in total gastrectomy cancer patients with perioperative transfusion.

PubMed

Shen, Jian Guo; Cheong, Jae Ho; Hyung, Woo Jin; Kim, Junuk; Choi, Seung Ho; Noh, Sung Hoon

2006-09-01

To investigate the interactions between splenectomy and perioperative transfusion in gastric cancer patients. Medical records of 449 gastric cancer patients who had undergone total gastrectomies for curative intent between 1991 and 1995 were reviewed. The influence of splenectomy on tumor recurrence and survival both in the transfused and nontransfused patients were evaluated by univariate and multivariate analysis. The recurrence rate in the splenectomy group was 48.1% as compared with 22.6% in the spleen-preserved group among transfused patients (P=.001); it was 40.7% compared with 26.5% among nontransfused patients (P=.086). There was no significant difference in the mean survival between the splenectomy group and the spleen-preserved group in a subgroup analysis by stage. Multivariate analysis identified splenectomy as an independent risk factor for recurrence but not as a predictor for survival among transfused patients. Splenectomy does not appear to abrogate the adverse effect of perioperative transfusion on prognosis in gastric cancer patients. Moreover, it may increase postoperative recurrence in transfused patients.

SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in pulmonary squamous cell carcinoma.

PubMed

Chang, Dong; Ma, Kai; Gong, Min; Cui, Yong; Liu, Zhi-hua; Zhou, Xiao-ge; Zhou, Chuan-nong; Wang, Tian-you

2010-03-01

To investigate the role of stomatin-like protein 2 (SLP-2), a novel cancer-related gene, in pulmonary squamous cell carcinoma (PSCC) and its implications. Immunohistochemical detection of SLP-2 was performed on 96 cases of PSCC with a tissue microarray. SLP-2 was overexpressed in lung cancer compared with normal lung tissue (p <0.001). High-level SLP-2 expression was significantly correlated with distant metastasis (p = 0.025), decreased overall survival (p = 0.018) and disease-free survival (p = 0.017). SLP-2 overexpression was an independent prognostic factor in multivariate analysis using the Cox regression model (p <0.05). SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in PSCC. SLP-2 could be regarded as a new significant prognostic biomarker for patients with PSCC.

[Mantle cell lymphoma, response to treatment and prognosis in 45 patients].

PubMed

Sorigue, Marc; Sancho, Juan-Manuel; García, Olga; Vila, Jordi; Moreno, Miriam; Ribera, Josep-Maria

2016-07-01

Mantle cell lymphoma (MCL) is a rare lymphoproliferative disorder, with frequent relapses and a poor prognosis. This study analyzes response to treatment and prognosis in a series of MCL patients. Retrospective study of MCL patients diagnosed in a single institution between 1996 and 2013. The cohort was divided according to the treatment received. Forty-five patients were included (32 male) with a median age of 66 years old. Twenty-one received intensive chemotherapy or chemoimmunotherapy (based on high-dose cytarabine), 13 semi-intensive (without high-dose cytarabine), 8 not intensive and 3 did not require treatment. Overall response rate was 85% in the intensive and 77% in the semi-intensive treatment groups. In multivariate analysis, intensive treatment was correlated with a longer progression-free survival (hazard ratio 9.8 [95% CI 2.7-35.5], P=.001) and overall survival (4.5 [1.2-17.8], P=.03). In this retrospective series of MCL patients, intensive treatment was correlated with better outcomes than the other treatment modalities. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

CRC-113 gene expression signature for predicting prognosis in patients with colorectal cancer

PubMed Central

Nguyen, Dinh Truong; Kim, Jin-Hwan; Jo, Yong Hwa; Shahid, Muhammad; Akter, Salima; Aryal, Saurav Nath; Yoo, Ji Youn; Ahn, Yong-Joo; Cho, Kyoung Min; Lee, Ju-Seog; Choe, Wonchae; Kang, Insug; Ha, Joohun; Kim, Sung Soo

2015-01-01

Colorectal cancer (CRC) is the third leading cause of global cancer mortality. Recent studies have proposed several gene signatures to predict CRC prognosis, but none of those have proven reliable for predicting prognosis in clinical practice yet due to poor reproducibility and molecular heterogeneity. Here, we have established a prognostic signature of 113 probe sets (CRC-113) that include potential biomarkers and reflect the biological and clinical characteristics. Robustness and accuracy were significantly validated in external data sets from 19 centers in five countries. In multivariate analysis, CRC-113 gene signature showed a stronger prognostic value for survival and disease recurrence in CRC patients than current clinicopathological risk factors and molecular alterations. We also demonstrated that the CRC-113 gene signature reflected both genetic and epigenetic molecular heterogeneity in CRC patients. Furthermore, incorporation of the CRC-113 gene signature into a clinical context and molecular markers further refined the selection of the CRC patients who might benefit from postoperative chemotherapy. Conclusively, CRC-113 gene signature provides new possibilities for improving prognostic models and personalized therapeutic strategies. PMID:26397224

CRC-113 gene expression signature for predicting prognosis in patients with colorectal cancer.

PubMed

Nguyen, Minh Nam; Choi, Tae Gyu; Nguyen, Dinh Truong; Kim, Jin-Hwan; Jo, Yong Hwa; Shahid, Muhammad; Akter, Salima; Aryal, Saurav Nath; Yoo, Ji Youn; Ahn, Yong-Joo; Cho, Kyoung Min; Lee, Ju-Seog; Choe, Wonchae; Kang, Insug; Ha, Joohun; Kim, Sung Soo

2015-10-13

Colorectal cancer (CRC) is the third leading cause of global cancer mortality. Recent studies have proposed several gene signatures to predict CRC prognosis, but none of those have proven reliable for predicting prognosis in clinical practice yet due to poor reproducibility and molecular heterogeneity. Here, we have established a prognostic signature of 113 probe sets (CRC-113) that include potential biomarkers and reflect the biological and clinical characteristics. Robustness and accuracy were significantly validated in external data sets from 19 centers in five countries. In multivariate analysis, CRC-113 gene signature showed a stronger prognostic value for survival and disease recurrence in CRC patients than current clinicopathological risk factors and molecular alterations. We also demonstrated that the CRC-113 gene signature reflected both genetic and epigenetic molecular heterogeneity in CRC patients. Furthermore, incorporation of the CRC-113 gene signature into a clinical context and molecular markers further refined the selection of the CRC patients who might benefit from postoperative chemotherapy. Conclusively, CRC-113 gene signature provides new possibilities for improving prognostic models and personalized therapeutic strategies.

The long-term outcome of atomic bomb survivors with gastric carcinoma.

PubMed

Yamamoto, Manabu; Matsuyama, Ayumi; Kameyama, Toshifumi; Okamoto, Masahiro; Okazaki, Jin; Utsunomiya, Tohru; Tsutsui, Shinichi; Ishida, Teruyoshi

2009-12-01

During the decade following the 1945 atomic bombing of Hiroshima, a high incidence of leukemia was observed among atomic bomb survivors. Subsequently, the incidence of other cancers gradually increased while that of leukemia decreased. We examined the long-term clinical outcome of gastric cancer and second primary cancer in atomic bomb survivors. Results of surgical treatment of gastric cancer were reviewed in 231 atomic bomb survivors and 759 control patients between 1995 and 2006. Long-term prognosis of gastric cancer in atomic bomb survivors was significantly poorer than that in control patients (P < 0.05). In a multivariate analysis, age, depth of tumor invasion, lymph node metastases, and curability were found to be significant and independent prognostic factors for gastric cancer. The incidence of second primary cancer after gastric cancer was significantly higher in survivors than in control patients (P < 0.01), because the number of elderly patients in the survivors was higher. Gastric cancer in survivors had a significantly poorer prognosis. Although the frequency of second primary cancer after gastric cancer in survivors was higher than that in control patients, it did not influence the prognosis.

Prognosis after surgical treatment for pancreatic cancer in patients aged 80 years or older: a multicenter study.

PubMed

Sho, Masayuki; Murakami, Yoshiaki; Kawai, Manabu; Motoi, Fuyuhiko; Satoi, Sohei; Matsumoto, Ippei; Honda, Goro; Uemura, Kenichiro; Yanagimoto, Hiroaki; Kurata, Masanao; Akahori, Takahiro; Kinoshita, Shoichi; Nagai, Minako; Nishiwada, Satoshi; Fukumoto, Takumi; Unno, Michiaki; Yamaue, Hiroki; Nakajima, Yoshiyuki

2016-03-01

The optimal therapeutic strategy for very elderly pancreatic cancer patients remains to be determined. The aim of this study was to clarify the role of pancreatic resection in patients 80 years of age or older. A retrospective multicenter analysis of 1401 patients who had undergone pancreatic resection for pancreatic cancer was performed. The patients aged ≥ 80 years (n = 99) were compared with a control group <80 years of age (n = 1302). There were no significant differences in the postoperative complications and mortality between the two groups. However, the prognosis of octogenarians was poorer than that of younger patients for both resectable and borderline resectable tumors. Importantly, there were few long-term survivors in the elderly group, especially among those with borderline resectable pancreatic cancer. A multivariate analysis of the prognostic factors in the very elderly patients indicated that the completion of adjuvant chemotherapy was the only significant factor. In addition, preoperative albumin level was the only independent risk factor for a failure to complete adjuvant chemotherapy. This study demonstrates that the postoperative prognosis in octogenarian patients was not good as that in younger patients possibly due to less frequent completion of adjuvant chemotherapy. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Increased levels of SLP-2 correlate with poor prognosis in gastric cancer.

PubMed

Liu, Dongning; Zhang, Lei; Shen, Zhiyong; Tan, Fei; Hu, Yanfeng; Yu, Jiang; Li, Guoxin

2013-10-01

Stomatin-like protein 2 (SLP-2) is a member of the highly conserved stomatin protein family whose homologues span from Archaea to humans and include stomatin, SLP-1, and SLP-3. Several studies have indicated that overexpression of SLP-2 is strongly associated with adhesion and migration in several human cancers. The aim of the present study was to evaluate SLP-2 expression at the mRNA and protein level in patients with gastric cancer (GC) and to examine the relationships between SLP-2 expression, clinicopathological features, and prognosis. We investigated SLP-2 expression in primary GC and paired normal gastric tissue by real-time PCR (RT-PCR; n = 16) and Western blot analysis (n = 32). Additionally, we performed immunohistochemistry (IHC) on 113 paraffin-embedded GC specimens, 30 matched normal specimens, and 30 paired metastatic lymph node samples. SLP-2 is overexpressed in GC compared with the adjacent normal gastric epithelium (p < 0.001), and high-level SLP-2 expression is significantly correlated with the depth of invasion, lymph node metastasis, distant metastasis, and American Joint Committee on Cancer (AJCC) stage. Furthermore, elevated SLP-2 expression is an independent prognostic factor in multivariate analysis using the Cox regression model (p = 0.005). Overexpression of SLP-2 may contribute to the progression and poor prognosis of GC.

Influence of arterial hypertension, type 2 diabetes and cardiovascular risk factors on ALS outcome: a population-based study.

PubMed

Moglia, Cristina; Calvo, Andrea; Canosa, Antonio; Bertuzzo, Davide; Cugnasco, Paolo; Solero, Luca; Grassano, Maurizio; Bersano, Enrica; Cammarosano, Stefania; Manera, Umberto; Pisano, Fabrizio; Mazzini, Letizia; Dalla Vecchia, Laura A; Mora, Gabriele; Chiò, Adriano

2017-11-01

To assess the prognostic influence of pre-morbid type 2 diabetes mellitus, arterial hypertension and cardiovascular (CV) risk profile on ALS phenotype and outcome in a population-based cohort of Italian patients. A total of 650 ALS patients from the Piemonte/Valle d'Aosta Register for ALS, incident in the 2007-2011 period, were recruited. Information about premorbid presence of type 2 diabetes mellitus, arterial hypertension was collected at the time of diagnosis. Patients' CV risk profile was calculated according to the Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice (JBS2). At the univariate analysis, the presence of pre-morbid arterial hypertension was associated with a higher age at onset of ALS and a shorter survival, and patients with a high CV risk profile had a worse prognosis than those with a low CV risk profile. The Cox multivariable analysis did not confirm such findings. Type 2 diabetes mellitus did not modify either the phenotype or the prognosis of ALS patients. This study performed on a large population-based cohort of ALS patients has demonstrated that arterial hypertension, type 2 diabetes and CV risk factors, calculated using the Framingham equation, do not influence ALS phenotype and prognosis.

Prognosis of patients presenting extreme acidosis (pH <7) on admission to intensive care unit.

PubMed

Allyn, Jérôme; Vandroux, David; Jabot, Julien; Brulliard, Caroline; Galliot, Richard; Tabatchnik, Xavier; Combe, Patrice; Martinet, Olivier; Allou, Nicolas

2016-02-01

The purpose was to determine prognosis of patients presenting extreme acidosis (pH <7) on admission to the intensive care unit (ICU) and to identify mortality risk factors. We retrospectively analyzed all patients who presented with extreme acidosis within 24 hours of admission to a polyvalent ICU in a university hospital between January 2011 and July 2013. Multivariate analysis and survival analysis were used. Among the 2156 patients admitted, 77 patients (3.6%) presented extreme acidosis. Thirty (39%) patients suffered cardiac arrest before admission. Although the mortality rate predicted by severity score was 93.6%, death occurred in 52 cases (67.5%) in a median delay of 13 (5-27) hours. Mortality rate depended on reason for admission, varying between 22% for cases linked to diabetes mellitus and 100% for cases of mesenteric infarction (P = .002), cardiac arrest before admission (P < .001), type of lactic acidosis (P = .007), high Simplified Acute Physiology Score II (P = .008), and low serum creatinine (P = .012). Patients with extreme acidosis on admission to ICU have a less severe than expected prognosis. Whereas mortality is almost 100% in cases of cardiac arrest before admission, mortality is much lower in the absence of cardiac arrest before admission, which justifies aggressive ICU therapies. Copyright © 2015 Elsevier Inc. All rights reserved.

Distal hyperintense vessels alleviate insula infarction in proximal middle cerebral artery occlusion.

PubMed

Song, Jiacheng; Ma, Zhanlong; Meng, Huan; Yu, Jing; Li, Yan; Hong, Xunning; Shi, Haibin

2016-11-01

Insula involvement in acute cerebral ischemia more likely causes penumbral loss and poor clinical outcome than infarct-sparing insula. Our objective was to prove the hypothesis that abundant collateral circulation represented by distal hyperintense vessels (HV) on MRI alleviates insula infarction and facilitates prognosis. One hundred and fourteen stroke cases with M1 totally occlusion on MR angiography were documented consecutively from 2012 to 2014. The degree of HV was graded as absent, subtle or prominent. Clinical data were recorded retrospectively by reviewing the medical records. The infarct volume on diffusion-weighted image, along with National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS), was used to evaluate the clinical severity and prognosis. The degree of HV was more abundant in insula-uninvolved stroke compared with stroke involving insula infarction (p = 0.026). Insula-involved stroke patients were older (p = 0.039) with a higher percentage of atrial fibrillation history (p = 0.042). Univariate analysis revealed that insula infarction, age, infarct volume and NIHSS predicted unfavorable prognosis of stroke, whereas HV had a favorable effect. The protective effect of HV was confirmed by multivariate analysis. HV is a protective barrier between insula infarction and severity of clinical symptoms among stroke patients.

p53 and PCNA expression in advanced colorectal cancer: response to chemotherapy and long-term prognosis.

PubMed

Paradiso, A; Rabinovich, M; Vallejo, C; Machiavelli, M; Romero, A; Perez, J; Lacava, J; Cuevas, M A; Rodriquez, R; Leone, B; Sapia, M G; Simone, G; De Lena, M

1996-12-20

In a series of 71 patients with advanced colorectal cancer treated with biochemically modulated 5-fluorouracil (5-FU) and methotrexate (MTX), we investigated the relationship between the proliferating-cell nuclear antigen (PCNA) (PC10) and p53 (Pab1801) primary-tumor immunohistochemical expression with respect to clinical response and long-term prognosis. Nuclear p53 expression was demonstrated in 44% of samples (any number of positive tumor cells) while all tumors showed a certain degree of PCNA immunostaining. PCNA immunostaining was correlated with histopathologic grade and p53 expression, while p53 was not correlated with any of the parameters considered. The probability of clinical response to biochemically modulated 5-FU was independent of p53 and PCNA expression. p53 expression (all cut-off values) was not associated with short- or long-term clinical prognosis, whereas patients with higher PCNA primary-tumor expression showed longer survival from treatment and survival from diagnosis, according to univariate and multivariate analysis, particularly in the sub-set of colon-cancer patients. We conclude that the clinical response of advanced-colorectal-cancer patients to biochemically modulated 5-FU and MTX cannot be predicted by PCNA and p53 primary-tumor expression, but high PCNA expression appears to be independently related to long-term prognosis.

Loss of Bad expression confers poor prognosis in non-small cell lung cancer.

PubMed

Huang, Yi; Liu, Dan; Chen, Bojiang; Zeng, Jing; Wang, Lei; Zhang, Shangfu; Mo, Xianming; Li, Weimin

2012-09-01

Proapoptotic BH-3-only protein Bad (Bcl-Xl/Bcl-2-associated death promoter homolog, Bad) initiates apoptosis in human cells, and contributes to tumorigenesis and chemotherapy resistant in malignancies. This study explored association between the Bad expression level and prognosis in patients with non-small cell lung cancer (NSCLC). In our study, a cohort of 88 resected primary NSCLC cases were collected and analyzed. Bad expression level was determined via immunohistochemical staining assay. The prognostic significances of Bad expression were evaluated with univariate and multivariate survival analysis. The results showed that compared with normal lung tissues, Bad expression level significantly decreased in NSCLC (P < 0.05). Bad expression was associated with adjuvant therapy status. Loss of Bad independently predicted poor prognosis in whole NSCLC cohort and early stage subjects (T1 + T2 and N0 + N1) (all P < 0.05). Overall survival time was also drastically shortened for Bad negative phenotype in NSCLC patients with smoking history, especially lung squamous cell carcinoma (all P < 0.05). In conclusion, this study provided clinical evidence that loss of Bad is an independent and powerful predictor of adverse prognosis in NSCLC. Bad protein could be a new biomarker for selecting individual therapy strategies and predicting therapeutic response in subjects with NSCLC.

Low levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes

PubMed Central

2012-01-01

Introduction Signal transducer and activator of transcripton-5a (Stat5a) and its close homologue, Stat5b, mediate key physiological effects of prolactin and growth hormone in mammary glands. In breast cancer, loss of nuclear localized and tyrosine phosphorylated Stat5a/b is associated with poor prognosis and increased risk of antiestrogen therapy failure. Here we quantify for the first time levels of Stat5a and Stat5b over breast cancer progression, and explore their potential association with clinical outcome. Methods Stat5a and Stat5b protein levels were quantified in situ in breast-cancer progression material. Stat5a and Stat5b transcript levels in breast cancer were correlated with clinical outcome in 936 patients. Stat5a protein was further quantified in four archival cohorts totaling 686 patients with clinical outcome data by using multivariate models. Results Protein levels of Stat5a but not Stat5b were reduced in primary breast cancer and lymph node metastases compared with normal epithelia. Low tumor levels of Stat5a but not Stat5b mRNA were associated with poor prognosis. Experimentally, only limited overlap between Stat5a- and Stat5b-modulated genes was found. In two cohorts of therapy-naïve, node-negative breast cancer patients, low nuclear Stat5a protein levels were an independent marker of poor prognosis. Multivariate analysis of two cohorts treated with antiestrogen monotherapy revealed that low nuclear Stat5a levels were associated with a more than fourfold risk of unfavorable outcome. Conclusions Loss of Stat5a represents a new independent marker of poor prognosis in node-negative breast cancer and may be a predictor of response to antiestrogen therapy if validated in randomized clinical trials. PMID:23036105

Prognostic value of transformer 2β expression in prostate cancer.

PubMed

Diao, Yan; Wu, Dong; Dai, Zhijun; Kang, Huafeng; Wang, Ziming; Wang, Xijing

2015-01-01

Deregulation of transformer 2β (Tra2β) has been implicated in several cancers. However, the role of Tra2β expression in prostate cancer (PCa) is unclear. Therefore, this study was to investigate the expression of Tra2β in PCa and evaluated its association with clinicopathological variables and prognosis. Thirty paired fresh PCa samples were analyzed for Tra2β expression by Western blot analysis. Immunohistochemistry (IHC) assay was performed in 160 PCa samples after radical prostatectomy and adjacent non-cancerous tissues. Tra2β protein expression was divided into high expression group and low expression group by IHC. We also investigated the association of Tra2β expression with clinical and pathologic parameters. Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the association between Tra2β protein expression and prognosis of PCa patients. Our results showed that Tra2β was significantly upregulated in PCa tissues by western blot and IHC. Our data indicated that high expression of Tra2β was significantly associated with lymph node metastasis (P=0.002), clinical stage (P=0.015), preoperative prostate-specific antigen (P=0.003), Gleason score (P=0.001), and biochemical recurrence (P=0.021). High Tra2β expression was a significant predictor of poor biochemical recurrence free survival and overall survival both in univariate and multivariate analysis. We show that Tra2β was significantly upregulated in PCa patients after radical prostatectomy, and multivariate analysis confirmed Tra2β as an independent prognostic factor.

Glycolytic activity in breast cancer using 18F-FDG PET/CT as prognostic predictor: A molecular phenotype approach.

PubMed

Garcia Vicente, A M; Soriano Castrejón, A; Amo-Salas, M; Lopez Fidalgo, J F; Muñoz Sanchez, M M; Alvarez Cabellos, R; Espinosa Aunion, R; Muñoz Madero, V

2016-01-01

To explore the relationship between basal (18)F-FDG uptake in breast tumors and survival in patients with breast cancer (BC) using a molecular phenotype approach. This prospective and multicentre study included 193 women diagnosed with BC. All patients underwent an (18)F-FDG PET/CT prior to treatment. Maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N), and the N/T index was obtained in all the cases. Metabolic stage was established. As regards biological prognostic parameters, tumors were classified into molecular sub-types and risk categories. Overall survival (OS) and disease free survival (DFS) were obtained. An analysis was performed on the relationship between semi-quantitative metabolic parameters with molecular phenotypes and risk categories. The effect of molecular sub-type and risk categories in prognosis was analyzed using Kaplan-Meier and univariate and multivariate tests. Statistical differences were found in both SUVT and SUVN, according to the molecular sub-types and risk classifications, with higher semi-quantitative values in more biologically aggressive tumors. No statistical differences were observed with respect to the N/T index. Kaplan-Meier analysis revealed that risk categories were significantly related to DFS and OS. In the multivariate analysis, metabolic stage and risk phenotype showed a significant association with DFS. High-risk phenotype category showed a worst prognosis with respect to the other categories with higher SUVmax in primary tumor and lymph nodes. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

A Selected Immunohistochemical Panel Aids in Differential Diagnosis and Prognostic Stratification of Subtypes of High-grade Endometrial Carcinoma: A Clinicopathologic and Immunohistochemical Study at a Single Institution.

PubMed

Taskin, Orhun Çiğ; Onder, Semen; Topuz, Samet; Sozen, Hamdullah; Sen, Fatma; Ilhan, Ridvan; Yavuz, Ekrem

This study aimed to investigate whether a selected immunohistochemical panel (estrogen receptor, p53, ARID1A, PPP2R1A, HNF-1β) could contribute to the diagnostic process of high-grade endometrial carcinomas (HG-ECs). We also aimed to analyze the correlation of these immunohistochemical results with several morphologic variables and survival data. After revising the diagnosis of 78 HG-ECs, immunohistochemical analysis was performed for each case. After immunohistochemical analysis, a specific diagnosis of prototypic HG-EC was established in most of the cases that were uncertain due to morphologic ambiguity. In the univariate analysis, older patient age, type II morphology, undifferentiated carcinoma and carcinosarcoma type of histology, altered p53 immunostaining, strong membranous staining of PPP2R1A, presence of lymphovascular invasion in serous carcinoma, and microcystic, elongated, and fragmented-type infiltration pattern in endometrioid carcinoma were significantly related to poor prognosis. In the multivariate analysis, only older patient age and carcinosarcoma or undifferentiated/dedifferentiated carcinoma type histology were found to be significantly poor prognostic factors (P=0.011), whereas advanced FIGO stage and type II histology were found to be correlated with poor prognosis, but did not reach statistical significance. We suggest that immunohistochemistry should be used in the differential diagnosis of HG-ECs, especially those with ambiguous morphology. Markers used in this study made a valuable contribution to the diagnostic process as well as prediction of prognosis.

Ventricular fibrillation in acute myocardial infarction in Spanish patients: Results of the ARIAM database.

PubMed

Ruiz-Bailén, Manuel; Aguayo de Hoyos, Eduardo; Ruiz-Navarro, Silvia; Issa-Khozouz, Ziad; Reina-Toral, Antonio; Díaz-Castellanos, Miguel Angel; Rodríguez-García, Juan-José; Torres-Ruiz, Juan Miguel; Cárdenas-Cruz, Antonio; Camacho-Víctor, Angel

2003-08-01

The aim of this study has been to investigate the factors predisposing to primary or secondary ventricular fibrillation (VF) and the prognosis in Spanish patients with acute myocardial infarction (AMI) during their admission to the intensive care unit or the coronary care unit. A retrospective, observational study. The intensive care units and coronary care units of 119 Spanish hospitals. A retrospective cohort study including all the AMI patients listed in the ARIAM registry (Analysis of Delay in Acute Myocardial Infarction), a Spanish multicenter study. The study period was January 1995 to January 2001. Factors associated with the onset of VF were studied by univariate analysis. Multivariate analysis was used to evaluate the independent factors for the onset of VF and for mortality. A total of 17,761 patients with AMI were included in the study; 964 (5.4%) developed VF (primary in 735 patients, secondary in 229). In multivariate analysis, the variables that continued to show an association with the development of VF were the Killip and Kimball class, peak creatine kinase, APACHE II score, age, and time from the onset of symptoms to the initiation of thrombolysis. The mortality in the patients with any VF was 31.8% (27.8% in patients with primary VF and 49.1% in patients with secondary VF). The development of VF is an independent predictive factor for mortality in patients with AMI, with a crude odds ratio of 5.12 (95% confidence interval, 4.41-5.95) and an adjusted odds ratio of 2.73 (95% confidence interval, 2.12-3.51). Despite the considerable improvement in the treatment of AMI in recent years, the onset of either primary or secondary VF is associated with a poor prognosis. It is usually accompanied by extensive necrosis.

Clinical implications of six inflammatory biomarkers as prognostic indicators in Ewing sarcoma

PubMed Central

Li, Yong-Jiang; Yang, Xi; Zhang, Wen-Biao; Yi, Cheng; Wang, Feng; Li, Ping

2017-01-01

Cancer-related systemic inflammation responses have been correlated with cancer development and progression. The prognostic significance of several inflammatory indicators, including neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), Glasgow Prognostic Score (GPS), C-reactive protein to albumin ratio (CRP/Alb ratio), lymphocyte–monocyte ratio (LMR), and neutrophil–platelet score (NPS), were found to be correlated with prognosis in several cancers. However, the prognostic role of these inflammatory biomarkers in Ewing sarcoma has not been evaluated. This study enrolled 122 Ewing patients. Receiver operating characteristic (ROC) analysis was generated to determine optimal cutoff values; areas under the curves (AUCs) were assessed to show the discriminatory ability of the biomarkers; Kaplan–Meier analysis was conducted to plot the survival curves; and Cox multivariate survival analysis was performed to identify independent prognostic factors. The optimal cutoff values of CRP/Alb ratio, NLR, PLR, and LMR were 0.225, 2.38, 131, and 4.41, respectively. CRP/Alb ratio had a significantly larger AUC than NLR, PLR, LMR, and NPS. Higher levels of CRP/Alb ratio (hazard ratio [HR] 2.41, P=0.005), GPS (HR 2.27, P=0.006), NLR (HR 2.07, P=0.013), and PLR (HR 1.85, P=0.032) were significantly correlated with poor prognosis. As the biomarkers had internal correlations, only the CRP/Alb ratio was involved in the multivariate Cox analysis and remained an independent prognostic indicator. The study demonstrated that CRP/Alb ratio, GPS, and NLR were effective prognostic indicators for patients with Ewing sarcoma, and the CRP/Alb ratio was the most robust prognostic indicator with a discriminatory ability superior to that of the other indicators; however, PLR, LMR, and NPS may not be suitable as prognostic indicators in Ewing sarcoma. PMID:29033609

Increased Prognostic Value of Query Amyloid Late Enhancement Score in Light-Chain Cardiac Amyloidosis.

PubMed

Wan, Ke; Sun, Jiayu; Han, Yuchi; Liu, Hong; Yang, Dan; Li, Weihao; Wang, Jie; Cheng, Wei; Zhang, Qing; Zeng, Zhi; Chen, Yucheng

2018-02-23

Late gadolinium enhancement (LGE) pattern is a powerful imaging biomarker for prognosis of cardiac amyloidosis. It is unknown if the query amyloid late enhancement (QALE) score in light-chain (AL) amyloidosis could provide increased prognostic value compared with LGE pattern.Methods and Results:Seventy-eight consecutive patients with AL amyloidosis underwent contrast-enhanced cardiovascular magnetic resonance imaging. Patients with cardiac involvement were grouped by LGE pattern and analyzed using QALE score. Receiver operating characteristic curve was used to identify the optimal cut-off for QALE score in predicting all-cause mortality. Survival of these patients was analyzed with the Kaplan-Meier method and multivariate Cox regression. During a median follow-up of 34 months, 53 of 78 patients died. The optimal cut-off for QALE score to predict mortality at 12-month follow-up was 9.0. On multivariate Cox analysis, QALE score ≥9 (HR, 5.997; 95% CI: 2.665-13.497; P<0.001) and log N-terminal pro-brain natriuretic peptide (HR, 1.525; 95% CI: 1.112-2.092; P=0.009) were the only 2 independent predictors of all-cause mortality. On Kaplan-Meier analysis, patients with subendocardial LGE can be further risk stratified using QALE score ≥9. The QALE scoring system provides powerful independent prognostic value in AL cardiac amyloidosis. QALE score ≥9 has added value to differentiate prognosis in AL amyloidosis patients with a subendocardial LGE pattern.

[The significance of lymph node status in papillary and follicular thyroid gland carcinoma for the nuclear medicine physician].

PubMed

Farahati, J; Mörtl, M; Reiners, C

2000-01-01

The impact of lymph node metastases on prognosis of differentiated thyroid cancer is discussed controversially. Therefore the data of 596 patients with papillary or follicular thyroid cancer are analysed retrospectively, which have been treated between 1980 and 1995 at the Clinic and Policlinic for Nuclear Medicine of the University of Würzburg. The influence of lymph node metastases on prognosis with respect to survival is analysed with the univariate Kaplan-Meier-method and with the multivariate discriminant analysis. In addition, the influence of the prognostic factor "lymph node involvement" on distant metastases is analysed by a stratified comparison and an univariate test. In papillary thyroid cancer, the 15 year-survival-rate for stage pN1 is significantly lower (p < 0.001) with 88.7% as compared to stage pN0 (99.4%). In patients with follicular thyroid cancer this difference is even more pronounced (64.7% versus 97.2%, p < 0.001). However, the multivariate discriminant analysis shows that the only prognostic factors are tumour stage and distant metastases, and--in papillary thyroid cancer--patient's age. So lymph node metastases are not an independent prognostic factor concerning survival. However, lymph node metastases have a prognostic unfavourable influence with respect to distant metastases especially in papillary thyroid cancer stage pT4 (distant metastases in patients with negative lymph nodes 0% and in patients with positive lymph nodes 35.3% [p < 0.001]).

The Glasgow Prognostic Score, an inflammation based prognostic score, predicts survival in patients with hepatocellular carcinoma

PubMed Central

2013-01-01

Background Elevated Glasgow Prognostic Score (GPS) has been related to poor prognosis in patients with hepatocellular carcinoma (HCC) undergoing surgical resection or receiving sorafenib. The aim of this study was to investigate the prognostic value of GPS in patients with various stages of the disease and with different liver functional status. Methods One hundred and fifty patients with newly diagnosed HCC were prospectively evaluated. Patients were divided according to their GPS scores. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with overall survival; the identified variables were then compared with those of other validated staging systems. Results Elevated GPS were associated with increased asparate aminotransferase (P<0.0001), total bilirubin (P<0.0001), decreased albumin (P<0.0001), α-fetoprotein (P=0.008), larger tumor diameter (P=0.003), tumor number (P=0.041), vascular invasion (P=0.0002), extra hepatic metastasis (P=0.02), higher Child-Pugh scores (P<0.0001), and higher Cancer Liver Italian Program scores (P<0.0001). On multivariate analysis, the elevated GPS was independently associated with worse overall survival. Conclusions Our results demonstrate that the GPS can serve as an independent marker of poor prognosis in patients with HCC in various stages of disease and different liver functional status. PMID:23374755

HLA-G 3'UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment.

PubMed

Garziera, Marica; Bidoli, Ettore; Cecchin, Erika; Mini, Enrico; Nobili, Stefania; Lonardi, Sara; Buonadonna, Angela; Errante, Domenico; Pella, Nicoletta; D'Andrea, Mario; De Marchi, Francesco; De Paoli, Antonino; Zanusso, Chiara; De Mattia, Elena; Tassi, Renato; Toffoli, Giuseppe

2015-01-01

An important hallmark of CRC is the evasion of immune surveillance. HLA-G is a negative regulator of host's immune response. Overexpression of HLA-G protein in primary tumour CRC tissues has already been associated to worse prognosis; however a definition of the role of immunogenetic host background is still lacking. Germline polymorphisms in the 3'UTR region of HLA-G influence the magnitude of the protein by modulating HLA-G mRNA stability. Soluble HLA-G has been associated to 3'UTR +2960 Ins/Ins and +3035 C/T (lower levels) and +3187 G/G (high levels) genotypes. HLA-G 3'UTR SNPs have never been explored in CRC outcome. The purpose of this study was to investigate if common HLA-G 3'UTR polymorphisms have an impact on DFS and OS of 253 stage II-III CRC patients, after primary surgery and ADJ-CT based on FL. The 3'UTR was sequenced and SNPs were analyzed for their association with survival by Kaplan-Meier and multivariate Cox models; results underwent internal validation using a resampling method (bootstrap analysis). In a multivariate analysis, we estimated an association with improved DFS in Ins allele (Ins/Del +Ins/Ins) carriers (HR 0.60, 95% CI 0.38-0.93, P = 0.023) and in patients with +3035 C/T genotype (HR 0.51, 95% CI 0.26-0.99, P = 0.045). The +3187 G/G mutated carriers (G/G vs A/A+A/G) were associated to a worst prognosis in both DFS (HR 2.46, 95% CI 1.19-5.05, P = 0.015) and OS (HR 2.71, 95% CI 1.16-6.63, P = 0.022). Our study shows a prognostic and independent role of 3 HLA-G 3'UTR SNPs, +2960 14-bp INDEL, +3035 C>T, and +3187 A>G.

Prognostic Value of the Amount of Bleeding After Aneurysmal Subarachnoid Hemorrhage: A Quantitative Volumetric Study.

PubMed

Lagares, Alfonso; Jiménez-Roldán, Luis; Gomez, Pedro A; Munarriz, Pablo M; Castaño-León, Ana M; Cepeda, Santiago; Alén, José F

2015-12-01

Quantitative estimation of the hemorrhage volume associated with aneurysm rupture is a new tool of assessing prognosis. To determine the prognostic value of the quantitative estimation of the amount of bleeding after aneurysmal subarachnoid hemorrhage, as well the relative importance of this factor related to other prognostic indicators, and to establish a possible cut-off value of volume of bleeding related to poor outcome. A prospective cohort of 206 patients consecutively admitted with the diagnosis of aneurysmal subarachnoid hemorrhage to Hospital 12 de Octubre were included in the study. Subarachnoid, intraventricular, intracerebral, and total bleeding volumes were calculated using analytic software. For assessing factors related to prognosis, univariate and multivariate analysis (logistic regression) were performed. The relative importance of factors in determining prognosis was established by calculating their proportion of explained variation. Maximum Youden index was calculated to determine the optimal cut point for subarachnoid and total bleeding volume. Variables independently related to prognosis were clinical grade at admission, age, and the different bleeding volumes. The proportion of variance explained is higher for subarachnoid bleeding. The optimal cut point related to poor prognosis is a volume of 20 mL both for subarachnoid and total bleeding. Volumetric measurement of subarachnoid or total bleeding volume are both independent prognostic factors in patients with aneurysmal subarachnoid hemorrhage. A volume of more than 20 mL of blood in the initial noncontrast computed tomography is related to a clear increase in poor outcome risk. : aSAH, aneurysmal subarachnoid hemorrhage.

High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers

PubMed Central

Peng, Li; Liu, Zhao-Yang; Li, Wen-Ling; Zhang, Chao-Yang; Zhang, Ya-Qin; Pan, Xi; Chen, Jun; Li, Yue-Hui

2017-01-01

Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients. PMID:27926484

High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers.

PubMed

Peng, Li; Yuan, Xiao-Qing; Liu, Zhao-Yang; Li, Wen-Ling; Zhang, Chao-Yang; Zhang, Ya-Qin; Pan, Xi; Chen, Jun; Li, Yue-Hui; Li, Guan-Cheng

2017-01-03

Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients.

Long-Term Prognostic Implications of the Admission Shock Index in Patients With Acute Myocardial Infarction Who Received Percutaneous Coronary Intervention.

PubMed

Abe, Naoyuki; Miura, Takashi; Miyashita, Yusuke; Hashizume, Naoto; Ebisawa, Soichiro; Motoki, Hirohiko; Tsujimura, Takuya; Ishihara, Takayuki; Uematsu, Masaaki; Katagiri, Toshio; Ishihara, Ryuma; Tosaka, Atsushi; Ikeda, Uichi

2017-04-01

The admission shock index (SI) enables prediction of short-term prognosis. This study investigated the prognostic implications of admission SI for predicting long-term prognoses for acute myocardial infarction (AMI). The participants were 680 patients with AMI who received percutaneous coronary intervention. Shock index is the ratio of heart rate and systolic blood pressure. Patients were classified as admission SI <0.66 (normal) and ≥0.66 (elevated; 75th percentile). The end point was 5-year major adverse cardiac events (MACEs). Elevated admission SI was seen in 176 patients. Peak creatine kinase levels were significantly higher and left ventricular ejection fraction was lower in the elevated SI group, which had a worse MACEs. In multivariate Cox regression analysis, SI ≥0.66 was a risk factor for MACE. Elevated admission SI was associated with poorer long-term prognosis.

Delta-like ligand 4: A predictor of poor prognosis in clear cell renal cell carcinoma

PubMed Central

WANG, WEI; YU, YI; WANG, YA; LI, XIAOMING; BAO, JUNSHENG; WU, GONGJIN; CHANG, HONG; SHI, TINGKAI; YUE, ZHONGJIN

2014-01-01

Delta-like ligand 4 (Dll4)-Notch signaling is important in tumor angiogenesis; however, the prognostic value of D114 detection in patients with clear cell renal cell carcinoma (CCRCC) remains unclear. The present study aimed to determine whether the presence of high Dll4 expression levels was correlated with poor prognosis in CCRCC following curative resection. The D114 expression levels in four paired samples of CCRCC tissues and adjacent normal renal tissues were assayed by western blotting. Surgical specimens comprised 121 CCRCC tissue samples and 65 normal renal tissue samples, obtained from patients with CCRCC. The specimens were immunohistochemically assessed to determine Dll4 and vascular endothelial growth factor receptor 2 (VEGFR-2) expression levels. The prognostic significance of Dll4 expression levels was evaluated by the Kaplan-Meier method and Cox regression analysis. The correlation between Dll4 expression levels and VEGFR-2 expression levels, tumor stage, tumor grade and metastasis, was examined by χ2 test and multivariate logistic regression. As determined by the western blotting results, Dll4 protein expression levels were significantly increased in CCRCC tissues compared with those in adjacent non-cancerous tissues. From the analysis of the surgical specimens, 53 (43.8%) CCRCC patients exhibited immunohistochemically high Dll4 expression levels and 68 (56.2%) patients exhibited low Dll4 expression levels. The survival curves revealed that the patients with high Dll4 expression levels had significantly shorter survival times than the patients with low Dll4 expression levels (P<0.001). Multivariate survival analysis demonstrated that the presence of high Dll4 expression levels was independently associated with reduced overall survival and progression-free survival times (P=0.021 and 0.034, respectively). A positive correlation was also identified between Dll4 and VEGFR-2 expression levels (P=0.001). In conclusion, the results show that the presence of high Dll4 expression levels was clearly associated with high VEGFR-2 expression levels, tumor grade, tumor stage and poor prognosis in CCRCC patients. Therefore, inhibition of Dll4 may exert potent growth inhibitory effects on tumors resistant to anti-VEGF therapies for CCRCC. PMID:25364440

Evaluation of prognostic factors on recurrence after curative resections for hepatocellular carcinoma

PubMed Central

Han, Jae Hyun; Kim, Dong Goo; Na, Gun Hyung; Kim, Eun Young; Lee, Soo Ho; Hong, Tae Ho; You, Young Kyoung

2014-01-01

AIM: To select appropriate patients before surgical resection for hepatocellular carcinoma (HCC), especially those with advanced tumors. METHODS: From January 2000 to December 2012, we retrospectively analyzed the medical records of 298 patients who had undergone surgical resections for HCC with curative intent at our hospital. We evaluated preoperative prognostic factors associated with histologic grade of tumor, recurrence and survival, especially the findings of pre-operative imaging studies such as positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI). And then, we established a scoring system to predict recurrence and survival after surgery dividing the patients into two groups based on a tumor size of 5 cm. RESULTS: Of the 298 patients, 129 (43.3%) developed recurrence during the follow-up period. The 5 year disease free survival and overall survival were 47.0% and 58.7% respectively. In multivariate analysis, a serum alpha-fetoprotein (AFP) level of > 100 ng/mL and a standardized uptake value (SUV) of PET-CT of > 3.5 were predictive factors for histologic grade of tumor, recurrence, and survival. Tumor size of > 5 cm and a relative enhancement ratio (RER) calculated from preoperative MRI were also significantly associated with prognosis in univariate analysis. We established a scoring system to predict prognosis using AFP, SUV, and RER. In those with tumors of > 5 cm, it showed predicted both recurrence (P = 0.005) and survival (P = 0.001). CONCLUSION: The AFP, tumor size, SUV and RER are useful for prognosis preoperatively. An accurate prediction of prognosis is possible using our scoring system in large size tumors. PMID:25493027

Evaluation of prognostic factors on recurrence after curative resections for hepatocellular carcinoma.

PubMed

Han, Jae Hyun; Kim, Dong Goo; Na, Gun Hyung; Kim, Eun Young; Lee, Soo Ho; Hong, Tae Ho; You, Young Kyoung

2014-12-07

To select appropriate patients before surgical resection for hepatocellular carcinoma (HCC), especially those with advanced tumors. From January 2000 to December 2012, we retrospectively analyzed the medical records of 298 patients who had undergone surgical resections for HCC with curative intent at our hospital. We evaluated preoperative prognostic factors associated with histologic grade of tumor, recurrence and survival, especially the findings of pre-operative imaging studies such as positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI). And then, we established a scoring system to predict recurrence and survival after surgery dividing the patients into two groups based on a tumor size of 5 cm. Of the 298 patients, 129 (43.3%) developed recurrence during the follow-up period. The 5 year disease free survival and overall survival were 47.0% and 58.7% respectively. In multivariate analysis, a serum alpha-fetoprotein (AFP) level of > 100 ng/mL and a standardized uptake value (SUV) of PET-CT of > 3.5 were predictive factors for histologic grade of tumor, recurrence, and survival. Tumor size of > 5 cm and a relative enhancement ratio (RER) calculated from preoperative MRI were also significantly associated with prognosis in univariate analysis. We established a scoring system to predict prognosis using AFP, SUV, and RER. In those with tumors of > 5 cm, it showed predicted both recurrence (P = 0.005) and survival (P = 0.001). The AFP, tumor size, SUV and RER are useful for prognosis preoperatively. An accurate prediction of prognosis is possible using our scoring system in large size tumors.

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

PubMed

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

2000-01-01

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

[Predictive value of pre-treatment hypoalbuminemia in prognosis of resected colorectal cancer].

PubMed

Borda, Fernando; Borda, Ana; Jiménez, Javier; Zozaya, José Manuel; Prieto, Carlos; Gómez, Marta; Urman, Jesús; Ibáñez, Berta

2014-05-01

Albuminemia is part of the antitumoral systemic inflammatory response. We therefore analyzed its possible value in establishing the preoperative prognosis of colorectal carcinoma (CRC). We conducted a retrospective, observational study of a series of consecutive patients who underwent CRC resection. Univariate and multivariate analyses of survival curves were performed in patients with and without pre-treatment hypoalbuminemia (<3.5g/dl), both in the overall group of patients and in the subgroup of those with pTNM stage ii tumors. In addition, we compared the 5-year tumor-related mortality in patients with and without hypoalbuminemia. A total of 207 patients were reviewed (median follow-up: 81 months). In the overall multivariate analysis, survival curves were better in patients with normal albumin levels than in those with hypoalbuminemia (HR=2.82; CI 95%=[1.54-5.19]; P=.001). This better prognostic value of normal albumin levels was also significant in pTNM stage ii tumors: (HR=3.76; CI 95%=[1.40-10.08]; P=.009). The 5-year mortality index was lower in patients with normal albumin levels: overall series=18.8% vs 42.9% (OR=3.24; CI 95%=[1.48-7.12]; p=0.001); pTNM stage ii=13.3% vs 44.4% (OR=5.2; CI 95%=[1.36-20.34]; P=0.004). Pre-treatment hypoalbuminemia (<3.5g/dl) was independently related to shorter survival after tumor resection, both in the overall series of patients and in pTNM stage ii CRC. If these results are confirmed, hypoalbuminemia would be a simple and significant marker of poor prognosis, available at the initial diagnosis. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

Multivariate functional response regression, with application to fluorescence spectroscopy in a cervical pre-cancer study.

PubMed

Zhu, Hongxiao; Morris, Jeffrey S; Wei, Fengrong; Cox, Dennis D

2017-07-01

Many scientific studies measure different types of high-dimensional signals or images from the same subject, producing multivariate functional data. These functional measurements carry different types of information about the scientific process, and a joint analysis that integrates information across them may provide new insights into the underlying mechanism for the phenomenon under study. Motivated by fluorescence spectroscopy data in a cervical pre-cancer study, a multivariate functional response regression model is proposed, which treats multivariate functional observations as responses and a common set of covariates as predictors. This novel modeling framework simultaneously accounts for correlations between functional variables and potential multi-level structures in data that are induced by experimental design. The model is fitted by performing a two-stage linear transformation-a basis expansion to each functional variable followed by principal component analysis for the concatenated basis coefficients. This transformation effectively reduces the intra-and inter-function correlations and facilitates fast and convenient calculation. A fully Bayesian approach is adopted to sample the model parameters in the transformed space, and posterior inference is performed after inverse-transforming the regression coefficients back to the original data domain. The proposed approach produces functional tests that flag local regions on the functional effects, while controlling the overall experiment-wise error rate or false discovery rate. It also enables functional discriminant analysis through posterior predictive calculation. Analysis of the fluorescence spectroscopy data reveals local regions with differential expressions across the pre-cancer and normal samples. These regions may serve as biomarkers for prognosis and disease assessment.

Long-term prognosis of patients with acute myocardial infarction due to unprotected left main coronary artery disease: a single-centre experience over 14 years.

PubMed

Xu, Li; Sun, Hao; Wang, Le-Feng; Yang, Xin-Chun; Li, Kui-Bao; Zhang, Da-Peng; Wang, Hong-Shi; Li, Wei-Ming

2016-07-01

Acute myocardial infarction (AMI) due to unprotected left main coronary artery (ULMCA) disease is clinically catastrophic although it has a low incidence. Studies on the long-term prognosis of these patients are rare. From January 1999 to September 2013, 55 patients whose infarct-related artery was the ULMCA were enrolled. Clinical, angiographic and interventional data was collected. Short-term and long-term clinical follow-up results as well as prognostic determinants during hospitalisation and follow-up were analysed. Cardiogenic shock (CS) occurred in 30 (54.5%) patients. During hospitalisation, 22 (40.0%) patients died. Multivariate logistic regression analysis showed that CS (odds ratio [OR] 5.86; p = 0.03), collateral circulation of Grade 2 or 3 (OR 0.14; p = 0.02) and final flow of thrombolysis in myocardial infarction (TIMI) Grade 3 (OR 0.05; p = 0.03) correlated with death during hospitalisation. 33 patients survived to discharge; another seven patients died during the follow-up period of 44.6 ± 31.3 (median 60, range 0.67-117.00) months. The overall mortality rate was 52.7% (n = 29). Kaplan-Meier analysis showed that the total cumulative survival rate was 30.7%. Cox multivariate regression analysis showed that CS during hospitalisation was the only predictor of overall mortality (hazard ratio 4.07, 95% confidence interval 1.40-11.83; p = 0.01). AMI caused by ULMCA lesions is complicated by high incidence of CS and mortality. CS, poor collateral blood flow and failure to restore final flow of TIMI Grade 3 correlated with death during hospitalisation. CS is the only predictor of long-term overall mortality. Copyright: © Singapore Medical Association.

Brain volume reduction after whole-brain radiotherapy: quantification and prognostic relevance.

PubMed

Hoffmann, Christian; Distel, Luitpold; Knippen, Stefan; Gryc, Thomas; Schmidt, Manuel Alexander; Fietkau, Rainer; Putz, Florian

2018-01-22

Recent studies have questioned the value of adding whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) for brain metastasis treatment. Neurotoxicity, including radiation-induced brain volume reduction, could be one reason why not all patients benefit from the addition of WBRT. In this study, we quantified brain volume reduction after WBRT and assessed its prognostic significance. Brain volumes of 91 patients with cerebral metastases were measured during a 150-day period after commencing WBRT and were compared with their pretreatment volumes. The average daily relative change in brain volume of each patient, referred to as the "brain volume reduction rate," was calculated. Univariate and multivariate Cox regression analyses were performed to assess the prognostic significance of the brain volume reduction rate, as well as of 3 treatment-related and 9 pretreatment factors. A one-way analysis of variance was used to compare the brain volume reduction rate across recursive partitioning analysis (RPA) classes. On multivariate Cox regression analysis, the brain volume reduction rate was a significant predictor of overall survival after WBRT (P < 0.001), as well as the number of brain metastases (P = 0.002) and age (P = 0.008). Patients with a relatively favorable prognosis (RPA classes 1 and 2) experienced significantly less brain volume decrease after WBRT than patients with a poor prognosis (RPA class 3) (P = 0.001). There was no significant correlation between delivered radiation dose and brain volume reduction rate (P = 0.147). In this retrospective study, a smaller decrease in brain volume after WBRT was an independent predictor of longer overall survival. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia.

PubMed

Vidriales, María-Belén; Pérez-López, Estefanía; Pegenaute, Carlota; Castellanos, Marta; Pérez, José-Juan; Chandía, Mauricio; Díaz-Mediavilla, Joaquín; Rayón, Consuelo; de Las Heras, Natalia; Fernández-Abellán, Pascual; Cabezudo, Miguel; de Coca, Alfonso García; Alonso, Jose M; Olivier, Carmen; Hernández-Rivas, Jesús M; Montesinos, Pau; Fernández, Rosa; García-Suárez, Julio; García, Magdalena; Sayas, María-José; Paiva, Bruno; González, Marcos; Orfao, Alberto; San Miguel, Jesús F

2016-01-01

The clinical utility of minimal residual disease (MRD) analysis in acute myeloid leukaemia (AML) is not yet defined. We analysed the prognostic impact of MRD level at complete remision after induction therapy using multiparameter flow cytometry in 306 non-APL AML patients. First, we validated the prognostic value of MRD-thresholds we have previously proposed (≥ 0.1%; ≥ 0.01-0.1%; and <0.01), with a 5-year RFS of 38%, 50% and 71%, respectively (p=0.002). Cytogenetics is the most relevant prognosis factor in AML, however intermediate risk cytogenetics represent a grey zone that require other biomarkers for risk stratification, and we show that MRD evaluation discriminate three prognostic subgroups (p=0.03). Also, MRD assessments yielded relevant information on favourable and adverse cytogenetics, since patients with favourable cytogenetics and high MRD levels have poor prognosis and patients with adverse cytogenetics but undetectable MRD overcomes the adverse prognosis. Interestingly, in patients with intermediate or high MRD levels, intensification with transplant improved the outcome as compared with chemotherapy, while the type of intensification therapy did not influenced the outcome of patients with low MRD levels. Multivariate analysis revealed age, MRD and cytogenetics as independent variables. Moreover, a scoring system, easy in clinical practice, was generated based on MRD level and cytogenetics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prognostic factors of Pneumocystis jirovecii pneumonia in patients without HIV infection.

PubMed

Kim, Soo Jung; Lee, Jinwoo; Cho, Young-Jae; Park, Young Sik; Lee, Chang-Hoon; Yoon, Ho Il; Lee, Sang-Min; Yim, Jae-Joon; Lee, Jae Ho; Yoo, Chul-Gyu; Lee, Choon-Taek; Kim, Young Whan; Han, Sung Koo; Kim, Hong Bin; Park, Jong Sun

2014-07-01

The incidence of Pneumocystis jirovecii pneumonia (PCP) in patients without HIV infection (non-HIV PCP) has been increasing along with the increased use of chemotherapeutic agents and immunosuppressants, but the prognostic factors of non-HIV PCP remain unclear. This study aimed to identify the prognostic factors of non-HIV PCP. Immunocompromised patients without HIV infection who were diagnosed and treated for PCP were included. The PCP diagnosis was based on positive direct fluorescent antibody (DFA) or polymerase chain reaction (PCR) results and compatible clinical symptoms and radiological findings. In total, 372 non-HIV patients with positive PCP DFA or PCR findings were screened and 173 were included. Univariate analysis indicated that age, smoking, chronic lung disease or hematologic malignancy, chemotherapeutic agents, high alveolar-arterial oxygen gradient (D[A-a]O2), C-reactive protein, albumin, blood urea nitrogen (BUN), CMV antigenemia, combined bacteremia, high percentage of neutrophils and rate of co-infection in BAL fluid, and mechanical ventilator care were related to the prognosis of non-HIV PCP. Multivariate analysis revealed that high D(A-a)O2, combined bacteremia, increased BUN and preexisting lung disease were indicators of a poor prognosis. High D(A-a)O2, combined bacteremia, increased BUN and preexisting lung disease were independent factors of poor prognosis in non-HIV PCP patients. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor.

PubMed

Dahlin, Anna M; Henriksson, Maria L; Van Guelpen, Bethany; Stenling, Roger; Oberg, Ake; Rutegård, Jörgen; Palmqvist, Richard

2011-05-01

The aim of this study was to relate the density of tumor infiltrating T cells to cancer-specific survival in colorectal cancer, taking into consideration the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) screening status. The T-cell marker CD3 was stained by immunohistochemistry in 484 archival tumor tissue samples. T-cell density was semiquantitatively estimated and scored 1-4 in the tumor front and center (T cells in stroma), and intraepithelially (T cells infiltrating tumor cell nests). Total CD3 score was calculated as the sum of the three CD3 scores (range 3-12). MSI screening status was assessed by immunohistochemistry. CIMP status was determined by quantitative real-time PCR (MethyLight) using an eight-gene panel. We found that patients whose tumors were highly infiltrated by T cells (total CD3 score ≥7) had longer survival compared with patients with poorly infiltrated tumors (total CD3 score ≤4). This finding was statistically significant in multivariate analyses (multivariate hazard ratio, 0.57; 95% confidence interval, 0.31-1.00). Importantly, the finding was consistent in rectal cancer patients treated with preoperative radiotherapy. Although microsatellite unstable tumor patients are generally considered to have better prognosis, we found no difference in survival between microsatellite unstable and microsatellite stable (MSS) colorectal cancer patients with similar total CD3 scores. Patients with MSS tumors highly infiltrated by T cells had better prognosis compared with intermediately or poorly infiltrated microsatellite unstable tumors (log rank P=0.013). Regarding CIMP status, CIMP-low was associated with particularly poor prognosis in patients with poorly infiltrated tumors (multivariate hazard ratio for CIMP-low versus CIMP-negative, 3.07; 95% confidence interval, 1.53-6.15). However, some subset analyses suffered from low power and are in need of confirmation by independent studies. In conclusion, patients whose tumors are highly infiltrated by T cells have a beneficial prognosis, regardless of MSI, whereas the role of CIMP status in this context is less clear.

Prognostic Significance of POLE Proofreading Mutations in Endometrial Cancer

PubMed Central

Church, David N.; Stelloo, Ellen; Nout, Remi A.; Valtcheva, Nadejda; Depreeuw, Jeroen; ter Haar, Natalja; Noske, Aurelia; Amant, Frederic; Wild, Peter J.; Lambrechts, Diether; Jürgenliemk-Schulz, Ina M.; Jobsen, Jan J.; Smit, Vincent T. H. B. M.; Creutzberg, Carien L.; Bosse, Tjalling

2015-01-01

Background: Current risk stratification in endometrial cancer (EC) results in frequent over- and underuse of adjuvant therapy, and may be improved by novel biomarkers. We examined whether POLE proofreading mutations, recently reported in about 7% of ECs, predict prognosis. Methods: We performed targeted POLE sequencing in ECs from the PORTEC-1 and -2 trials (n = 788), and analyzed clinical outcome according to POLE status. We combined these results with those from three additional series (n = 628) by meta-analysis to generate multivariable-adjusted, pooled hazard ratios (HRs) for recurrence-free survival (RFS) and cancer-specific survival (CSS) of POLE-mutant ECs. All statistical tests were two-sided. Results: POLE mutations were detected in 48 of 788 (6.1%) ECs from PORTEC-1 and-2 and were associated with high tumor grade (P < .001). Women with POLE-mutant ECs had fewer recurrences (6.2% vs 14.1%) and EC deaths (2.3% vs 9.7%), though, in the total PORTEC cohort, differences in RFS and CSS were not statistically significant (multivariable-adjusted HR = 0.43, 95% CI = 0.13 to 1.37, P = .15; HR = 0.19, 95% CI = 0.03 to 1.44, P = .11 respectively). However, of 109 grade 3 tumors, 0 of 15 POLE-mutant ECs recurred, compared with 29 of 94 (30.9%) POLE wild-type cancers; reflected in statistically significantly greater RFS (multivariable-adjusted HR = 0.11, 95% CI = 0.001 to 0.84, P = .03). In the additional series, there were no EC-related events in any of 33 POLE-mutant ECs, resulting in a multivariable-adjusted, pooled HR of 0.33 for RFS (95% CI = 0.12 to 0.91, P = .03) and 0.26 for CSS (95% CI = 0.06 to 1.08, P = .06). Conclusion: POLE proofreading mutations predict favorable EC prognosis, independently of other clinicopathological variables, with the greatest effect seen in high-grade tumors. This novel biomarker may help to reduce overtreatment in EC. PMID:25505230

Preoperative Carcinoembryonic Antigen and Prognosis of Colorectal Cancer. An Independent Prognostic Factor Still Reliable

PubMed Central

Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

2015-01-01

To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this—to date—has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging. PMID:25875542

Preoperative carcinoembryonic antigen and prognosis of colorectal cancer. An independent prognostic factor still reliable.

PubMed

Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

2015-04-01

To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this-to date-has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging.

The correlations between alteration of p16 gene and clinicopathological factors and prognosis in squamous cell carcinomas of the buccal mucosa.

PubMed

Dong, Yuying; Wang, Jie; Dong, Fusheng; Wang, Xu; Zhang, Yinghuai

2012-07-01

To evaluate relationships between the alteration of p16 gene and the clinical status and prognosis of the patients with squamous cell carcinoma of the buccal mucosa. Thirty buccal cancers were included in the analysis. Deletion analysis was performed by PCR. Point mutation analysis was used by PCR-SSCP and direct sequencing. Methylation-specific PCR methods were adopted for the evaluation of p16 methylation. The correlation between alteration of p16 gene and clinicopathological factors buccal cancer was evaluated by Fisher's exact test. Kaplan-Meier and Cox regression were used to investigate the relationship between p16 alteration and survival time. The frequency of p16 alteration was 63.3% in buccal carcinomas. P16 deletion was associated significantly with tumor size (P = 0.01). P16 point mutation was associated significantly with differentiation (P = 0.006). P16 methylation was associated significantly with nodes metastasis (P = 0.027). The overall survival rate of 30 buccal carcinomas was 53.3%. The Log-rank test (P = 0.021) and univariate Cox regression analysis (P = 0.030) revealed that p16 methylation was significantly associated with the overall survival rate. Multivariate analysis showed that p16 deletion, p16 mutation, and p16 methylation were not statistically significant. The alterations of p16 gene may play a major role in malignancy and development and metastases of buccal carcinoma and may be an excellent marker of aggressive clinical behavior. P16 methylation has a prognostic value in buccal carcinoma but not an independent prognosis factor. P16 point mutation and p16 deletion have not prognostic significance in buccal carcinoma. © 2012 John Wiley & Sons A/S.

Analysis of clinical risk factors associated with the prognosis of severe multiple-trauma patients with acute lung injury.

PubMed

Wu, Junsong; Sheng, Lei; Wang, Shenhua; Li, Qiang; Zhang, Mao; Xu, Shaowen; Gan, Jianxin

2012-09-01

Several clinical risk factors have been reported to be associated with the prognosis of acute lung injury (ALI). However, these studies have included a general trauma patient population, without singling out the severely injured multiple-trauma patient population. To identify the potential risk factors that could affect the prognosis of ALI in multiple-trauma patients and investigate the prognostic effects of certain risk factors among different patient subpopulations. In this retrospective cohort study, severely injured multiple-trauma patients with early onset of ALI from several trauma centers were studied. Potential risk factors affecting the prognosis of ALI were examined by univariate and multivariate logistic analyses. There were 609 multiple-trauma patients with ALI admitted to the emergency department and emergency intensive care unit during the study period. The nine risk factors that affected prognosis, as indicated by the unadjusted odds ratios with 95% confidence intervals, were the APACHE II (Acute Physiology and Chronic Health Evaluation II) score, duration of trauma, age, gastrointestinal hemorrhage, pulmonary contusion, disseminated intravascular coagulation (DIC), multiple blood transfusions in 6 h, Injury Severity Score (ISS), and aspiration of gastric contents. Specific risk factors also affected different patient subpopulations in different ways. Patients older than 65 years and with multiple (> 10 units) blood transfusions in the early stage after multiple trauma were found to be independent risk factors associated with deterioration of ALI. The other factors studied, including pulmonary contusion, APACHE II score ≥ 20, ISS ≥ 16, gastrointestinal hemorrhage, and aspiration of gastric contents, may predict the unfavorable prognosis of ALI in the early stage of trauma, with their effects attenuating in the later stage. Duration of trauma ≥ 1 h and the presence of DIC may also indicate unfavorable prognosis during the entire treatment period. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Prognostic value of continuous electroencephalography monitoring in children with severe brain damage.

PubMed

Lan, Yan-huai; Zhu, Xiao-mei; Zhou, Yuan-feng; Qiu, Peng-ling; Lu, Guo-ping; Sun, Dao-kai; Wang, Yi

2015-06-01

The purpose of this study is to determine whether there is a relationship between continuous electroencephalography (EEG) monitoring patterns and prognosis for children with severe brain damage. Patients and The different patterns of EEG were analyzed for 103 children (Glasgow Coma Scale [GCS] score < 8) who were monitored with continuous video-EEG (CVEEG) within 72 hours after the onset of coma. The clinical outcomes were scored and evaluated at hospital discharge by the modified Pediatric Cerebral and Overall Performance Category Scale (PCOPCS). EEG parameters of the different prognosis groups were compared and risk factors for prognosis were identified. Of the 103 children, 36 were in the good prognosis group (PCOPCS scores 1 and 2) and 67 were in the poor prognosis group (PCOPCS scores 3-6). The poor prognosis group had the lower proportion of events in reactive EEG patterns and sleep architecture, and a higher proportion of low-voltage events. Multivariate analyses showed that the lower GCS score and no sleep architecture were significantly associated with poor prognosis. Comatose children with higher GCS score and sleep architecture have better clinical outcomes in terms of morbidity and mortality. Georg Thieme Verlag KG Stuttgart · New York.

Prognostic factors of Bell's palsy: prospective patient collected observational study.

PubMed

Fujiwara, Takashi; Hato, Naohito; Gyo, Kiyofumi; Yanagihara, Naoaki

2014-07-01

The purpose of this study was to evaluate various parameters potentially influencing poor prognosis in Bell's palsy and to assess the predictive value for Bell's palsy. A single-center prospective patient collected observation and validation study was conducted. To evaluate the correlation between patient characteristics and poor prognosis, we performed univariate and multivariate analyzes of age, gender, side of palsy, diabetes mellitus, hypertension, and facial grading score 1 week after onset. To evaluate the accuracy of the facial grading score, we prepared a receiver operating characteristic (ROC) curve and calculated the area under the ROC curve (AUROC). We also calculated sensitivity, specificity, positive/negative likelihood ratio, and positive/negative predictive value. We included Bell's palsy patients who attended Ehime University Hospital within 1 week after onset between 1977 and 2011. We excluded patients who were less than 15 years old and lost-to-follow-up within 6 months. The main outcome was defined as non-recovery at 6 months after onset. In total, 679 adults with Bell's palsy were included. The facial grading score at 1 week showed a correlation with non-recovery in the multivariate analysis, although age, gender, side of palsy, diabetes mellitus, and hypertension did not. The AUROC of the facial grading score was 0.793. The Y-system score at 1 week moderate accurately predicted non-recovery at 6 months in Bell's palsy.

Clinicopathologic significance of minichromosome maintenance protein 2 and Tat-interacting protein 30 expression in benign and malignant lesions of the gallbladder.

PubMed

Liu, Dong-cai; Yang, Zhu-lin

2011-11-01

Gallbladder cancers are aggressive tumors with a poor prognosis and high mortality rate. To find specific biological markers for early diagnosis and prognosis and to develop possible alternative treatment strategies, we examined minichromosome maintenance protein 2 (MCM2) and Tat-interacting protein 30 (TIP30) expression in 108 gallbladder adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues using immunohistochemistry. Expression of MCM2 was significantly higher in adenocarcinomas than in peritumoral tissues (χ² = 8.41; P < .01), adenomatous polyps (χ² = 6.81; P < .01), and chronic cholecystitis (χ² = 21.00; P < .01). In contrast, Tat-interacting protein 30 expression was significantly less in adenocarcinomas than in peritumoral tissues (χ² = 13.26; P < .01), adenomatous polyps (χ² = 4.76; P < .05), and chronic cholecystitis (χ² = 18.93; P < .01). The benign lesions in gallbladder epithelium with positive MCM2 or negative Tat-interacting protein 30 expression showed moderate to severe atypical hyperplasia. Expression of MCM2 and absence of Tat-interacting protein 30 were significantly associated with poor differentiation, large tumor mass, lymph node metastasis, and invasion of adenocarcinoma. Univariate Kaplan-Meier analysis showed that either elevated MCM2 (P = .006) or lowered Tat-interacting protein 30 (P = .006) expression was closely associated with shorter overall survival. Multivariate Cox regression analysis revealed that expression of MCM2 (P = .007) or nonexpression of Tat-interacting protein 30 (P = .009) was an independent predictor of a poor prognosis in adenocarcinoma. Our results suggest that overexpression of MCM2 or loss of expression of Tat-interacting protein 30 is closely related to carcinogenesis, progression, biological behavior, and prognosis of gallbladder adenocarcinoma. Copyright © 2011 Elsevier Inc. All rights reserved.

Prognostic Role of Host Cyclooxygenase and Cytokine Genotypes in a Caucasian Cohort of Patients with Gastric Adenocarcinoma

PubMed Central

García-González, María Asunción; Nicolás-Pérez, David; Lanas, Angel; Bujanda, Luis; Carrera, Patricia; Benito, Rafael; Strunk, Mark; Sopeña, Federico; Santolaria, Santos; Piazuelo, Elena; Jiménez, Pilar; Campo, Rafael; Espinel, Jesús; Manzano, Marisa; Geijo, Fernando; Pellisé, María; González-Huix, Ferrán; Espinós, Jorge; Zaballa, Manuel; Titó, Llúcia; Barranco, Luis; Pazo, Roberto; Quintero, Enrique

2012-01-01

Background Genetic factors influencing the prognosis of gastric adenocarcinoma (GAC) are not well known. Given the relevance of cytokines and other pro-inflammatory mediators in cancer progression and invasiveness, we aimed to assess the prognostic role of several functional cytokine and cyclooxygenase gene polymorphisms in patients with GAC. Methodology Genomic DNA from 380 Spanish Caucasian patients with primary GAC was genotyped for 23 polymorphisms in pro-inflammatory (IL1B, TNFA, LTA, IL6, IL12p40), anti-inflammatory (IL4, IL1RN, IL10, TGFB1) cytokine, and cyclooxygenase (PTGS1 and PTGS2) genes by PCR, RFLP and TaqMan assays. Clinical and histological information was collected prospectively. Survival curves were estimated by the Kaplan-Meier method and compared using the log rank test. Outcome was determined by analysis of Cox proportional hazards, adjusting for confounding factors. Results The median follow-up period and median overall survival (OS) time were 9.9 months (range 0.4–120.3) and 10.9 months (95% CI: 8.9–14.1), respectively. Multivariate analysis identified tumor stages III (HR, 3.23; 95% CI:2–5.22) and IV (HR, 5.5; 95% CI: 3.51–8.63) as independent factors associated with a significantly reduced OS, whereas surgical treatment (HR: 0.44; 95%CI: 0.3–0.6) was related to a better prognosis of the disease. Concerning genetic factors, none of the 23 polymorphisms evaluated in the current study did influence survival. Moreover, no gene-environment interactions on GAC prognosis were observed. Conclusions Our results show that, in our population, the panel of selected pro- and anti-inflammatory cytokine, and cyclooxygenase gene polymorphisms are not relevant in determining the prognosis of gastric adenocarcinoma. PMID:23029430

Imbalance between vascular endothelial growth factor and endostatin correlates with the prognosis of operable non-small cell lung cancer.

PubMed

Hu, Y; Hu, M-m; Shi, G-L; Han, Y; Li, B-L

2014-09-01

Angiogenesis is regulated by a balance of pro-angiogenic and anti-angiogenic factors. Vascular endothelial growth factor (VEGF) and endostatin respectively represents a frequent component of inducers and inhibitors in the process of angiogenesis. The ratio of VEGF/endostatin may reflect the balance of angiogenic switch. This study aimed to determine whether an imbalance between VEGF/endostatin exists in operable non-small cell lung cancer (NSCLC) patients and to assess the correlation, if any, between the imbalance and the prognosis. Preoperative serum levels of VEGF and endostatin were simultaneously determined by quantitiative enzyme-linked immunosorbent assay (ELISA) and the ratio of them was calculated among 98 NSCLC patients and 51 healthy controls. The relationship between these factors and clinicopathological features, including prognosis, was examined. The ratio of VEGF/endostatin levels was significantly higher in operable NSCLC patients [median, 10.4; interquartile range (IQR), 5.9-19.8] than in normal controls [median, 5.1; IQR, 3.3-9.7] (P = 0.002). While the ratio in patients who were still alive for more than 60 months was 8.3 (IQR, 4.3-17.9), the ratio in those who died was 12.9 (IQR, 8.0-22.1) (p = 0.017). In subgroup analysis of patients with pathological stage N0, there was a statistically significant increase of the survival time in the group with a lower ratio than in the group with a higher ratio (p = 0.032). Multivariate analysis confirmed that the VEGF/endostatin ratio was an independent prognostic factor (p = 0.018). There was an imbalance between VEGF and endostatin in serum of operable NSCLC patients. The imbalance correlated with the prognosis of operable NSCLC. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Increased expression of Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 correlated with poor prognosis of hepatocellular carcinoma.

PubMed

Yang, Lian-Yue; Tao, Yi-Ming; Ou, Di-Peng; Wang, Wei; Chang, Zhi-Gang; Wu, Fan

2006-10-01

Because of its role in cell migration, the Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) 2 has been implicated in cancer metastasis. Evidence to support such a role of WAVE2 in human cancer, however, is lacking. We thus examined the expression of WAVE2 in hepatocellular carcinoma (HCC) tissues to test whether the levels of WAVE2 expression correlated to the progression of HCC. Samples of 112 HCC patients were determined immunohistochemically for WAVE2 expression and the correlation of WAVE2 levels with prognosis was analyzed. Among the 112 cases, 31 paired HCC and paracarcinomatous liver tissue specimens were analyzed for WAVE2 levels by reverse transcription-PCR and Western blotting, respectively. Among 112 cases of HCCs, the immunohistochemistry data indicated significant increase of WAVE2 expression levels in 71 cases. Importantly, the increased WAVE2 expression correlated with the multiple tumor nodules (P = 0.008), the absence of capsular formation (P = 0.035), Edmondson-Steiner grade (P = 0.009), vein invasion (P = 0.023), and a shortened median survival time (326 versus 512 days; P = 0.003). Multivariable Cox regression analysis revealed the WAVE2 expression level was an independent factor for prognosis. The immunohistochemistry data were further confirmed by results of reverse transcription-PCR and Western analysis of 31 HCC cases, in which the WAVE2 mRNA and protein in HCC tissues were significantly elevated when compared with paracarcinomatous liver tissue (P < 0.001). WAVE2 expression is elevated in HCC tissues, which correlates with a poor prognosis, suggesting WAVE2 as a candidate prognostic marker of HCC.

Prognostic factors in patients with advanced renal cell carcinoma.

PubMed

Muriel López, Carolina; Esteban, Emilio; Berros, Jose Pablo; Pardo, Pablo; Astudillo, Aurora; Izquierdo, Marta; Crespo, Guillermo; Sanmamed, Miguel; Fonseca, Paula J; Martínez-Camblor, Pablo

2012-12-01

The purpose of this study was to evaluate prognostic factors in patients with RCC. The expression of several biomarkers were measured by immunohistochemistry (IHC), together with 2 analytic factors (thrombocytosis and neutrophilia), in 135 patients with advanced RCC treated with new targeted drugs (NTDs) (n = 67) and/or cytokines (CKs) (n = 68)-with 23 of the patients who received CKs also receiving NTDs-between July 1996 and February 2010. Relationships with overall survival (OS) and progression-free survival (PFS) were searched for. Univariate statistical analysis revealed that high expression of hypoxia-inducible factor-1α (HIF-1α) correlated with poor prognosis in NTD treatment (PFS, 5.4 vs. 13.5, low expression months; P = .033) and CK treatment (PFS, 3.3 vs. 5.7, low expression; P = .003). Overexpression of carbonic anhydrase IX (CAIX) was associated with better prognosis with NTD treatment (OS, 32.1 vs. 7.8 months; P < .001) and CK treatment (OS, 32.9 vs. 5.9 months; P = .001). Positive PTEN was related to good prognosis with sunitinib (PFS, 15.1 vs. 6.5 months; P = .003) and CKs (OS, 13.7 vs. 7.9 months; P = .039). Increased expression of p21 was related to poor prognosis with NTD treatment (PFS, 5.9 vs. 16.8 months; P = .024) and CK treatment (PFS, 3.9 vs. 7.5 months; P < .001) Thrombocytosis was related to poor prognosis with NTDs (OS, 15.9 vs. 26.7 months; P = .007) and CKs (OS, 5.9 vs. 14.3 months; P = .010). Neutrophilia was related to poor prognosis with NTDs (OS, 17.6 vs. 25.4 months; P = .063) and CKs (OS, 5.9 vs. 12.8 months; P = .035). Multivariate analysis revealed that overexpression of CAIX was a favorable prognostic factor independent of PFS (hazard ratio [HR], 0.107; P < .001) and OS (HR, 0.055; P < .001). HIF-1α, PTEN, p21, thrombocytosis, neutrophilia, and CAIX in particular are useful prognostic factors in patients with advanced RCC. Copyright © 2012 Elsevier Inc. All rights reserved.

Use of nitrates in ischemic heart disease.

PubMed

Giuseppe, Cocco; Paul, Jerie; Hans-Ulrich, Iselin

2015-01-01

Short-acting nitrates are beneficial in acute myocardial ischemia. However, many unresolved questions remain about the use of long-acting nitrates in stable ischemic heart disease. The use of long-acting nitrates is weakened by the development of endothelial dysfunction and tolerance. Also, we currently ignore whether lower doses of transdermal nitroglycerin would be better than those presently used. Multivariate analysis data from large nonrandomized studies suggested that long-acting nitrates increase the incidence of acute coronary syndromes, while data from another multivariate study indicate that they have positive effects. Because of methodological differences and open questions, the two studies cannot be compared. A study in Japanese patients with vasospastic angina has shown that, when compared with calcium antagonists, long-acting nitrates do not improve long-term prognosis and that the risk for cardiac adverse events increases with the combined therapy. We have many unanswered questions.

Fibulin-3 as a diagnostic biomarker in patients with malignant mesothelioma.

PubMed

Kaya, Halide; Demir, Melike; Taylan, Mahsuk; Sezgi, Cengizhan; Tanrikulu, Abdullah Cetin; Yilmaz, Sureyya; Bayram, Mehmet; Kaplan, Ibrahim; Senyigit, Abdurrahman

2015-01-01

New tumour biomarkers are being intensely investigated for malignant mesothelioma (MM). Fibulin-3 is produced in MM but its role remains uncertain. The aim of this study was to evaluate the validity of measuring serum fibulin-3 in the diagnosis and prognosis of MM. This prospective study was performed on 43 patients and 40 healthy controls who were admitted to our hospital between January 2012 and January 2014. Data from MM patients, including demographic and clinical features, routine laboratory data, levels of serum fibulin-3, and treatment outcomes were defined as potential prognostic factors. The receiver operating characteristic (ROC) curve for fibulin-3 was used to detect the cut-off value with highest sensitivity and specificity. Univariate survival analysis was performed using the Kaplan-Meier method in patients with MM. Afterwards, the possible factors identified with univariate analyses were entered into the cox regression analysis. Our results revealed that patients with MM had significantly higher serum levels of fibulin-3 than controls. The results showed that the best cut-off point was 36.6 ng/ml with an AUC (area under the curve)=0.976, sensitivity=93.0% and specificity=90.0. In our study, the initial significant poor prognostic factors were advanced stage, high white blood cell count, high platelet count, high C-reactive protein (p<0.05 for each variable). Later, according to multivariate analysis the results showed only advanced stage as significant parameter (p=0.040). We determined that real use for serum fibulin-3 was not for prognosis but for diagnosis in MM. Also advanced stage was associated with poor MM prognosis.

Element-based prognostics of occupational pneumoconiosis using micro-proton-induced X-ray emission analysis.

PubMed

He, Xiaodong; Shen, Hao; Chen, Zidan; Rong, Caicai; Ren, Minqin; Hou, Likun; Wu, Chunyan; Mao, Ling; Lu, Quan; Su, Bo

2017-12-01

Pneumoconiosis is an occupational disease accompanied by long-term lung impairment, for which prediction of prognosis is poorly understood because of the complexity of the inhaled particles. Micro-proton-induced X-ray emission (micro-PIXE) analysis, which is advantageous for high-sensitivity, two-dimensional element mapping of lung tissues, was used to investigate element-based predictive factors of prognosis in Chinese patients with welder's and coal miner's pneumoconiosis. Chest radiographs and lung function tests showed that most of the coal miners deteriorated, whereas symptoms in some welders were alleviated after 5 yr, as determined by comparing percent vital capacity (%VC) and forced expiratory volume in the 1st second over forced vital capacity (FEV1.0/FVC) to values taken at the initial diagnosis. Micro-PIXE analysis suggested that the most abundant particulates in welder's pneumoconiosis were Fe, Mn, and Ti (metallic oxide),which were accompanied by particulates containing Si, Al, and Ca (aluminum silicate) or only Si (SiO 2 ); the most abundant particulates in coal miner's pneumoconiosis were composed of C, Si, Al, K, and Ti, which were accompanied by particulates containing Ca or Fe. Particulates containing Al, Si, S, K, Ca, and Ti (orthoclase and anorthite) were correlated with severity of fibrosis. Multivariable linear regression suggested that long-term FEV1.0/FVC decrease was independently associated with Si and smoking index, whereas %VC decrease was associated with Si and Ti. A risk index comprised of these factors was developed to predict the prognosis of pneumoconiosis. Micro-PIXE analysis is feasible for the evaluation of elemental composition and dust exposure, especially for patients whose exposure is mixed or uncertain. Copyright © 2017 the American Physiological Society.

miR-125b-1 and miR-378a are predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer.

PubMed

Tanaka, Hironori; Hazama, Shoichi; Iida, Michihisa; Tsunedomi, Ryouichi; Takenouchi, Hiroko; Nakajima, Masao; Tokumitsu, Yukio; Kanekiyo, Shinsuke; Shindo, Yoshitaro; Tomochika, Shinobu; Tokuhisa, Yoshihiro; Sakamoto, Kazuhiko; Suzuki, Nobuaki; Takeda, Shigeru; Yamamoto, Shigeru; Yoshino, Shigefumi; Ueno, Tomio; Hamamoto, Yoshihiko; Fujita, Yusuke; Tanaka, Hiroaki; Tahara, Ko; Shimizu, Ryoichi; Okuno, Kiyotaka; Fujita, Koji; Kuroda, Masahiko; Nakamura, Yusuke; Nagano, Hiroaki

2017-11-01

Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of the present study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. First, we carried out microarray analysis of pretreatment cancer tissues in a phase I study, in which peptide vaccines alone were given. Candidate miRNAs were selected by comparison of the better prognosis group with the poorer prognosis group. Next, we conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Candidate miRNAs were further selected by a similar comparison of prognosis. Subsequently, we carried out reverse-transcription PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR-125b-1 in cancer cells (P = 0.040), and miR-378a in both cancer cells (P = 0.009) and stromal cells (P < 0.001). Multivariate analysis showed that expression of miR-378a in stromal cells was the best among the three predictors (HR, 2.730; 95% CI, 1.027-7.585; P = 0.044). In conclusion, miR-125b-1 and miR-378a expression might be considered as novel biomarkers to predict the efficacy of vaccine treatment against colorectal cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases.

PubMed

Rajput, Ashish B; Turbin, Dmitry A; Cheang, Maggie Cu; Voduc, David K; Leung, Sam; Gelmon, Karen A; Gilks, C Blake; Huntsman, David G

2008-01-01

We have previously demonstrated in a pilot study of 348 invasive breast cancers that mast cell (MC) infiltrates within primary breast cancers are associated with a good prognosis. Our aim was to verify this finding in a larger cohort of invasive breast cancer patients and examine the relationship between the presence of MCs and other clinical and pathological features. Clinically annotated tissue microarrays (TMAs) containing 4,444 cases were constructed and stained with c-Kit (CD-117) using standard immunoperoxidase techniques to identify and quantify MCs. For statistical analysis, we applied a split-sample validation technique. Breast cancer specific survival was analyzed by Kaplan-Meier [KM] method and log rank test was used to compare survival curves. Survival analysis by KM method showed that the presence of stromal MCs was a favourable prognostic factor in the training set (P = 0.001), and the validation set group (P = 0.006). X-tile plot generated to define the optimal number of MCs showed that the presence of any number of stromal MCs predicted good prognosis. Multivariate analysis showed that the MC effect in the training set (Hazard ratio [HR] = 0.804, 95% Confidence interval [CI], 0.653-0.991, P = 0.041) and validation set analysis (HR = 0.846, 95% CI, 0.683-1.049, P = 0.128) was independent of age, tumor grade, tumor size, lymph node, ER and Her2 status. This study concludes that stromal MC infiltration in invasive breast cancer is an independent good prognostic marker and reiterates the critical role of local inflammatory responses in breast cancer progression.

Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases

PubMed Central

Rajput, Ashish B.; Turbin, Dmitry A.; Cheang, Maggie CU; Voduc, David K.; Leung, Sam; Gelmon, Karen A.; Gilks, C. Blake

2007-01-01

Purpose We have previously demonstrated in a pilot study of 348 invasive breast cancers that mast cell (MC) infiltrates within primary breast cancers are associated with a good prognosis. Our aim was to verify this finding in a larger cohort of invasive breast cancer patients and examine the relationship between the presence of MCs and other clinical and pathological features. Experimental design Clinically annotated tissue microarrays (TMAs) containing 4,444 cases were constructed and stained with c-Kit (CD-117) using standard immunoperoxidase techniques to identify and quantify MCs. For statistical analysis, we applied a split-sample validation technique. Breast cancer specific survival was analyzed by Kaplan–Meier [KM] method and log rank test was used to compare survival curves. Results Survival analysis by KM method showed that the presence of stromal MCs was a favourable prognostic factor in the training set (P = 0.001), and the validation set group (P = 0.006). X-tile plot generated to define the optimal number of MCs showed that the presence of any number of stromal MCs predicted good prognosis. Multivariate analysis showed that the MC effect in the training set (Hazard ratio [HR] = 0.804, 95% Confidence interval [CI], 0.653–0.991, P = 0.041) and validation set analysis (HR = 0.846, 95% CI, 0.683–1.049, P = 0.128) was independent of age, tumor grade, tumor size, lymph node, ER and Her2 status. Conclusions This study concludes that stromal MC infiltration in invasive breast cancer is an independent good prognostic marker and reiterates the critical role of local inflammatory responses in breast cancer progression. PMID:17431762

Comparative evaluation of spectroscopic models using different multivariate statistical tools in a multicancer scenario

NASA Astrophysics Data System (ADS)

Ghanate, A. D.; Kothiwale, S.; Singh, S. P.; Bertrand, Dominique; Krishna, C. Murali

2011-02-01

Cancer is now recognized as one of the major causes of morbidity and mortality. Histopathological diagnosis, the gold standard, is shown to be subjective, time consuming, prone to interobserver disagreement, and often fails to predict prognosis. Optical spectroscopic methods are being contemplated as adjuncts or alternatives to conventional cancer diagnostics. The most important aspect of these approaches is their objectivity, and multivariate statistical tools play a major role in realizing it. However, rigorous evaluation of the robustness of spectral models is a prerequisite. The utility of Raman spectroscopy in the diagnosis of cancers has been well established. Until now, the specificity and applicability of spectral models have been evaluated for specific cancer types. In this study, we have evaluated the utility of spectroscopic models representing normal and malignant tissues of the breast, cervix, colon, larynx, and oral cavity in a broader perspective, using different multivariate tests. The limit test, which was used in our earlier study, gave high sensitivity but suffered from poor specificity. The performance of other methods such as factorial discriminant analysis and partial least square discriminant analysis are at par with more complex nonlinear methods such as decision trees, but they provide very little information about the classification model. This comparative study thus demonstrates not just the efficacy of Raman spectroscopic models but also the applicability and limitations of different multivariate tools for discrimination under complex conditions such as the multicancer scenario.

Positive peritoneal cytology at interval surgery is a poor prognostic factor in patients with stage T3c advanced ovarian carcinoma: A retrospective study.

PubMed

Nagasaka, Kazunori; Kawana, Kei; Tomio, Kensuke; Tsuruga, Tetsushi; Mori-Uchino, Mayuyo; Miura, Shiho; Tanikawa, Michihiro; Miyamoto, Yuichiro; Ikeda, Yuji; Sone, Kenbun; Adachi, Katsuyuki; Matsumoto, Yoko; Arimoto, Takahide; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

2015-05-01

The purpose of our study is to investigate clinically significant prognostic factors at the time of interval surgery (IS), comprising interval look surgery and interval debulking surgery, for T3c (International Federation of Gynecology and Obstetrics stage IIIc to IV) advanced ovarian cancer (AOC) patients during primary treatment. We reviewed records of patients with T3c AOC who underwent IS following neoadjuvant chemotherapy or up-front primary debulking surgery with adjuvant chemotherapy at our institution between January 1996 and December 2010. For analysis of prognostic factors, cytology of peritoneal exfoliative cells at IS was added to clinicopathological variables. A retrospective analysis was performed on 50 cases. The median age was 61.1 years (range, 38-78), with median follow-up of 45.9 months (range, 12-122). Macroscopic tumors were completely resected in 32 cases (64%) at IS. Univariate analyses of clinicopathological factors for IS identified preoperative serum cancer antigen-125 levels (≥20 IU/mL; P = 0.0539), number of residual lesions at IS (≥20; P = 0.0554), incomplete surgery at IS (P = 0.0171) and positive peritoneal cytology at IS (P = 0.0015) as significant factors for prognosis regarding progression-free survival (PFS). Multivariate analysis identified positive peritoneal cytology (P = 0.0303) as a unique independent predictor of poor prognosis in PFS. Positive peritoneal cytology at IS appears to be a significant factor for poor prognosis in PFS, which may provide useful information for post-IS chemotherapy planning. IS in the treatment of AOC may be useful for not only complete resection, but also for identification of patients with poor prognosis. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Inflammatory mediators in chronic heart failure in North India.

PubMed

Fedacko, Jan; Singh, Ram B; Gupta, Aditya; Hristova, Krasimira; Toda, Eri; Kumar, Adarsh; Saxena, Manoj; Baby, Anjum; Singh, Ranjana; Toru, Takahashi; Wilson, Douglas W

2014-08-01

Recent evidence shows that pro-inflammatory cytokines may be important in the assessment of severity and prognosis in congestive heart failure (CHF). In the present study, we examine the association of cytokines with causes, grade and prognosis of CHF patients. Of 127 patients with CHF, 11 were excluded and the remaining 116 patients with different aetiologies of CHF, and 250 age- and sex-matched control subjects, were evaluated in this case study. Severity of disease based on the New York Heart Association (NYHA) standards, fell within functional classes II to IV. The diagnosis of HF was based on clinical manifestations as well as on echocardiographic heart enlargement. Cytokines were measured by chemiluminescence. Causes of death were assessed based on death certificates. Multivariate logistic regression analysis was used to determine the risk factors of heart failure. Echocardiographic ejection fraction was 39.1 +/- 8.2% (mean +/- SD) in the study group indicating class II-IV heart failure. Laboratory data showed increase in biomarkers of oxidative stress, among HF patients compared to healthy subjects. Pro-inflammatory cytokines; IL-6 and TNF-alpha were significantly higher among HF patients compared to healthy subjects. TNF-alpha and IL-6, showed significant increase among patients with CHF due to ischaemic heart disease and cardiomyopathy compared to levels among CHF patients with valvular heart disease and hypertensive heart diseases. The levels of the cytokines were significantly higher among patients with class III and IV heart failure and those who died, compared to patients with class II heart failure. Multivariate logistic regression analysis revealed that CAD, cardiomyopathy, and IL-6 were strongly associated--and low ejection fraction and TNF-alpha--weakly associated with HF. Of 116 patients, 20 (17.2%) died during a follow-up of two years, and the deaths were mainly among NYHA class III and IV patients in whom the cause of CHF was CAD (10.9%) and cardiomyopathy (6.9%) which had greater levels of cytokines. The findings indicated that pro-inflammatory cytokines may be important indicators of causes, severity of CHF and prognosis among these patients.

Frequency and prognostic significance of additional cytogenetic abnormalities to the Philadelphia chromosome in young and older adults with acute lymphoblastic leukemia.

PubMed

Motlló, Cristina; Ribera, Josep-Maria; Morgades, Mireia; Granada, Isabel; Montesinos, Pau; Mercadal, Santiago; González-Campos, José; Moreno, María-José; Barba, Pere; Cervera, Marta; Barrios, Manuel; Novo, Andrés; Bernal, Teresa; Hernández-Rivas, Jesús-María; Abella, Eugenia; Amigo, María-Luz; Tormo, Mar; Martino, Rodrigo; Lavilla, Esperanza; Bergua, Juan; Serrano, Alfons; García-Belmonte, Daniel; Guàrdia, Ramon; Grau, Javier; Feliu, Evarist

2018-01-01

About 25-35% of adult patients with acute lymphoblastic leukemia show the Philadelphia (Ph) chromosome. Few series have evaluated the prognosis of additional cytogenetic alterations (ACA) to the Ph chromosome. We analyzed the frequency, type and prognostic significance ofACA in adults (18-60 years) treated in the ALL-Ph-08 trial. Fifty-two out of 74 patients (70%) showed ACA and 19 (26%) presented monosomies associated with t(9;22) (monosomal karyotype, MK). Similar complete response (CR) rate, CR duration, overall survival and event-free survival (EFS) were observed in patients with or without ACA, but patients with MK showed shorter CR duration and EFS than the remaining. On multivariate analysis, the only variable with prognostic impact for CR duration and EFS was the presence of MK (p = .003 and p = .036, respectively). Although ACA associated with the Ph chromosome are frequent, only monosomies were associated with poor prognosis in this group of patients.

Low Serum Interleukin-13 Levels Correlate with Poorer Prognoses for Colorectal Cancer Patients

PubMed Central

Saigusa, Susumu; Tanaka, Koji; Inoue, Yasuhiro; Toiyama, Yuji; Okugawa, Yoshinaga; Iwata, Takashi; Mohri, Yasuhiko; Kusunoki, Masato

2014-01-01

Interleukin-13 (IL-13) is an immunosuppressive cytokine produced by several immune cells and cancer cells. The aim of this retrospective study was to determine if serum IL-13 levels have an association with clinical outcome in patients with colorectal cancer. A total of 241 patients with colorectal cancer were enrolled in the present study. Preoperative serum IL-13 concentrations were measured by enzyme-linked immunosorbent assay. We analyzed the association of serum IL-13 levels with clinicopathological variables. Patients with lymph node metastasis, lymphatic invasion, vascular invasion, distant metastases or advanced stage of disease had significantly lower serum IL-13 levels. Low serum IL-13 was significantly associated with both poor recurrence-free and overall survival. Multivariate analysis showed that low IL-13 levels were an independent predictive marker for poor prognosis. In conclusion, our data suggest that low serum IL-13 levels may be a useful predictive marker for poor prognosis in colorectal cancer. PMID:24833143

Clinical applicability of Tokyo guidelines 2018/2013 in diagnosis and severity evaluation of acute cholangitis and determination of a new severity model.

PubMed

Gravito-Soares, Elisa; Gravito-Soares, Marta; Gomes, Dário; Almeida, Nuno; Tomé, Luís

2018-03-01

To determine the diagnostic accuracy of Tokyo guidelines (TG) 2018/2013 (TG18/TG13) and predictors of poor prognosis in acute cholangitis. Retrospective 1-year study of consecutive hospital admissions for acute cholangitis. Prognosis was defined in terms of 30 d in-hospital mortality. Of the 183 patients with acute cholangitis, diagnostic accuracy based on Charcot's triad, TG07 and TG18/TG13 was 67.8, 86.9 and 92.3% (p < .001), respectively. Regarding severity based on TG18/TG13, 30.6% of cases were severe. A poor prognosis was found in 10.9% of patients. After multivariate analysis, systolic blood pressure <90 mmHg (OR 11.010; p < .001), serum albumin <3 g/dL (OR 1.355; p = .006), active oncology disease (OR 3.818; p = .006) and malignant aetiology of obstructive jaundice (OR 2.224; p = .021) were independent predictors of poor prognosis. The discriminative ability of the model with these four variables was high (AUROC 0.842; p < .001), being superior to TG18/TG13 (AUROC 0.693; p = .005). TG18/TG13 showed high diagnostic accuracy in acute cholangitis. Compared with TG18/TG13, the simplified severity model ≥2 allows easy selection of patients who will benefit from admission to the intensive care unit and early biliary decompression.

EMMPRIN co-expressed with matrix metalloproteinases predicts poor prognosis in patients with osteosarcoma.

PubMed

Futamura, Naohisa; Nishida, Yoshihiro; Urakawa, Hiroshi; Kozawa, Eiji; Ikuta, Kunihiro; Hamada, Shunsuke; Ishiguro, Naoki

2014-06-01

Several studies have focused on the relationships between the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and the prognosis of patients with malignant tumors. However, few of these have investigated the expression of EMMPRIN in osteosarcoma. We examined expression levels of EMMPRIN immunohistochemically in 53 cases of high-grade osteosarcoma of the extremities and analyzed the correlation of its expression with patient prognosis. The correlation between matrix metalloproteinases (MMPs) and EMMPRIN expression and the prognostic value of co-expression were also analyzed. Staining positivity for EMMPRIN was negative in 7 cases, low in 17, moderate in 19, and strong in 10. The overall and disease-free survivals (OS and DFS) in patients with higher EMMPRIN expression (strong-moderate) were significantly lower than those in the lower (weak-negative) group (0.037 and 0.024, respectively). In multivariate analysis, age (P=0.004), location (P=0.046), and EMMPRIN expression (P=0.038) were significant prognostic factors for overall survival. EMMPRIN expression (P=0.024) was also a significant prognostic factor for disease-free survival. Co-expression analyses of EMMPRIN and MMPs revealed that strong co-expression of EMMPRIN and membrane-type 1 (MT1)-MMP had a poor prognostic value (P=0.056 for DFS, P=0.006 for OS). EMMPRIN expression and co-expression with MMPs well predict the prognosis of patients with extremity osteosarcoma, making EMMPRIN a possible therapeutic target in these patients.

B cells in tertiary lymphoid structures are associated with favorable prognosis in gastric cancer.

PubMed

Sakimura, Chie; Tanaka, Hiroaki; Okuno, Takahiro; Hiramatsu, Soichiro; Muguruma, Kazuya; Hirakawa, Kosei; Wanibuchi, Hideki; Ohira, Masaichi

2017-07-01

The role of tumor-infiltrating B cells in the tumor microenvironment is still unclear. Recent studies have reported that B cells and tertiary lymphoid structures (TLSs) that contain B cell follicles correlate with the favorable prognosis of cancer patients. The aim of this study was to investigate the association between tumor-infiltrating B cells and clinicopathological features in gastric cancer. Tumor blocks were obtained from 226 patients with stage Ib to stage IV gastric cancer. The density of CD20 + B cells within the tumor and in the invasive margin area was assessed using immunohistochemistry. We also evaluated CD3 + T cells, CD21 + follicular dendritic cells, Bcl6 + germinal center B cells, and PNAd + high endothelial venules to show the presence of TLSs. Tumor-infiltrating B cells were mostly organized as clusters that were surrounded by CD3 + T cells. The B cell area contained follicular dendritic cells and some clusters contained Bcl6 + B cells. High endothelial venules were present around follicles. We identified these follicles as TLSs. A high number of CD20 + B cells were associated with significantly better overall survival, and multivariate analysis also showed that CD20 high was one of the independent predictors of prognosis. In addition, there was a significant correlation between CD20 + B cell and CD8 + T cell infiltration. B cells mostly infiltrated tumors as TLSs and were associated with better prognosis in patients with gastric cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute liver failure caused by hepatitis E virus genotype 3 and 4: A systematic review and pooled analysis.

PubMed

Haffar, Samir; Shalimar; Kaur, Ravinder J; Wang, Zhen; Prokop, Larry J; Murad, Mohammad H; Bazerbachi, Fateh

2018-04-19

Acute liver failure caused by hepatitis E virus genotype 3 and 4 has been rarely described. Because of the presence of a short golden therapeutic window in patients with viral acute liver failure from other causes, it is possible that early recognition and treatment might reduce the morbidity and mortality. We performed a systematic review and pooled analysis of acute liver failure caused by hepatitis E virus genotype 3 and 4. Two reviewers appraised studies after searching multiple databases on June 12th, 2017. Appropriate tests were used to compare hepatitis E virus genotype 3 vs 4, suspected vs confirmed genotypes, hepatitis E virus-RNA positive vs negative, and to discern important mortality risk factors. We identified 65 patients, with median age 58 years (range: 3-79), and a male to female ratio of 1.2:1. The median bilirubin, ALT, AST and alkaline phosphatase (expressed by multiplication of the upper limit of normal) levels were 14.8, 45.3, 34.8 and 1.63 respectively. Antihepatitis E virus IgG, antihepatitis E virus IgM and hepatitis E virus-RNA were positive in 84%, 91% and 86% of patients respectively. The median interval from symptoms onset to acute liver failure was 23 days, and 16 patients underwent liver transplantation. Final outcome was reported in 58 patients and mortality was 46%. Age was a predictor of poor prognosis in multivariate analysis. No important differences were found between patients infected with genotype 3 vs 4, patients with confirmed vs suspected genotypes, or patients with positive vs negative RNA. Acute liver failure caused by hepatitis E virus genotype 3 and 4 is rare, similar between genotypes, occurs commonly in middle-aged/elderly patients and has a very high mortality. Age is predictive of poor prognosis in multivariate analysis. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

TROP2 correlates with microvessel density and poor prognosis in hilar cholangiocarcinoma.

PubMed

Ning, Shanglei; Guo, Sen; Xie, Jianjun; Xu, Yunfei; Lu, Xiaofei; Chen, Yuxin

2013-02-01

Trophoblast cell surface antigen 2 (TROP2) was found to be associated with tumor progression and poor prognosis in a variety of epithelial carcinomas. The aim of the study was to investigate TROP2 expression and its prognostic impact in hilar cholangiocarcinoma. Immunohistochemistry and quantitative real-time PCR were used to determine TROP2 expression in surgical specimens from 70 hilar cholangiocarcinoma patients receiving radical resection. The relationship between TROP2 expression and microvessel density was investigated and standard statistical analysis was used to evaluate TROP2 prognosis significance in hilar cholangiocarcinoma. High TROP2 expression by immunohistochemistry was found in 43 (61.4 %) of the 70 tumor specimens. Quantitative real-time PCR confirmed that TROP2 level in tumor was significantly higher than in non-tumoral biliary tissues (P = 0.001). Significant correlations were found between TROP2 expression and histological differentiation (P = 0.016) and tumor T stage (P = 0.031) in hilar cholangiocarcinoma. TROP2 expression correlated with microvessel density in hilar cholangiocarcinoma (P = 0.026). High TROP2 expression patients had a significantly poorer overall survival rate than those with low TROP2 expression (30 vs. 68.5 %, P = 0.001), and multivariate Cox regression analysis indicated TROP2 as an independent prognostic factor for hilar cholangiocarcinoma (P = 0.004). TROP2 expression correlates with microvessel density significantly and is an independent prognostic factor in human hilar cholangiocarcinoma.

Resection line involvement after gastric cancer surgery: clinical outcome in nonsurgically retreated patients.

PubMed

Morgagni, P; Garcea, D; Marrelli, D; De Manzoni, G; Natalini, G; Kurihara, H; Marchet, A; Saragoni, L; Scarpi, E; Pedrazzani, C; Di Leo, A; De Santis, F; Panizzo, V; Nitti, D; Roviello, F

2008-12-01

Resection line infiltration (RLI) after surgical treatment represents an unfavorable prognostic factor in advanced gastric cancer. We performed a retrospective analysis of 89 patients with resection line involvement who did not undergo reoperation. On behalf of the Italian Research Group for Gastric Cancer, we present the characteristics and outcome of 89 patients who were submitted to surgical resection for gastric cancer from 1988 to 2001 and did not undergo reoperation because of disease extension or associated pathologies. RLI was significantly higher in patients with T4 tumors and diffuse histological type. Anastomotic leakages were observed in 4.8% of infiltrated esophageal resection margins, whereas 1.9% of infiltrated duodenal resection lines showed duodenal fistulas. Five-year overall survival of patients with RLI was 29%. Prognosis was not affected by RLI in early forms (100% 5-year survival); however, 5-year survival in T2 and T3 stages was significantly lower with respect to the same stages without residual tumor. The influence of RLI on prognosis was confirmed in N0 as well as in N1 and N2 patients. RLI also was an independent prognostic at multivariate analysis (odds ratio = 1.5; 95% confidence interval, 1.08-2.08; P = 0.0144). RLI significantly affects long-term survival of advanced gastric cancer. The impact on prognosis is independent of lymph node involvement. Patients in good general condition for whom radical surgery is possible should be considered for reoperation.

Value of sentinel lymph node biopsy and adjuvant interferon treatment in thick (>4 mm) cutaneous melanoma: an observational study.

PubMed

Morera-Sendra, Natalia; Tejera-Vaquerizo, Antonio; Traves, Víctor; Requena, Celia; Bolumar, Isidro; Pla, Angel; Vázquez, Carlos; Soriano, Virtudes; Nagore, Eduardo

2016-01-01

The role of sentinel lymph node biopsy and the benefit of immunotherapy with interferon in thick (>4 mm) melanomas remain uncertain. Our aim was to assess the value of both sentinel lymph node (SLN) biopsy and immunotherapy in the prognosis of thick melanomas. A retrospective study based on a computerized patient database in which patients have been prospectively collected since 2005 was performed. Age, sex, location, Breslow thickness, tumor ulceration, regression, Clark level, tumor infiltrating lymphocytes, tumor mitotic rate, microscopic satellite and vascular invasion were included in the analysis. Disease-free (DFS), disease-specific (DSS) and overall (OS) survivals were evaluated by the Kaplan-Meier method and Cox regression analysis. A series of 141 patients with melanomas thicker than 4 mm were included. Multivariate regression showed a worse prognosis in SLN-positive patients with respect to SLN biopsy-negative patients (DFS, hazard ratio [HR] 2, p = 0.04; DSS, HR 2.2, p = 0.002; OS, HR 2.4, p = 0.02). The observational group was shown to have a worse prognosis than the SLN-positive group but was very similar to the clinically positive group. Immunotherapy with high-dose interferon showed a protective effect (DFS, HR 0.5, p = 0.02; DSS, HR 0.3, p = 0.001; OS, HR 0.3, p = 0.001). Our data indicate that SLN biopsy and adjuvant interferon should be considered for patients with thick melanomas.

Polymorphisms of EpCAM gene and prognosis for non-small-cell lung cancer in Han Chinese

PubMed Central

Yang, Yuefan; Fei, Fei; Song, Yang; Li, Xiaofei; Zhang, Zhipei; Fei, Zhou; Su, Haichuan; Wan, Shaogui

2014-01-01

The epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety of human cancers and is associated with patient prognosis, including those with lung cancer. However, the association of single nucleotide polymorphisms (SNPs) in the EpCAM gene with the prognosis for non-small-cell lung cancer (NSCLC) patients has never been investigated. We evaluated the association between two SNPs, rs1126497 and rs1421, in the EpCAM gene and clinical outcomes in a Chinese cohort of 506 NSCLC patients. The SNPs were genotyped using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards model and Kaplan–Meier curves were used to assess the association of EpCAM gene genotypes with the prognosis of NSCLC. We found that the non-synonymous SNP rs1126497 was significantly associated with survival. Compared with the CC genotype, the CT+TT genotype was a risk factor for both death (hazard ratio, 1.40; 95% confidence interval [CI], 1.02–1.94; P = 0.040) and recurrence (hazard ratio, 1.34; 95% CI, 1.02–1.77; P = 0.039). However, the SNP rs1421 did not show any significant effect on patient prognosis. Instead, the AG+GG genotype in rs1421 was significantly associated with early T stages (T1/T2) when compared with the AA genotype (odds ratio for late stage = 0.65; 95% CI, 0.44–0.96, P = 0.029). Further stratified analysis showed notable modulating effects of clinical characteristics on the associations between variant genotypes of rs1126497 and NSCLC outcomes. In conclusion, our study indicated that the non-synonymous SNP rs1126497 may be a potential prognostic marker for NSCLC patients. PMID:24304228

FIB-4 index for assessing the prognosis of hepatocellular carcinoma in patients with Child-Pugh class A liver function.

PubMed

Ito, Takanori; Kumada, Takashi; Toyoda, Hidenori; Tada, Toshifumi

2015-07-01

We evaluated the prognosis of hepatocellular carcinoma (HCC) patients with Child-Pugh (C-P) class A based on FIB-4 index, which is a liver fibrosis marker. A total of 915 HCC patients with C-P class A were investigated. We assessed the prognosis using FIB-4 index, and factors associated with survival rates were analyzed in these patients. When patients were categorized according to FIB-4 index as <2.0 (n = 93), ≥ 2.0 and <4.0 (n = 311), and ≥ 4.0 (n = 511), survival rates at 5 years were 70.5% [95% confidence interval (CI) 59.0-79.9], 56.4% (95% CI 50.1-62.5), and 47.1% (95% CI 42.2-52.1), respectively. Patients with FIB-4 index <2.0 had a higher survival rate than the other groups (≥ 4.0 vs ≥ 2.0 and <4.0, p = 0.010; ≥ 2.0 and <4.0 vs <2.0, p = 0.028). We were able to predict prognosis in patients with C-P score 5 by FIB-4 index, but survival rate did not significantly differ in patients with C-P score 6. Multivariate analysis identified C-P score, FIB-4 index [≥ 2.0 and <4.0; hazard ratios (HRs) 1.638 (95% CI 1.084-2.474); p = 0.019/≥ 4.0; HR 1.828 (95% CI 1.217-2.744); p = 0.004], Lens culinaris agglutinin-reactive α-fetoprotein, tumor size, number, vascular invasion, antiviral therapy, and hepatectomy as independent predictive factors for survival. The FIB-4 index is useful for assessing prognosis in HCC patients with C-P class A, especially those with C-P score 5.

The effects of gene polymorphisms on glioma prognosis.

PubMed

Cui, Ying; Li, Guolin; Yan, Mengdan; Li, Jing; Jin, Tianbo; Li, Shanqu; Mu, Shijie

2017-11-01

Malignant gliomas are the most common primary brain tumors. Various genetic factors play important roles in the development and prognosis of glioma. The present study focuses on the impact of MPHOSPH6, TNIP1 and several other genes (ACYP2, NAF1, TERC, TERT, OBFC1, ZNF208 and RTEL1) on telomere length and how this affects the prognosis of glioma. Forty-three polymorphisms in nine genes from 605 glioma patients were selected. The association between genotype and survival outcome was analyzed using the Kaplan-Meier method, Cox regression analysis and the log-rank test. The 1-year overall survival (OS) rates of patients younger than 40 years of age was higher compared to those in patients older than 40 years of age. The 1-year OS rate of patients who underwent total resection was higher than that of patients whose gliomas were not completely resected. The 1-year OS rates of patients undergoing chemotherapy and of patients who did not undergo chemotherapy were 39.90% and 26.80%, respectively. Univariate analyses showed that ACYP2 rs12615793 and TERT rs2853676 loci affected progression-free survival in glioma patients; both ZNF208 rs8105767 and ACYP2 rs843720 affected the OS of patients with low-grade gliomas. Multivariate analyses suggested that MPHOSPH6 rs1056629 and rs1056654, and TERT rs2853676 loci were associated with good prognoses of patients with glioma or high-grade gliomas, whereas ZNF208 rs8105767 was associated with good prognosis of patients with low-grade glioma. Age, surgical resection and chemotherapy influenced the survival rates of glioma patients. TERT, MPHOSPH6, ACYP2 and ZNF208 genes were found to affect glioma prognosis. Copyright © 2017 John Wiley & Sons, Ltd.

The prognostic role of tumor size in early breast cancer in the era of molecular biology.

PubMed

Kasangian, Anaid Anna; Gherardi, Giorgio; Biagioli, Elena; Torri, Valter; Moretti, Anna; Bernardin, Elena; Cordovana, Andrea; Farina, Gabriella; Bramati, Annalisa; Piva, Sheila; Dazzani, Maria Chiara; Paternò, Emanuela; La Verde, Nicla Maria

2017-01-01

The prognosis of early breast cancer (EBC) depends on patient and tumor characteristics. The association between tumor size, the largest diameter in TNM staging, and prognosis is well recognized. According to TNM, tumors classified as T2, could have very different volumes; e.g. a tumor of 2.1 cm has a volume of 4500 mm3, while a tumor of 4.9 cm has a volume of 60.000 mm3 even belonging to the same class. The aim of the study is to establish if the prognostic role of tumor size, expressed as diameter and volume, has been overshadowed by other factors. The primary objective is to evaluate the association between tumor dimensions and overall survival (OS) / disease free survival (DFS), in our institution from January 1st 2005 to September 30th 2013 in a surgical T1-T2 population. Volume was evaluated with the measurement of three half-diameters of the tumor (a, b and c), and calculated using the following formula: 4/3π x a x b x c. 341 patients with T1-T2 EBC were included. 86.5% were treated with conservative surgery. 85.1% had a Luminal subtype, 9.1% were Triple negative and 7.4% were HER2 positive. Median volume was 942 mm3 (range 0.52-31.651.2). 44 patients (12.9%) relapsed and 23 patients died. With a median follow-up of 6.5 years, the univariate analysis for DFS showed an association between age, tumor size, volume, histological grading and molecular subtype. The multivariate analysis confirmed the statistically significant association only for molecular subtype (p 0.005), with a worse prognosis for Triple negative and HER2 positive subtypes compared with Luminal (HR: 2.65; 95%CI: 1.34-5.22). Likewise for OS, an association was shown by the multivariate analysis solely for molecular subtype (HER2 and Triple negative vs. Luminal. HR: 2.83; 95% CI:1.46-5.49; p 0.002). In our study, the only parameter that strongly influences survival is molecular subtype. These findings encourage clinicians to choose adjuvant treatment not based on dimensional criteria but on biological features.

Seven protective miRNA signatures for prognosis of cervical cancer.

PubMed

Liu, Bei; Ding, Jin-Feng; Luo, Jian; Lu, Li; Yang, Fen; Tan, Xiao-Dong

2016-08-30

Cervical cancer is the second cause of cancer death in females in their 20s and 30s, but there were limited studies about its prognosis. This study aims to identify miRNA related to prognosis and study their functions. TCGA data of patients with cervical cancer were used to build univariate Cox's model with single clinical parameter or miRNA expression level. Multivariate Cox's model was built using both clinical information and miRNA expression levels. At last, STRING was used to enrich gene ontology or pathway for validated targets of significant miRNAs, and visualize the interactions among them. Using univariate Cox's model with clinical parameters, we found that two clinical parameters, tobacco use and clinical stage, and seven miRNAs were highly correlated with the survival status. Only using the expression level of miRNA signatures, the model could separate patients into high-risk and low-risk groups successfully. An optimal feature-selected model was proposed based on two clinical parameters and seven miRNAs. Functional analysis of these seven miRNAs showed they were associated to various pathways related to cancer, including MAPK, VEGF and P53 pathways. These results helped the research of identifying targets for targeted therapy which could potentially allow tailoring of treatment for cervical cancer patients.

A four-gene signature predicts survival in clear-cell renal-cell carcinoma.

PubMed

Dai, Jun; Lu, Yuchao; Wang, Jinyu; Yang, Lili; Han, Yingyan; Wang, Ying; Yan, Dan; Ruan, Qiurong; Wang, Shaogang

2016-12-13

Clear-cell renal-cell carcinoma (ccRCC) is the most common pathological subtype of renal cell carcinoma (RCC), accounting for about 80% of RCC. In order to find potential prognostic biomarkers in ccRCC, we presented a four-gene signature to evaluate the prognosis of ccRCC. SurvExpress and immunohistochemical (IHC) staining of tissue microarrays were used to analyze the association between the four genes and the prognosis of ccRCC. Data from TCGA dataset revealed a prognostic prompt function of the four genes (PTEN, PIK3C2A, ITPA and BCL3). Further discovery suggested that the four-gene signature predicted survival better than any of the four genes alone. Moreover, IHC staining demonstrated a consistent result with TCGA, indicating that the signature was an independent prognostic factor of survival in ccRCC. Univariate and multivariate Cox proportional hazard regression analysis were conducted to verify the association of clinicopathological variables and the four genes' expression levels with survival. The results further testified that the risk (four-gene signature) was an independent prognostic factors of both Overall Survival (OS) and Disease-free Survival (DFS) (P<0.05). In conclusion, the four-gene signature was correlated with the survival of ccRCC, and therefore, may help to provide significant clinical implications for predicting the prognosis of patients.

Sudden sensorineural hearing loss: is there a relationship between routine haematological parameters and audiogram shapes?

PubMed

Salvago, Pietro; Rizzo, Serena; Bianco, Antonino; Martines, Francesco

2017-03-01

To investigate the relationship between haematological routine parameters and audiogram shapes in patients affected by sudden sensorineural hearing loss (SSNHL). A retrospective study. All patients were divided into four groups according to the audiometric curve and mean values of haematological parameters (haemoglobin, white blood cell, neutrophils and lymphocytes relative count, platelet count, haematocrit, prothrombin time, activated partial thromboplastin time, fibrinogen and neutrophil-to-lymphocite ratio) of each group were statistically compared. The prognostic role of blood profile and coagulation test was also examined. A cohort of 183 SSNHL patients without comorbidities. With a 48.78% of complete hearing recovery, individuals affected by upsloping hearing loss presented a better prognosis instead of flat (18.36%), downsloping (19.23%) and anacusis (2.45%) groups (p = 0.0001). The multivariate analysis of complete blood count values revealed lower mean percentage of lymphocytes (p = 0.041) and higher platelet levels (p = 0.015) in case of downsloping hearing loss; with the exception of fibrinogen (p = 0.041), none of the main haematological parameters studied resulted associated with poorer prognosis. Our work suggested a lack of association between haematological parameters and a defined audiometric picture in SSNHL patients; furthermore, only fibrinogen seems to influence the prognosis of this disease.

Downregulated SASH1 expression indicates poor clinical prognosis in gastric cancer.

PubMed

Zhou, Nan; Liu, Can; Wang, Xudong; Mao, Qinsheng; Jin, Qin; Li, Peng

2018-04-01

SASH1 (SAM- and SH3-domain containing 1), a novel candidate tumor suppressor, has attracted attention due to its role in intracellular signal transduction and its tumor prognostic value in diverse cancers. Reports have demonstrated that reduced SASH1 expression correlates with tumor proliferation, invasion, and metastasis. However, the expression and prognostic significance of SASH1 in gastric cancer (GC) remain unclear. In this study, 8 paired fresh-frozen GC tissues and corresponding gastric mucosal tissues were examined by Western blot to analyze the protein expression of SASH1. Seven hundred twenty-six formalin-fixed, paraffin-embedded (FFPE) gastric tissue samples were evaluated by immunohistochemical (IHC) to determine the correlations of SASH1 expression with clinicopathological factors and prognosis. Compared with adjacent noncancerous tissues, SASH1 was significantly downregulated in GC specimens. Analysis using the χ 2 test revealed that low SASH1 expression was significantly associated with advanced TNM stage (P < .001) in GC. Cox regression multivariable analyses demonstrated that SASH1 expression (P < .001), TNM stage (P < .001), preoperative CEA level (P = .003) and preoperative CA19-9 level (P = .002) were independent prognostic factors. Our clinical findings suggest that downregulated SASH1 expression could be used as an independent biomarker for poor prognosis in GC. Copyright © 2018. Published by Elsevier Inc.

Prognostic Significance of Solid and Micropapillary Components in Invasive Lung Adenocarcinomas Measuring ≤3 cm.

PubMed

Matsuoka, Yuki; Yurugi, Yohei; Takagi, Yuzo; Wakahara, Makoto; Kubouchi, Yasuaki; Sakabe, Tomohiko; Haruki, Tomohiro; Araki, Kunio; Taniguchi, Yuji; Nakamura, Hiroshige; Umekita, Yoshihisa

2016-09-01

We aimed to analyze the clinical impact of solid and micropapillary components in a series of Japanese patients resected for ≤3 cm lung adenocarcinoma. A total of 115 patients with ≤3 cm lung adenocarcinomas were reviewed and classified according to the American Thoracic Society and the European Respiratory Society classification. The presence of solid (S+) or micropapillary component (MP+) was defined when the component constituted ≥1% of the entire tumor. The impact of these components on disease-free (DFS) and disease-specific (DSS) survival was analyzed. Thirty (26.1%) cases with S+ and 27 (23.5%) with MP+ were identified, and multivariate analysis indicated that S+ status significantly reduced the duration of DFS and DSS. In 86 patients of acinar- and papillary-predominant subgroups, S+ and/or MP+ had the most significant effect on DFS and DSS by multivariate analysis. S+ and/or MP+ status predict worse prognosis in patients with acinar- and papillary-predominant lung adenocarcinoma. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Modified Glasgow Prognostic Score is Associated With Risk of Recurrence in Bladder Cancer Patients After Radical Cystectomy: A Multicenter Experience.

PubMed

Ferro, Matteo; De Cobelli, Ottavio; Buonerba, Carlo; Di Lorenzo, Giuseppe; Capece, Marco; Bruzzese, Dario; Autorino, Riccardo; Bottero, Danilo; Cioffi, Antonio; Matei, Deliu Victor; Caraglia, Michele; Borghesi, Marco; De Berardinis, Ettore; Busetto, Gian Maria; Giovannone, Riccardo; Lucarelli, Giuseppe; Ditonno, Pasquale; Perdonà, Sisto; Bove, Pierluigi; Castaldo, Luigi; Hurle, Rodolfo; Musi, Gennaro; Brescia, Antonio; Olivieri, Michele; Cimmino, Amelia; Altieri, Vincenzo; Damiano, Rocco; Cantiello, Francesco; Serretta, Vincenzo; De Placido, Sabino; Mirone, Vincenzo; Sonpavde, Guru; Terracciano, Daniela

2015-10-01

Recently, many studies explored the role of inflammation parameters in the prognosis of urinary cancers, but the results were not consistent. The modified Glasgow Prognostic Score (mGPS), a systemic inflammation marker, is a prognostic marker in various types of cancers. The aim of the present study was to investigate the usefulness of the preoperative mGPS as predictor of recurrence-free (RFS), overall (OS), and cancer-specific (CSS) survivals in a large cohort of urothelial bladder cancer (UBC) patients.A total of 1037 patients with UBC were included in this study with a median follow-up of 22 months (range 3-60 months). An mGPS = 0 was observed in 646 patients (62.3%), mGPS = 1 in 297 patients (28.6 %), and mGPS = 2 in 94 patients (9.1%).In our study cohort, subjects with an mGPS equal to 2 had a significantly shorter median RFS compared with subjects with mGPS equal to 1 (16 vs 19 months, hazard ratio [HR] 1.54, 95% CI 1.31-1.81, P < 0.001) or with subjects with mGPS equal to 0 (16 vs 29 months, HR 2.38, 95% CI 1.86-3.05, P < 0.001). The association between mGPS and RFS was confirmed by weighted multivariate Cox model. Although in univariate analysis higher mGPS was associated with lower OS and CSS, this association disappeared in multivariate analysis where only the presence of lymph node-positive bladder cancer and T4 stage were predictors of worse prognosis for OS and CSS.In conclusion, the mGPS is an easily measured and inexpensive prognostic marker that was significantly associated with RFS in UBC patients.

Modified Glasgow Prognostic Score is Associated With Risk of Recurrence in Bladder Cancer Patients After Radical Cystectomy

PubMed Central

Ferro, Matteo; De Cobelli, Ottavio; Buonerba, Carlo; Di Lorenzo, Giuseppe; Capece, Marco; Bruzzese, Dario; Autorino, Riccardo; Bottero, Danilo; Cioffi, Antonio; Matei, Deliu Victor; Caraglia, Michele; Borghesi, Marco; De Berardinis, Ettore; Busetto, Gian Maria; Giovannone, Riccardo; Lucarelli, Giuseppe; Ditonno, Pasquale; Perdonà, Sisto; Bove, Pierluigi; Castaldo, Luigi; Hurle, Rodolfo; Musi, Gennaro; Brescia, Antonio; Olivieri, Michele; Cimmino, Amelia; Altieri, Vincenzo; Damiano, Rocco; Cantiello, Francesco; Serretta, Vincenzo; De Placido, Sabino; Mirone, Vincenzo; Sonpavde, Guru; Terracciano, Daniela

2015-01-01

Abstract Recently, many studies explored the role of inflammation parameters in the prognosis of urinary cancers, but the results were not consistent. The modified Glasgow Prognostic Score (mGPS), a systemic inflammation marker, is a prognostic marker in various types of cancers. The aim of the present study was to investigate the usefulness of the preoperative mGPS as predictor of recurrence-free (RFS), overall (OS), and cancer-specific (CSS) survivals in a large cohort of urothelial bladder cancer (UBC) patients. A total of 1037 patients with UBC were included in this study with a median follow-up of 22 months (range 3–60 months). An mGPS = 0 was observed in 646 patients (62.3%), mGPS = 1 in 297 patients (28.6 %), and mGPS = 2 in 94 patients (9.1%). In our study cohort, subjects with an mGPS equal to 2 had a significantly shorter median RFS compared with subjects with mGPS equal to 1 (16 vs 19 months, hazard ratio [HR] 1.54, 95% CI 1.31–1.81, P < 0.001) or with subjects with mGPS equal to 0 (16 vs 29 months, HR 2.38, 95% CI 1.86–3.05, P < 0.001). The association between mGPS and RFS was confirmed by weighted multivariate Cox model. Although in univariate analysis higher mGPS was associated with lower OS and CSS, this association disappeared in multivariate analysis where only the presence of lymph node-positive bladder cancer and T4 stage were predictors of worse prognosis for OS and CSS. In conclusion, the mGPS is an easily measured and inexpensive prognostic marker that was significantly associated with RFS in UBC patients. PMID:26496339

Cancer Treatment in Patients With HIV Infection and Non-AIDS-Defining Cancers: A Survey of US Oncologists.

PubMed

Suneja, Gita; Boyer, Matthew; Yehia, Baligh R; Shiels, Meredith S; Engels, Eric A; Bekelman, Justin E; Long, Judith A

2015-05-01

HIV-infected individuals with non-AIDS-defining cancers are less likely to receive cancer treatment compared with uninfected individuals. We sought to identify provider-level factors influencing the delivery of oncology care to HIV-infected patients. A survey was mailed to 500 randomly selected US medical and radiation oncologists. The primary outcome was delivery of standard treatment, assessed by responses to three specialty-specific management questions. We used the χ(2) test to evaluate associations between delivery of standard treatment, provider demographics, and perceptions of HIV-infected individuals. Multivariable logistic regression identified associations using factor analysis to combine several correlated survey questions. Our response rate was 60%; 69% of respondents felt that available cancer management guidelines were insufficient for the care of HIV-infected patients with cancer; 45% never or rarely discussed their cancer management plan with an HIV specialist; 20% and 15% of providers were not comfortable discussing cancer treatment adverse effects and prognosis with their HIV-infected patients with cancer, respectively; 79% indicated that they would provide standard cancer treatment to HIV-infected patients. In multivariable analysis, physicians comfortable discussing adverse effects and prognosis were more likely to provide standard cancer treatment (adjusted odds ratio, 1.52; 95% CI, 1.12 to 2.07). Physicians with concerns about toxicity and efficacy of treatment were significantly less likely to provide standard cancer treatment (adjusted odds ratio, 0.67; 95% CI, 0.53 to 0.85). Provider-level factors are associated with delivery of nonstandard cancer treatment to HIV-infected patients. Policy change, provider education, and multidisciplinary collaboration are needed to improve access to cancer treatment. Copyright © 2015 by American Society of Clinical Oncology.

HR-MAS MR Spectroscopy of Breast Cancer Tissue Obtained with Core Needle Biopsy: Correlation with Prognostic Factors

PubMed Central

Choi, Ji Soo; Baek, Hyeon-Man; Kim, Suhkmann; Kim, Min Jung; Youk, Ji Hyun; Moon, Hee Jung; Kim, Eun-Kyung; Han, Kyung Hwa; Kim, Dong-hyun; Kim, Seung Il; Koo, Ja Seung

2012-01-01

The purpose of this study was to examine the correlation between high-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopy using core needle biopsy (CNB) specimens and histologic prognostic factors currently used in breast cancer patients. After institutional review board approval and informed consent were obtained for this study, CNB specimens were collected from 36 malignant lesions in 34 patients. Concentrations and metabolic ratios of various choline metabolites were estimated by HR-MAS MR spectroscopy using CNB specimens. HR-MAS spectroscopic values were compared according to histopathologic variables [tumor size, lymph node metastasis, histologic grade, status of estrogens receptor (ER), progesterone receptor (PR), HER2 (a receptor for human epidermal growth factor), and Ki-67, and triple negativity]. Multivariate analysis was performed with Orthogonal Projections to Latent Structure-Discriminant Analysis (OPLS-DA). HR-MAS MR spectroscopy quantified and discriminated choline metabolites in all CNB specimens of the 36 breast cancers. Several metabolite markers [free choline (Cho), phosphocholine (PC), creatine (Cr), taurine, myo-inositol, scyllo-inositol, total choline (tCho), glycine, Cho/Cr, tCho/Cr, PC/Cr] on HR-MAS MR spectroscopy were found to correlate with histologic prognostic factors [ER, PR, HER2, histologic grade, triple negativity, Ki-67, poor prognosis]. OPLS-DA multivariate models were generally able to discriminate the status of histologic prognostic factors (ER, PR, HER2, Ki-67) and prognosis groups. Our study suggests that HR-MAS MR spectroscopy using CNB specimens can predict tumor aggressiveness prior to surgery in breast cancer patients. In addition, it may be helpful in the detection of reliable markers for breast cancer characterization. PMID:23272149

Prognostic factors and survival according to tumour subtype in women presenting with breast cancer brain metastases at initial diagnosis.

PubMed

Leone, José Pablo; Leone, Julieta; Zwenger, Ariel Osvaldo; Iturbe, Julián; Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro

2017-03-01

The presence of brain metastases at the time of initial breast cancer diagnosis (BMIBCD) is uncommon. Hence, the prognostic assessment and management of these patients is very challenging. The aim of this study was to analyse the influence of tumour subtype compared with other prognostic factors in the survival of patients with BMIBCD. We evaluated women with BMIBCD, reported to Surveillance, Epidemiology and End Results program from 2010 to 2013. Patients with other primary malignancy were excluded. Univariate and multivariate analyses were performed to determine the effects of each variable on overall survival (OS). We included 740 patients. Median OS for the whole population was 10 months, and 20.7% of patients were alive at 36 months. Tumour subtype distribution was: 46.6% hormone receptor (HR)+/HER2-, 17% HR+/HER2+, 14.1% HR-/HER2+ and 22.3% triple-negative. Univariate analysis showed that the presence of liver metastases, lung metastases and triple-negative patients (median OS 6 months) had worse prognosis. The HR+/HER2+ subtype had the longest OS with a median of 22 months. In multivariate analysis, older age (hazard ratio 1.8), lobular histology (hazard ratio 2.08), triple-negative subtype (hazard ratio 2.25), liver metastases (hazard ratio 1.6) and unmarried patients (hazard ratio 1.39) had significantly shorter OS. Although the prognosis of patients with BMIBCD is generally poor, 20.7% were still alive 3 years after the diagnosis. There were substantial differences in OS according to tumour subtype. In addition to tumour subtype, other independent predictors of OS are age at diagnosis, marital status, histology and liver metastases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heterogeneous impact of alcohol consumption according to treatment method on survival in head and neck cancer: A prospective study.

PubMed

Sawabe, Michi; Ito, Hidemi; Oze, Isao; Hosono, Satoyo; Kawakita, Daisuke; Tanaka, Hideo; Hasegawa, Yasuhisa; Murakami, Shingo; Matsuo, Keitaro

2017-01-01

Alcohol consumption is an established risk factor, and also a potential prognostic factor, for squamous cell carcinoma of the head and neck (HNSCC). However, little is known about whether the prognostic impact of alcohol consumption differs by treatment method. We evaluated the association between alcohol drinking and survival by treatment method to the primary site in 427 patients with HNSCC treated between 2005 and 2013 at Aichi Cancer Center Central Hospital (Nagoya, Japan). The impact of alcohol on prognosis was measured by multivariable Cox regression analysis adjusted for established prognostic factors. Among all HNSCC patients, the overall survival rate was significantly poorer with increased levels of alcohol consumption in multivariable analysis (trend P = 0.038). Stratification by treatment method and primary site revealed that the impact of drinking was heterogeneous. Among laryngopharyngeal cancer (laryngeal, oropharyngeal, and hypopharyngeal cancer) patients receiving radiotherapy (n = 141), a significant dose-response relationship was observed (trend P = 0.034). In contrast, among laryngopharyngeal cancer patients treated with surgery (n = 80), no obvious impact of alcohol was observed. This heterogeneity in the impact of alcohol between surgery and radiotherapy was significant (for interaction, P = 0.048). Furthermore, among patients with oral cavity cancer treated by surgery, a significant impact of drinking on survival was seen with tongue cancer, but not with non-tongue oral cancer. We observed a significant inverse association between alcohol drinking and prognosis among HNSCC patients, and its impact was heterogeneous by treatment method and primary site. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Prostate-specific antigen density is predictive of outcome in suboptimal prostate seed brachytherapy.

PubMed

Benzaquen, David; Delouya, Guila; Ménard, Cynthia; Barkati, Maroie; Taussky, Daniel

In prostate seed brachytherapy, a D 90 of <130 Gy is an accepted predictive factor for biochemical failure (BF). We studied whether there is a subpopulation that does not need additional treatment after a suboptimal permanent seed brachytherapy implantation. A total of 486 patients who had either BF or a minimum followup of 48 months without BF were identified. BF was defined according to the Phoenix definition (nadir prostate-specific antigen + 2). Univariate and multivariate analyses were performed, adjusting for known prognostic factors such as D 90 and prostate-specific antigen density (PSAD) of ≥0.15 ng/mL/cm 3 , to evaluate their ability to predict BF. Median followup for patients without BF was 72 months (interquartile range 56-96). BF-free recurrence rate at 5 years was 95% and at 8 years 88%. In univariate analysis, PSAD and cancer of the prostate risk assessment score were predictive of BF. On multivariate analysis, none of the factors remained significant. The best prognosis had patients with a low PSAD (<0.15 ng/mL/cm 3 ) and an optimal implant at 30 days after implantation (as defined by D 90  ≥ 130 Gy) compared to patients with both factors unfavorable (p = 0.006). A favorable PSAD was associate with a good prognosis, independently of the D 90 (<130 Gy vs. ≥130 Gy, p = 0.7). Patients with a PSAD of <0.15 ng/mL/cm 3 have little risk of BF, even in the case of a suboptimal implant. These results need to be validated in other patients' cohorts. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

A high proportion of cells carrying trisomy 12 is associated with a worse outcome in patients with chronic lymphocytic leukemia.

PubMed

González-Gascón Y Marín, Isabel; Hernández-Sánchez, María; Rodríguez-Vicente, Ana-Eugenia; Sanzo, Carmen; Aventín, Anna; Puiggros, Anna; Collado, Rosa; Heras, Cecilia; Muñoz, Carolina; Delgado, Julio; Ortega, Margarita; González, María-Teresa; Marugán, Isabel; de la Fuente, Ignacio; Recio, Isabel; Bosch, Francesc; Espinet, Blanca; González, Marcos; Hernández-Rivas, Jesús-María; Hernández, José-Ángel

2016-06-01

The prognosis of chronic lymphocytic leukemia (CLL) patients displaying trisomy 12 (+12) remains unclear. In this study, we analyzed the influence of the proportion of cells with +12, and other clinical and biologic factors, in time to first therapy (TTFT) and overall survival (OS), in 289 patients diagnosed with CLL carrying +12. Median OS was 129 months. One hundred seventy-four patients (60.2%) presented +12 in <60% of cells. TTFT and OS for this subgroup were longer than for the subgroup with +12 in ≥60% of cells, with a median TTFT of 49 months (CI95%, 39-58) vs 30 months (CI95%, 22-38) (P = 0.001); and a median OS of 159 months (CI95%, 119-182), vs 96 months (CI95%, 58-134) (P = 0.015). Other factors associated with a shorter TTFT were: Binet stage, B symptoms, lymphadenopathy, splenomegaly, high lymphocyte count, 11q-, high β2 microglobulin, and high LDH. In the multivariate analysis, clinical stage, +12 in ≥60% of cells, high lymphocyte count, B symptoms, and 11q- in addition, resulted of significance in predicting shorter TTFT. Significant variables for OS were: Binet stage, lymphadenopathy, splenomegaly, high LDH, high β2 microglobulin, 11q-, and CD38. In the multivariate analysis, only Binet stage, 11q-, and high β2microglobulin significantly predicted shorter OS. CLL with +12 entails a heterogeneous group with intermediate prognosis. However, a high proportion of cells carrying +12 separates a subgroup of patients with poor outcome. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy.

PubMed

Miller, Marian; Ottesen, Rebecca A; Niland, Joyce C; Kruper, Laura; Chen, Steven L; Vito, Courtney

2014-10-01

Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods. Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I-III breast cancer who had NAC and pretreatment imaging at City of Hope (1997-2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0-0.4 (strong partial response, SPR), TRR > 0.4-1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan-Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders. There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016). TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.

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

PubMed

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

2018-01-01

Purpose To evaluate the association between tumor shrinkage patterns shown with magnetic resonance (MR) imaging during neoadjuvant chemotherapy (NAC) and prognosis in patients with low-grade luminal breast cancer. Materials and Methods This retrospective study was approved by the institutional review board and informed consent was obtained from all subjects. The low-grade luminal breast cancer was defined as hormone receptor-positive and human epidermal growth factor receptor 2-negative with nuclear grades 1 or 2. The patterns of tumor shrinkage as revealed at MR imaging were categorized into two types: concentric shrinkage (CS) and non-CS. Among 854 patients who had received NAC in a single institution from January 2000 to December 2009, 183 patients with low-grade luminal breast cancer were retrospectively evaluated for the development set. Another data set from 292 patients who had received NAC in the same institution between January 2010 and December 2012 was used for the validation set. Among these 292 patients, 121 patients with low-grade luminal breast cancer were retrospectively evaluated. Results In the development set, the median observation period was 67.9 months. Recurrence was observed in 31 patients, and 16 deaths were related to breast cancer. There were statistically significant differences in both the disease-free survival (DFS) and overall survival (OS) rates between patterns of tumor shrinkage (P < .001 and P < .001, respectively). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .001) and OS (P = .009) rate. In the validation set, the median follow-up period was 56.9 months. Recurrence was observed in 20 patients (16.5%) and eight (6.6%) deaths were related to breast cancer. DFS rate was significantly longer in patients with the CS pattern (72.8 months; 95% confidence interval [CI]: 69.9, 75.6 months) than in those with the non-CS pattern (56.0 months; 95% CI: 49.1, 62.9 months; P ≤ .001). The CS pattern was associated with an excellent prognosis (median OS, 80.6 months; 95% CI: 79.3, 81.8 months vs 65.0 months; 95% CI: 60.1, 69.8 months; P = .004). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .007) and OS (P = .037) rates. Conclusion The CS pattern as revealed at MR imaging during NAC had the only significant independent association with prognosis in patients with low-grade luminal breast cancer. © RSNA, 2017.

Multidisciplinary effort in treating children with hepatoblastoma in China.

PubMed

Yuan, Xiao-Jun; Wang, Huan-Min; Jiang, Hui; Tang, Meng-Jie; Li, Zhang-Lin; Zou, Xiang; Fang, Yong-Jun; Pan, Ci; Tou, Jin-Fa; Zhang, Ke-Ren; Liu, Xiang; Li, Wei-Song; Li, Yang; Lu, Jun; Wu, Ye-Ming

2016-05-28

The purpose of this study is to report the first nationwide protocol (Wuhan Protocol) developed by Chinese Children's Cancer Group and the results of multidisciplinary effort in treating hepatoblastoma. In this study, we reported the final analysis, which includes 153 hepatoblastoma patients in 13 hospitals from January 2006 to December 2013. The 6-year overall survival and event-free survival rates were 83.3 ± 3.1% and 71.0 ± 3.7%, respectively, in this cohort. The univariate analysis revealed that female (P = 0.027), under 5 years of age (P = 0.039), complete surgical resection (P = 0.000), no metastases (P = 0.000), and delayed surgery following neoadjuvant chemotherapy (P = 0.000) had better prognosis. In multivariate analysis, male, 5 years of age or above, stage PRETEXT III or IV, and incomplete surgical resection were among the some adverse factors contributing to poor prognosis. The preliminary results from this study showed that patients who underwent treatment following Wuhan Protocol had similar OS and EFS rates compared to those in developed countries. However, the protocol remains to be further optimized in standardizing surgical resection (including liver transplantation), refining risk stratification and risk-based chemotherapy. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

The Influence of Cyst Emptying, Lymph Node Resection and Chemotherapy on Survival in Stage IA and IC1 Epithelial Ovarian Cancer.

PubMed

Rosendahl, Mikkel; Mosgaard, Berit Jul; Høgdall, Claus

2016-10-01

To determine if survival in stage I ovarian cancer is influenced by cyst emptying, lymph node resection and chemotherapy. A survival analysis of 607 patients with ovarian cancer in stage IA, IA with cyst emptying (IAempty) and IC1 was performed. There was no difference in five-year survival between IA (87%) and IC1 (87%) (p=0.899), between IA and IAempty (86%) (p=0.500) nor between IA+IAempty (87%) and IC1 without IAempty (84%) (p=0.527). Five-year survival rate (5YSR) was significantly higher after lymph node resection in stage IA (94% vs. 85%; p=0.01) and IA+IC1 (93% vs. 85%; p=0.004). In multivariate analysis, lymph node resection improved prognosis significantly for all sub-stages, whereas stage and chemotherapy did not affect survival. In stage IA ovarian cancer, controlled cyst emptying without spill does not worsen prognosis. Lymph node resection is associated with improved survival in stage IA and IC1. Chemotherapy should only be offered where randomized controlled studies have shown a benefit. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

PubMed

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.

Ovarian cancer patients at high risk of BRCA mutation: the constitutional genetic characterization does not change prognosis.

PubMed

Sabatier, Renaud; Lavit, Elise; Moretta, Jessica; Lambaudie, Eric; Noguchi, Tetsuro; Eisinger, François; Cherau, Elisabeth; Provansal, Magali; Livon, Doriane; Rabayrol, Laetitia; Popovici, Cornel; Charaffe-Jauffret, Emmanuelle; Sobol, Hagay; Viens, Patrice

2016-10-01

Ovarian neoplasms secondary to germline BRCA mutations had been described to have a more favourable survival. There is only few data concerning the prognosis of non mutated patients presenting clinical features evocative of BRCA alterations. We retrospectively collected data from patients treated in our institution for an invasive ovarian carcinoma between 1995 and 2011. Patients considered at high risk of BRCA mutation were tested for BRCA1/2 germline mutations. We described clinical, pathological and therapeutic features and compared prognosis of BRCA mutation carriers and non-mutated patients. Out of 617 ovarian cancer patients, we identified 104 patients who were considered at high risk of mutation. The 33 mutated patients were more likely to present a personal (33 vs. 10 %, p = 0.003) or a family (42 vs. 24 %, p = 0.06) history of breast/ovarian cancers. BRCA1/2 mutation carriers and wild type patients displayed similar prognosis: median progression-free survival (PFS) of 20.9 versus 37.7 months (p = 0.21); median overall survival (OS) of 151.2 versus 122.5 months (p = 0.52). Personal history of breast cancer increased both PFS [HR = 0.45 (95CI 0.25-0.81)] and OS [HR = 0.35 (95CI 0.16-0.75)]. In multivariate analysis, this parameter was an independent prognostic feature, whereas the identification of a BRCA1/2 mutation was not. In our cohort, all patients at high risk of BRCA mutation share a similar prognosis, whatever is their germline mutation status. Prognosis seems to be more influenced by clinical history than by germline mutations identification. If it is confirmed in larger and independent series, this result suggests that the hypothesis of other BRCA pathway alterations (BRCAness phenotype) deserves to be deeply explored.

Identifying the association between contrast enhancement pattern, surgical resection, and prognosis in anaplastic glioma patients.

PubMed

Wang, Yinyan; Wang, Kai; Wang, Jiangfei; Li, Shaowu; Ma, Jun; Dai, Jianping; Jiang, Tao

2016-04-01

Contrast enhancement observable on magnetic resonance (MR) images reflects the destructive features of malignant gliomas. This study aimed to investigate the relationship between radiologic patterns of tumor enhancement, extent of resection, and prognosis in patients with anaplastic gliomas (AGs). Clinical data from 268 patients with histologically confirmed AGs were retrospectively analyzed. Contrast enhancement patterns were classified based on preoperative T1-contrast MR images. Univariate and multivariate analyses were performed to evaluate the prognostic value of MR enhancement patterns on progression-free survival (PFS) and overall survival (OS). The pattern of tumor contrast enhancement was associated with the extent of surgical resection in AGs. A gross total resection was more likely to be achieved for AGs with focal enhancement than those with diffuse (p = 0.001) or ring-like (p = 0.024) enhancement. Additionally, patients with focal-enhanced AGs had a significantly longer PFS and OS than those with diffuse (log-rank, p = 0.025 and p = 0.031, respectively) or ring-like (log-rank, p = 0.008 and p = 0.011, respectively) enhanced AGs. Furthermore, multivariate analysis identified the pattern of tumor enhancement as a significant predictor of PFS (p = 0.016, hazard ratio [HR] = 1.485) and OS (p = 0.030, HR = 1.446). Our results suggested that the contrast enhancement pattern on preoperative MR images was associated with the extent of resection and predictive of survival outcomes in AG patients.

The effect of distant metastases sites on survival in de novo stage-IV breast cancer: A SEER database analysis.

PubMed

Wu, San-Gang; Li, Hui; Tang, Li-Ying; Sun, Jia-Yuan; Zhang, Wen-Wen; Li, Feng-Yan; Chen, Yong-Xiong; He, Zhen-Yu

2017-06-01

To investigate the effect of distant metastases sites on survival in patients with de novo stage-IV breast cancer. From 2010 to 2013, patients with a diagnosis of de novo stage-IV breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on breast cancer-specific survival and overall survival. A total of 7575 patients were identified. The most common metastatic sites were bone, followed by lung, liver, and brain. Patients with hormone receptor+/human epidermal growth factor receptor 2- and hormone receptor+/human epidermal growth factor receptor 2+ status were more prone to bone metastases. Lung and brain metastases were common in hormone receptor-/human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2- subtypes, and patients with hormone receptor+/ human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2+ subtypes were more prone to liver metastases. Patients with liver and brain metastases had unfavorable prognosis for breast cancer-specific survival and overall survival, whereas bone and lung metastases had no effect on patient survival in multivariate analyses. The hormone receptor-/human epidermal growth factor receptor 2- subtype conferred a significantly poorer outcome in terms of breast cancer-specific survival and overall survival. hormone receptor+/human epidermal growth factor receptor 2+ disease was associated with the best prognosis in terms of breast cancer-specific survival and overall survival. Patients with liver and brain metastases were more likely to experience poor prognosis for breast cancer-specific survival and overall survival by various breast cancer subtypes. Distant metastases sites have differential impact on clinical outcomes in stage-IV breast cancer. Follow-up screening for brain and liver metastases might be effective in improving breast cancer-specific survival and overall survival.

Prognostic value of long non-coding RNA CCAT1 expression in patients with cancer: A meta-analysis.

PubMed

Shi, Deyao; Wu, Fashuai; Gao, Feng; Qing, Xiangcheng; Shao, Zengwu

2017-01-01

LncRNA CCAT1 is significantly overexpressed in various types of cancers, suggesting that it might be associated with prognosis and clinicopathological features in patients with cancer. A comprehensive search was performed in Pubmed, Web of Science, OVID and CNKI databases. We also retrieved articles from other sources, such as retrieving from the reference lists of relevant articles. Eligible studies were included based on defined exclusion and inclusion criteria to perform a meta-analysis. STATA 14.0 was used to estimate pooled hazard ratios (HRs) with 95% confidence interval (95% CI), the heterogeneity among studies and publication bias to judge the prognostic value. A total of 1587 patients from 11 eligible studies were included in the meta-analysis. The results showed that high expression level of CCAT1 was significantly associated with shorter overall survival in cancer patients (HR 2.335, 95% CI:1.551-3.517); in the subgroup analysis, region (China or UK), sample size (more or less than 100), type of cancer (digestive or non-digestive disease) and paper quality (score more or less than 7) did not alter the association between CCAT1 expression and cancer prognosis but preoperative treatment did. And CCAT1 expression was an independent prognostic marker for overall survival in patients with cancer (pooled HR 2.195, 95%CI:1.316-3.664) using Cox multivariate analyses. The clinicopathological parameters analysis further showed that increased expression level of CCAT1 was correlated with tumor size, lymph node metastasis, TNM stage, distant metastasis, microvascular invasion and capsular formation in relevant cancers. The meta-analysis results from present study suggested that increased expression level of CCAT1 was associated with poor prognosis and can serve as an independent biomarker. And the expression level of CCAT1 was associated with clinicopathological features in relevant cancers.

Effect of tumor size on prognosis in patients treated with radical radiotherapy or chemoradiotherapy for non-small cell lung cancer. An analysis of the staging project database of the International Association for the Study of Lung Cancer.

PubMed

Ball, David; Mitchell, Alan; Giroux, Dori; Rami-Porta, Ramon

2013-03-01

Analysis of the International Association for the Study of Lung Cancer database revealed that for patients with completely resected, node-negative, non-small-cell lung cancer (NSCLC), increasing tumor size was associated with worsening survival. This analysis was performed to determine the effect of size on prognosis in patients in the same database but who were treated with radiotherapy or chemoradiotherapy. Patients were eligible if they had pathologically confirmed NSCLC, no evidence of distant metastases, intended treatment was radical radiotherapy (minimum 50 Gy) or combined chemotherapy and radiotherapy, no surgery, and tumor diameter was available. Eight hundred and sixty-eight patients were available for analysis. Patient characteristics were: sex (men) 65.3%; median age 64 years (range, 32-88); Eastern Cooperative Oncology Group performance status 0: 55%, 1: 33%, 2 or more: 5%; chemotherapy 74%; no chemotherapy 18%; weight loss less than 5 %: 70%, and more than 5%: 25%. Primary tumor size was categorized according to tumor, node, metastasis 7th edition. On univariate analysis, the following factors were prognostic for survival: age (continuous) (p = 0.0035); performance status of 1 or more (p = 0.0021); weight loss less than 5% (p < 0.0001); chemotherapy (p = 0.0189); and primary tumor size (continuous) (p = 0.0002). Sex and clinical nodal stage were not significant. On multivariate analysis, age and weight loss remained significant factors for survival, as was tumor size less than 3 cm. In patients treated with radiotherapy with or without chemotherapy, tumor size less than 3 cm was associated with longer survival than larger tumors. Evidence of the effect of size on prognosis above this was weak. Five-year survival of more than 10% was observed in all four size categories.

Expression of CD10 predicts tumor progression and unfavorable prognosis in malignant melanoma.

PubMed

Oba, Junna; Nakahara, Takeshi; Hayashida, Sayaka; Kido, Makiko; Xie, Lining; Takahara, Masakazu; Uchi, Hiroshi; Miyazaki, Shogo; Abe, Takeru; Hagihara, Akihito; Moroi, Yoichi; Furue, Masutaka

2011-12-01

CD10 expression in malignant melanoma (MM) has been reported to increase according to tumor progression and metastasis; however, its association with patient outcome has not been clarified. We examined the immunohistochemical expression of CD10 in MM to determine whether or not it could serve as a marker for tumor progression and prognosis. A total of 64 formalin-fixed, paraffin-embedded samples of primary MM were immunostained for CD10. Similarly, 40 samples of melanocytic nevus and 20 of metastatic MM were analyzed for comparison. The following clinicopathologic variables were evaluated: age, gender, histologic type, tumor site, Breslow thickness, Clark level, the presence or absence of ulceration and tumor-infiltrating lymphocytes, and survival. Statistical analyses were performed to assess for associations. Several parameters were analyzed for survival using the Kaplan-Meier method and Cox proportional hazards model. Immunohistochemical analysis revealed that 34 of 64 cases (53%) of primary MM expressed CD10, compared with 15 of 20 cases (75%) of metastatic MM and only 4 of 40 cases (10%) of nevus. There was a significant positive relationship between CD10 expression and Breslow thickness, Clark level, and ulceration. Univariate analysis revealed 4 significant factors for shorter survival periods: CD10 expression, high Breslow thickness, high Clark level, and the presence of ulceration (P < .01 each). In multivariate analysis, CD10 expression was revealed to be a statistically significant and independent prognostic factor. The major limitation was the small sample size. CD10 expression may serve as a progression marker and can predict unfavorable prognosis in patients with MM. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma.

PubMed

Mendrzyk, Frank; Radlwimmer, Bernhard; Joos, Stefan; Kokocinski, Felix; Benner, Axel; Stange, Daniel E; Neben, Kai; Fiegler, Heike; Carter, Nigel P; Reifenberger, Guido; Korshunov, Andrey; Lichter, Peter

2005-12-01

Medulloblastoma is the most common malignant brain tumor in children. Despite multimodal aggressive treatment, nearly half of the patients die as a result of this tumor. Identification of molecular markers for prognosis and development of novel pathogenesis-based therapies depends crucially on a better understanding of medulloblastoma pathomechanisms. We performed genome-wide analysis of DNA copy number imbalances in 47 medulloblastomas using comparative genomic hybridization to large insert DNA microarrays (matrix-CGH). The expression of selected candidate genes identified by matrix-CGH was analyzed immunohistochemically on tissue microarrays representing medulloblastomas from 189 clinically well-documented patients. To identify novel prognostic markers, genomic findings and protein expression data were correlated to patient survival. Matrix-CGH analysis revealed frequent DNA copy number alterations of several novel candidate regions. Among these, gains at 17q23.2-qter (P < .01) and losses at 17p13.1 to 17p13.3 (P = .04) were significantly correlated to poor prognosis. Within 17q23.2-qter and 7q21.2, two of the most frequently gained chromosomal regions, confined amplicons were identified that contained the PPM1D and CDK6 genes, respectively. Immunohistochemistry revealed strong expression of PPM1D in 148 (88%) of 168 and CDK6 in 50 (30%) of 169 medulloblastomas. Overexpression of CDK6 correlated significantly with poor prognosis (P < .01) and represented an independent prognostic marker of overall survival on multivariate analysis (P = .02). We identified CDK6 as a novel molecular marker that can be determined by immunohistochemistry on routinely processed tissue specimens and may facilitate the prognostic assessment of medulloblastoma patients. Furthermore, increased protein-levels of PPM1D and CDK6 may link the TP53 and RB1 tumor suppressor pathways to medulloblastoma pathomechanisms.

[Bioinformatics on vascular invasion markers in hepatocellular carcinoma via Big-Data analysis].

PubMed

Chen, Q; Qiu, X Q

2017-04-10

Objective: To investigate the biomarkers in hepatocellular carcinoma and their prognostic value via GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) database. Methods: Datasets of hepatocellular carcinoma were downloaded from GEO (GSE67140) and TCGA. MicroRNA in SNU423, SNU449, HepG2, Hep3B, SNU398 cell lines which had low or high invasion capabilities were investigated and verified, in 81 patients with and 91 without vascular invasion hepatocellular carcinoma. The prognostic value of these microRNAs were studied via TCGA database,obtained from 362 patients with hepatocellular carcinoma, through Kaplan-Meier and Multivariate Cox proportional hazard analysis. Target genes were analyzed by GO and KEGG. Results: Expressions of hsa-mir-1180, hsa-mir-149, hsa-mir-744 and hsa-mir-940 were all up regulated in high invasion capable cell lines (SNU423, SNU449) and vascular invasion patients with hepatocellular carcinoma (logFC>1, P <0.05). Results from the Survival analysis showed that hsa-mir-1180 ( HR =1.623, 95 % CI : 1.114-2.365, P =0.012), hsa-mir-149 ( HR =2.400, 95 % CI : 1.639-3.514) and hsa-mir-940 ( HR =1.704, 95 %CI : 1.188-2.443, P =0.004) were independent risk factors on the prognosis of patients with hepatocellular carcinoma ( P <0.05). The mechanism might be related to factors as immune response, focal adhesion and adherence junction signaling pathways. Conclusion: With TCGA and GEO data mining, we found that hsa-mir-1180, hsa-mir-149, hsa-mir-744 and hsa-mir-940 were all highly related to the prognosis of hepatocellular carcinoma, that enabled it to be used to further study the biomarkers related to the prognosis of hepatocellular carcinoma.

The autophagy-related marker LC3 can predict prognosis in human hepatocellular carcinoma.

PubMed

Lee, Yoo Jin; Hah, Yu Jin; Ha, Yu Jin; Kang, Yu Na; Kang, Koo Jeong; Hwang, Jae Seok; Chung, Woo Jin; Cho, Kwang Bum; Park, Kyung Sik; Kim, Eun Soo; Seo, Hye-Young; Kim, Mi-Kyung; Park, Keun-Gyu; Jang, Byoung Kuk

2013-01-01

Defects of autophagy and endoplasmic reticulum (ER) stress are related to many diseases and tumors. However, only a few studies have examined hepatocellular carcinoma (HCC) as related to these processes. Therefore, in this study, we investigated the expression and extent of autophagy and ER stress-related markers in HCC and their influence on clinical characteristics and prognosis for each protein. The expression of autophagy-related markers (LC3 and Beclin-1) and ER stress-related markers (GRP78 and CHOP) was analyzed by immunohistochemistry on tissues from completely resected specimens of 190 HCC patients. Their influence on clinicopathologic features and prognosis were evaluated using the chi-square test and Kaplan-Meier analysis. Correlations of each protein were determined by Spearman's correlation analysis. LC3 expression was not correlated with TNM, BCLC stage, or Edmonson-Steiner grading, whereas it was correlated with longer overall survival (OS) (p = 0.039) and tended to be related with longer time to recurrence (TTR) (p=0.068) although it did not show statistical significance. Multivariate analysis indicated that LC3 expression was a significantly independent prognostic factor of OS (HR, 0.42; 95% CI, 0.22-0.80; p-value=0.009) and TTR (HR, 0.54; 95% CI, 0.33-0.90; p=0.017). Expression of LC3 in advanced stages of TNM (III) (p=0.045) and Edmonson-Steiner Grades (III and IV) (p=0.043) was correlated with longer survival, but not in the early stages. A positive correlation was not observed between the expression of autophagy-related markers and ER stress-related markers. Our results suggest that the expression and extent of LC3 might be a strong prognostic factor of HCC, especially in patients with surgical resection.

Prognosis of chronic lymphocytic leukemia from infrared spectra of lymphocytes

NASA Astrophysics Data System (ADS)

Schultz, Christian P.; Liu, Kan-Zhi; Johnston, James B.; Mantsch, Henry H.

1997-06-01

Peripheral mononuclear cells obtained from blood of normal individuals and from patients with chronic lymphocytic leukemia (CLL) were investigated by infrared spectroscopy and multivariate statistical analysis. Not only are the spectra of CLL cells different from those of normal cells, but hierarchical clustering also separated the CLL cells into a number of subclusters, based on their different DNA content, a fact which may provide a useful diagnostic tool for staging (progression of the disease) and multiple clone detection. Moreover, there is evidence for a correlation between the increased amount of DNA in the CLL cells and the in-vivo doubling time of the lymphocytes in a given patient.

Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: A meta-analysis.

PubMed

Yin, Yongmei; Wang, Jun; Wang, Xuedong; Gu, Lan; Pei, Hao; Kuai, Shougang; Zhang, Yingying; Shang, Zhongbo

2015-07-01

Recently, a series of studies explored the correlation between the neutrophil to lymphocyte ratio and the prognosis of lung cancer. However, the current opinion regarding the prognostic role of the neutrophil to lymphocyte ratio in lung cancer is inconsistent. We performed a meta-analysis of published articles to investigate the prognostic value of the neutrophil to lymphocyte ratio in lung cancer. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated. An elevated neutrophil to lymphocyte ratio predicted worse overall survival, with a pooled HR of 1.243 (95%CI: 1.106-1.397; P(heterogeneity)=0.001) from multivariate studies and 1.867 (95%CI: 1.487-2.344; P(heterogeneity)=0.047) from univariate studies. Subgroup analysis showed that a high neutrophil to lymphocyte ratio yielded worse overall survival in non-small cell lung cancer (NSCLC) (HR=1.192, 95%CI: 1.061-1.399; P(heterogeneity)=0.003) as well as small cell lung cancer (SCLC) (HR=1.550, 95% CI: 1.156-2.077; P(heterogeneity)=0.625) in multivariate studies. The synthesized evidence from this meta-analysis of published articles demonstrated that an elevated neutrophil to lymphocyte ratio was a predictor of poor overall survival in patients with lung cancer.

Comparison of DNA aneuploidy, chromosome 1 abnormalities, MYCN amplification and CD44 expression as prognostic factors in neuroblastoma.

PubMed

Christiansen, H; Sahin, K; Berthold, F; Hero, B; Terpe, H J; Lampert, F

1995-01-01

A comparison of the prognostic impact of five molecular variables in a large series was made, including tests of their nonrandom association and multivariate analysis. Molecular data were available for 377 patients and MYCN amplification, cytogenetic chromosome 1p deletion, loss of chromosome 1p heterozygosity, DNA ploidy and CD44 expression were investigated. Their interdependence and influence on event-free survival was tested uni- and multivariately using Pearson's chi 2-test, Kaplan-Meier estimates, log rank tests and the Cox's regression model. MYCN amplification was present in 18% (58/322) of cases and predicted poorer prognosis in localised (P < 0.001), metastatic (P = 0.002) and even 4S (P = 0.040) disease. CD44 expression was found in 86% (127/148) of cases, and was a marker for favourable outcome in patients with neuroblastoma stages 1-3 (P = 0.003) and 4 (P = 0.017). Chromosome 1p deletion was cytogenetically detected in 51% (28/55), and indicated reduced event-free survival in localised neuroblastoma (P = 0.020). DNA ploidy and loss of heterozygosity on chromosome 1p were of less prognostic value. Most factors of prognostic significance were associated with each other. By multivariate analysis, MYCN was selected as the only relevant factor. Risk estimation of high discriminating power is, therefore, possible for patients with localised and metastatic neuroblastoma using stage and MYCN.

AURKA mRNA expression is an independent predictor of poor prognosis in patients with non-small cell lung cancer.

PubMed

Al-Khafaji, Ahmed S K; Marcus, Michael W; Davies, Michael P A; Risk, Janet M; Shaw, Richard J; Field, John K; Liloglou, Triantafillos

2017-06-01

Deregulation of mitotic spindle genes has been reported to contribute to the development and progression of malignant tumours. The aim of the present study was to explore the association between the expression profiles of Aurora kinases ( AURKA , AURKB and AURKC ), cytoskeleton-associated protein 5 ( CKAP5 ), discs large-associated protein 5 ( DLGAP5 ), kinesin-like protein 11 ( KIF11 ), microtubule nucleation factor ( TPX2 ), monopolar spindle 1 kinase ( TTK ), and β-tubulins ( TUBB ) and ( TUBB3 ) genes and clinicopathological characteristics in human non-small cell lung carcinoma (NSCLC). Reverse transcription-quantitative polymerase chain reaction-based RNA gene expression profiles of 132 NSCLC and 44 adjacent wild-type tissues were generated, and Cox's proportional hazard regression was used to examine associations. With the exception of AURKC , all genes exhibited increased expression in NSCLC tissues. Of the 10 genes examined, only AURKA was significantly associated with prognosis in NSCLC. Multivariate Cox's regression analysis demonstrated that AURKA mRNA expression [hazard ratio (HR), 1.81; 95% confidence interval (CI), 1.16-2.84; P=0.009], age (HR, 1.03; 95% CI, 1.00-1.06; P=0.020), pathological tumour stage 2 (HR, 2.43; 95% CI, 1.16-5.10; P=0.019) and involvement of distal nodes (pathological node stage 2) (HR, 3.14; 95% CI, 1.24-7.99; P=0.016) were independent predictors of poor prognosis in patients with NSCLC. Poor prognosis of patients with increased AURKA expression suggests that those patients may benefit from surrogate therapy with AURKA inhibitors.

Preoperative subclinical hypothyroidism in patients with papillary thyroid carcinoma.

PubMed

Ahn, Dongbin; Sohn, Jin Ho; Kim, Jae Hyug; Shin, Chang Min; Jeon, Jae Han; Park, Ji Young

2013-01-01

To assess the effect of preoperative subclinical hypothyroidism on prognosis and on the tumour's clinicopathological features at initial diagnosis of papillary thyroid carcinoma (PTC). 328 patients who underwent surgery for PTC between January 2001 and December 2006 were enrolled in this study. Of these, we compared 35 patients with preoperative subclinical hypothyroidism with 257 patients who were euthyroid before the operation, with respect to clinicopathological characteristics and prognosis. No significant differences were observed in tumour size, extrathyroidal extension, and multifocality between subclinical hypothyroidism and euthyroid patients. Patients with subclinical hypothyroidism had a considerably lower percentage of lymph node metastasis than did euthyroid patients (8.6% vs. 21.8%, p=0.068). Although preoperative subclinical hypothyroidism decreased the risk of lymph node metastasis at 0.313 of odds ratio in the multivariate analysis, its significance was not verified (95% confidence internal, 0.089-1.092; p=0.068). Patients with preoperative subclinical hypothyroidism tended to have a better prognosis than did preoperative euthyroid patients, for both recurrence (2.9% vs. 14.0%, p=0.099) and 7-year disease-free survival (97.1% vs. 87.8%, p=0.079), during the 82-month mean follow-up period. However, even as thyroid-stimulating hormone (TSH) concentration increased, there were no consistent relationships observed between the TSH levels and the prognostic parameters. We could find neither a consistent positive nor a negative linear relationship between TSH levels and several prognostic parameters, indicating that subclinical hypothyroidism with elevated TSH is not an independent predictor of tumour aggressiveness and poor prognosis in PTC. Copyright © 2013 Elsevier Inc. All rights reserved.

Cystic brain metastasis is associated with poor prognosis in patients with advanced breast cancer.

PubMed

Sun, Bing; Huang, Zhou; Wu, Shikai; Ding, Lijuan; Shen, Ge; Cha, Lei; Wang, Junliang; Song, Santai

2016-11-08

Brain metastasis (BM) with a cystic component from breast cancer is rare and largely uncharacterized. The purpose of this study was to identify the characteristics of cystic BM in a large cohort of breast cancer patients. A total of 35 eligible patients with cystic BM and 255 patients with solid BM were analyzed. Three factors were significantly associated with an increased probability of developing cystic lesions: age at diagnosis ≤ 40 years, age at BM ≤ 45 years, and poor histological grade (p < 0.05). Patients with cystic metastasis were also characterized by a larger metastasis volume, a shorter progression-free survival (PFS) following their first treatment for BM, and poor overall survival after BM (p < 0.05). Multivariate analysis further demonstrated that local control of cystic BM was only potentially achieved for HER2-negative primary tumors (p = 0.084). Breast cancer patients with parenchymal BM were reviewed from consecutive cases treated at our institution. Cystic BM was defined when the volume of a cystic lesion was greater than 50% of the aggregated volume of all lesions present. Clinicopathologic and radiographic variables were correlated with development of cystic lesions and with prognosis of cystic BM. This study shows that cystic BM from breast cancer, a special morphological type of BM, had worse prognosis than the more commonly observed solid BM. Younger age and low tumor grade were associated with the development of cystic lesions. Further comprehensive research and management of cystic BM are warranted to improve its poor prognosis.

The prognostic value of tumor-infiltrating neutrophils in gastric adenocarcinoma after resection.

PubMed

Zhao, Jing-jing; Pan, Ke; Wang, Wei; Chen, Ju-gao; Wu, Yan-heng; Lv, Lin; Li, Jian-jun; Chen, Yi-bing; Wang, Dan-dan; Pan, Qiu-zhong; Li, Xiao-dong; Xia, Jian-chuan

2012-01-01

Several pieces of evidence indicate that tumor-infiltrating neutrophils (TINs) are correlated to tumor progression. In the current study, we explore the relationship between TINs and clinicopathological features of gastric adenocarcinoma patients. Furthermore, we investigated the prognostic value of TINs. The study was comprised of two groups, training group (115 patients) and test group (97 patients). Biomarkers (intratumoral CD15+ neutrophils) were assessed by immunohistochemistry. The relationship between clinicopathological features and patient outcome were evaluated using Cox regression and Kaplan-Meier analysis. Immunohistochemical detection showed that the tumor-infiltrating neutrophils (TINs) in the training group ranged from 0.00-115.70 cells/high-power microscopic field (HPF) and the median number was 21.60 cells/HPF. Based on the median number, the patients were divided into high and low TINs groups. Chi-square test analysis revealed that the density of CD15+ TINs was positively associated with lymph node metastasis (p = 0.024), distance metastasis (p = 0.004) and UICC (International Union Against Cancer) staging (p = 0.028). Kaplan-Meier analysis showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.002). Multivariate Cox's analysis showed that the density of CD15+ TINs was an independent prognostic factor for overall survival of gastric adenocarcinoma patients. Using another 97 patients as a test group and basing on the median number of TINs (21.60 cells/HPF) coming from the training group, Kaplan-Meier analysis also showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.032). The results verify that the number of CD15+ TINs can predict the survival of gastric adenocarcinoma surgical patients. The presence of CD15+ TINs is an independent and unfavorable factor in the prognosis of gastric adenocarcinoma patients. Targeting CD15+ TINs may be a potential intervenient therapy in the future.

Prognostic role of methylated GSTP1, p16, ESR1 and PITX2 in patients with breast cancer: A systematic meta-analysis under the guideline of PRISMA.

PubMed

Sheng, Xianneng; Guo, Yu; Lu, Yang

2017-07-01

BRCA1 and RASSF1A promoter methylation has been reported to be correlated with a worse survival in patients with breast cancer. However, the prognostic values of GSTP1, p16, ESR1, and PITX2 promoter methylation in breast cancer remain to be determined. Here, we performed this study to evaluate the prognostic significance of GSTP1, p16, ESR1, and PITX2 promoter methylation in breast cancer. A range of online databases was systematically searched to identify available studies based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. The pooled hazard ratios (HRs) with their 95% confidence intervals (95% CIs) were applied to estimate the prognostic effect of GSTP1, p16, ESR1, and PITX2 promoter methylation in breast cancer for multivariate regression analysis. 13 eligible articles involving 3915 patients with breast cancer were analyzed in this meta-analysis. In a large patient population, GSTP1 showed a trend toward a worse prognosis in overall survival (OS) (HR = 1.64, 95% CI = 0.93-2.87, P = .085). PITX2 promoter methylation was significantly correlated with a worse prognosis in OS (HR = 1.57, 95% CI = 1.15-2.14, P = .004), but no association between p16 promoter methylation and OS (HR = 0.92, 95% CI = 0.31-2.71, P = .884). PITX2 promoter methylation was significantly correlated with an unfavorable prognosis of patients with breast cancer in metastasis-free survival (MFS) (HR = 1.73, 95% CI = 1.33-2.26, P < .001). The result from 3 studies with 227 cases showed that ESR1 promoter methylation was linked to a worse prognosis in OS (HR = 1.55, 95% CI = 1.06-2.28, P = .025). Our findings suggest ESR1 and PITX2 promoter methylation may be correlated with a worse survival of patients with breast cancer (ESR1: OS, PITX2: OS and MFS). The clinical utility of aberrantly methylated ESR1 and PITX2 could be a promising factor for the prognosis of breast cancer.

Nonanaplastic follicular cell-derived thyroid carcinoma: mitosis and necrosis in long-term follow-up.

PubMed

Skansing, Daniel Bräuner; Londero, Stefano Christian; Asschenfeldt, Pia; Larsen, Stine Rosenkilde; Godballe, Christian

2017-06-01

Nonanaplastic follicular cell-derived thyroid carcinoma (NAFCTC) includes differentiated- (DTC) and poorly differentiated thyroid carcinoma (PDTC). DTC has an excellent prognosis, while PDTC is situated between DTC and anaplastic carcinomas. Short-term studies suggest that PDTC patients diagnosed only on tumor necrosis and/or mitosis have a prognosis similar to those diagnosed according to the TURIN proposal. The purpose of this study was to evaluate prognosis for NAFCTC based on long-term follow-up illuminating the significance of tumor necrosis and mitosis. A cohort of 225 patients with NAFCTC was followed more than 20 years. Age, sex, distant metastasis, histology, tumor size, extrathyroidal invasion, lymph node metastasis, tumor necrosis and mitosis were examined as possible prognostic factors. Median follow-up time for patients alive was 28 years (range 20-43 years). Age, distant metastasis, extrathyroidal invasion, tumor size, tumor necrosis and mitosis were independent prognostic factors in multivariate analysis for overall survival (OS). In disease specific survival (DSS) age was not significant. Using only necrosis and/or mitosis as criteria for PDTC the 5-, 10- and 20-year OS for DTC was 87, 79 and 69%, respectively. In DSS it was 95, 92 and 90%. For PDTC the 5-, 10- and 20-year OS was 57, 40 and 25%, respectively. In DSS it was 71, 55 and 48%. Tumor necrosis and mitosis are highly significant prognostic indicators in analysis of long time survival of nonanaplastic follicular cell-derived thyroid carcinoma indicating that a simplification of the actually used criteria for poorly differentiated carcinomas may be justified.

Clinical and prognosis value of the CIMP status combined with MLH1 or p16 INK4a methylation in colorectal cancer.

PubMed

Saadallah-Kallel, Amana; Abdelmaksoud-Dammak, Rania; Triki, Mouna; Charfi, Slim; Khabir, Abdelmajid; Sallemi-Boudawara, Tahia; Mokdad-Gargouri, Raja

2017-08-01

Aberrant DNA methylation of CpG islands occurred frequently in CRC and associated with transcriptional silencing of key genes. In this study, the CIMP combined with MLH1 or p16 INK4a methylation status was determined in CRC patients and correlated with clinicopathological parameters and overall survival. Our data showed that CIMP+ CRCs were identified in 32.9% of cases and that CACNAG1 is the most frequently methylated promoter. When we combined the CIMP with the MLH1 or the p16 INK4a methylation status, we found that CIMP-/MLH1-U (37.8%) and CIMP-/p16 INK4a -U (35.4%) tumors were the most frequent among the four subtypes. Statistical analysis showed that tumor location, lymphovascular invasion, TNM stage, and MSI differed among the group of patients. Kaplan-Meier analyses revealed differences in overall survival according to the CIMP combined with MLH1 or p16 INK4a methylation status. In a multivariate analysis, CIMP/MLH1 and CIMP/p16 INK4a methylation statuses were predictive of prognosis, and the OS was longer for patients with tumors CIMP-/MLH1-M, as well as CIMP-/p16 INK4a -M. Furthermore, DNMT1 is significantly overexpressed in tumors than in normal tissues as well as in CIMP+ than CIMP- tumors. Our results suggest that tumor classification based on the CIMP status combined with MLH1 or p16 INK4a methylation is useful to predict prognosis in CRC patients.

Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients.

PubMed

Gao, Chun; Fang, Long; Li, Jing-Tao; Zhao, Hong-Chuan

2016-02-28

To determine the significance of increased serum direct bilirubin level for lymph node metastasis (LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded. A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM (49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012. The baseline serum direct bilirubin concentration was (median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin (2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin was independently associated with LNM (OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that: (1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification; (2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and (3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis. Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers.

Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients

PubMed Central

Gao, Chun; Fang, Long; Li, Jing-Tao; Zhao, Hong-Chuan

2016-01-01

AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis (LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded. METHODS: A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM (49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012. RESULTS: The baseline serum direct bilirubin concentration was (median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin (2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin was independently associated with LNM (OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that: (1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification; (2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and (3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis. CONCLUSION: Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers. PMID:26937145

Comparative study of outcome measures and analysis methods for traumatic brain injury trials.

PubMed

Alali, Aziz S; Vavrek, Darcy; Barber, Jason; Dikmen, Sureyya; Nathens, Avery B; Temkin, Nancy R

2015-04-15

Batteries of functional and cognitive measures have been proposed as alternatives to the Extended Glasgow Outcome Scale (GOSE) as the primary outcome for traumatic brain injury (TBI) trials. We evaluated several approaches to analyzing GOSE and a battery of four functional and cognitive measures. Using data from a randomized trial, we created a "super" dataset of 16,550 subjects from patients with complete data (n=331) and then simulated multiple treatment effects across multiple outcome measures. Patients were sampled with replacement (bootstrapping) to generate 10,000 samples for each treatment effect (n=400 patients/group). The percentage of samples where the null hypothesis was rejected estimates the power. All analytic techniques had appropriate rates of type I error (≤5%). Accounting for baseline prognosis either by using sliding dichotomy for GOSE or using regression-based methods substantially increased the power over the corresponding analysis without accounting for prognosis. Analyzing GOSE using multivariate proportional odds regression or analyzing the four-outcome battery with regression-based adjustments had the highest power, assuming equal treatment effect across all components. Analyzing GOSE using a fixed dichotomy provided the lowest power for both unadjusted and regression-adjusted analyses. We assumed an equal treatment effect for all measures. This may not be true in an actual clinical trial. Accounting for baseline prognosis is critical to attaining high power in Phase III TBI trials. The choice of primary outcome for future trials should be guided by power, the domain of brain function that an intervention is likely to impact, and the feasibility of collecting outcome data.

A retrospective study on the role of diabetes and metformin in colorectal cancer disease survival

PubMed Central

Ramjeesingh, R.; Orr, C.; Bricks, C.S.; Hopman, W.M.; Hammad, N.

2016-01-01

Background Recent studies have suggested an effect of metformin on mortality for patients with both diabetes and colorectal cancer (crc). However, the literature is contradictory, with both positive and negative effects being identified. We set out to determine the effect of metformin with respect to prognosis in crc patients. Methods After a retrospective chart review of crc patients treated at the Cancer Centre of Southeastern Ontario, Kaplan–Meier analyses and Cox proportional hazards regression models were used to compare overall survival (os) in patients with and without diabetes. Results We identified 1304 crc patients treated at the centre. No significant differences between the diabetic and nondiabetic groups were observed with respect to tumour pathology, extent of metastatic disease, time or toxicity of chemotherapy, and the os rate (1-year os: 85.6% vs. 86.4%, p = 0.695; 2-year os: 73.6% vs. 77.0%, p = 0.265). In subgroup analysis, diabetic patients taking metformin survived significantly longer than their counterparts taking other diabetes treatments (os for the metformin group: 91% at 1 year; 80.5% at 2 years; os for the group taking other treatments, including diet control: 80.6% at 1 year, 67.4% at 2 years). Multivariate analysis suggests that patients with diabetes taking treatments other than metformin experience worse survival (p = 0.025). Conclusions Our results suggest that crc patients with diabetes, excluding those taking metformin, might have a worse crc prognosis. Taking metformin appears to have a positive association with prognosis. The protective nature of metformin needs further evaluation in prospective analyses. PMID:27122979

D816 mutation of the KIT gene in core binding factor acute myeloid leukemia is associated with poorer prognosis than other KIT gene mutations.

PubMed

Yui, Shunsuke; Kurosawa, Saiko; Yamaguchi, Hiroki; Kanamori, Heiwa; Ueki, Toshimitsu; Uoshima, Nobuhiko; Mizuno, Ishikazu; Shono, Katsuhiro; Usuki, Kensuke; Chiba, Shigeru; Nakamura, Yukinori; Yanada, Masamitsu; Kanda, Junya; Tajika, Kenji; Gomi, Seiji; Fukunaga, Keiko; Wakita, Satoshi; Ryotokuji, Takeshi; Fukuda, Takahiro; Inokuchi, Koiti

2017-10-01

The clinical impact of KIT mutations in core binding factor acute myeloid leukemia (CBF-AML) is still unclear. In the present study, we analyzed the prognostic significance of each KIT mutation (D816, N822K, and other mutations) in Japanese patients with CBF-AML. We retrospectively analyzed 136 cases of CBF-AML that had gone into complete remission (CR). KIT mutations were found in 61 (45%) of the patients with CBF-AML. D816, N822K, D816 and N822K, and other mutations of the KIT gene were detected in 29 cases (21%), 20 cases (15%), 7 cases (5%), and 5 cases (4%), respectively. The rate of relapse-free survival (RFS) and overall survival (OS) in patients with D816 and with both D816 and N822K mutations was significantly lower than in patients with other or with no KIT mutations (RFS: p < 0.001, OS: p < 0.001). Moreover, stratified analysis of the chromosomal abnormalities t(8;21)(q22;q22) and inv(16)(p13.1q22), t(16;16)(p13.1;q22) showed that D816 mutation was associated with a significantly worse prognosis. In a further multivariate analysis of RFS and OS, D816 mutation was found to be an independent risk factor for significantly poorer prognosis. In the present study, we were able to establish that, of all KIT mutations, D816 mutation alone is an unfavorable prognostic factor.

Ward mortality after ICU discharge: a multicenter validation of the Sabadell score.

PubMed

Fernandez, Rafael; Serrano, Jose Manuel; Umaran, Isabel; Abizanda, Ricard; Carrillo, Andres; Lopez-Pueyo, Maria Jesus; Rascado, Pedro; Balerdi, Begoña; Suberviola, Borja; Hernandez, Gonzalo

2010-07-01

Tools for predicting post-ICU patients' outcomes are scarce. A single-center study showed that the Sabadell score classified patients into four groups with clear-cut differences in ward mortality. To validate the Sabadell score using a prospective multicenter approach. Thirty-one ICUs in Spain. All patients admitted in the 3-month study period. We recorded variables at ICU admission (age, sex, severity of illness, and do-not-resuscitate orders), during the ICU stay (ICU-specific treatments, ICU-acquired infection, and acute renal failure), and at ICU discharge (Sabadell score). Statistical analyses included one-way ANOVA and multiple regression analysis with ward mortality as the dependent variable. We admitted 4,132 patients (mean age 61.5 +/- 16.7 years) with mean predicted mortality of 23.8 +/- 22.7%; 545 patients (13%) died in the ICU and 3,587 (87%) were discharged to the ward. Overall ward mortality was 6.7%; ward mortality was 1.5% (36/2,422) in patients with score 0 (good prognosis), 9% (64/725) in patients with score 1 (long-term poor prognosis), 23% (79/341) in patients with score 2 (short-term poor prognosis), and 64% (63/99) in patients with score 3 (expected hospital death). Variables associated with ward mortality in the multivariate analysis were predicted risk of death (OR 1.016), ICU readmission (OR 5.9), Sabadell score 1 (OR 4.7), Sabadell score 2 (OR 15.7), and Sabadell score 3 (OR 107.2). We confirm the ability of the Sabadell score at ICU discharge to define four groups of patients with very different likelihoods of hospital survival.

Zinc finger AN1-type containing 4 is a novel marker for predicting metastasis and poor prognosis in oral squamous cell carcinoma.

PubMed

Kurihara-Shimomura, Miyako; Sasahira, Tomonori; Nakamura, Hiroshi; Nakashima, Chie; Kuniyasu, Hiroki; Kirita, Tadaaki

2018-05-01

Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth most common cancer worldwide and has a high potential for locoregional invasion and nodal metastasis. Therefore, discovery of a useful molecular biomarker capable of predicting tumour progression and metastasis of OSCC is crucial. We have previously reported zinc finger AN1-type containing 4 (ZFAND4) as one of the most upregulated genes in recurrent OSCC using a cDNA microarray analysis. Although ZFAND4 has been shown to promote cell proliferation of gastric cancer, its expression and clinicopathological roles in OSCC remain unclear. In this study, we examined ZFAND4 expression by immunohistochemistry in 214 cases of OSCC. High cytoplasmic expression of ZFAND4 was observed in 45 out of 214 (21%) patients with OSCC. Expression levels of ZFAND4 were strongly associated with metastasis to the lymph nodes (p=0.0429) and distant organs (p=0.0068). Cases with high expression of ZFAND4 had a significantly unfavourable prognosis compared with patients with low expression of ZFAND4 (p<0.0001). Furthermore, ZFAND4 overexpression was an independent poor prognostic factor for OSCC as determined by multivariate analysis using the Cox proportional hazards model (p<0.0001). These results suggest that ZFAND4 is a useful marker for predicting metastasis and poor prognosis in patients with OSCC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparative Study of Outcome Measures and Analysis Methods for Traumatic Brain Injury Trials

PubMed Central

Alali, Aziz S.; Vavrek, Darcy; Barber, Jason; Dikmen, Sureyya; Nathens, Avery B.

2015-01-01

Abstract Batteries of functional and cognitive measures have been proposed as alternatives to the Extended Glasgow Outcome Scale (GOSE) as the primary outcome for traumatic brain injury (TBI) trials. We evaluated several approaches to analyzing GOSE and a battery of four functional and cognitive measures. Using data from a randomized trial, we created a “super” dataset of 16,550 subjects from patients with complete data (n=331) and then simulated multiple treatment effects across multiple outcome measures. Patients were sampled with replacement (bootstrapping) to generate 10,000 samples for each treatment effect (n=400 patients/group). The percentage of samples where the null hypothesis was rejected estimates the power. All analytic techniques had appropriate rates of type I error (≤5%). Accounting for baseline prognosis either by using sliding dichotomy for GOSE or using regression-based methods substantially increased the power over the corresponding analysis without accounting for prognosis. Analyzing GOSE using multivariate proportional odds regression or analyzing the four-outcome battery with regression-based adjustments had the highest power, assuming equal treatment effect across all components. Analyzing GOSE using a fixed dichotomy provided the lowest power for both unadjusted and regression-adjusted analyses. We assumed an equal treatment effect for all measures. This may not be true in an actual clinical trial. Accounting for baseline prognosis is critical to attaining high power in Phase III TBI trials. The choice of primary outcome for future trials should be guided by power, the domain of brain function that an intervention is likely to impact, and the feasibility of collecting outcome data. PMID:25317951

Multivariate pattern recognition for diagnosis and prognosis in clinical neuroimaging: state of the art, current challenges and future trends.

PubMed

Haller, Sven; Lovblad, Karl-Olof; Giannakopoulos, Panteleimon; Van De Ville, Dimitri

2014-05-01

Many diseases are associated with systematic modifications in brain morphometry and function. These alterations may be subtle, in particular at early stages of the disease progress, and thus not evident by visual inspection alone. Group-level statistical comparisons have dominated neuroimaging studies for many years, proving fascinating insight into brain regions involved in various diseases. However, such group-level results do not warrant diagnostic value for individual patients. Recently, pattern recognition approaches have led to a fundamental shift in paradigm, bringing multivariate analysis and predictive results, notably for the early diagnosis of individual patients. We review the state-of-the-art fundamentals of pattern recognition including feature selection, cross-validation and classification techniques, as well as limitations including inter-individual variation in normal brain anatomy and neurocognitive reserve. We conclude with the discussion of future trends including multi-modal pattern recognition, multi-center approaches with data-sharing and cloud-computing.

Characterization and Long-Term Prognosis of Postmyocarditic Dilated Cardiomyopathy Compared With Idiopathic Dilated Cardiomyopathy.

PubMed

Merlo, Marco; Anzini, Marco; Bussani, Rossana; Artico, Jessica; Barbati, Giulia; Stolfo, Davide; Gigli, Marta; Muça, Matilda; Naso, Paola; Ramani, Federica; Di Lenarda, Andrea; Pinamonti, Bruno; Sinagra, Gianfranco

2016-09-15

Dilated cardiomyopathy (DC) is the final common pathway of different pathogenetic processes and presents a significant prognostic heterogeneity, possibly related to its etiologic variety. The characterization and long-term prognosis of postmyocarditic dilated cardiomyopathy (PM-DC) remain unknown. This study assesses the clinical-instrumental evolution and long-term prognosis of a large cohort of patients with PM-DC. We analyzed 175 patients affected with DC consecutively enrolled from 1993 to 2008 with endomyocardial biopsy (EMB) data available. PM-DC was defined in the presence of borderline myocarditis at EMB or persistent left ventricular dysfunction 1 year after diagnosis of active myocarditis at EMB. Other patients were defined as affected by idiopathic dilated cardiomyopathy (IDC). Analysis of follow-up evaluations was performed at 24, 60, and 120 months. We found 72 PM-DC of 175 enrolled patients (41%). Compared with IDC, patients with PM-DC were more frequently females and less frequently presented a familial history of DC. No other baseline significant differences were found. During the long-term follow-up (median 154, first to third interquartile range 78 to 220 months), patients with PM-DC showed a trend toward slower disease progression. Globally, 18 patients with PM-DC (25%) versus 49 with IDC (48%) experienced death/heart transplantation (p = 0.045). The prognostic advantage for patients with PM-DC became significant beyond 40 months of follow-up. At multivariable time-dependent Cox analysis, PM-DC was confirmed to have a global independent protective role (hazard ratio 0.53, 95% confidence interval 0.28 to 0.97, p = 0.04). In conclusion, PM-DC is characterized by better long-term prognosis compared with IDC. An exhaustive etiologic characterization appears relevant in the prognostic assessment of DC. Copyright © 2016 Elsevier Inc. All rights reserved.

Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusions: Clinical Features, Treatments and Prognosis.

PubMed

Liu, Ning; Wang, Zhen; Gan, Weidong; Xiong, Lei; Miao, Baolei; Chen, Xiancheng; Guo, Hongqian; Li, Dongmei

2016-01-01

To investigate the clinical characteristics, treatments and prognosis of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions (Xp11.2 tRCC), the epidemiological features and treatment results of 34 cases of Xp11.2 tRCC, which were diagnosed by immunohistochemistry staining of TFE3 and fluorescence in situ hybridization at our center, were retrospectively reviewed. The 34 patients included 21 females and 13 males aged 3 to 64 years (median age: 27 years). Four patients were children or adolescents (<18 years of age), and 26 patients were young or middle-aged adults (18-45 years). Radical nephrectomy was performed on 25 patients. Laparoscopic nephron-sparing surgery was performed on 9 patients who presented with an isolated mass with a small diameter (<7 cm) and well-defined boundary on computed tomography imaging. Postoperative staging showed that 25 cases (73.53%) were at stage I/II, while 9 cases (26.47%) were at stage III/IV. All stage I/II patients received a favorable prognosis with a three-year overall survival rate of 100%, including the patients who underwent laparoscopic nephron-sparing surgery. With the exception of 2 children, the other 7 stage III/IV patients died or developed recurrence with a median follow-up of 29 months. On univariate analysis, maximum diameter, adjuvant treatment, TNM stage, lymph node metastasis, inferior vena cava tumor thrombosis and tumor boundary were identified as statistically significant factors impacting survival (P<0.05). Multivariate analysis indicated that TNM stage and inferior vena cava tumor thrombosis were independent prognostic factors (P<0.05). In conclusion, Xp11.2 tRCC is a rare subtype of renal cell carcinoma that mainly occurs in young females. Nephron-sparing surgery was confirmed effective preliminarily in the treatment of small Xp11.2 tRCCs with clear rims. Advanced TNM stage and inferior vena cava tumor thrombosis were associated with poor prognosis.

Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusions: Clinical Features, Treatments and Prognosis

PubMed Central

Gan, Weidong; Xiong, Lei; Miao, Baolei; Chen, Xiancheng; Guo, Hongqian; Li, Dongmei

2016-01-01

To investigate the clinical characteristics, treatments and prognosis of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions (Xp11.2 tRCC), the epidemiological features and treatment results of 34 cases of Xp11.2 tRCC, which were diagnosed by immunohistochemistry staining of TFE3 and fluorescence in situ hybridization at our center, were retrospectively reviewed. The 34 patients included 21 females and 13 males aged 3 to 64 years (median age: 27 years). Four patients were children or adolescents (<18 years of age), and 26 patients were young or middle-aged adults (18–45 years). Radical nephrectomy was performed on 25 patients. Laparoscopic nephron-sparing surgery was performed on 9 patients who presented with an isolated mass with a small diameter (<7 cm) and well-defined boundary on computed tomography imaging. Postoperative staging showed that 25 cases (73.53%) were at stage I/II, while 9 cases (26.47%) were at stage III/IV. All stage I/II patients received a favorable prognosis with a three-year overall survival rate of 100%, including the patients who underwent laparoscopic nephron-sparing surgery. With the exception of 2 children, the other 7 stage III/IV patients died or developed recurrence with a median follow-up of 29 months. On univariate analysis, maximum diameter, adjuvant treatment, TNM stage, lymph node metastasis, inferior vena cava tumor thrombosis and tumor boundary were identified as statistically significant factors impacting survival (P<0.05). Multivariate analysis indicated that TNM stage and inferior vena cava tumor thrombosis were independent prognostic factors (P<0.05). In conclusion, Xp11.2 tRCC is a rare subtype of renal cell carcinoma that mainly occurs in young females. Nephron-sparing surgery was confirmed effective preliminarily in the treatment of small Xp11.2 tRCCs with clear rims. Advanced TNM stage and inferior vena cava tumor thrombosis were associated with poor prognosis. PMID:27893792

MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4.

PubMed

Cheng, Dantong; Zhao, Senlin; Tang, Huamei; Zhang, Dongyuan; Sun, Hongcheng; Yu, Fudong; Jiang, Weiliang; Yue, Ben; Wang, Jingtao; Zhang, Meng; Yu, Yang; Liu, Xisheng; Sun, Xiaofeng; Zhou, Zongguang; Qin, Xuebin; Zhang, Xin; Yan, Dongwang; Wen, Yugang; Peng, Zhihai

2016-07-19

Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known. miR-20a-5p negatively regulated Smad4 by directly targeting its 3'UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients' clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients. Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan-Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data. miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer.

MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4

PubMed Central

Zhang, Dongyuan; Sun, Hongcheng; Yu, Fudong; Yue, Ben; Wang, Jingtao; Zhang, Meng; Yu, Yang; Liu, Xisheng; Sun, Xiaofeng; Zhou, Zongguang; Qin, Xuebin; Zhang, Xin; Yan, Dongwang; Wen, Yugang; Peng, Zhihai

2016-01-01

Background Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known. Results miR-20a-5p negatively regulated Smad4 by directly targeting its 3′UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients’ clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients. Methods Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan–Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data. Conclusions miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer. PMID:27286257

The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer

PubMed Central

Yamaguchi, Rin; Nishimura, Reiki; Osako, Tomofumi; Arima, Nobuyuki; Okumura, Yasuhiro; Okido, Masayuki; Yamada, Mai; Kai, Masaya; Kishimoto, Junji; Oda, Yoshinao; Nakamura, Masafumi

2017-01-01

This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.6%) tumors. PD-L1 expression correlated with high levels of TILs, but was not a prognostic factor. Patients with TILs-high tumors had better overall survival than those with TILs-low tumors (P = 0.016). There was a strong interaction between PD-L1 expression and TILs that was associated with both recurrence-free survival (P = 0.0018) and overall survival (P = 0.015). Multivariate Cox proportional hazards model analysis showed that PD-L1-positive/TILs-low was an independent negative prognostic factor for both recurrence-free survival and overall survival. Our findings suggest that PD-L1-positive/TILs-low tumors are associated with a poor prognosis in patients with TNBC, and that it is important to focus on the combination of PD-L1 expression on tumor cells and TILs present in the tumor microenvironment. These biomarkers may be useful for stratification of TNBCs and for predicting prognosis and developing novel cancer immunotherapies. PMID:28107186

[Neck lymphatic metastasis, surgical methods and prognosis in early tongue squamous cell carcinoma].

PubMed

Wang, L S; Zhou, F T; Han, C B; He, X P; Zhang, Z X

2018-02-09

Objective: To investigate the different pattern of neck lymph node metastasis, the choice of surgical methods and prognosis in early tongue squamous cell carcinoma. Methods: A total of 157 patients with early oral tongue squamous cell carcinoma were included in this study. Statistical analysis was performed to identify the pattern of lymph node metastasis, to determine the best surgical procedure and to analyze the prognosis. Results: The occurrence of cervical lymph node metastasis rate was 31%(48/157). Neck lymphatic metastasis was significantly related to tumor size ( P= 0.026) and histology differentiation type ( P= 0.022). The rate of metastasis was highest in level Ⅱ [33% (16/48)]. In level Ⅳ, the incidence of lymph node metastasis was 5%(7/157), and there was no skip metastases. The possibility of level Ⅳ metastasis was higher, when level Ⅱ ( P= 0.000) or Ⅲ ( P= 0.000) involved. The differentiation tumor recurrence, neck lymphatic metastasis and adjuvant radiotherapy were prognostic factors ( P< 0.05). Multivariate analyses revealed histology differentiation type, neck lymphatic metastases and adjuvant radiotherapy were the independent prognostic factors. Conclusions: Neck lymphatic metastasis rate is high in early tongue squamous cell carcinoma, simultaneous glossectomy and neck dissection should be performed. Level Ⅳ metastasis rate is extremely low, so supraomohyoid neck dissection is sufficient for most of the time. The histology differentiation type, neck lymphatic metastasis and adjuvant radiotherapy are independent prognostic factors.

Elevated preoperative neutrophil-to-lymphocytes ratio predicts poor prognosis after esophagectomy in T1 esophageal cancer.

PubMed

Nakamura, Kenichi; Yoshida, Naoya; Baba, Yoshifumi; Kosumi, Keisuke; Uchihara, Tomoyuki; Kiyozumi, Yuki; Ohuchi, Mayuko; Ishimoto, Takatsugu; Iwatsuki, Masaaki; Sakamoto, Yasuo; Watanabe, Masayuki; Baba, Hideo

2017-06-01

The neutrophil-to-lymphocyte ratio (NLR) has been reported to predict the prognosis of various malignant tumors, including esophageal cancer. However, no previous reports have supported the use of the preoperative NLR as an independent prognostic marker focused on superficial (T1) esophageal cancer. The aim of this study was to elucidate the prognostic impact of the preoperative NLR in T1 esophageal cancer. This retrospective study recruited 245 consecutive patients with T1 esophageal cancer who underwent subtotal esophagectomy between 2005 and 2016. The relationship between the preoperative NLR and clinicopathological characteristics was analyzed. The preoperative NLR was significantly higher in male patients (p = 0.029), patients with T1b esophageal cancer (p = 0.0274), and patients with venous vessel invasion (p = 0.0082). In the Kaplan-Meier analysis, the elevated preoperative NLR was significantly associated with a poorer disease-free survival (p < 0.0001) and overall survival (p = 0.0004). In the multivariate Cox model, the elevated preoperative NLR was an independent prognostic marker for both disease-free survival (p = 0.0013) and overall survival (p = 0.0027). An elevated preoperative NLR predicts poor prognosis in T1 esophageal cancer, suggesting the utility of the NLR as an easily measurable and generally available independent prognostic marker.

Efficiency and prognosis of whole brain irradiation combined with precise radiotherapy on triple-negative breast cancer.

PubMed

Wu, Xinhong; Luo, Bo; Wei, Shaozhong; Luo, Yan; Feng, Yaojun; Xu, Juan; Wei, Wei

2013-11-01

To investigate the treatment efficiency of whole brain irradiation combined with precise radiotherapy on triple-negative (TN) phenotype breast cancer patients with brain metastases and their survival times. A total of 112 metastatic breast cancer patients treated with whole brain irradiation and intensity modulated radiotherapy (IMRT) or 3D conformal radiotherapy (3DCRT) were analyzed. Thirty-seven patients were of TN phenotype. Objective response rates were compared. Survival times were estimated by using the Kaplan-Meier method. Log-rank test was used to compare the survival time difference between the TN and non-TN groups. Potential prognostic factors were determined by using a Cox proportional hazard regression model. The efficiency of radiotherapy treatment on TN and non-TN phenotypes was 96.2% and 97%, respectively. TN phenotype was associated with worse survival times than non-TN phenotype after radiotherapy (6.9 months vs. 17 months) (P < 0.01). On multivariate analysis, good prognosis was associated with non-TN status, lower graded prognosis assessment class, and nonexistence of active extracranial metastases. After whole brain irradiation followed by IMRT or 3DCRT treatment, TN phenotype breast cancer patients with intracranial metastasis had high objective response rates but shorter survival time. With respect to survival in breast cancer patients with intracranial metastasis, the TN phenotype represents a significant adverse prognostic factor.

Prognosis of neonatal tetanus in the modern management era: an observational study in 107 Vietnamese infants

PubMed Central

Lam, Phung Khanh; Trieu, Huynh T.; Lubis, Inke Nadia D.; Loan, Huynh T.; Thuy, Tran Thi Diem; Wills, Bridget; Parry, Christopher M.; Day, Nicholas P.J.; Qui, Phan T.; Yen, Lam Minh; Thwaites, C. Louise

2015-01-01

Summary Objectives Most data regarding the prognosis in neonatal tetanus originate from regions where limited resources have historically impeded management. It is not known whether recent improvements in critical care facilities in many low- and middle-income countries have affected indicators of a poor prognosis in neonatal tetanus. We aimed to determine the factors associated with worse outcomes in a Vietnamese hospital with neonatal intensive care facilities. Methods Data were collected from 107 cases of neonatal tetanus. Clinical features on admission were analyzed against mortality and a combined endpoint of ‘death or prolonged hospital stay’. Results Multivariable analysis showed that only younger age (odds ratio (OR) for mortality 0.69, 95% confidence interval (CI) 0.48–0.98) and lower weight (OR for mortality 0.06, 95% CI 0.01–0.54) were significantly associated with both the combined endpoint and death. A shorter period of onset (OR 0.94, 95% CI 0.88–0.99), raised white cell count (OR 1.17, 95% CI 1.02–1.35), and time between first symptom and admission (OR 3.77, 95% CI 1.14–12.51) were also indicators of mortality. Conclusions Risk factors for a poor outcome in neonatal tetanus in a setting with critical care facilities include younger age, lower weight, delay in admission, and leukocytosis. PMID:25499039

Prognosis of neonatal tetanus in the modern management era: an observational study in 107 Vietnamese infants.

PubMed

Lam, Phung Khanh; Trieu, Huynh T; Lubis, Inke Nadia D; Loan, Huynh T; Thuy, Tran Thi Diem; Wills, Bridget; Parry, Christopher M; Day, Nicholas P J; Qui, Phan T; Yen, Lam Minh; Thwaites, C Louise

2015-04-01

Most data regarding the prognosis in neonatal tetanus originate from regions where limited resources have historically impeded management. It is not known whether recent improvements in critical care facilities in many low- and middle-income countries have affected indicators of a poor prognosis in neonatal tetanus. We aimed to determine the factors associated with worse outcomes in a Vietnamese hospital with neonatal intensive care facilities. Data were collected from 107 cases of neonatal tetanus. Clinical features on admission were analyzed against mortality and a combined endpoint of 'death or prolonged hospital stay'. Multivariable analysis showed that only younger age (odds ratio (OR) for mortality 0.69, 95% confidence interval (CI) 0.48-0.98) and lower weight (OR for mortality 0.06, 95% CI 0.01-0.54) were significantly associated with both the combined endpoint and death. A shorter period of onset (OR 0.94, 95% CI 0.88-0.99), raised white cell count (OR 1.17, 95% CI 1.02-1.35), and time between first symptom and admission (OR 3.77, 95% CI 1.14-12.51) were also indicators of mortality. Risk factors for a poor outcome in neonatal tetanus in a setting with critical care facilities include younger age, lower weight, delay in admission, and leukocytosis. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Importance of the Postoperative Carcinoembryonic Antigen Level during Follow-Up after Curative Resection in Patients with Liver Metastatic Colorectal Carcinoma.

PubMed

Hashimoto, Takuzo; Itabashi, Michio; Ogawa, Shinpei; Hirosawa, Tomoichiro; Bamba, Yoshiko; Kaji, Sanae; Ubukata, Mamiko; Shimizu, Satoru; Sugihara, Kenichi; Kameoka, Shingo

2014-06-01

To validate the conventional Japanese grading of liver metastasis for no residual tumor resection in Stage IV colorectal cancer (CRC) with liver metastasis and to identify risk factors for postoperative recurrence. The subjects of this study were 1792 Stage IV CRC patients with liver metastasis. In 1792 cases, including unresectable cases, there was a significantly different prognosis by grade (P < 0.0001). In 421 R0 cases, there was no significant difference between Grade A and Grade B (P = 0.8527). In 381 cases without extra-hepatic metastasis, the prognosis was not significantly different among three grades. On multivariate analysis, carcinoembryonic antigen within 3 months from R0 operation (3M-CEA) was an independent risk factor regardless of extrahepatic metastasis. There was a significantly different prognosis (P < 0.0001) among Grade A', defined as a normal 3M-CEA level, Grade B', defined as Grade A or B and an abnormal 3M-CEA level, and Grade C', defined as Grade C and an abnormal 3M-CEA level. The postoperative CEA level is an important risk factor during follow-up after curative resection in patients with liver metastatic colorectal carcinoma. The combination of the 3M-CEA level and conventional grading of liver metastasis is useful for follow-up of R0 resection cases.

18F-Fluoride PET/CT tumor burden quantification predicts survival in breast cancer.

PubMed

Brito, Ana E; Santos, Allan; Sasse, André Deeke; Cabello, Cesar; Oliveira, Paulo; Mosci, Camila; Souza, Tiago; Amorim, Barbara; Lima, Mariana; Ramos, Celso D; Etchebehere, Elba

2017-05-30

In bone-metastatic breast cancer patients, there are no current imaging biomarkers to identify which patients have worst prognosis. The purpose of our study was to investigate if skeletal tumor burden determined by 18F-Fluoride PET/CT correlates with clinical outcomes and may help define prognosis throughout the course of the disease. Bone metastases were present in 49 patients. On multivariable analysis, skeletal tumor burden was significantly and independently associated with overall survival (p < 0.0001) and progression free-survival (p < 0.0001). The simple presence of bone metastases was associated with time to bone event (p = 0.0448). We quantified the skeletal tumor burden on 18F-Fluoride PET/CT images of 107 female breast cancer patients (40 for primary staging and the remainder for restaging after therapy). Clinical parameters, primary tumor characteristics and skeletal tumor burden were correlated to overall survival, progression free-survival and time to bone event. The median follow-up time was 19.5 months. 18F-Fluoride PET/CT skeletal tumor burden is a strong independent prognostic imaging biomarker in breast cancer patients.

GATA3 rs3824662 gene polymorphism as possible risk factor in a cohort of Egyptian patients with pediatric acute lymphoblastic leukemia and its prognostic impact.

PubMed

Mosaad, Youssef M; Elashery, Rasha; Darwish, Ahmad; Sharaf Eldein, Omar A; Barakat, Tarek; Marouf, Samy; Abou El-Khier, Noha T; Youssef, Laila F; Fawzy, Iman M

2017-03-01

To investigate the possible role of GATA3 rs3824662 polymorphism as risk factor for the development of acute lymphoblastic leukemia (ALL) in a cohort of Egyptian children and to evaluate its prognostic role. Typing of GATA3 rs3824662 polymorphism was done using real-time PCR for 116 patients with ALL and 273 healthy controls. The A allele and AA genotype were significantly higher in ALL patients (p = .015 and .016, respectively) especially B-ALL (p = .014 and .01, respectively). The AA genotype was associated with shorter disease free survival (DFS) in univariate (p = .017) and multivariate cox regression analysis (p = .028), increased incidence of relapse (p = .008) and poor prognosis (p = .028) in pediatric ALL. The GATA3 rs3824662 A allele and AA genotype may be risk factors for the development of pediatric ALL especially B-ALL in the studied cohort of Egyptian patients. The AA genotype is associated with shorter DSF, increased incidence of relapse and poor prognosis in pediatric ALL.

Prognostic value of DNA repair based stratification of hepatocellular carcinoma

PubMed Central

Lin, Zhuo; Xu, Shi-Hao; Wang, Hai-Qing; Cai, Yi-Jing; Ying, Li; Song, Mei; Wang, Yu-Qun; Du, Shan-Jie; Shi, Ke-Qing; Zhou, Meng-Tao

2016-01-01

Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy. PMID:27174663

High-level mRNA quantification of proliferation marker pKi-67 is correlated with favorable prognosis in colorectal carcinoma.

PubMed

Ihmann, Thomas; Liu, Jian; Schwabe, Wolfgang; Häusler, Peter; Behnke, Detlev; Bruch, Hans-Peter; Broll, Rainer; Windhövel, Ute; Duchrow, Michael

2004-12-01

The present study retrospectively examines the expression of pKi-67 mRNA and protein in colorectal carcinoma and their correlation to the outcome of patients. Immunohistochemistry and quantitative RT-PCR were used to analyze the expression of pKi-67 in 43 archival specimens of patients with curatively resected primary colorectal carcinoma, who were not treated with neo-adjuvant therapy. We determined a median pKi-67 (MIB-1) labeling index of 31.3% (range 10.3-66.4%), and a mean mRNA level of 0.1769 (DeltaC(T): range 0.01-0.69); indices and levels did not correlate. High pKi-67 mRNA DeltaC(T) values were associated with a significantly favorable prognosis, while pKi-67 labeling indices were not correlated to prognostic outcome. A multivariate analysis of clinical and biological factors indicated that tumor stage (UICC) and pKi-67 mRNA expression level were independent prognostic factors. Quantitatively determined pKi-67 mRNA can be a good and new prognostic indicator for primary resected colorectal carcinoma.

Raman exfoliative cytology for oral precancer diagnosis

NASA Astrophysics Data System (ADS)

Sahu, Aditi; Gera, Poonam; Pai, Venkatesh; Dubey, Abhishek; Tyagi, Gunjan; Waghmare, Mandavi; Pagare, Sandeep; Mahimkar, Manoj; Murali Krishna, C.

2017-11-01

Oral premalignant lesions (OPLs) such as leukoplakia, erythroplakia, and oral submucous fibrosis, often precede oral cancer. Screening and management of these premalignant conditions can improve prognosis. Raman spectroscopy has previously demonstrated potential in the diagnosis of oral premalignant conditions (in vivo), detected viral infection, and identified cancer in both oral and cervical exfoliated cells (ex vivo). The potential of Raman exfoliative cytology (REC) in identifying premalignant conditions was investigated. Oral exfoliated samples were collected from healthy volunteers (n=20), healthy volunteers with tobacco habits (n=20), and oral premalignant conditions (n=27, OPL) using Cytobrush. Spectra were acquired using Raman microprobe. Spectral acquisition parameters were: λex: 785 nm, laser power: 40 mW, acquisition time: 15 s, and average: 3. Postspectral acquisition, cell pellet was subjected to Pap staining. Multivariate analysis was carried out using principal component analysis and principal component-linear discriminant analysis using both spectra- and patient-wise approaches in three- and two-group models. OPLs could be identified with ˜77% (spectra-wise) and ˜70% (patient-wise) sensitivity in the three-group model while with 86% (spectra-wise) and 83% (patient-wise) in the two-group model. Use of histopathologically confirmed premalignant cases and better sampling devices may help in development of improved standard models and also enhance the sensitivity of the method. Future longitudinal studies can help validate potential of REC in screening and monitoring high-risk populations and prognosis prediction of premalignant lesions.

Prognostic Value of Protocadherin10 (PCDH10) Methylation in Serum of Prostate Cancer Patients.

PubMed

Deng, Qiu-Kui; Lei, Yong-Gang; Lin, Ying-Li; Ma, Jian-Guo; Li, Wen-Ping

2016-02-16

BACKGROUND Prostate cancer is a heterogeneous malignancy with outcome difficult to predict. Currently, there is an urgent need to identify novel biomarkers that can accurately predict patient outcome and improve the treatment strategy. The aim of this study was to investigate the methylation status of PCDH10 in serum of prostate cancer patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS The methylation status of PCDH10 in serum of 171 primary prostate cancer patients and 65 controls was evaluated by methylation-specific PCR (MSP), after which the relationship between PCDH10 methylation and clinicopathologic features was evaluated. Kaplan-Meier survival analysis and Cox analysis were used to evaluate the correlation between PCDH10 methylation and prognosis. RESULTS PCDH10 methylation occurred frequently in serum of prostate cancer patients. Moreover, PCDH10 methylation was significantly associated with higher preoperative PSA level, advanced clinical stage, higher Gleason score, lymph node metastasis, and biochemical recurrence (BCR). In addition, patients with methylated PCDH10 had shorter BCR-free survival and overall survival than patients with unmethylated PCDH10. Univariate and multivariate Cox proportional hazards model analysis indicated that PCDH10 methylation in serum is an independent predictor of worse BCR-free survival and overall survival. CONCLUSIONS PCDH10 methylation in serum is a potential prognostic biomarker for prostate cancer.

A Comparative Performance Analysis of Multispectral and RGB Imaging on HER2 Status Evaluation for the Prediction of Breast Cancer Prognosis.

PubMed

Liu, Wenlou; Wang, Linwei; Liu, Jiuyang; Yuan, Jingping; Chen, Jiamei; Wu, Han; Xiang, Qingming; Yang, Guifang; Li, Yan

2016-12-01

Despite the extensive application of multispectral imaging (MSI) in biomedical multidisciplinary researches, there is a paucity of data available regarding the implication of MSI in tumor prognosis prediction. We compared the behaviors of multispectral (MS) and conventional red-green-blue (RGB) images on assessment of human epidermal growth factor receptor 2 (HER2) immunohistochemistry to explore their impact on outcome in patients with invasive breast cancer (BC). Tissue microarrays containing 240 BC patients were introduced to compare the performance of MS and RGB imaging methods on the quantitative assessment of HER2 status and the prognostic value of 5-year disease-free survival (5-DFS). Both the total and average signal optical density values of HER2 MS and RGB images were analyzed, and all patients were divided into two groups based on the different 5-DFS. The quantification of HER2 MS images was negatively correlated with 5-DFS in lymph node-negative and -positive patients (P<.05), but RGB images were not in lymph node-positive patients (P=.101). Multivariate analysis indicated that the hazard ratio (HR) of HER2 MS was higher than that of HER2 RGB (HR=2.454; 95% confidence interval [CI], 1.636-3.681 vs HR=2.060; 95% CI, 1.361-3.119). Additionally, area under curve (AUC) by receiver operating characteristic analysis for HER2 MS was greater than that for HER2 RGB (AUC=0.649; 95% CI, 0.577-0.722 vs AUC=0.596; 95% CI, 0.522-0.670) in predicting the risk for recurrence. More importantly, the quantification of HER2 MS images has higher prediction accuracy than that of HER2 RGB images (69.6% vs 65.0%) on 5-DFS. Our study suggested that better information on BC prognosis could be obtained from the quantification of HER2 MS images and MS images might perform better in predicting BC prognosis than conventional RGB images. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Histologic prognosticators in feline osteosarcoma: a comparison with phenotypically similar canine osteosarcoma.

PubMed

Dimopoulou, Maria; Kirpensteijn, Jolle; Moens, Hester; Kik, Marja

2008-07-01

To investigate the histologic characteristics of feline osteosarcoma (OS) and compare the histologic data with phenotypically comparable canine OS. The effects of histologic and clinical variables on survival statistics were evaluated. Retrospective study. Cats (n=62) and dogs (22). Medical records of 62 cats with OS were reviewed for clinically relevant data. Clinical outcome was obtained by telephone interview. Histologic characteristics of OS were classified using a standardized grading system. Histologic characteristics in 22 feline skeletal OS were compared with 22 canine skeletal OS of identical location and subtype. Prognostic variables for clinical outcome were determined using multivariate analysis. Feline OS was characterized by moderate to abundant cellular pleomorphism, low mitotic index, small to moderate amounts of matrix, high cellularity, and a moderate amount of necrosis. There was no significant difference between histologic variables in feline and canine OS. Histologic grade, surgery, and mitotic index significantly influenced clinical outcome as determined by multivariate analysis. Tumor invasion into vessels was not identified as a significant prognosticator. Feline and canine skeletal OS have similar histologic but different prognostic characteristics. Prognosis for cats with OS is related to histologic grade and mitotic index of the tumor.

Baseline β-catenin, programmed death-ligand 1 expression and tumour-infiltrating lymphocytes predict response and poor prognosis in BRAF inhibitor-treated melanoma patients.

PubMed

Massi, Daniela; Romano, Emanuela; Rulli, Eliana; Merelli, Barbara; Nassini, Romina; De Logu, Francesco; Bieche, Ivan; Baroni, Gianna; Cattaneo, Laura; Xue, Gongda; Mandalà, Mario

2017-06-01

The activation of oncogenic Wnt/β-catenin pathway in melanoma contributes to a lack of T-cell infiltration. Whether baseline β-catenin expression in the context of tumour-infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of metastatic melanoma patients (MMPs) treated with mitogen-activated protein kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully clarified. Sixty-four pre-treatment formalin-fixed and paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n = 39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of β-catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein P3 (FOXP3) expression by immunohistochemistry, and results were correlated with clinical outcome. Quantitative assessment of mRNA transcripts associated with Wnt/β-catenin pathway and immune response was performed in 51 patients. We found an inverse correlation between tumoural β-catenin expression and the level of CD8, CD103 or forkhead box protein P3 (FOXP3) positivity in the tumour microenvironment (TME). By multivariate analysis, PD-L1 <5% (odds ratio, OR 0.12, 95% confidence interval, CI 0.03-0.53, p = 0.005) and the presence of CD8+ T cells (OR 18.27, 95%CI 2.54-131.52, p = 0.004) were significantly associated with a higher probability of response to MAPKi monotherapy. Responding patients showed a significantly increased expression of mRNA transcripts associated with adaptive immunity and antigen presentation. By multivariate analysis, progression-free survival (PFS) (hazards ratio (HR) = 0.25 95%CI 0.10-0.61, p = 0.002) and overall survival (OS) (HR = 0.24 95%CI 0.09-0.67, p = 0.006) were longer in patients with high density of CD8+ T cells and β-catenin <10% than those without CD8+ T cells infiltration and β-catenin ≥10%. Our findings provide evidence that in the context of MAPKi monotherapy, immune subsets in the (TME) and gene signature predict prognosis in MMPs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Copy number increase of ACTN4 is a prognostic indicator in salivary gland carcinoma

PubMed Central

Watabe, Yukio; Mori, Taisuke; Yoshimoto, Seiichi; Nomura, Takeshi; Shibahara, Takahiko; Yamada, Tesshi; Honda, Kazufumi

2014-01-01

Copy number increase (CNI) of ACTN4 has been associated with poor prognosis and metastatic phenotypes in various human carcinomas. To identify a novel prognostic factor for salivary gland carcinoma, we investigated the copy number of ACTN4. We evaluated DNA copy number of ACTN4 in 58 patients with salivary gland carcinoma by using fluorescent in situ hybridization (FISH). CNI of ACTN4 was recognized in 14 of 58 patients (24.1%) with salivary gland carcinoma. The cases with CNI of ACTN4 were closely associated with histological grade (P = 0.047) and vascular invasion (P = 0.033). The patients with CNI of ACTN4 had a significantly worse prognosis than the patients with normal copy number of ACTN4 (P = 0.0005 log-rank test). Univariate analysis by the Cox proportional hazards model showed that histological grade, vascular invasion, and CNI of ACTN4 were independent risk factors for cancer death. Vascular invasion (hazard ratio [HR]: 7.46; 95% confidence interval [CI]: 1.98–28.06) and CNI of ACTN4 (HR: 3.23; 95% CI: 1.08–9.68) remained as risk factors for cancer death in multivariate analysis. Thus, CNI of ACTN4 is a novel indicator for an unfavorable outcome in patients with salivary gland carcinoma. PMID:24574362

A Risk Stratification Model for Lung Cancer Based on Gene Coexpression Network and Deep Learning

PubMed Central

2018-01-01

Risk stratification model for lung cancer with gene expression profile is of great interest. Instead of previous models based on individual prognostic genes, we aimed to develop a novel system-level risk stratification model for lung adenocarcinoma based on gene coexpression network. Using multiple microarray, gene coexpression network analysis was performed to identify survival-related networks. A deep learning based risk stratification model was constructed with representative genes of these networks. The model was validated in two test sets. Survival analysis was performed using the output of the model to evaluate whether it could predict patients' survival independent of clinicopathological variables. Five networks were significantly associated with patients' survival. Considering prognostic significance and representativeness, genes of the two survival-related networks were selected for input of the model. The output of the model was significantly associated with patients' survival in two test sets and training set (p < 0.00001, p < 0.0001 and p = 0.02 for training and test sets 1 and 2, resp.). In multivariate analyses, the model was associated with patients' prognosis independent of other clinicopathological features. Our study presents a new perspective on incorporating gene coexpression networks into the gene expression signature and clinical application of deep learning in genomic data science for prognosis prediction. PMID:29581968

Expression of CD105 cancer stem cell marker in three subtypes of renal cell carcinoma.

PubMed

Saeednejad Zanjani, Leili; Madjd, Zahra; Abolhasani, Maryam; Shariftabrizi, Ahmad; Rasti, Arezoo; Asgari, Mojgan

2018-01-01

CD105 is recently described as a cancer stem cell (CSC) marker. The present study was aimed to investigate the expression and prognostic significance of the CSC marker CD105 in different histological subtypes of renal cell carcinoma (RCC). Expression of CD105 was evaluated using immunohistochemistry in RCC samples on tissue microarrays including clear cell RCCs (ccRCCs), papillary, and chromophobe RCCs. The association between CD105 expression and clinicopathological features as well as survival outcomes was determined. In ccRCC, increased tumoral cytoplasmic and endothelial expression of CD105 were significantly associated with advanced stage, renal vein invasion, and microvascular invasion (MVI). In addition, MVI was associated with a worse overall survival (OS). Moreover, in multivariate analysis tumor stage and nuclear grade were independent prognostic factors for OS both in case of tumoral cytoplasmic and endothelial CD105 expression. Additionally, CD105 expression was found to be a predictor of worse OS in univariate analysis. However, in papillary and chromophobe RCC, no significant association was found between CD105 expression and clinicopathological parameters or prognosis. We showed that CD105 expression was associated with more aggressive tumor behavior, more advanced disease, and worse prognosis in ccRCC but not in the other RCC subtypes.

B7-H3 expression and its correlation with clinicopathologic features, angiogenesis, and prognosis in intrahepatic cholangiocarcinoma.

PubMed

Cheng, Rui; Chen, Yongqin; Zhou, Haohui; Wang, Bi; Du, Qiang; Chen, Yanling

2018-05-01

This study was designed to explore the expression of B7-H3 in human intrahepatic cholangiocarcinoma (ICC) and its association with the clinicopathologic factors. In the current study, the expression of B7-H3 in 45 patients with intrahepatic cholangiocarcinoma and 8 patients with hepatolithiasis was analyzed by immunohistochemistry, which revealed that B7-H3 was not expressed in hepatolithiatic tissues, but positively expressed in 57.8% (26/45) of the ICC cases. The expression of B7-H3 was significantly associated with lymph node metastases and venous invasion. A positive correlation was also observed between the expression of B7-H3 and MVD, an index for tumor angiogenesis. Further survival analysis indicated that patients with B7-H3 negative expression had higher overall survival (OS) and cancer-specific survival (CSS) rates than those with B7-H3 positive expression. Multivariate analysis revealed that B7-H3 expression was an independent prognostic indicator for poor OS and CSS of ICC patients. Our results suggest that B7-H3 may be a valuable biomarker in determining tumor progression and prognosis of intrahepatic cholangiocarcinoma. It is also a potential target for antivascular therapy of ICC. © 2018 APMIS. Published by John Wiley & Sons Ltd.

Expression of Notch1 and Numb in small cell lung cancer.

PubMed

Kikuchi, Hajime; Sakakibara-Konishi, Jun; Furuta, Megumi; Yokouchi, Hiroshi; Nishihara, Hiroshi; Yamazaki, Shigeo; Uramoto, Hidetaka; Tanaka, Fumihiro; Harada, Masao; Akie, Kenji; Sugaya, Fumiko; Fujita, Yuka; Takamura, Kei; Kojima, Tetsuya; Harada, Toshiyuki; Higuchi, Mitsunori; Honjo, Osamu; Minami, Yoshinori; Watanabe, Naomi; Oizumi, Satoshi; Suzuki, Hiroyuki; Ishida, Takashi; Dosaka-Akita, Hirotoshi; Isobe, Hiroshi; Munakata, Mitsuru; Nishimura, Masaharu

2017-02-07

Notch signaling in tumorigenesis functions as an oncogene or tumor suppressor according to the type of malignancy. Numb represses intracellular Notch signaling. Previous studies have demonstrated that Notch signaling suppresses the proliferation of small cell lung cancer (SCLC) cell lines. However, in SCLC, the association between Notch1 and Numb expression and clinicopathological factors or prognosis has remained unclear. In this study, we evaluated the expression of Notch1 and Numb in SCLC. We immunohistochemically assessed 125 SCLCs that were surgically resected at 16 institutions participating in either the Hokkaido Lung Cancer Clinical Study Group Trial (HOT) or the Fukushima Investigative Group for Healing Thoracic Malignancy (FIGHT) between 2003 and 2013. Correlations between Notch1 or Numb expression and various clinicopathological features were evaluated. Notch1 expression was associated with ECOG performance status. Numb expression was associated with age, sex, and pathological histology (SCLC or Combined SCLC). Analysis of cellular biological expression did not demonstrate a significant correlation between the expression of Notch1 and of Numb. Multivariate Cox regression analysis showed that high Notch1 expression was an independent favorable prognostic factor for SCLC(hazard ratio = 0.503, P = 0.023). High Notch1 expression, but not Numb expression, is associated with favorable prognosis in SCLC.

Edmondson-Steiner grade: A crucial predictor of recurrence and survival in hepatocellular carcinoma without microvascular invasio.

PubMed

Zhou, Li; Rui, Jing-An; Zhou, Wei-Xun; Wang, Shao-Bin; Chen, Shu-Guang; Qu, Qiang

2017-07-01

Microvascular invasion (MVI), an important pathologic parameter, has been proven to be a powerful predictor of long-term prognosis in hepatocellular carcinoma (HCC). However, prognostic factors in HCC without MVI remain unknown. The present study aimed to identify the risk factors of recurrence and poor post-resectional survival in this type of HCC. A total of 109 patients with MVI-absent HCC underwent radical hepatectomy were enrolled. The influence of clinicopathologic variables on recurrence and patient survival was assessed using univariate and multivariate analyses. Chi-square test found that Edmondson-Steiner grade and satellite nodule were significantly associated with recurrence, while the former was the single marker for early recurrence. Stepwise logistic regression analysis demonstrated the independent predictive role of Edmondson-Steiner grade for recurrence. On the other hand, Edmondson-Steiner grade, serum AFP level and satellite nodule were significant for overall and disease-free survival in univariate analysis, whereas tumor size was linked to disease-free survival. Of the variables, Edmondson-Steiner grade, serum AFP level and satellite nodule were independent indicators. Edmondson-Steiner grade, a histological classification, carries robust prognostic implications for all the endpoints for prognosis, thus being potential to be a crucial prognosticator in HCC without MVI. Copyright © 2017 Elsevier GmbH. All rights reserved.

Dissecting DNA repair in adult high grade gliomas for patient stratification in the post-genomic era

PubMed Central

Perry, Christina; Agarwal, Devika; Abdel-Fatah, Tarek M.A.; Lourdusamy, Anbarasu; Grundy, Richard; Auer, Dorothee T.; Walker, David; Lakhani, Ravi; Scott, Ian S.; Chan, Stephen; Ball, Graham; Madhusudan, Srinivasan

2014-01-01

Deregulation of multiple DNA repair pathways may contribute to aggressive biology and therapy resistance in gliomas. We evaluated transcript levels of 157 genes involved in DNA repair in an adult glioblastoma Test set (n=191) and validated in ‘The Cancer Genome Atlas’ (TCGA) cohort (n=508). A DNA repair prognostic index model was generated. Artificial neural network analysis (ANN) was conducted to investigate global gene interactions. Protein expression by immunohistochemistry was conducted in 61 tumours. A fourteen DNA repair gene expression panel was associated with poor survival in Test and TCGA cohorts. A Cox multivariate model revealed APE1, NBN, PMS2, MGMT and PTEN as independently associated with poor prognosis. A DNA repair prognostic index incorporating APE1, NBN, PMS2, MGMT and PTEN stratified patients in to three prognostic sub-groups with worsening survival. APE1, NBN, PMS2, MGMT and PTEN also have predictive significance in patients who received chemotherapy and/or radiotherapy. ANN analysis of APE1, NBN, PMS2, MGMT and PTEN revealed interactions with genes involved in transcription, hypoxia and metabolic regulation. At the protein level, low APE1 and low PTEN remain associated with poor prognosis. In conclusion, multiple DNA repair pathways operate to influence biology and clinical outcomes in adult high grade gliomas. PMID:25026297

Long-term prognosis in patients continuing taking antithrombotics after peptic ulcer bleeding

PubMed Central

Wang, Xi-Xu; Dong, Bo; Hong, Biao; Gong, Yi-Qun; Wang, Wei; Wang, Jue; Zhou, Zhen-Yu; Jiang, Wei-Jun

2017-01-01

AIM To investigate the long-term prognosis in peptic ulcer patients continuing taking antithrombotics after ulcer bleeding, and to determine the risk factors that influence the prognosis. METHODS All clinical data of peptic ulcer patients treated from January 1, 2009 to January 1, 2014 were retrospectively collected and analyzed. Patients were divided into either a continuing group to continue taking antithrombotic drugs after ulcer bleeding or a discontinuing group to discontinue antithrombotic drugs. The primary outcome of follow-up in peptic ulcer bleeding patients was recurrent bleeding, and secondary outcome was death or acute cardiovascular disease occurrence. The final date of follow-up was December 31, 2014. Basic demographic data, complications, and disease classifications were analyzed and compared by t- or χ2-test. The number of patients that achieved various outcomes was counted and analyzed statistically. A survival curve was drawn using the Kaplan-Meier method, and the difference was compared using the log-rank test. COX regression multivariate analysis was applied to analyze risk factors for the prognosis of peptic ulcer patients. RESULTS A total of 167 patients were enrolled into this study. As for the baseline information, differences in age, smoking, alcohol abuse, and acute cardiovascular diseases were statistically significant between the continuing and discontinuing groups (70.8 ± 11.4 vs 62.4 ± 12.0, P < 0.001; 8 (8.2%) vs 15 (21.7%), P < 0.05; 65 (66.3%) vs 13 (18.8%), P < 0.001). At the end of the study, 18 patients had recurrent bleeding and three patients died or had acute cardiovascular disease in the continuing group, while four patients had recurrent bleeding and 15 patients died or had acute cardiovascular disease in the discontinuing group. The differences in these results were statistically significant (P = 0.022, P = 0.000). The Kaplan-Meier survival curve indicated that the incidence of recurrent bleeding was higher in patients in the continuing group, and the risk of death and developing acute cardiovascular disease was higher in patients in the discontinuing group (log-rank test, P = 0.000 for both). Furthermore, COX regression multivariate analysis revealed that the hazard ratio (HR) for recurrent bleeding was 2.986 (95%CI: 067-8.356, P = 0.015) in the continuing group, while HR for death or acute cardiovascular disease was 5.216 (95%CI: 1.035-26.278, P = 0.028). CONCLUSION After the occurrence of peptic ulcer bleeding, continuing antithrombotics increases the risk of recurrent bleeding events, while discontinuing antithrombotics would increase the risk of death and developing cardiovascular disease. This suggests that clinicians should comprehensively consider the use of antithrombotics after peptic ulcer bleeding. PMID:28216980

Long-term prognosis in patients continuing taking antithrombotics after peptic ulcer bleeding.

PubMed

Wang, Xi-Xu; Dong, Bo; Hong, Biao; Gong, Yi-Qun; Wang, Wei; Wang, Jue; Zhou, Zhen-Yu; Jiang, Wei-Jun

2017-01-28

To investigate the long-term prognosis in peptic ulcer patients continuing taking antithrombotics after ulcer bleeding, and to determine the risk factors that influence the prognosis. All clinical data of peptic ulcer patients treated from January 1, 2009 to January 1, 2014 were retrospectively collected and analyzed. Patients were divided into either a continuing group to continue taking antithrombotic drugs after ulcer bleeding or a discontinuing group to discontinue antithrombotic drugs. The primary outcome of follow-up in peptic ulcer bleeding patients was recurrent bleeding, and secondary outcome was death or acute cardiovascular disease occurrence. The final date of follow-up was December 31, 2014. Basic demographic data, complications, and disease classifications were analyzed and compared by t - or χ 2 -test. The number of patients that achieved various outcomes was counted and analyzed statistically. A survival curve was drawn using the Kaplan-Meier method, and the difference was compared using the log-rank test. COX regression multivariate analysis was applied to analyze risk factors for the prognosis of peptic ulcer patients. A total of 167 patients were enrolled into this study. As for the baseline information, differences in age, smoking, alcohol abuse, and acute cardiovascular diseases were statistically significant between the continuing and discontinuing groups (70.8 ± 11.4 vs 62.4 ± 12.0, P < 0.001; 8 (8.2%) vs 15 (21.7%), P < 0.05; 65 (66.3%) vs 13 (18.8%), P < 0.001). At the end of the study, 18 patients had recurrent bleeding and three patients died or had acute cardiovascular disease in the continuing group, while four patients had recurrent bleeding and 15 patients died or had acute cardiovascular disease in the discontinuing group. The differences in these results were statistically significant ( P = 0.022, P = 0.000). The Kaplan-Meier survival curve indicated that the incidence of recurrent bleeding was higher in patients in the continuing group, and the risk of death and developing acute cardiovascular disease was higher in patients in the discontinuing group (log-rank test, P = 0.000 for both). Furthermore, COX regression multivariate analysis revealed that the hazard ratio (HR) for recurrent bleeding was 2.986 (95%CI: 067-8.356, P = 0.015) in the continuing group, while HR for death or acute cardiovascular disease was 5.216 (95%CI: 1.035-26.278, P = 0.028). After the occurrence of peptic ulcer bleeding, continuing antithrombotics increases the risk of recurrent bleeding events, while discontinuing antithrombotics would increase the risk of death and developing cardiovascular disease. This suggests that clinicians should comprehensively consider the use of antithrombotics after peptic ulcer bleeding.

Combination of blood tests for significant fibrosis and cirrhosis improves the assessment of liver-prognosis in chronic hepatitis C.

PubMed

Boursier, J; Brochard, C; Bertrais, S; Michalak, S; Gallois, Y; Fouchard-Hubert, I; Oberti, F; Rousselet, M-C; Calès, P

2014-07-01

Recent longitudinal studies have emphasised the prognostic value of noninvasive tests of liver fibrosis and cross-sectional studies have shown their combination significantly improves diagnostic accuracy. To compare the prognostic accuracy of six blood fibrosis tests and liver biopsy, and evaluate if test combination improves the liver-prognosis assessment in chronic hepatitis C (CHC). A total of 373 patients with compensated CHC, liver biopsy (Metavir F) and blood tests targeting fibrosis (APRI, FIB4, Fibrotest, Hepascore, FibroMeter) or cirrhosis (CirrhoMeter) were included. Significant liver-related events (SLRE) and liver-related deaths were recorded during follow-up (started the day of biopsy). During the median follow-up of 9.5 years (3508 person-years), 47 patients had a SLRE and 23 patients died from liver-related causes. For the prediction of first SLRE, most blood tests allowed higher prognostication than Metavir F [Harrell C-index: 0.811 (95% CI: 0.751-0.868)] with a significant increase for FIB4: 0.879 [0.832-0.919] (P = 0.002), FibroMeter: 0.870 [0.812-0.922] (P = 0.005) and APRI: 0.861 [0.813-0.902] (P = 0.039). Multivariate analysis identified FibroMeter, CirrhoMeter and sustained viral response as independent predictors of first SLRE. CirrhoMeter was the only independent predictor of liver-related death. The combination of FibroMeter and CirrhoMeter classifications into a new FM/CM classification improved the liver-prognosis assessment compared to Metavir F staging or single tests by identifying five subgroups of patients with significantly different prognoses. Some blood fibrosis tests are more accurate than liver biopsy for determining liver prognosis in CHC. A new combination of two complementary blood tests, one targeted for fibrosis and the other for cirrhosis, optimises assessment of liver-prognosis. © 2014 John Wiley & Sons Ltd.

Value of FDG-PET/CT Volumetry After Chemoradiotherapy in Rectal Cancer.

PubMed

Okuno, Takayuki; Kawai, Kazushige; Koyama, Keitaro; Takahashi, Miwako; Ishihara, Soichiro; Momose, Toshimitsu; Morikawa, Teppei; Fukayama, Masashi; Watanabe, Toshiaki

2018-03-01

Neoadjuvant chemoradiotherapy followed by an optimal surgery is the standard treatment for patients with locally advanced rectal cancer. FDG-PET/CT is commonly used as the modality for assessing the effect of chemoradiotherapy. The purpose of this study was to investigate whether PET/CT-based volumetry could contribute to the prediction of pathological complete response or prognosis after neoadjuvant chemoradiotherapy. This was a retrospective cohort study. This study was conducted at a single research center. Ninety-one consecutive patients with locally advanced rectal cancer were enrolled between January 2005 and December 2015. Patients underwent PET/CT before and after neoadjuvant chemoradiotherapy. Maximum standardized uptake value and total lesion glycolysis on PET/CT before and after neoadjuvant chemoradiotherapy were calculated using isocontour methods. Correlations between these variables and clinicopathological factors and prognosis were assessed. PET/CT-associated variables before chemoradiotherapy were not correlated with either clinicopathological factors or prognosis. Maximum standardized uptake value was associated with pathological complete response, but total lesion glycolysis was not. Maximum standardized uptake value correlated with ypT, whereas total lesion glycolysis correlated with both ypT and ypN. High total lesion glycolysis was associated with a considerably poorer prognosis; the 5-year recurrence rate was 65% and the 5-year mortality rate 42%, whereas in lesions with low total lesion glycolysis, these were 6% and 2%. On multivariate analysis, high total lesion glycolysis was an independent risk factor for recurrence (HR = 4.718; p = 0.04). The gain in fluoro-2-deoxy-D-glucose uptake may differ between scanners, thus the general applicability of this threshold should be validated. In patients with locally advanced rectal cancer, high total lesion glycolysis after neoadjuvant chemoradiotherapy is strongly associated with a worse prognosis. Total lesion glycolysis after chemoradiotherapy may be a promising preoperative predictor of recurrence and death. See Video Abstract at http://links.lww.com/DCR/A464.

Factors affecting survival outcomes of patients with non-metastatic Ewing's sarcoma family tumors in the spine: a retrospective analysis of 63 patients in a single center.

PubMed

Wan, Wei; Lou, Yan; Hu, Zhiqi; Wang, Ting; Li, Jinsong; Tang, Yu; Wu, Zhipeng; Xu, Leqin; Yang, Xinghai; Song, Dianwen; Xiao, Jianru

2017-01-01

Little information has been published in the literature regarding survival outcomes of patients with Ewing's sarcoma family tumors (ESFTs) of the spine. The purpose of this study is to explore factors that may affect the prognosis of patients with non-metastatic spinal ESFTs. A retrospective analysis of survival outcomes was performed in patients with non-metastatic spinal ESFTs. Univariate and multivariate analyses were employed to identify prognostic factors for recurrence and survival. Recurrence-free survival (RFS) and overall survival (OS) were defined as the date of surgery to the date of local relapse and death. Kaplan-Meier methods were applied to estimate RFS and OS. Log-rank test was used to analyze single factors for RFS and OS. Factors with p values ≤0.1 were subjected to multivariate analysis. A total of 63 patients with non-metastatic spinal ESFTs were included in this study. The mean follow-up period was 35.1 months (range 1-155). Postoperative recurrence was detected in 25 patients, and distant metastasis and death occurred in 22 and 36 patients respectively. The result of multivariate analysis suggested that age older than 25 years and neoadjuvant chemotherapy were favorable independent prognostic factors for RFS and OS. In addition, total en-bloc resection, postoperative chemotherapy, radiotherapy and non-distant metastasis were favorable independent prognostic factors for OS. Age older than 25 years and neoadjuvant chemotherapy are favorable prognostic factors for both RFS and OS. In addition, total en-bloc resection, postoperative chemotherapy, radiotherapy and non-distant metastasis are closely associated with favorable survival.

Quantitative fibrosis parameters highly predict esophageal-gastro varices in primary biliary cirrhosis.

PubMed

Wu, Q-M; Zhao, X-Y; You, H

2016-01-01

Esophageal-gastro Varices (EGV) may develop in any histological stages of primary biliary cirrhosis (PBC). We aim to establish and validate quantitative fibrosis (qFibrosis) parameters in portal, septal and fibrillar areas as ideal predictors of EGV in PBC patients. PBC patients with liver biopsy, esophagogastroscopy and Second Harmonic Generation (SHG)/Two-photon Excited Fluorescence (TPEF) microscopy images were retrospectively enrolled in this study. qFibrosis parameters in portal, septal and fibrillar areas were acquired by computer-assisted SHG/TPEF imaging system. Independent predictor was identified using multivariate logistic regression analysis. PBC patients with liver biopsy, esophagogastroscopy and Second Harmonic Generation (SHG)/Two-photon Excited Fluorescence (TPEF) microscopy images were retrospectively enrolled in this study. qFibrosis parameters in portal, septal and fibrillar areas were acquired by computer-assisted SHG/TPEF imaging system. Independent predictor was identified using multivariate logistic regression analysis. Among the forty-nine PBC patients with qFibrosis images, twenty-nine PBC patients with both esophagogastroscopy data and qFibrosis data were selected out for EGV prognosis analysis and 44.8% (13/29) of them had EGV. The qFibrosis parameters of collagen percentage and number of crosslink in fibrillar area, short/long/thin strings number and length/width of the strings in septa area were associated with EGV (p < 0.05). Multivariate logistic analysis showed that the collagen percentage in fibrillar area ≥ 3.6% was an independent factor to predict EGV (odds ratio 6.9; 95% confidence interval 1.6-27.4). The area under receiver operating characteristic (ROC), diagnostic sensitivity and specificity was 0.9, 100% and 75% respectively. Collagen percentage in Collagen percentage in the fibrillar area as an independent predictor can highly predict EGV in PBC patients.

The Perseus computational platform for comprehensive analysis of (prote)omics data.

PubMed

Tyanova, Stefka; Temu, Tikira; Sinitcyn, Pavel; Carlson, Arthur; Hein, Marco Y; Geiger, Tamar; Mann, Matthias; Cox, Jürgen

2016-09-01

A main bottleneck in proteomics is the downstream biological analysis of highly multivariate quantitative protein abundance data generated using mass-spectrometry-based analysis. We developed the Perseus software platform (http://www.perseus-framework.org) to support biological and biomedical researchers in interpreting protein quantification, interaction and post-translational modification data. Perseus contains a comprehensive portfolio of statistical tools for high-dimensional omics data analysis covering normalization, pattern recognition, time-series analysis, cross-omics comparisons and multiple-hypothesis testing. A machine learning module supports the classification and validation of patient groups for diagnosis and prognosis, and it also detects predictive protein signatures. Central to Perseus is a user-friendly, interactive workflow environment that provides complete documentation of computational methods used in a publication. All activities in Perseus are realized as plugins, and users can extend the software by programming their own, which can be shared through a plugin store. We anticipate that Perseus's arsenal of algorithms and its intuitive usability will empower interdisciplinary analysis of complex large data sets.

Single nucleotide polymorphisms in MLH1 predict poor prognosis of hepatocellular carcinoma in a Chinese population.

PubMed

Zhu, Xiaonian; Liu, Wei; Qiu, Xiaoqiang; Wang, Zhigang; Tan, Chao; Bei, Chunhua; Qin, Linyuan; Ren, Yuan; Tan, Shengkui

2017-10-03

Hepatocellular carcinoma (HCC) is a malignant cancer causing deleterious health effect worldwide, especially in China. So far clinical cure rate and long-term survival rate of HCC remains low. Most HCC patients after cancer resection have recurrence or metastasis within 5 years. This study aims to explore the genetic association of mutL homolog 1 ( MLH1 ) polymorphisms with HCC risk and prognosis. Four candidate MLH1 polymorphisms, rs1800734, rs10849, rs3774343 and rs1540354 were studied from a hospital-based case-control study including 1,036 cases (HCC patients) and 1,036 controls (non-HCC patients) in Guangxi, China. All these SNPs interacted with environmental risk factors, such as HBV infection, alcohol intake and smoking in the pathogenesis of HCC. However, only rs1800734 had significant difference between cases and controls. Compared to the AA genotype, patients with AG, GG and AG/GG genotype of rs1800734 had an increased risk of HCC [ORs (95% CI) = 1.217 (1.074∼1.536), 1.745 (1.301∼2.591) and 1.291 (1.126∼1.687)] and a decreased survival time [co-dominant, HR (95% CI) = 1.553 (1.257∼1.920); dominant, HR (95% CI) = 2.207 (1.572∼3.100)]. Furthermore, we found that tumor number, tumor staging, metastasis and rs1800734 were associated with the overall survival of HCC patients by multivariate COX regression analysis. No significant difference was found between the other three MLH1 polymorphisms with HCC risk and prognosis. Our study suggests MLH1 SNP, rs1800734 as a new predictor for poor prognosis of HCC patients.

Evaluation of clinical characteristics and prognosis of chronic pulmonary aspergillosis depending on the underlying lung diseases: Emphysema vs prior tuberculosis.

PubMed

Koyama, Kazuya; Ohshima, Nobuharu; Suzuki, Junko; Kawashima, Masahiro; Okuda, Kenichi; Sato, Ryota; Suzukawa, Maho; Nagai, Hideaki; Matsui, Hirotoshi; Ohta, Ken

2015-11-01

There have been scarce data evaluating the differences of clinical characteristics and prognosis of chronic pulmonary aspergillosis (CPA) depending on underlying pulmonary diseases. We tried to clarify them in CPA patients who had pulmonary emphysema or previous pulmonary tuberculosis. We reviewed and evaluated CPA patients diagnosed between 2007 and 2013 with pulmonary emphysema (PE group; n = 29), with previous pulmonary tuberculosis (PT group; n = 47) and with combination of these 2 underlying conditions (CTE group; n = 24). In CT findings, fungus balls were rare in PE group (7% in PE group and 36% in PT group; p = 0.006). Compared with PT group, PE group patients exhibited more frequent preceding antibiotics administration (45% vs 11%; p = 0.002) and fever (52% vs 17%; p = 0.002), less frequent hemosputum (24% vs 57%; p = 0.008), and more frequent consolidations in imaging (79% vs 38%; p = 0.001) and respiratory failure (34% vs 13%; p = 0.020), possibly suggesting more acute clinical manifestations of CPA in emphysematous patients. Trend of the differences between PT and PE group was not changed when patients with fungal balls were excluded. Multivariate Cox regression analysis of risks for all-cause mortality revealed age (HR, 1.079; p = 0.002) and emphysema (HR, 2.45; p = 0.040) as risk factors. Assessment of underlying lung diseases is needed when we estimate prognosis and consider treatment of CPA patients. Particularly, emphysematous patients can be presented as refractory pneumonia and show poor prognosis. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors.

PubMed

Fizazi, Karim; Culine, Stéphane; Kramar, Andrew; Amato, Robert J; Bouzy, Jeannine; Chen, Isan; Droz, Jean-Pierre; Logothetis, Christopher J

2004-10-01

The prognostic relevance of the rate of decline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy for nonseminomatous germ cell tumors (NSGCT) was studied in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Data from 653 patients prospectively recruited in clinical trials were studied. Tumor markers were obtained before chemotherapy and 3 weeks later. Decline rates were calculated using a logarithmic formula and expressed as a predicted time to normalization (TTN). A favorable TTN was defined when both AFP and HCG had a favorable decline rate, including cases with normal values. The median follow-up was 50 months (range, 2 to 151 months). Tumor decline rate expressed as a predicted TTN was associated with both progression-free survival (PFS; P <.0001) and overall survival (OS; P <.0001). The 4-year PFS rates were 64% and 38% in patients from the poor-prognosis group who had a favorable and an unfavorable TTN, respectively. The 4-year OS rates were 83% and 58%, respectively. This effect was independent from the initial tumor marker values, the primary tumor site, and the presence of nonpulmonary visceral metastases: tumor marker decline rate remained a strong predictor for both PFS (hazard ratio = 2.5; P =.01) and OS (hazard ratio = 4.6; P =.002) in patients from the IGCCCG poor-prognosis group in multivariate analysis. Early predicted time to tumor marker normalization is an independent prognostic factor in patients with poor-prognosis NSGCT and may be a useful tool in the therapeutic management of these patients.

Serum Hepatocyte Growth Factor Is Probably Associated With 3-Month Prognosis of Acute Ischemic Stroke.

PubMed

Zhu, Zhengbao; Xu, Tan; Guo, Daoxia; Huangfu, Xinfeng; Zhong, Chongke; Yang, Jingyuan; Wang, Aili; Chen, Chung-Shiuan; Peng, Yanbo; Xu, Tian; Wang, Jinchao; Sun, Yingxian; Peng, Hao; Li, Qunwei; Ju, Zhong; Geng, Deqin; Chen, Jing; Zhang, Yonghong; He, Jiang

2018-02-01

Serum hepatocyte growth factor (HGF) is positively associated with poor prognosis of heart failure and myocardial infarction, and it can also predict the risk of ischemic stroke in population. The goal of this study was to investigate the association between serum HGF and prognosis of ischemic stroke. A total of 3027 acute ischemic stroke patients were included in this post hoc analysis of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). The primary outcome was composite outcome of death or major disability (modified Rankin Scale score ≥3) within 3 months. After multivariate adjustment, elevated HGF levels were associated with an increased risk of primary outcome (odds ratio, 1.50; 95% confidence interval, 1.10-2.03; P trend =0.015) when 2 extreme quartiles were compared. Each SD increase of log-transformed HGF was associated with 14% (95% confidence interval, 2%-27%) increased risk of primary outcome. Adding HGF quartiles to a model containing conventional risk factors improved the predictive power for primary outcome (net reclassification improvement: 17.50%, P <0.001; integrated discrimination index: 0.23%, P =0.022). The association between serum HGF and primary outcome could be modified by heparin pre-treatment ( P interaction =0.001), and a positive linear dose-response relationship between HGF and primary outcome was observed in patients without heparin pre-treatment ( P linearity <0.001) but not in those with heparin pre-treatment. Serum HGF levels were higher in the more severe stroke at baseline, and elevated HGF levels were probably associated with 3-month poor prognosis independently of stroke severity among ischemic stroke patients, especially in those without heparin pre-treatment. Further studies from other samples of ischemic stroke patients are needed to validate our findings. © 2018 American Heart Association, Inc.

Impact of Exhaled Breath Acetone in the Prognosis of Patients with Heart Failure with Reduced Ejection Fraction (HFrEF). One Year of Clinical Follow-up

PubMed Central

Saldiva, Paulo H. N.; Mangini, Sandrigo; Issa, Victor S.; Ayub-Ferreira, Silvia M.; Bocchi, Edimar A.

2016-01-01

Background The identification of new biomarkers of heart failure (HF) could help in its treatment. Previously, our group studied 89 patients with HF and showed that exhaled breath acetone (EBA) is a new noninvasive biomarker of HF diagnosis. However, there is no data about the relevance of EBA as a biomarker of prognosis. Objectives To evaluate whether EBA could give prognostic information in patients with heart failure with reduced ejection fraction (HFrEF). Methods After breath collection and analysis by gas chromatography-mass spectrometry and by spectrophotometry, the 89 patients referred before were followed by one year. Study physicians, blind to the results of cardiac biomarker testing, ascertained vital status of each study participant at 12 months. Results The composite endpoint death and heart transplantation (HT) were observed in 35 patients (39.3%): 29 patients (32.6%) died and 6 (6.7%) were submitted to HT within 12 months after study enrollment. High levels of EBA (≥3.7μg/L, 50th percentile) were associated with a progressively worse prognosis in 12-month follow-up (log-rank = 11.06, p = 0.001). Concentrations of EBA above 3.7μg/L increased the risk of death or HT in 3.26 times (HR = 3.26, 95%CI = 1.56–6.80, p = 0.002) within 12 months. In a multivariable cox regression model, the independent predictors of all-cause mortality were systolic blood pressure, respiratory rate and EBA levels. Conclusions High EBA levels could be associated to poor prognosis in HFrEF patients. PMID:28030609

Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia

PubMed Central

Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

2015-01-01

Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was −0.99 standard deviation (SD) (range −4.01–+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972. PMID:26315930

Sarcopenia in COPD: relationship with COPD severity and prognosis

PubMed Central

Costa, Tatiana Munhoz da Rocha Lemos; Costa, Fabio Marcelo; Moreira, Carolina Aguiar; Rabelo, Leda Maria; Boguszewski, César Luiz; Borba, Victória Zeghbi Cochenski

2015-01-01

Objective: To evaluate the prevalence of sarcopenia in COPD patients, as well as to determine whether sarcopenia correlates with the severity and prognosis of COPD. Methods: A cross-sectional study with COPD patients followed at the pulmonary outpatient clinic of our institution. The patients underwent dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was made on the basis of the skeletal muscle index, defined as appendicular lean mass/height2 only for low-weight subjects and adjusted for fat mass in normal/overweight subjects. Disease severity (COPD stage) was evaluated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. The degree of obstruction and prognosis were determined by the Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index. Results: We recruited 91 patients (50 females), with a mean age of 67.4 ± 8.7 years and a mean BMI of 25.8 ± 6.1 kg/m2. Sarcopenia was observed in 36 (39.6%) of the patients, with no differences related to gender, age, or smoking status. Sarcopenia was not associated with the GOLD stage or with FEV1 (used as an indicator of the degree of obstruction). The BMI, percentage of body fat, and total lean mass were lower in the patients with sarcopenia than in those without (p < 0.001). Sarcopenia was more prevalent among the patients in BODE quartile 3 or 4 than among those in BODE quartile 1 or 2 (p = 0.009). The multivariate analysis showed that the BODE quartile was significantly associated with sarcopenia, regardless of age, gender, smoking status, and GOLD stage. Conclusions: In COPD patients, sarcopenia appears to be associated with unfavorable changes in body composition and with a poor prognosis. PMID:26578132

Significant association of increased PD-L1 and PD-1 expression with nodal metastasis and a poor prognosis in oral squamous cell carcinoma.

PubMed

Maruse, Y; Kawano, S; Jinno, T; Matsubara, R; Goto, Y; Kaneko, N; Sakamoto, T; Hashiguchi, Y; Moriyama, M; Toyoshima, T; Kitamura, R; Tanaka, H; Oobu, K; Kiyoshima, T; Nakamura, S

2018-07-01

Programmed cell death ligand 1 (PD-L1) and its receptor PD-1 are immune checkpoint molecules that attenuate the immune response. Blockade of PD-L1 enhances the immune response in a variety of tumours and thus serves as an effective anti-cancer treatment. However, the biological and prognostic roles of PD-L1/PD-1 signalling in oral squamous cell carcinoma (OSCC) remain to be elucidated. The purpose of this study was to examine the correlation of PD-L1/PD-1 signalling with the prognosis of OSCC patients to assess its potential therapeutic relevance. The expression of PD-L1 and of PD-1 was determined immunohistochemically in 97 patients with OSCC and the association of this expression with clinicopathological characteristics was examined. Increased expression of PD-L1 was found in 64.9% of OSCC cases and increased expression of PD-1 was found in 61.9%. Univariate and multivariate analysis revealed that increased expression of PD-L1 and PD-1 positively correlated with cervical lymph node metastasis. The expression of CD25, an activated T-cell marker, was negatively correlated with the labelling index of PD-L1 and PD-1. Moreover, the patient group with PD-L1-positive and PD-1-positive expression showed a more unfavourable prognosis than the group with PD-L1-negative and PD-1-negative expression. These data suggest that increased PD-L1 and PD-1 expression is predictive of nodal metastasis and a poor prognosis and is possibly involved in cancer progression via attenuating the immune response. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia.

PubMed

Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

2015-12-01

Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was -0.99 standard deviation (SD) (range -4.01-+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972. Copyright© Ferrata Storti Foundation.

[Treatment outcome and prognosis of autologous hematopoietic stem cell transplantation combined with high dose radiotherapy/chemotherapy in 22 patients with nasal NK/T cell lymphoma].

PubMed

Cui, Xiu-Zhen; Wang, Hua-Qing; Liu, Xian-Ming; Zhang, Hui-Lai; Li, Wei

2007-09-01

To analyze the outcome and prognosis of autologous hematopoietic stem cell transplantation (AHSCT) combined with high dose radiotherapy/chemotherapy in 22 patients with nasal NK/T cell lymphoma. From July 1992 to December 2005, 22 patients with nasal NK/T cell lymphoma were diagnosed pathologically. Immunophenotyping was performed in 13 cases. The patients were classified by Ann Arbor staging system and international prognosis index (IPI). The patients received cycles of chemotherapy every other two weeks or combined with radiotherapy for remission induction, followed high dose radiotherapy/chemotherapy, combined with autologous peripheral blood stem cell transplantation (APBSCT), or autologous bone-marrow transplantation (ABMT). Patients were given complementary radiotherapy after transplantation if they did not have it before. Twelve patients of IPI 3 -4 received consolidation chemotherapy, and one of them received the second transplantation. The median follow-up duration was 64 (12 - 168) months. The 5 and 8-year overall survivals (OS) were 79.3% and 64.1%, and disease free survivals (DFS) were 36.4% and 27.3%, respectively. The 5-year OS were as follows: for stage I - II and III - IV disease were 90.0% and 70.0% (P = 0. 041); for patients without and with B symptom were 100.0% and 70.7% (P = 0.045); and for IPI 1 - 2 and 3 - 4 were 100.0% and 60.0% (P = 0.035), respectively. Multivariate analysis by COX regression revealed that disease stage, B symptom and IPI were independent prognostic factors. AHSCT combined with high dose radiotherapy/chemotherapy is an effective treatment for patients with poor prognosis nasal NK/T cell lymphoma.

Sarcopenia in COPD: relationship with COPD severity and prognosis.

PubMed

Costa, Tatiana Munhoz da Rocha Lemos; Costa, Fabio Marcelo; Moreira, Carolina Aguiar; Rabelo, Leda Maria; Boguszewski, César Luiz; Borba, Victória Zeghbi Cochenski

2015-01-01

To evaluate the prevalence of sarcopenia in COPD patients, as well as to determine whether sarcopenia correlates with the severity and prognosis of COPD. A cross-sectional study with COPD patients followed at the pulmonary outpatient clinic of our institution. The patients underwent dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was made on the basis of the skeletal muscle index, defined as appendicular lean mass/height2 only for low-weight subjects and adjusted for fat mass in normal/overweight subjects. Disease severity (COPD stage) was evaluated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. The degree of obstruction and prognosis were determined by the Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index. We recruited 91 patients (50 females), with a mean age of 67.4 ± 8.7 years and a mean BMI of 25.8 ± 6.1 kg/m2. Sarcopenia was observed in 36 (39.6%) of the patients, with no differences related to gender, age, or smoking status. Sarcopenia was not associated with the GOLD stage or with FEV1 (used as an indicator of the degree of obstruction). The BMI, percentage of body fat, and total lean mass were lower in the patients with sarcopenia than in those without (p < 0.001). Sarcopenia was more prevalent among the patients in BODE quartile 3 or 4 than among those in BODE quartile 1 or 2 (p = 0.009). The multivariate analysis showed that the BODE quartile was significantly associated with sarcopenia, regardless of age, gender, smoking status, and GOLD stage. In COPD patients, sarcopenia appears to be associated with unfavorable changes in body composition and with a poor prognosis.

Long-term prognosis of AL and AA renal amyloidosis: a Japanese single-center experience.

PubMed

Ozawa, Masatoyo; Komatsuda, Atsushi; Ohtani, Hiroshi; Nara, Mizuho; Sato, Ryuta; Togashi, Masaru; Takahashi, Naoto; Wakui, Hideki

2017-04-01

Few studies have been conducted on the long-term prognosis of patients with amyloid light chain (AL) and amyloid A (AA) renal amyloidosis in the same cohort. We retrospectively examined 68 patients with biopsy-proven renal amyloidosis (38 AL and 30 AA). Clinicopathological findings at the diagnosis and follow-up data were evaluated in each patient. We analyzed the relationship between clinicopathological parameters and survival data. Significant differences were observed in several clinicopathological features, such as proteinuria levels, between the AL and AA groups. Among all patients, 84.2 % of the AL group and 93.3 % of the AA group received treatments for the underlying diseases of amyloidosis. During the follow-up period (median 18 months in AL and 61 months in AA), 36.8 % of the AL group and 36.7 % of the AA group developed end-stage renal failure requiring dialysis, while 71.1 % of the AL group and 56.7 % of the AA group died. Patient and renal survivals were significantly longer in the AA group than in the AL group. eGFR of >60 mL/min/1.73 m 2 at biopsy and an early histological stage of glomerular amyloid deposition were identified as low-risk factors. A multivariate analysis showed that cardiac amyloidosis and steroid therapy significantly influenced patient and renal survivals. Our results showed that heart involvement was the major predictor of poor outcomes in renal amyloidosis, and that the prognosis of AA renal amyloidosis was markedly better than that in previously reported cohorts. Therapeutic advances in inflammatory diseases are expected to improve the prognosis of AA amyloidosis.

External validation of the DRAGON score in an elderly Spanish population: prediction of stroke prognosis after IV thrombolysis.

PubMed

Giralt-Steinhauer, Eva; Rodríguez-Campello, Ana; Cuadrado-Godia, Elisa; Ois, Ángel; Jiménez-Conde, Jordi; Soriano-Tárraga, Carolina; Roquer, Jaume

2013-01-01

Intravenous (i.v.) thrombolysis within 4.5 h of symptom onset has proven efficacy in acute ischemic stroke treatment, although half of all outcomes are unfavorable. The recently published DRAGON score aims to predict the 3-month outcome in stroke patients who have received i.v. alteplase. The purpose of this study was an external validation of the results of the DRAGON score in a Spanish cohort. Patients with acute stroke treated with alteplase were prospectively registered in our BasicMar database. We collected demographic characteristics, vascular risk factors, the time from stroke onset to treatment, baseline serum glucose levels and stroke severity for this population. We then reviewed hyperdense cerebral artery signs and signs of early infarct on the admission CT scan. We calculated the DRAGON score and used the developers' 3-month prognosis categories: good [modified Rankin Scale score (mRS) 0-2], poor (mRS 3-6) and miserable (mRS 5-6) outcome. Discrimination was tested using the area under the receiver operator curve (AUC-ROC). Calibration was assessed by the Hosmer-Lemeshow test. Our final cohort of 297 patients was older (median age 74 years, IQR 65-80) and had more risk factors and severe strokes [median National Institutes of Health Stroke Scale (NIHSS) points 13, IQR 7-19] than the original study population. Poor prognosis was observed in 143 (48.1%) patients. Higher DRAGON scores were associated with a higher risk of poor prognosis. None of our treated stroke patients with a DRAGON score ≥8 at admission experienced a favorable outcome after 3 months. All DRAGON variables were significantly associated with a worse outcome in the multivariate analysis except for onset-to-treatment time (p = 0.334). Discrimination to predict poor prognosis was very good (AUC-ROC 0.84) and the score had good Hosmer-Lemeshow calibration (p = 0.84). The DRAGON score is easy to perform and offers a rapid, reliable prediction of poor prognosis in acute-stroke patients treated with alteplase. This study replicates the original results in a different population. Copyright © 2013 S. Karger AG, Basel.

The single-nucleotide polymorphisms in CHD5 affect the prognosis of patients with hepatocellular carcinoma

PubMed Central

Zhu, Xiao; Kong, Qingming; Xie, Liwei; Chen, Zhihong; Li, Hongmei; Zhu, Zhu; Huang, Yongmei; Lan, Feifei; Luo, Haiqing; Zhan, Jingting; Ding, Hongrong; Lei, Jinli; Xiao, Qin; Fu, Weiming; Fan, Wenguo; Zhang, Jinfang; Luo, Hui

2018-01-01

Previous studies showed that the low expressions of chromodomain-helicase-DNA-binding protein 5 (CHD5) were intensively associated with deteriorative biologic and clinical characteristics as well as outcomes in many tumors. The aim of this study is to determine whether CHD5 single nucleotide polymorphisms (SNPs) contribute to the prognosis of hepatocellular carcima (HCC). The SNPs were selected according to their linkage disequilibrium (LD) in the targeted next-generation sequencing (NGS) and then genotyped with TaqMan probers. We revealed a rare haplotype AG in CHD5 (SNPs: rs12564469-rs9434711) was markedly associated with HCC prognosis. The univariate and multivariate regression analyses revealed the patients with worse overall survival time were those with tumor metastasis and haplotype AG, as well as cirrhosis, poor differentiation and IV-TNM stage. Based on the available public databases, we discovered the significant association between haplotype AG and CHD5 mRNA expressions only existed in Chinese. These data proposed that the potentially genetic haplotype might functionally contribute to HCC prognosis and CHD5 mRNA expressions. PMID:29568352

Blood neutrophil-lymphocyte ratio predicts survival in locally advanced cancer stomach treated with neoadjuvant chemotherapy FOLFOX 4.

PubMed

el Aziz, Lamiss Mohamed Abd

2014-12-01

Accurate predictors of survival for patients with advanced gastric cancer treated with neoadjuvant chemotherapy are currently lacking. In this study, we aimed to evaluate the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with stage III-IV gastric cancer who received neoadjuvant chemotherapy FOLFOX 4 as neoadjuvant chemotherapy. We enrolled 70 patients with stage III-IV cancer stomach in this study. Patients received FOLFOX 4 as neoadjuvant chemotherapy. Blood sample was collected before chemotherapy. The NLR was divided into two groups: high (>3) and low (≤ 3). Univariate analysis on progression-free survival (PFS) and overall survival (OS) was performed using the Kaplan-Meier and log-rank tests, and multivariate analysis was conducted using the Cox proportional hazards regression model. The toxicity was evaluated according to National Cancer Institute Common Toxicity Criteria. The univariate analysis showed that PFS and OS were both worse for patients with high NLR than for those with low NLR before chemotherapy (median PFS 28 and 44 months, respectively, P = 0.001; median OS 30 and 48 months, P = 0.001). Multivariate analysis showed that NLRs before chemotherapy were independent prognostic factors of OS but not for progression-free survival. NLR may serve as a potential biomarker for survival prognosis in patients with stage III-IV gastric cancer receiving neoadjuvant chemotherapy. The FOLFOX 4 demonstrated an acceptable toxicity.

Intratumoral heterogeneity analysis reveals hidden associations between protein expression losses and patient survival in clear cell renal cell carcinoma

PubMed Central

Devarajan, Karthik; Parsons, Theodore; Wang, Qiong; O'Neill, Raymond; Solomides, Charalambos; Peiper, Stephen C.; Testa, Joseph R.; Uzzo, Robert; Yang, Haifeng

2017-01-01

Intratumoral heterogeneity (ITH) is a prominent feature of kidney cancer. It is not known whether it has utility in finding associations between protein expression and clinical parameters. We used ITH that is detected by immunohistochemistry (IHC) to aid the association analysis between the loss of SWI/SNF components and clinical parameters.160 ccRCC tumors (40 per tumor stage) were used to generate tissue microarray (TMA). Four foci from different regions of each tumor were selected. IHC was performed against PBRM1, ARID1A, SETD2, SMARCA4, and SMARCA2. Statistical analyses were performed to correlate biomarker losses with patho-clinical parameters. Categorical variables were compared between groups using Fisher's exact tests. Univariate and multivariable analyses were used to correlate biomarker changes and patient survivals. Multivariable analyses were performed by constructing decision trees using the classification and regression trees (CART) methodology. IHC detected widespread ITH in ccRCC tumors. The statistical analysis of the “Truncal loss” (root loss) found additional correlations between biomarker losses and tumor stages than the traditional “Loss in tumor (total)”. Losses of SMARCA4 or SMARCA2 significantly improved prognosis for overall survival (OS). Losses of PBRM1, ARID1A or SETD2 had the opposite effect. Thus “Truncal Loss” analysis revealed hidden links between protein losses and patient survival in ccRCC. PMID:28445125

Genetic Polymorphisms in RNA Binding Proteins Contribute to Breast Cancer Survival

PubMed Central

Upadhyay, Rohit; Sanduja, Sandhya; Kaza, Vimala; Dixon, Dan A.

2012-01-01

The RNA-binding proteins TTP and HuR control expression of numerous genes associated with breast cancer pathogenesis by regulating mRNA stability. However, the role of genetic variation in TTP (ZFP36) and HuR (ELAVL1) genes is unknown in breast cancer prognosis. A total of 251 breast cancer patients (170 Caucasians and 81 African-Americans) were enrolled and followed-up from 2001 to 2011 (or until death). Genotyping was performed for 10 SNPs in ZFP36 and 7 in ELAVL1 genes. On comparing both races with one another, significant differences were found for clinical and genetic variables. The influence of genetic polymorphisms on survival was analyzed by using Cox-regression, Kaplan-Meier analysis, and the log-rank test. Univariate (Kaplan-Meier/Cox-regression) and multivariate (Cox-regression) analysis showed that the TTP gene polymorphism ZFP36*2 A>G was significantly associated with poor prognosis of Caucasian patients (HR = 2.03; 95% CI = 1.09–3.76; P = 0.025; log-rank P = 0.022). None of the haplotypes, but presence of more than six risk genotypes in Caucasian patients, was significantly associated with poor prognosis (HR=2.42; 95% CI=1.17–4.99; P = 0.017; log-rank P = 0.007). The effect of ZFP36*2 A>G on gene expression was evaluated from patients' tissue samples. Both TTP mRNA and protein expression was significantly decreased in ZFP36*2 G allele carriers compared to A allele homozygotes. Conversely, upregulation of the TTP-target gene COX-2 was observed ZFP36*2 G allele carriers. Through its ability to attenuate TTP gene expression, the ZFP36*2 A>G gene polymorphism has appeared as a novel prognostic breast cancer marker in Caucasian patients. PMID:22907529

A High RORγT/CD3 Ratio is a Strong Prognostic Factor for Postoperative Survival in Advanced Colorectal Cancer: Analysis of Helper T Cell Lymphocytes (Th1, Th2, Th17 and Regulatory T Cells).

PubMed

Yoshida, Naohiro; Kinugasa, Tetsushi; Miyoshi, Hiroaki; Sato, Kensaku; Yuge, Kotaro; Ohchi, Takafumi; Fujino, Shinya; Shiraiwa, Sachiko; Katagiri, Mitsuhiro; Akagi, Yoshito; Ohshima, Koichi

2016-03-01

Tumor-infiltrating lymphocytes (TILs), part of the host immune response, have been widely reported as influential factors in the tumor microenvironment for the clinical outcome of colorectal cancer (CRC). However, the network of helper T cells is very complex, and which T-cell subtypes affect the progression of CRC and postoperative prognosis remains unclear. This study investigated the expression of several subtypes of TILs including T helper type 1 (Th1), Th2, Th17, and regulatory T (Treg) cells to determine their correlation with clinicopathologic features and postoperative prognosis. The study investigated the expression of TILs using immunohistochemistry of tissue microarray samples for 199 CRC patients. The number of each T-cell subtype infiltrating tumors was counted using ImageJ software. The relationship between TIL marker expression, clinicopathologic features, and prognosis was analyzed. A high RORγT/CD3 ratio (Th17 ratio) was significantly correlated with lymph node metastasis (p = 0.002), and a high of Foxp3/CD3 ratio (Treg ratio) was correlated with tumor location in the colon (p = 0.04), as shown by the Chi square test. In multivariate analysis, a high RORγT/CD3 ratio was the only independent prognostic factor for overall survival (p = 0.04; hazard ratio [HR], 1.84; 95% confidence interval [CI] 1.02-3.45). This study confirmed a high RORγT/CD3 ratio as a strong prognostic marker for postoperative survival. The immunohistochemistry results suggest that Th17 may affect lymph node metastasis in CRC. If new immunotherapies reducing Th17 expression are established, they may improve the efficiency of cancer treatment and prolong the survival of patients with CRC.

Circulating tumor cells (CTCs) in malignant pleural mesothelioma (MPM).

PubMed

Yoneda, Kazue; Tanaka, Fumihiro; Kondo, Nobuyuki; Hashimoto, Masaki; Takuwa, Teruhisa; Matsumoto, Seiji; Okumura, Yoshitomo; Tsubota, Noriaki; Sato, Ayuko; Tsujimura, Tohru; Kuribayashi, Kozo; Fukuoka, Kazuya; Tabata, Chiharu; Nakano, Takashi; Hasegawa, Seiki

2014-12-01

To investigate the diagnostic and prognostic value of circulating tumor cells (CTCs), a potential surrogate of micrometastasis, in malignant pleural mesothelioma (MPM). We prospectively evaluated CTCs in 7.5 mL of peripheral blood sampled from patients with a suspicion of MPM. A semiautomated system was used to capture CTCs with an antibody against the epithelial cell adhesion molecule. Of 136 eligible patients, 32 were finally diagnosed with nonmalignant diseases (NM), and 104 had MPM. CTCs were detected in 32.7 % (34 of 104) of MPM patients but in only 9.4 % (3 of 32) of NM patients (P = 0.011). The CTC count was significantly higher in MPM patients than in NM patients (P = 0.007), and a receiver operating characteristic (ROC) curve analysis showed an insufficient capability of the CTC test in discrimination between MPM and NM, with an area under ROC curve of 0.623 (95 % confidence interval, 0.523-0.723; P = 0.036). Among MPM patients, CTCs were more frequently detected in patients with epithelioid subtype (39.7 %, 31 of 78) than in those with nonepithelioid subtypes (11.5 %, 3 of 26; P = 0.016). Positive CTCs (CTC count ≥ 1) were a significant factor to predict a poor prognosis among epithelioid patients (median overall survival, 22.3 months for positive CTCs vs. 12.6 months for negative CTCs; P = 0.004) and not in nonepithelioid patients (P = 0.649). A multivariate analysis showed that positive CTCs were a significant and independent factor to predict a poor prognosis (hazard ratio, 2.904; 95 % confidence interval, 1.530-5.511; P = 0.001) for epithelioid MPM patients. CTC was a promising marker in diagnosis and prediction of prognosis in MPM, especially in epithelioid MPM.

Elevated AQP1 Expression Is Associated With Unfavorable Oncologic Outcome in Patients With Hilar Cholangiocarcinoma.

PubMed

Li, Chunxiang; Li, Xiaofu; Wu, Linfeng; Jiang, Zheng

2017-08-01

Hilar cholangiocarcinomas are malignant tumors with a poor prognosis. An early prediction of prognosis for patients may help us determine treatment strategies. Aquaporin 1 is a cell membrane channel involved in water transport, cell motility, and proliferation. Increasing evidences showed that aquaporin 1 played a role in tumor prognosis and diagnosis. The purpose of this study is to evaluate the role of aquaporin 1 in hilar cholangiocarcinoma. Here, we analyzed messenger RNA expression data of genes function as bile secretion in a data set of 169 samples using the R2 bioinformatic platform ( http://r2.amc.nl ). Quantitative polymerase chain reaction was performed to verify the gene expression in 17 hilar cholangiocarcinoma samples. Immunohistochemistry was also performed in a series of specimens from 62 hilar cholangiocarcinoma tissues, and its clinical significance was assessed by clinical correlation and Kaplan-Meier analyses. All data were analyzed using the R2 web application, aquaporin 1 was selected for further analysis. The significant expression variation of aquaporin 1 among 17 cases with cholangiocarcinoma was also found using quantitative polymerase chain reaction. The expression level of aquaporin 1 protein significantly correlated with tumor-node-metastasis stage ( P = .002) and overall survival time ( P = .010). Higher aquaporin 1 expression indicated poor prognostic outcomes ( P <.05, log-rank test). Multivariate analysis also showed strong aquaporin 1 protein expression was an independent adverse prognosticator in hilar cholangiocarcinoma ( P = .002). This study highlighted the prognostic value of aquaporin 1 in hilar cholangiocarcinoma. Strong aquaporin 1 expression predicts poor survival, regardless of pathological features. Immunohistochemical detection of aquaporin 1, as a prognostic marker, may contribute to predicting clinical outcome for patients with hilar cholangiocarcinoma.

Thai venous stroke prognostic score: TV-SPSS.

PubMed

Poungvarin, Niphon; Prayoonwiwat, Naraporn; Ratanakorn, Disya; Towanabut, Somchai; Tantirittisak, Tassanee; Suwanwela, Nijasri; Phanthumchinda, Kamman; Tiamkoa, Somsak; Chankrachang, Siwaporn; Nidhinandana, Samart; Laptikultham, Somsak; Limsoontarakul, Sansern; Udomphanthuruk, Suthipol

2009-11-01

Prognosis of cerebral venous sinus thrombosis (CVST) has never been studied in Thailand. A simple prognostic score to predict poor prognosis of CVST has also never been reported. The authors are aiming to establish a simple and reliable prognostic score for this condition. The medical records of CVST patients from eight neurological training centers in Thailand who received between April 1993 and September 2005 were reviewed as part of this retrospective study. Clinical features included headache, seizure, stroke risk factors, Glasgow coma scale (GCS), blood pressure on arrival, papilledema, hemiparesis, meningeal irritation sign, location of occluded venous sinuses, hemorrhagic infarction, cerebrospinal fluid opening pressure, treatment options, length of stay, and other complications were analyzed to determine the outcome using modified Rankin scale (mRS). Poor prognosis (defined as mRS of 3-6) was determined on the discharge date. One hundred ninety four patients' records, 127 females (65.5%) and mean age of 36.6 +/- 14.4 years, were analyzed Fifty-one patients (26.3%) were in the poor outcome group (mRS 3-6). Overall mortality was 8.4%. Univariate analysis and then multivariate analysis using SPSS version 11.5 revealed only four statistically significant predictors influencing outcome of CVST They were underlying malignancy, low GCS, presence of hemorrhagic infarction (for poor outcome), and involvement of lateral sinus (for good outcome). Thai venous stroke prognostic score (TV-SPSS) was derived from these four factors using a multiple logistic model. A simple and pragmatic prognostic score for CVST outcome has been developed with high sensitivity (93%), yet low specificity (33%). The next study should focus on the validation of this score in other prospective populations.

Long non-coding RNA LSINCT5 predicts negative prognosis and exhibits oncogenic activity in gastric cancer.

PubMed

Xu, Mi-Die; Qi, Peng; Weng, Wei-Wei; Shen, Xiao-Han; Ni, Shu-Juan; Dong, Lei; Huang, Dan; Tan, Cong; Sheng, Wei-Qi; Zhou, Xiao-Yan; Du, Xiang

2014-12-01

Long non-coding RNAs (lncRNAs) are recently discovered RNA transcripts that are aberrantly expressed in many tumor types. Numerous studies have suggested that lncRNAs can be utilized for cancer diagnosis and prognosis. LSINCT5 (long stress-induced non-coding transcript 5) is dramatically upregulated in breast and ovarian cancer and affects cellular proliferation. However, the expression pattern of LSINCT5 in gastrointestinal cancer and the association between aberrant expression of LSINCT5 in gastrointestinal cancer and malignancy, metastasis, or prognosis remain unknown. LSINCT5 expression was detected in gastrointestinal cancer and paired adjacent normal tissue samples or cell lines using reverse transcription quantitative PCR (RT-qPCR). We also investigated the potential relationship between tumor LSINCT5 levels and clinicopathological features of gastrointestinal cancer. Finally, we assessed whether LSINCT5 influences in vitro cell proliferation. The expression of LSINCT5 is significantly upregulated in gastrointestinal cancer tissues and cell lines relative to their normal counterparts. In addition, increased LSINCT5 expression was correlated with a larger tumor size, deeper tumor depth, and advanced clinical stage. Kaplan-Meier analysis indicated that gastric cancer (GC) and colorectal cancer (CRC) patients with higher LSINCT5 expression levels have worse disease-free survival (DFS) and disease-specific survival (DSS) rates. Moreover, multivariate analysis revealed that increased expression of LSINCT5 is an independent predictor of DFS and DSS rates in GC patients. The ectopic expression of LSINCT5 in gastrointestinal cancer cell lines resulted in an increase in cellular proliferation; conversely, knock down of LSINCT5 significantly inhibited proliferation. These results suggest that LSINCT5 may represent a novel prognostic indicator and a target for gene therapy in gastrointestinal cancer.

CpG Island Methylator Phenotype Positive Tumors in the Absence of MLH1 Methylation Constitute a Distinct Subset of Duodenal Adenocarcinomas and Are Associated with Poor Prognosis

PubMed Central

Fu, Tao; Pappou, Emmanouil P.; Guzzetta, Angela A.; Jeschke, Jana; Kwak, Ruby; Dave, Pujan; Hooker, Craig M.; Morgan, Richard; Baylin, Stephen B.; Iacobuzio-Donahue, Christine A.; Wolfgang, Christopher L.; Ahuja, Nita

2012-01-01

Purpose Little information is available on genetic and epigenetic changes in duodenal adenocarcinomas. The purpose was to identify possible subsets of duodenal adenocarcinomas based on microsatellite instability (MSI), DNA methylation, mutations in the KRAS and BRAF genes, clinicopathologic features, and prognosis. Experimental Design Demographics, tumor characteristics and survival were available for 99 duodenal adenocarcinoma patients. Testing for KRAS and BRAF mutations, MSI, MLH1 methylation and CpG island methylator phenotype (CIMP) status was performed. A Cox proportional hazard model was built to predict survival. Results CIMP+ was detected in 27 of 99 (27.3%) duodenal adenocarcinomas, and was associated with MSI (P = 0.011) and MLH1 methylation (P < 0.001), but not with KRAS mutations (P = 0.114), as compared to CIMP− tumors. No BRAF V600E mutation was detected. Among the CIMP+ tumors, 15 (55.6%) were CIMP+/MLH1-unmethylated (MLH1-U). Kaplan-Meier analysis showed tumors classified by CIMP, CIMP/MLH1 methylation status or CIMP/MSI status could predict overall survival (OS; P = 0.047, 0.002, and 0.002, respectively), while CIMP/MLH1 methylation status could also predict time-to-recurrence (TTR; P = 0.016). In multivariate analysis, CIMP/MLH1 methylation status showed a significant prognostic value regarding both OS (P < 0.001) and TTR (P = 0.023). Patients with CIMP+/MLH1-U tumors had the worst OS and TTR. Conclusions Our results demonstrate existence of CIMP in duodenal adenocarcinomas. The combination of CIMP+/MLH1-U appears to be independently associated with poor prognosis in patients with duodenal adenocarcinomas. This study also suggests that BRAF mutations are not involved in duodenal tumorigenesis, MSI or CIMP development. PMID:22825585

Telangiectatic osteosarcoma: a review of 87 cases.

PubMed

Angelini, Andrea; Mavrogenis, Andreas F; Trovarelli, Giulia; Ferrari, Stefano; Picci, Piero; Ruggieri, Pietro

2016-10-01

Telangiectatic osteosarcoma (TOS) is a rare subtype of osteosarcoma. We analyzed (1) oncologic outcome in a large homogeneous series and (2) the role of prognostic factors on prognosis, local recurrence and metastasis. Eighty-seven patients (47 males, 54 %) were retrospectively analyzed. All except 4 had extracompartmental disease, and ten patients had lung metastasis at diagnosis. Pathologic fracture was present in 27 cases (31 %). Seventy-eight patients were treated with neoadjuvant chemotherapy; nine had surgery as first treatment. Limb-salvage surgery was performed in 71 cases, amputation in 14, and rotationplasty in one. One patient died before surgery. Possible prognostic factors were statistically evaluated. Overall survival was 60.7 % at 10 years of follow-up. Fifty-one patients were disease-free (58.6 %), 2 were alive with disease (2.3 %), 31 died with disease (35.6 %), and 3 died of other causes (3.4 %). Ten local recurrences were observed (11 %). Twenty-five patients (29 %) developed lung (22) or bone (3) metastases. No statistical difference was found considering age, metastases at diagnosis, gender, pathologic fracture, tumor volume, compartmental status, number of neoadjuvant chemotherapy agents and treatment. Induced necrosis was significant at both univariate and multivariate analysis (p < 0.0001). TOS does not have a poor prognosis as previously reported in literature, with a survival of about 60 % at 10 years. Most of patients can be cured with neoadjuvant chemotherapy plus surgery (limb sparing surgery is possible and safe). Tumor response to chemotherapy as induced necrosis was the only significant prognostic factors on survival, even if small tumor volume at diagnosis correlates with better prognosis at univariate analysis. IV.

Association of vascular indices with novel circulating biomarkers as prognostic factors for cardiovascular complications in patients with type 2 diabetes mellitus.

PubMed

Naka, Katerina K; Papathanassiou, Katerina; Bechlioulis, Aris; Pappas, Konstantinos; Tigas, Stelios; Makriyiannis, Dimitrios; Antoniou, Sophia; Kazakos, Nikolaos; Margeli, Alexandra; Papassotiriou, Ioannis; Tsatsoulis, Agathocles; Michalis, Lampros K

2018-03-01

The pathophysiology of atherosclerosis in type 2 diabetes mellitus (T2DM) is multifactorial. The association of vascular indices with circulating biomarkers of inflammation and insulin resistance and their role in the long-term cardiovascular prognosis in T2DM patients were currently investigated. Patients with T2DM and poor glycemic control without known cardiovascular diseases (n=119) at baseline were enrolled and followed for about 9years. The end-point was the occurrence of any cardiovascular event (coronary heart disease, stroke, peripheral artery disease or cardiovascular death). Aortic pulse wave velocity (PWV), augmentation index (AIx), brachial flow-mediated dilation (FMD), hsCRP, Chitinase-3-like protein 1 (YKL-40), Neutrophil Gelatinase-Associated Lipocalin (NGAL), Fatty Acid Binding Protein (FABP-4) were assessed. Higher YKL-40 and NGAL were associated with higher PWV, while higher YKL-40 and FABP-4 were related to higher AIx (p<0.05 for all). In univariate Cox regression analysis, PWV>10m/s, YKL-40>78ng/ml and NGAL>42ng/ml were associated with cardiovascular events (p<0.05 for all). In multivariate analysis, after adjusting for classical risk factors and glycemic control, increased NGAL, YKL-40 and PWV and decreased FMD (i.e. ≤2.2%) (p<0.05 for all) were independently associated with cardiovascular events. In T2DM patients without established cardiovascular disease, novel indices of vascular inflammation (NGAL and YKL-40) were associated with subclinical atherosclerosis (arterial stiffness) but also with adverse clinical prognosis. Arterial stiffness and endothelial dysfunction were also independently related to adverse prognosis. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Aberrant Expression of Calretinin, D2-40 and Mesothelin in Mucinous and Non-Mucinous Colorectal Carcinomas and Relation to Clinicopathological Features and Prognosis.

PubMed

Foda, Abd AlRahman Mohammad; El-Hawary, Amira Kamal; Hamed, Hazem

2016-10-01

CRC is a heterogeneous disease in terms of morphology, invasive behavior, metastatic capacity, and clinical outcome. Recently, many so-called mesothelial markers, including calretinin, D2-40, WT1, thrombomodulin, mesothelin, and others, have been certified. The aim of this study was to assess the immunohistochemical expression of calretinin and other mesothelial markers (D2-40 and mesothelin) in colorectal mucinous adenocarcinoma (MA) and non mucinous adenocarcinoma (NMA) specimens and relation to clinicopathological features and prognosis using manual tissue microarray technique. We studied tumor tissue specimens from 150 patients with colorectal MA and NMA who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using Calretinin, D2-40 and mesothelin expressions. We found that NMA showed significantly more calretinin and D2-40 expression than MA In contrast, no statistically significant difference between NMA and MA was detected in mesothelin expression. There were no statistically significant relations between any of the clinicopathological or histological parameters and any of the three markers. In a univariate analysis, neither calretinin nor D2-40 expressions showed any significant relations to DFS or OS. However, mesothelin luminal expression was significantly associated with worse DFS. Multivariate Cox regression analysis proved that luminal mesothelin expression was an independent negative prognostic factor in NMA. In conclusion, Calretinin, D2-40 and mesothelin are aberrantly expressed in a proportion of CRC cases with more expression in NMA than MA. Aberrant expression of these mesothelial markers was not associated with clinicopathological or histological features of CRCs. Only mesothelin expression appears to be a strong predictor of adverse prognosis.

The Value of the Electrocardiogram for Evaluating Prognosis in Patients with Idiopathic Pulmonary Arterial Hypertension.

PubMed

Cheng, Xiao-Ling; He, Jian-Guo; Liu, Zhi-Hong; Gu, Qing; Ni, Xin-Hai; Zhao, Zhi-Hui; Luo, Qin; Xiong, Chang-Ming

2017-02-01

Association between electrocardiography (ECG) features and right ventricular anatomy and physiology has been established. This study is aimed to identify the value of 12-lead ECG in evaluating prognosis of patients with idiopathic pulmonary arterial hypertension (IPAH). 194 patients with newly diagnosed IPAH were included in this study. Correlations between electrocardiography variables and hemodynamics were assessed. Univariate and multivariable cox regression analysis were performed to identify ECG variables for predicting all-cause mortality in IPAH. Partial correlation analysis showed that P wave amplitude in lead II correlated with the mean pulmonary arterial pressure (mPAP, r = 0.349, p ≤ 0.001) and cardiac index (CI, r = -0.224, p = 0.002); R wave amplitude in V1 correlated with mPAP (r = 0.359, p ≤ 0.001); S wave amplitude in V6 correlated with mPAP (r = 0.259, p = 0.030) and CI (r = -0.220, p = 0.003). P wave amplitude in lead II (HR 1.555, p = 0.033) and R wave amplitude in lead aVR (HR 5.058, p < 0.001) were the independent predictors of all-cause mortality. Kaplan-Meier survival curves showed patients with a p ≥ 0.25 mv in lead II, and R ≥ 0.4 mv in lead aVR had lower 3-year survival (55 vs. 91%, p < 0.001). Specific lead-12 ECG features could reflect right ventricular overload hemodynamics, and are useful to evaluate prognosis of patients with IPAH.

Impact of Remote Monitoring on Long-Term Prognosis in Heart Failure Patients in a Real-World Cohort: Results From All-Comers COMMIT-HF Trial.

PubMed

Kurek, Anna; Tajstra, Mateusz; Gadula-Gacek, Elzbieta; Buchta, Piotr; Skrzypek, Michal; Pyka, Lukasz; Wasiak, Michal; Swietlinska, Malgorzata; Hawranek, Michal; Polonski, Lech; Gasior, Mariusz; Kosiuk, Jedrzej

2017-04-01

Randomized controlled trials demonstrate that remote monitoring (RM) of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy devices (CRT-Ds) may improve quality of care and prognosis in heart failure (HF) patients. However, the impact of RM on long-term mortality in a real-world cohort is still not well examined. This study was designed as a matched cohort study based on the COMMIT-HF trial--a single-center, ongoing prospective observational registry (NCT02536443). Complete patient demographics, medical history, in-hospital results, hospitalizations, and mortality data were collected based on institutional registries and healthcare providers' records. Patients were divided into 2 groups based on RM presence and matched by means of propensity scores according to clinical characteristics. The primary endpoint of this study was the long-term all-cause mortality. Out of 1,429 consecutive patients, 822 patients with a first implantation of an ICD/CRT-D were included in the analysis. The final matched study population contained 574 patients in RM and in a control group. Although demographic and echocardiographic parameters as well as pharmacological treatments were similar in both groups, a significantly lower 1-year mortality was detected in the RM group (2.1% vs. 11.5%, P < 0.0001). This was also maintained during a 3-year follow-up (4.9% vs. 22.3%, P < 0.0001). Multivariate analysis showed that RM was associated with an improved prognosis (hazard ratio 0.187, 95% confidence interval 0.075-0.467, P = 0.0003). RM of HF patients with ICDs/CRT-Ds significantly reduced long-term mortality in a real-world clinical condition. © 2017 Wiley Periodicals, Inc.

Prognostic relevance of aberrant DNA methylation in g1 and g2 pancreatic neuroendocrine tumors.

PubMed

Stefanoli, Michele; La Rosa, Stefano; Sahnane, Nora; Romualdi, Chiara; Pastorino, Roberta; Marando, Alessandro; Capella, Carlo; Sessa, Fausto; Furlan, Daniela

2014-01-01

The occurrence and clinical relevance of DNA hypermethylation and global hypomethylation in pancreatic neuroendocrine tumours (PanNETs) are still unknown. We evaluated the frequency of both epigenetic alterations in PanNETs to assess the relationship between methylation profiles and chromosomal instability, tumour phenotypes and prognosis. In a well-characterized series of 56 sporadic G1 and G2 PanNETs, methylation-sensitive multiple ligation-dependent probe amplification was performed to assess hypermethylayion of 33 genes and copy number alterations (CNAs) of 53 chromosomal regions. Long interspersed nucleotide element-1 (LINE-1) hypomethylation was quantified by pyrosequencing. Unsupervised hierarchical clustering allowed to identify a subset of 22 PanNETs (39%) exhibiting high frequency of gene-specific methylation and low CNA percentages. This tumour cluster was significantly associated with stage IV (p = 0.04) and with poor prognosis in univariable analysis (p = 0.004). LINE-1 methylation levels in PanNETs were significantly lower than in normal samples (p < 0.01) and were approximately normally distributed. 12 tumours (21%) were highly hypomethylated, showing variable levels of CNA. Interestingly, only 5 PanNETs (9%) were observed to show simultaneously LINE-1 hypomethylation and high frequency of gene-specific methylation. LINE-1 hypomethylation was strongly correlated with advanced stage (p = 0.002) and with poor prognosis (p < 0.0001). In the multivariable analysis, low LINE-1 methylation status and methylation clusters were the only independent significant predictors of outcome (p = 0.034 and p = 0.029, respectively). The combination of global DNA hypomethylation and gene hypermethylation analyses may be useful to define distinct subsets of PanNETs. Both alterations are common in PanNETs and could be directly correlated with tumour progression. © 2014 S. Karger AG, Basel.

High leukocyte mitochondrial DNA content contributes to poor prognosis in glioma patients through its immunosuppressive effect

PubMed Central

Chen, Y; Zhang, J; Huang, X; Zhang, J; Zhou, X; Hu, J; Li, G; He, S; Xing, J

2015-01-01

Background: Epidemiological studies have indicated significant associations of leukocyte mitochondrial DNA (mtDNA) copy number with risk of several malignancies, including glioma. However, whether mtDNA content can predict the clinical outcome of glioma patients has not been investigated. Methods: The mtDNA content of peripheral blood leukocytes from 336 glioma patients was examined using a real-time PCR-based method. Kaplan–Meier curves and Cox proportional hazards regression model were used to examine the association of mtDNA content with overall survival (OS) and progression-free survival (PFS) of patients. To explore the potential mechanism, the immune phenotypes of peripheral blood mononuclear cells (PBMCs) and plasma concentrations of several cytokines from another 20 glioma patients were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Results: Patients with high mtDNA content showed both poorer OS and PFS than those with low mtDNA content. Multivariate Cox regression analysis demonstrated that mtDNA content was an independent prognostic factor for both OS and PFS. Stratified analyses showed that high mtDNA content was significantly associated with poor prognosis of patients with younger age, high-grade glioma or adjuvant radiochemotherapy. Immunological analysis indicated that patients with high mtDNA content had significantly lower frequency of natural killer cells in PBMCs and higher plasma concentrations of interleukin-2 and tumour necrosis factor-α, suggesting an immunosuppression-related mechanism involved in mtDNA-mediated prognosis. Conclusions: Our study for the first time demonstrated that leukocyte mtDNA content could serve as an independent prognostic marker and an indicator of immune functions in glioma patients. PMID:26022928

PAI-1, CAIX and VEGFA expressions as prognosis markers in oral squamous cell carcinoma.

PubMed

Peterle, Gabriela Tonini; Maia, Lucas Lima; Trivilin, Leonardo Oliveira; de Oliveira, Mayara Mota; Dos Santos, Joaquim Gasparini; Mendes, Suzanny Oliveira; Stur, Elaine; Agostini, Lidiane Pignaton; Rocha, Lília Alves; Moysés, Raquel Ajub; Cury, Patrícia Maluf; Nunes, Fábio Daumas; Louro, Iúri Drumond; Dos Santos, Marcelo; da Silva, Adriana Madeira Álvares

2018-04-25

In oral squamous cell carcinoma (OSCC), the HIF-1 complex promotes the expression of genes involved in specific mechanisms of cell survival under hypoxic conditions, such as plasminogen activator inhibitor-1 (PAI-1), carbonic anhydrase 9 (CAIX) and vascular endothelial growth factor A (VEGFA). The study aimed to investigate the presence and prognostic value of PAI-1, CAIX, and VEGFA in OSCC. Immunohistochemistry was used to analyze the expressions of these proteins in 52 tumoral tissue samples of patients with OSCC, surgically treated and followed by a minimum of 24 months after surgery. The correlations between proteins expressions and clinicopathological parameters and prognosis were analyzed. Positive PAI-1 membrane expression was significantly associated with local disease relapse (p=0.027). Multivariate analysis revealed that the positive PAI-1 membrane expression is an independent marker for local disease relapse, with approximately 14-fold increased risk when compared to negative expression (OR=14.49; CI=1.40-150.01, p=0.025). Strong PAI-1 cytoplasmic expression was significantly associated with the less differentiation grade (p=0.027). Strong CAIX membrane expression was significantly associated with local disease-free survival (p=0.038). Positive CAIX cytoplasmic expression was significantly associated with lymph node affected (p=0.025) and with disease-specific survival (p=0.022). Multivariate analysis revealed that the positive CAIX cytoplasmic expression is an independent risk factor for disease-related death, increasing their risk approximately 3-fold when compared to negative expression (HR=2.84; CI=1.02-7.87, p=0.045). Positive VEGFA cytoplasmic expression was significantly associated with less differentiation grade (p=0.035). Our results suggest a potential role for these expressions profiles as tumor prognostic markers in OSCC patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Predictors of overall and recurrence-free survival after neoadjuvant chemotherapy for gastroesophageal adenocarcinoma: Pooled analysis of individual patient data (IPD) from randomized controlled trials (RCTs).

PubMed

Ronellenfitsch, U; Schwarzbach, M; Hofheinz, R; Kienle, P; Nowak, K; Kieser, M; Slanger, T E; Burmeister, B; Kelsen, D; Niedzwiecki, D; Schuhmacher, C; Urba, S; van de Velde, C; Walsh, T N; Ychou, M; Jensen, K

2017-08-01

Neoadjuvant chemotherapy improves prognosis of patients with locally advanced gastroesophageal adenocarcinoma. The aim of this study was to identify predictors for postoperative survival following neoadjuvant therapy. These could be useful in deciding about postoperative continuation of chemotherapy. This meta-analysis used IPD from RCTs comparing neoadjuvant chemotherapy with surgery alone for gastroesophageal adenocarcinoma. Trials providing IPD on age, sex, performance status, pT/N stage, resection status, overall and recurrence-free survival were included. Survival was calculated in the entire study population and subgroups stratified by supposed predictors and compared using the log-rank test. Multivariable Cox models were used to identify independent survival predictors. Four RCTs providing IPD from 553 patients fulfilled the inclusion criteria. (y)pT and (y)pN stage and resection status strongly predicted postoperative survival both after neoadjuvant therapy and surgery alone. Patients with R1 resection after neoadjuvant therapy survived longer than those with R1 resection after surgery alone. Patients with stage pN0 after surgery alone had better prognosis than those with ypN0 after neoadjuvant therapy. Patients with stage ypT3/4 after neoadjuvant therapy survived longer than those with stage pT3/4 after surgery alone. Multivariable regression identified resection status and (y)pN stage as predictors of survival in both groups. (y)pT stage predicted survival only after surgery alone. After neoadjuvant therapy for gastroesophageal adenocarcinoma, survival is determined by the same factors as after surgery alone. However, ypT stage is not an independent predictor. These results can facilitate the decision about postoperative continuation of chemotherapy in pretreated patients. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma

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

Liu, Li-Ting; Tang, Lin-Quan; Chen, Qiu-Yan

Purpose: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). Patients and Methods: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse–free survival (LRFS) and distant metastasis–free survival (DMFS). Results: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels aftermore » NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). Conclusion: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.« less

Treatment results of nasopharyngeal carcinoma: a 15-year single institutional experience.

PubMed

Khademi, Bijan; Mahmoodi, Jalal; Omidvari, Shapour; Mohammadianpanah, Mohammad

2006-06-01

Nasopharyngeal Carcinoma (NPC) is a common malignant neoplasm of the head and neck that occurs most commonly in people in the South Eastern Asia but its condition in Iran is not much clear. In this retrospective study, we evaluated the treatment characteristics determining the outcome in patients with NPC. In this retrospective study, we reviewed the records of one hundred and seven patients with biopsy proven diagnosis of NPC who were referred to the radiation oncology department, Nemazee Hospital, Shiraz University of Medical Sciences, Iran, during the time period from January 1985 to December 2000. Eightyfive patients (79.4%) received 60-70Gy radiation (1.8- 2Gy/fraction, one fraction per day, and 5 fractions per week). Sixty-two patients (57.5%) received radiotherapy combined with adjuvant chemotherapy which consisted of cisplatin and 5-fluorouracil. Eighty-six patients (80.4%) had WHO II-III histopathologic diagnosis. According to the AJCC 1997 staging system, 4 (3.6%), 3 (2.7%), 33 (30.8%) and 67 (62%) patients were in stages I, II, III and IV, respectively. With a median follow-up of 12 months, the 2-year overall and disease-free survival rates were 35% and 21%, respectively. According to the multivariate analysis for overall survival, patients under 40 years had a better prognosis (p=0.041). Node stage and stage of disease were significant prognostic factors (p=0.0001). On multivariate analysis for disease-free survival, age and node stage were significant prognostic factors. The patients who received more than 60Gy radiation had a better prognosis (p=0.02), however; sequential adjuvant chemotherapy had no impact on survival and response (p=0.6). Our experience confirmed earlier reports showing poor outcomes for locoregionally advanced nasopharyngeal carcinomas. This study failed to demonstrate improvement in the outcome regarding overall and disease-free survival by adding sequential adjuvant chemotherapy after radiotherapy for patients with advanced NPC.

The status of perineural invasion predicts the outcomes of postoperative radiotherapy in locally advanced esophageal squamous cell carcinoma.

PubMed

Ning, Zhong-Hua; Zhao, Wei; Li, Xiao-Dong; Chen, Lu-Jun; Xu, Bin; Gu, Wen-Dong; Shao, Ying-Jie; Xu, Yun; Huang, Jin; Pei, Hong-Lei; Jiang, Jing-Ting

2015-01-01

Prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remains dismal even after curative resection and adjuvant radiotherapy. New biomarkers for predicting prognosis and treatment outcomes are needed for improved treatment stratification of patients with locally advanced ESCC. The prognostic and treatment predictive significance of perineural invasion (PNI) in the locally advanced ESCC remains unclear. This study aimed to examine the effect of PNI on the outcomes of locally advanced ESCC patients after curative resection with or without postoperative radiotherapy (PORT). We retrospectively reviewed 262 consecutive locally advanced ESCC patients who underwent curative resection. Tumors sections were re-evaluated for PNI by an independent pathologist blinded to the patients' outcomes. Overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan-Meier method; univariate log-rank test and multivariate Cox proportional hazard model were used to evaluate the prognostic value of PNI. Finally, 243 patients were analyzed and enrolled into this study, of which 132 received PORT. PNI was identified in 22.2% (54/243) of the pathologic sections. The 5-year DFS was favorable for PNI-negative patients versus PNI-positive patients (21.3% vs. 36.7%, respectively; P = 0.005). The 5-year OS was 40.3% for PNI-negative patients versus 21.7% for PNI-positive patients (P < 0.001). On multivariate analysis, PNI was an independent prognostic factor. In a subset analysis for patients received PORT, PNI was evaluated as a prognostic predictor as well (P < 0.05). In contrast to patients without PORT, PORT couldn't improve the disease recurrence and survival in locally advanced ESCC patients with PNI-positive (P > 0.05). PNI could serve as an independent prognostic factor and prognosticate treatment outcomes in locally advanced ESCC patients. The PNI status should be considered when stratifying high-risk locally advanced ESCC patients for adjuvant radiotherapy. Future prospective study is warranted to confirm our results.

Dual oxidase 1: A predictive tool for the prognosis of hepatocellular carcinoma patients.

PubMed

Chen, Shengsen; Ling, Qingxia; Yu, Kangkang; Huang, Chong; Li, Ning; Zheng, Jianming; Bao, Suxia; Cheng, Qi; Zhu, Mengqi; Chen, Mingquan

2016-06-01

Dual oxidase 1 (DUOX1), which is the main source of reactive oxygen species (ROS) production in the airway, can be silenced in human lung cancer and hepatocellular carcinomas. However, the prognostic value of DUOX1 expression in hepatocellular carcinoma patients is still unclear. We investigated the prognostic value of DUOX1 expression in liver cancer patients. DUOX1 mRNA expression was determined in tumor tissues and non-tumor tissues by real‑time PCR. For evaluation of the prognostic value of DUOX1 expression, Kaplan-Meier method and Cox's proportional hazards model (univariate analysis and multivariate analysis) were employed. A simple risk score was devised by using significant variables obtained from the Cox's regression analysis to further predict the HCC patient prognosis. We observed a reduced DUOX1 mRNA level in the cancer tissues in comparison to the non‑cancer tissues. More importantly, Kaplan-Meier analysis showed that patients with high DUOX1 expression had longer disease-free survival and overall survival compared with those with low expression of DUOX1. Cox's regression analysis indicated that DUOX1 expression, age, and intrahepatic metastasis may be significant prognostic factors for disease-free survival and overall survival. Finally, we found that patients with total scores of >2 and >1 were more likely to relapse and succumb to the disease than patients whose total scores were ≤2 and ≤1. In conclusion, DUOX1 expression in liver tumors is a potential prognostic tool for patients. The risk scoring system is useful for predicting the survival of liver cancer patients after tumor resection.

Evaluation of functional outcome of the floating knee injury using multivariate analysis.

PubMed

Yokoyama, Kazuhiko; Tsukamoto, Tatsuro; Aoki, Shinichi; Wakita, Ryuji; Uchino, Masataka; Noumi, Takashi; Fukushima, Nobuaki; Itoman, Moritoshi

2002-11-01

The objective of this study is to evaluate significant contributing factors affecting the functional prognosis of floating knee injuries using multivariate analysis. A total of 68 floating knee injuries (67 patients) were treated at Kitasato University Hospital from 1986 to 1999. Both the femoral fractures and the tibial fractures were managed surgically by various methods. The functional results of these injuries were evaluated using the grading system of Karlström and Olerud. Follow-up periods ranged from 2 to 19 years (mean 50.2 months) after the original injury. We defined satisfactory (S) outcomes as those cases with excellent or good results and unsatisfactory (US) outcomes as those cases with acceptable or poor results. Logistic regression analysis was used as a multivariate analysis, and the dependent variables were defined as a satisfactory outcome or as an unsatisfactory outcome. The explanatory variables were predicting factors influencing the functional outcome such as age at trauma, gender, severity of soft-tissue injury in the femur and the tibia, AO fracture grade in the femur and the tibia, Fraser type (type I or type II), Injury Severity Score (ISS), and fixation time after injury (less than 1 week or more than 1 week) in the femur and the tibia. The final functional results were as follows: 25 cases had excellent results, 15 cases good results, 16 cases acceptable results, and 12 cases poor results. The predictive logistic regression equation was as follows: Log 1-p/p = 3.12-1.52 x Fraser type - 1.65 x severity of soft-tissue injury in the tibia - 1.31 x fixation time after injury in the tibia - 0.821 x AO fracture grade in the tibia + 1.025 x fixation time after injury in the femur - 0.687 x AO fracture grade in the femur ( p=0.01). Among the variables, Fraser type and the severity of soft-tissue injury in the tibia were significantly related to the final result. The multivariate analysis showed that both the involvement of the knee joint and the severity grade of soft-tissue injury in the tibia represented significant risk factors of poor outcome in floating knee injuries in this study.

The pro-apoptotic serum activity is an independent mortality predictor of patients with heart failure.

PubMed

Rössig, Lothar; Fichtlscherer, Stephan; Heeschen, Christopher; Berger, Jürgen; Dimmeler, Stefanie; Zeiher, Andreas M

2004-09-01

Systemic inflammation with elevated serum levels of circulating pro-inflammatory cytokines is a major determinant of prognosis in heart failure (HF). Since serum of patients with HF induces apoptosis of endothelial cells (EC), we aimed to determine whether the pro-apoptotic activity in the serum may predict prognosis of patients with HF. We measured the pro-apoptotic activity in the serum of 48 patients with HF of different aetiology by an ex vivo cell culture assay and subsequently monitored these patients for the single endpoint all-cause mortality. During follow-up, 16 patients died and 11 patients received a heart transplant. Survivors had a lower pro-apoptotic serum activity (P=0.007). By univariate analysis, pro-apoptotic serum activity, NYHA class, pro-BNP, low blood pressure, and creatinine levels were significantly associated with mortality. In a multivariable stepwise Cox-regression model, the pro-apoptotic serum activity (adjusted hazard ratio, HR=1.85 per %, P=0.008), elevated pro-BNP levels (HR=9.35 per log[pro-BNP], P=0.001), and low blood pressure (HR=0.96 per mmHg, P=0.041) remained as independent predictors of death. In this exploratory study, the pro-apoptotic serum capacity is independently associated with a worse prognosis in patients with HF, suggesting that the assessment of serum-induced EC apoptosis could provide an integrative estimate of the deleterious effects of various pro-inflammatory cytokines and other cytotoxic factors in HF.

MDAS: an integrated system for metabonomic data analysis.

PubMed

Liu, Juan; Li, Bo; Xiong, Jiang-Hui

2009-03-01

Metabonomics, the latest 'omics' research field, shows great promise as a tool in biomarker discovery, drug efficacy and toxicity analysis, disease diagnosis and prognosis. One of the major challenges now facing researchers is how to process this data to yield useful information about a biological system, e.g., the mechanism of diseases. Traditional methods employed in metabonomic data analysis use multivariate analysis methods developed independently in chemometrics research. Additionally, with the development of machine learning approaches, some methods such as SVMs also show promise for use in metabonomic data analysis. Aside from the application of general multivariate analysis and machine learning methods to this problem, there is also a need for an integrated tool customized for metabonomic data analysis which can be easily used by biologists to reveal interesting patterns in metabonomic data.In this paper, we present a novel software tool MDAS (Metabonomic Data Analysis System) for metabonomic data analysis which integrates traditional chemometrics methods and newly introduced machine learning approaches. MDAS contains a suite of functional models for metabonomic data analysis and optimizes the flow of data analysis. Several file formats can be accepted as input. The input data can be optionally preprocessed and can then be processed with operations such as feature analysis and dimensionality reduction. The data with reduced dimensionalities can be used for training or testing through machine learning models. The system supplies proper visualization for data preprocessing, feature analysis, and classification which can be a powerful function for users to extract knowledge from the data. MDAS is an integrated platform for metabonomic data analysis, which transforms a complex analysis procedure into a more formalized and simplified one. The software package can be obtained from the authors.

Meta-analysis of prognostic value of inflammation parameter in breast cancer.

PubMed

Chen, Jie; Pan, Yuqin; He, Bangshun; Ying, Houqun; Sun, Huiling; Deng, Qiwen; Liu, Xian; Wang, Shukui

2018-01-01

Recently, increasing studies investigated the association between inflammation parameter such as neutrophil to lymphocyte ratio (NLR) and the prognosis of cancers. However, the clinical and prognostic significance of NLR in breast cancer remains controversial. This meta-analysis was conducted to establish the overall accuracy of the NLR test in the diagnosis of breast cancer. A comprehensive search of the literature was conducted using PubMed and Web of Science. Six studies dating up to July 2014 with 2267 patients were enrolled in the present study. STATA 11.0 software (STATA Corporation, College Station, TX, USA) was selected for data analysis. In order to evaluate the association between NLR and overall survival (OS), disease-free survival (DFS), recurrence-free survival or cancer-specific survival, the hazard ratios (HRs), and their 95% confidence intervals (CIs) were extracted. Subgroup analyses showed that NLR was a strong prognostic factor for OS in multivariate analysis (HR = 2.81, 95% CI = 2.13-3.71, P H = 0.992) and without metastasis (HR = 1.45, 95% CI = 0.37-5.66, P H < 0.001). Elevated NLR was associated with a high risk for DFS in subgroups of multivariate analysis (HR = 2.16, 95% CI = 1.67-2.80, P H = 0.977) and mixed metastasis (HR = 2.13, 95% CI = 1.38-3.30, P H = 0.84). In summary, NLR may be considered as a predictive factor for patients with breast cancer.

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

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

Martin, Katherine J.; Patrick, Denis R.; Bissell, Mina J.

2008-10-20

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

Correlation of PD-1/PD-L1 polymorphisms and expressions with clinicopathologic features and prognosis of ovarian cancer.

PubMed

Tan, Dan; Sheng, Li; Yi, Qing-Hua

2018-02-06

To explore the correlation of PD-1/PD-L1 polymorphisms and their expressions with clinicopathologic features and prognosis of ovarian cancer. A total of 164 patients with ovarian cancer were enrolled as case group and 170 healthy women as control group. We conducted quantitative reverse transcription-PCR (qRT-PCR) to determine PD-1/PD-L1 expressions in peripheral blood mononuclear cells (PBMCs). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific amplification were used to detect PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G. PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G polymorphisms increased the risk for ovarian cancer. PD-1 rs2227982 C>T was associated with FIGO stage and differentiation grade, while PD-L1 rs4143815 C>G was correlated with histological type and differentiation grade. Besides, PD-1/PD-L1 expressions were positively correlated in PBMCs of patients with ovarian cancer to be associated with differentiation grade. Compared with wild homozygous patients, PD-1/PD-L1 expressions were significantly decreased in PBMCs of ovarian cancer patients carried with the mutant genotypes of rs2227982 C>T and rs4143815 C>G. The PFS and OS in ovarian cancer patients with wild homozygous genotype of rs2227982 C>T and rs4143815 C>G were significantly higher than those with mutant genotypes, which were significantly lower in patients with low expressions of PD-1/PD-L1 than those with high expressions. Univariate COX regression analysis identified FIGO staging, differentiation grade, rs2227982 C>T, rs4143815 C>G and expressions of PD-1/PD-L1 as the prognostic factors, and multivariate COX regression analysis demonstrated that high FIGO stage and low expressions of PD-1/PD-L1 were independent risk factors for the prognosis of ovarian cancer. PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G polymorphisms increased the risk of ovarian cancer, leading to a poor prognosis, associated with low expressions of PD-1 and PD-L1. While high PD-1 and PD-L1 expressions are indicators of a favorable prognosis in ovarian cancer.

Conditional Survival in Anal Carcinoma Using the National Population-Based Survey of Epidemiology and End Results Database (1988-2012).

PubMed

Kim, Ellen; Kim, Jong S; Choi, Mehee; Thomas, Charles R

2016-04-01

Conditional survival can provide valuable information for both patients and healthcare providers about the changing prognosis in surviving patients over time. This study estimated conditional survival for patients with anal cancer in the United States through analysis of a national population-based cancer registry. Log-rank test identified significant covariates of cause-specific survival (defined as time from diagnosis until death from anal cancer). Significant covariates were considered in the multivariable regression of cause-specific survival using Cox proportional hazards models. Covariates included cancer stage and demographic variables. Patients in Surveillance, Epidemiology, and End Results regions diagnosed with anal squamous cell carcinoma as their first and only cancer diagnosis from 1988 to 2012 were selected from this database, and 5145 patients were included in the retrospective cohort study. Five-year conditional survival stratified by each variable in the final Cox models was measured : The final multivariable models of overall and cause-specific survivals included stage, grade, sex, age, race, and relationship status. Over the first 6 years after diagnosis, conditional survival of distant stage increased from 37% to 89%, whereas regional stage increased from 65% to 93% and localized stage increased from 84% to 96%. The other variables had increasing prognosis as well, but the subgroups increased at a more similar rate over time. The data source used does not include information on chemotherapy treatment, patient comorbidities, or socioeconomic status. Conditional survival showed improvement over time. Patients with advanced stage had the greatest improvement in conditional survival. This is the first study to provide specific conditional survival probabilities for patients with anal cancer.

New simple radiological criteria proposed for multiple primary lung cancers.

PubMed

Matsunaga, Takeshi; Suzuki, Kenji; Takamochi, Kazuya; Oh, Shiaki

2017-11-01

Controversies remain as to the differential diagnosis between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IM) in lung cancers. We have investigated the clinical criteria for MPLC and here propose a set of new and simple criteria from the stand point of prognosis. A retrospective study was conducted on 588 consecutive patients with resected lung cancer of clinical Stage IA between 2009 and 2012. Multiple lung cancers (MLCs) were observed in 103 (17.5%) of the 588 patients. All main and other tumors were divided into solid tumor (ST) and non-solid tumor (non-ST). We defined Group A as MLCs having at least one non-ST and Group B as all tumors being ST. Cox's proportional hazard model was used for the multivariate analyses to investigate the preoperative prognostic factors. We divided the MLCs into MPLC and IM based on the preoperative prognostic factors, and survival was estimated by the Kaplan-Meier method. A multivariate analysis with Cox's proportional hazards model revealed that Group A independently predicted good overall survival (HR = 0.165, 95% CI: 0.041-0.672).Differences in the 3- and 5-year overall survivals between Groups A and B were statistically significant (96.3%/92.2% vs. 70.0%/60.0%, Pvalue = 0.0002). We suggest that Group A, defined as the presence of at least one tumor with a ground glass opacity component and clinical N0, should be excluded from the conventional concept of multiple lung cancers based on the criteria of Martini and Melamed as it has a very good prognosis. This group would be considered to be radiological MPLC. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pathological response to neoadjuvant chemotherapy: a new prognosis tool for the curative management of peritoneal colorectal carcinomatosis.

PubMed

Passot, Guillaume; You, Benoît; Boschetti, Gilles; Fontaine, Juliette; Isaac, Sylvie; Decullier, Evelyne; Maurice, Christele; Vaudoyer, Delphine; Gilly, François-Noël; Cotte, Eddy; Glehen, Olivier

2014-08-01

The primary objective of this study was to determine the incidence rate of pathological complete responses (pCRs) following neoadjuvant systemic chemotherapy for the treatment of peritoneal carcinomatosis (PC) of colorectal origin. The secondary objective was to evaluate whether pathological response assessments predict survival of patients treated with curative intent by complete cytoreductive surgery (CRS). A retrospective review was performed of 115 patients who underwent preoperative irinotecan- or oxaliplatin-based chemotherapy, followed by 124 procedures of complete CRS alone or combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The pathological response was defined as the mean percentage of cancer cells remaining within all specimens. Univariate and multivariate analyses were performed to identify predictors of survival and pathological response outcome. Twelve procedures (9.7 %) resulted in pCRs, defined as no residual cancer cells in all specimens, 25 (20.2 %) resulted in major responses (1 to 49 % residual cancer cells), and 87 (70.1 %) resulted in minor or no responses (>50 % residual cancer cells). The cumulative 5-year survival rates were 75 and 57 % for patients with pCR and major responses, respectively. Using multivariate analysis, pathological response was the only independent predictor of survival (P = 0.01; major response: hazard ratio [HR] = 4.91; minor response: HR = 13.46). No significant predictor of pathological response was identified. Pathological complete response can be achieved with preoperative systemic chemotherapy for patients with PC of colorectal origin. The degree of pathological response can be assessed and represented as a new outcome for prognosis following treatment with curative intent.

The impact of treatment on quality of life of patients with head and neck cancer and its association with prognosis.

PubMed

Carrillo, J F; Carrillo, L C; Ramirez-Ortega, M C; Ochoa-Carrillo, F J; Oñate-Ocaña, L F

2016-10-01

Information is scarce regarding the impact of treatment on Health-Related Quality of Life (HRQL) of patients with Head and Neck (H&N) cancers. We assessed the effect of treatment on HRQL and its association with prognosis in H&N cancer. Patients with H&N cancer in whom HRQL was assessed before and after treatment. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-H&N35 instruments were used. Association of changes in patients' HRQL after treatment with Loco-Regional Recurrence (LRR) and Overall Survival (OS) was investigated. One hundred sixty patients were included; scales of the baseline assessment of HRQL were moderately associated with LRR and OS, but the impact of treatment on most HRQL scales was strongly associated with OS. By multivariate analysis, baseline assessment of Global Health, Physical, HN Teeth, HN Dry mouth, and HN Cough scales, and impact of treatment on the Physical and Pain scales comprised independent variables associated with LRR. Male gender, positive lymph nodes, baseline assessment of Role, HN Pain, HN Cough, and impact of treatment on Emotion, Pain, Financial, HN Swallowing, HN Social contact, and the interaction of HN Pain-change in Pain scales were associated with OS. Both multivariate models were adjusted by the neoplasm's site of origin. Aside from well-known clinical-pathologic prognostic factors in H&N cancers, HRQL assessment, both prior to and after treatment, provides significant prognostic information and should be measured. Design of therapeutic clinical trials in patients with H&N cancers should consider these novel prognostic factors. Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Mutations in TP53 are a prognostic factor in colorectal hepatic metastases undergoing surgical resection.

PubMed

Molleví, David G; Serrano, Teresa; Ginestà, Mireia M; Valls, Joan; Torras, Jaume; Navarro, Matilde; Ramos, Emilio; Germà, Josep R; Jaurrieta, Eduardo; Moreno, Víctor; Figueras, Joan; Capellà, Gabriel; Villanueva, Alberto

2007-06-01

The aim of this study was to analyze the prognostic value of TP53 mutations in a consecutive series of patients with hepatic metastases (HMs) from colorectal cancer undergoing surgical resection. Ninety-one patients with liver metastases from colorectal carcinoma were included. Mutational analysis of TP53, exons 4-10, was performed by single-strand conformation polymorphism and sequencing. P53 and P21 protein immunostaining was assessed. Multivariate Cox models were adjusted for gender, number of metastasis, resection margin, presence of TP53 mutations and chemotherapy treatment. Forty-six of 91 (50.05%) metastases showed mutations in TP53, observed mainly in exons 5-8, although 14.3% (n = 13) were located in exons 9 and 10. Forty percent (n = 22) were protein-truncating mutations. TP53 status associated with multiple (> or =3) metastases (65.6%, P = 0.033), advanced primary tumor Dukes' stage (P = 0.011) and younger age (<57 years old, P = 0.03). Presence of mutation associated with poor prognosis in univariate (P = 0.017) and multivariate Cox model [hazard ratio (HR) = 1.80, 95% confidence interval (CI) = 1.07-3.06, P = 0.028]. Prognostic value was maintained in patients undergoing radical resection (R0 series, n = 79, P = 0.014). Mutation associated with a worse outcome in chemotherapy-treated patients (HR = 2.54, 95% CI = 1.12-5.75, P = 0.026). The combination of > or =3 metastases and TP53 mutation identified a subset of patients with very poor prognosis (P = 0.009). P53 and P21 protein immunostaining did not show correlation with survival. TP53 mutational status seems to be an important prognostic factor in patients undergoing surgical resection of colorectal cancer HMs.

Methylation of tissue factor pathway inhibitor 2 as a prognostic biomarker for hepatocellular carcinoma after hepatectomy.

PubMed

Sun, Feng-Kai; Sun, Qi; Fan, Yu-Chen; Gao, Shuai; Zhao, Jing; Li, Feng; Jia, Yi-Bin; Liu, Chuan; Wang, Li-Yuan; Li, Xin-You; Ji, Xiang-Fen; Wang, Kai

2016-02-01

Methylation of tissue factor pathway inhibitor 2 (TFPI2) gene has been detected in hepatocellular carcinoma (HCC). However, the clinicopathologcial significance and prognostic value of TFPI2 methylation in HCC remains largely unknown. This study aimed to investigate the prognostic value of TFPI2 methylation in HCC after hepatectomy. Methylation status of TFPI2 gene was examined in 178 surgical specimens of HCC and 20 normal liver samples using methylation-specific polymerase chain reaction. Methylation of TFPI2 gene was detected in 44.9% (80 of 178) of primary HCC samples, 10.7% (19 of 178) of the corresponding non-tumorous liver samples, and 5.0% (1/20) of the normal liver samples. The mRNA concentrations of TFPI2 in primary HCC tissues were significantly lower than those in corresponding non-tumorous liver tissues and those in normal liver tissues. TFPI2 methylation was significantly associated with higher TNM stage. Patients with TFPI2 methylation demonstrated a significantly poorer prognosis than those without TFPI2 methylation for both overall survival and disease-free survival (P < 0.001, respectively). Multivariate analyses confirmed that TFPI2 methylation was an independent prognostic factor for both overall survival (P = 0.002) and disease-free survival (P = 0.000) in HCC after hepatectomy. Moreover, TFPI2 methylation was found to be the only independent predictor for early tumor recurrence of HCC after resection based on multivariate analysis (P = 0.002). Methylation of TFPI2 predicts high risk of advanced tumor stage, early tumor recurrence, and poor prognosis, and it could be a potential prognostic biomarker in patients with HCC after hepatectomy. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Overexpression of MutSα Complex Proteins Predicts Poor Prognosis in Oral Squamous Cell Carcinoma.

PubMed

Wagner, Vivian Petersen; Webber, Liana Preto; Salvadori, Gabriela; Meurer, Luise; Fonseca, Felipe Paiva; Castilho, Rogério Moraes; Squarize, Cristiane Helena; Vargas, Pablo Agustin; Martins, Manoela Domingues

2016-05-01

The DNA mismatch repair (MMR) system is responsible for the detection and correction of errors created during DNA replication, thereby avoiding the incorporation of mutations in dividing cells. The prognostic value of alterations in MMR system has not previously been analyzed in oral squamous cell carcinoma (OSCC).The study comprised 115 cases of OSCC diagnosed between 1996 and 2010. The specimens collected were constructed into tissue microarray blocks. Immunohistochemical staining for MutSα complex proteins hMSH2 and hMSH6 was performed. The slides were subsequently scanned into high-resolution images, and nuclear staining of hMSH2 and hMSH6 was analyzed using the Nuclear V9 algorithm. Univariable and multivariable Cox proportional hazard regression models were performed to evaluate the prognostic value of hMSH2 and hMSH6 in OSCC.All cases in the present cohort were positive for hMSH2 and hMSH6 and a direct correlation was found between the expression of the proteins (P < 0.05). The mean number of positive cells for hMSH2 and hMSH6 was 64.44 ± 15.21 and 31.46 ± 22.38, respectively. These values were used as cutoff points to determine high protein expression. Cases with high expression of both proteins simultaneously were classified as having high MutSα complex expression. In the multivariable analysis, high expression of the MutSα complex was an independent prognostic factor for poor overall survival (hazard ratio: 2.75, P = 0.02).This study provides a first insight of the prognostic value of alterations in MMR system in OSCC. We found that MutSα complex may constitute a molecular marker for the poor prognosis of OSCC.

Epidermal growth factor receptor pathway polymorphisms and the prognosis of hepatocellular carcinoma

PubMed Central

Wang, Wenjia; Ma, Xiao-Pin; Shi, Zhuqing; Zhang, Pengyin; Ding, Dong-Lin; Huang, Hui-Xing; Saiyin, Hexi Ge; Chen, Tao-Yang; Lu, Pei-Xin; Wang, Neng-Jin; Yu, Hongjie; Sun, Jielin; Zheng, S Lilly; Yu, Long; Xu, Jianfeng; Jiang, De-Ke

2015-01-01

The EGFR signaling pathway is important in the control of vital processes in the carcinogenesis of hepatocellular carcinoma (HCC), including cell survival, cell cycle progression, tumor invasion and angiogenesis. In the current study, we aim to assess if genetic variants in the genes of the EGFR signaling pathway are associated with the prognosis of HCC. We genotyped 36 single nucleotide polymorphisms (SNP) in four core genes (EGF, EGFR, VEGF, and VEGFR2) by using DNA from blood samples of 363 HCC patients with surgical resection. The associations between genotypes and overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) and 95% confident intervals (CIs) were estimated for the multivariate survival analyses by Cox proportional hazards regression models, adjusting for age, gender, family history, HBsAg and AFP. We found that five SNPs in the VEGFR2 gene were significantly associated with clinical outcomes of HCC patients. Among them, four SNPs (rs7692791, rs2305948, rs13109660, rs6838752) were associated with OS (p=0.035, 0.038, 0.029 and 0.028, respectively), and two SNPs (rs7692791 and rs2034965) were associated with DFS (p=0.039 and 0.017, respectively). Particularly, rs7692791 TT genotype was associated with both reduced OS (p=0.037) and DFS (p=0.043). However, only one SNP rs2034965 with the AA genotype was shown to be an independent effect on DFS (p=0.009) in the multivariate analysis. None of the other 31 polymorphisms or 9 haplotypes attained from the four genes was significantly associated with OS or DFS. Our results illustrated the potential use of VEGFR2 polymorphisms as prognostic markers for HCC patients. PMID:25628948

Hilar fat infiltration: A new prognostic factor in metastatic clear cell renal cell carcinoma with first-line sunitinib treatment.

PubMed

Kammerer-Jacquet, Solène-Florence; Brunot, Angelique; Bensalah, Karim; Campillo-Gimenez, Boris; Lefort, Mathilde; Bayat, Sahar; Ravaud, Alain; Dupuis, Frantz; Yacoub, Mokrane; Verhoest, Gregory; Peyronnet, Benoit; Mathieu, Romain; Lespagnol, Alexandra; Mosser, Jean; Edeline, Julien; Laguerre, Brigitte; Bernhard, Jean-Christophe; Rioux-Leclercq, Nathalie

2017-10-01

The selection of patients with metastatic clear cell renal cell carcinoma (ccRCC) who may benefit from targeted tyrosine kinase inhibitors has been a challenge, even more so now with the advent of new therapies. Hilar fat infiltration (HFI) is a validated prognostic factor in nonmetastatic ccRCC (TNM 2009 staging system) but has never been studied in metastatic patients. We aimed to assess its phenotype and prognostic effect in patients with metastatic ccRCC treated with first-line sunitinib. In a multicentric study, we retrospectively included 90 patients and studied the corresponding ccRCC at the pathological, immunohistochemical, and molecular levels. Patient and tumor characteristics were compared using univariate and multivariate analysis. All the features were then studied by Cox models for prognostic effect. HFI was found in 42 patients (46.7%), who had worse prognosis (Heng criteria) (P = 0.003), liver metastases (P = 0.036), and progressive diseases at first radiological evaluation (P = 0.024). The corresponding ccRCC was associated with poor pathological prognostic factors that are well known in nonmetastatic ccRCC. For these patients, median progression-free survival was 4 months vs. 13 months (P = 0.02), and median overall survival was 14 months vs. 29 months (P = 0.006). In a multivariate Cox model integrating all the variables, only poor prognosis, according to the Heng criteria and HFI, remained independently associated with both progression-free survival and overall survival. HFI was demonstrated for the first time to be an independent poor prognostic factor. Its potential role in predicting resistance to antiangiogenic therapy warrants further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

Incorporation of N0 Stage with Insufficient Numbers of Lymph Nodes into N1 Stage in the Seventh Edition of the TNM Classification Improves Prediction of Prognosis in Gastric Cancer: Results of a Single-Institution Study of 1258 Chinese Patients.

PubMed

Li, Bofei; Li, Yuanfang; Wang, Wei; Qiu, Haibo; Seeruttun, Sharvesh Raj; Fang, Cheng; Chen, Yongming; Liang, Yao; Li, Wei; Chen, Yingbo; Sun, Xiaowei; Guan, Yuanxiang; Zhan, Youqing; Zhou, Zhiwei

2016-01-01

This study examined the prognosis of the "node-negative with eLNs ≤ 15" designation and the additional value of incorporating it into the pN1 designation in the seventh edition of the N classification. From January 2000 to September 2010, a total of 1258 gastric cancer patients (patients with eLNs > 15 or node-negative with eLNs ≤ 15) undergoing radical gastric resection were enrolled in this study. We incorporated node-negative patients with eLNs ≤ 15 into pN1 and compared this designation with the current 7th edition UICC N stage for 3, 5-year overall survival by univariate and multivariate analysis. Homogeneity, discriminatory ability, and monotonicity of gradients in the hypothetical N stage and the UICC N stage were compared using linear trend χ2, likelihood ratio χ2 statistics, and Akaike information criterion (AIC) calculations. Node-negative patients with eLNs ≤ 15 had worse survival compared with those with eLNs > 15. In univariate and multivariate analyses, the hypothetical N stage showed superiority to the 7th edition pN staging. The hypothetical staging system had higher linear trend and likelihood ratio χ (2) scores and smaller AIC values compared with those for the TNM system, which represented the optimum prognostic stratification. Node-negative patients with eLNs ≤ 15 can be considered to be incorporated into the pN1 stage in the 7th edition of the TNM classification.

The positive impact of surgeon specialization on survival for gastric cancer patients after surgery with curative intent.

PubMed

Liang, Yuexiang; Wu, Liangliang; Wang, Xiaona; Ding, Xuewei; Liang, Han

2015-10-01

Many studies have affirmed the survival benefit for cancer patients treated by specialized surgeons. A total of 967 patients with gastric cancer (GC) who underwent gastrectomy with curative intent in our center were enrolled. Patients were categorized into two groups based on surgeon specialization: the specialized group (SG) and nonspecialized group (NSG). To overcome bias due to the different distribution of covariates for the two groups, a one-to-one match was applied using propensity score analysis. After matching, prognosis and recurrence data were analyzed. After one-to-one matching, 261 patients in the SG and 261 patients in the NSG had the same characteristics excluding factors associated with surgery. In multivariate analysis for the whole study series, surgeon specialization was an independent prognostic factor for GC patients after surgery. Patients in the SG demonstrated a significantly higher 5-year overall survival than those in the NSG (50.7 vs. 37.2 %, p = 0.001). With the strata analysis, significant prognostic differences between the two groups were only observed in patients at stage IIIa-b or N1-2. The proportion of locoregional recurrence was greater in the NSG than in the SG. GC patients treated by specialized surgeons tended to have a better prognosis and lower locoregional recurrence rate. Surgeon specialization was an independent prognostic factor for GC patients after surgery. GC should be treated by specialized surgeons in large-volume centers.

PTEN loss increases PD-L1 protein expression and affects the correlation between PD-L1 expression and clinical parameters in colorectal cancer.

PubMed

Song, Minmin; Chen, Defeng; Lu, Biyan; Wang, Chenliang; Zhang, Junxiao; Huang, Lanlan; Wang, Xiaoyan; Timmons, Christine L; Hu, Jun; Liu, Bindong; Wu, Xiaojian; Wang, Lei; Wang, Jianping; Liu, Huanliang

2013-01-01

Programmed death ligand-1 (PD-L1) has been identified as a factor associated with poor prognosis in a range of cancers, and was reported to be mainly induced by PTEN loss in gliomas. However, the clinical effect of PD-L1 and its regulation by PTEN has not yet been determined in colorectal cancer (CRC). In the present study, we verified the regulation of PTEN on PD-L1 and further determined the effect of PTEN on the correlation between PD-L1 expression and clinical parameters in CRC. RNA interference approach was used to down-regulate PTEN expression in SW480, SW620 and HCT116 cells. It was showed that PD-L1 protein, but not mRNA, was significantly increased in cells transfected with siRNA PTEN compared with the negative control. Moreover, the capacity of PTEN to regulate PD-L1 expression was not obviously affected by IFN-γ, the main inducer of PD-L1. Tissue microarray immunohistochemistry was used to detect PD-L1 and PTEN in 404 CRC patient samples. Overexpression of PD-L1 was significantly correlated with distant metastasis (P<0.001), TNM stage (P<0.01), metastatic progression (P<0.01) and PTEN expression (P<0.001). Univariate analysis revealed that patients with high PD-L1 expression had a poor overall survival (P<0.001). However, multivariate analysis did not support PD-L1 as an independent prognostic factor (P = 0.548). Univariate (P<0.001) and multivariate survival (P<0.001) analysis of 310 located CRC patients revealed that high level of PD-L1 expression was associated with increased risks of metastatic progression. Furthermore, the clinical effect of PD-L1 on CRC was not statistically significant in a subset of 39 patients with no PTEN expression (distant metastasis: P = 0.102; TNM stage: P = 0.634, overall survival: P = 0.482). PD-L1 can be used to identify CRC patients with high risk of metastasis and poor prognosis. This clinical manifestation may be partly associated with PTEN expression.

[Clinical features and risk factors of biloma formation after transcatheter arterial chemoembolization].

PubMed

Zhaolin, Zeng; Xuelian, Liu; Wensou, Huang; Mingyue, Cai; Haofan, Wang; Ming'an, Li; Hong, Shan; Zhu, Kangshun

2015-04-07

To explore the risk factors, treatment and outcomes of biloma after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). A total of 481 patients with a diagnosis of HCC underwent TACE at our hospital from January 2011 to December 2013. Biloma was tracked by the follow-ups of computed tomography or magnetic resonance imaging (CT/ MRI) . Retrospective analyses were conducted for their clinical features, treatments and prognosis. The statistically significant factors for univariate analysis were introduced into Logistic regression models for multivariate analysis to obtain the risk factors of biloma post-TACE. There were 43 cases of complicated biloma after TACE. And 38 patients (88.4% ) developed biloma at 0.5-3 months post-TACE while another 5 (9.7%) did so at 3-5 months. The multivariate analysis showed that bile duct dilation, a history of hepatectomy prior to TACE, use of polyvinyl alcohol (PVA) particles and nonsuperselective embolization were the risk factors of biloma formation after TACE. Among 9 symptomatics, there were jaundice (n =2) and fever (n =7). The diameter of bilomas was (8.07 ± 3.53) cm for 9 symptomatics and (2.81 ± 1.26) cm for 35 asymptomatics. And the difference was statistically significant (P <0. 01). Nine symptomatic patients underwent percutaneous drainage with tube and biloma diminished (n = 7) and even vanished (n = 2). Only conservative treatment was offered for 35 asymptomatics. During the follow-ups, it showed no change (n = 24) , diminishing (n = 8) and disappearance (n = 2). One case died from a greatly enlarged biloma due to hepatic failure and septic shock via a rupture into abdominal cavity and choleperitonitis. The risk factors of biloma formation after TACE for HCC are bile duct dilation, a history of hepatectomy before TACE, use of PVA particles and nonsuperselective embolization. For symptomatics, drainage must be performed timely and the prognosis is fair. For asymptomatics, regular imaging follow-ups are needed. Drainage must be performed timely when the diameter of biloma increased significantly during the follow-ups.

Prognostic Impact of the 6th and 7th American Joint Committee on Cancer TNM Staging Systems on Esophageal Cancer Patients Treated With Chemoradiotherapy

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

Nomura, Motoo, E-mail: excell@hkg.odn.ne.jp; Department of Radiation Oncology, Aichi Cancer Center Hospital; Shitara, Kohei

2012-02-01

Purpose: The new 7th edition of the American Joint Committee on Cancer TNM staging system is based on pathologic data from esophageal cancers treated by surgery alone. There is no information available on evaluation of the new staging system with regard to prognosis of patients treated with chemoradiotherapy (CRT). The objective of this study was to evaluate the prognostic impact of the new staging system on esophageal cancer patients treated with CRT. Methods and Materials: A retrospective review was performed on 301 consecutive esophageal squamous cell carcinoma patients treated with CRT. Comparisons were made of the prognostic impacts of themore » 6th and 7th staging systems and the prognostic impacts of stage and prognostic groups, which were newly defined in the 7th edition. Results: There were significant differences between Stages I and III (p < 0.01) according to both editions. However, the 7th edition poorly distinguishes the prognoses of Stages III and IV (p = 0.36 by multivariate analysis) in comparison to the 6th edition (p = 0.08 by multivariate analysis), although these differences were not significant. For all patients, T, M, and gender were independent prognostic factors by multivariate analysis (p < 0.05). For the Stage I and II prognostic groups, survival curves showed a stepwise decrease with increase in stage, except for Stage IIA. However, there were no significant differences seen between each prognostic stage. Conclusions: Our study indicates there are several problems with the 7th TNM staging system regarding prognostic factors in patients undergoing CRT.« less

The Prognostic Value of Tumor-Infiltrating Neutrophils in Gastric Adenocarcinoma after Resection

PubMed Central

Wang, Wei; Chen, Ju-gao; Wu, Yan-heng; Lv, Lin; Li, Jian-jun; Chen, Yi-bing; Wang, Dan-dan; Pan, Qiu-zhong; Li, Xiao-dong; Xia, Jian-chuan

2012-01-01

Background Several pieces of evidence indicate that tumor-infiltrating neutrophils (TINs) are correlated to tumor progression. In the current study, we explore the relationship between TINs and clinicopathological features of gastric adenocarcinoma patients. Furthermore, we investigated the prognostic value of TINs. Patients and Methods The study was comprised of two groups, training group (115 patients) and test group (97 patients). Biomarkers (intratumoral CD15+ neutrophils) were assessed by immunohistochemistry. The relationship between clinicopathological features and patient outcome were evaluated using Cox regression and Kaplan-Meier analysis. Results Immunohistochemical detection showed that the tumor-infiltrating neutrophils (TINs) in the training group ranged from 0.00–115.70 cells/high-power microscopic field (HPF) and the median number was 21.60 cells/HPF. Based on the median number, the patients were divided into high and low TINs groups. Chi-square test analysis revealed that the density of CD15+ TINs was positively associated with lymph node metastasis (p = 0.024), distance metastasis (p = 0.004) and UICC (International Union Against Cancer) staging (p = 0.028). Kaplan-Meier analysis showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.002). Multivariate Cox's analysis showed that the density of CD15+ TINs was an independent prognostic factor for overall survival of gastric adenocarcinoma patients. Using another 97 patients as a test group and basing on the median number of TINs (21.60 cells/HPF) coming from the training group, Kaplan-Meier analysis also showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.032). The results verify that the number of CD15+ TINs can predict the survival of gastric adenocarcinoma surgical patients. Conclusions The presence of CD15+ TINs is an independent and unfavorable factor in the prognosis of gastric adenocarcinoma patients. Targeting CD15+ TINs may be a potential intervenient therapy in the future. PMID:22442706

Protein Z efficiently depletes thrombin generation in disseminated intravascular coagulation with poor prognosis.

PubMed

Lee, Nuri; Kim, Ji-Eun; Gu, Ja-Yoon; Yoo, Hyun Ju; Kim, Inho; Yoon, Sung-Soo; Park, Seonyang; Han, Kyou-Sup; Kim, Hyun Kyung

2016-01-01

Disseminated intravascular coagulation (DIC) is characterized by consumption of coagulation factors and anticoagulants. Thrombin generation assay (TGA) gives useful information about global hemostatic status. We developed a new TGA system that anticoagulant addition can deplete thrombin generation in plasma, which may reflect defective anticoagulant system in DIC. TGAs were measured on the calibrated automated thrombogram with and without thrombomodulin or protein Z in 152 patients who were suspected of having DIC, yielding four parameters including lag time, endogenous thrombin potential, peak thrombin and time-to-peak in each experiment. Nonsurvivors showed significantly prolonged lag time and time-to-peak in TGA-protein Z system, which was performed with added protein Z. In multivariate Cox regression analysis, lag time and time-to-peak in TGA system were significant independent prognostic factors. In TGA-protein Z system, lag time and time-to-peak were revealed as independent prognostic factors of DIC. Protein Z addition could potentiate its anticoagulant effect in DIC with poor prognosis, suggesting the presence of defective protein Z system. The prolonged lag time and time-to-peak in both TGA and TGA-protein Z systems are expected to be used as independent prognostic factors of DIC.

Outcome of Heart Failure with Preserved Ejection Fraction: A Multicentre Spanish Registry

PubMed Central

Castillo, Juan C; Anguita1, Manuel P; Jiménez, Manuel

2009-01-01

Background: Studies on clinical features, treatment and prognosis of patients with congestive heart failure (CHF) and preserved left ventricular ejection fraction (LVEF) are few and their results frequently conflicting. Aims: To investigate the characteristics and long term prognosis of patients with CHF and preserved (≥ 45%) LVEF. Methods and Results: We conducted a prospective multicentre study with 4720 patients attended in 62 heart failure clinics from 1999 to 2003 in Spain (BADAPIC registry). LVEF was preserved in 30% patients. Age, female gender, prevalence of atrial fibrillation, hypertension and non-ischaemic cardiopathy were all significantly greater in patients with preserved LVEF. Mean follow-up was 40±12 months. Mortality and other cardiovascular complication rates during follow up were similar in both groups. On multivariate analysis ejection fraction was not an independent predictor for mortality. Survival at one and five years was similar in both groups (79% and 59% for patients with preserved LVEF and 78% and 57% for those with reduced LVEF, respectively). Conclusions: In the BADAPIC registry, a high percentage of heart failure patients had preserved LVEF. Although clinical differences were seen between groups, morbidity and mortality were similar in both groups. PMID:21037850

Clinical application and prognostic assessment of serum Tumor Associated Material (TAM) from esophageal cancer patients.

PubMed

Zhou, K; Yan, Y; Zhao, S; Li, B

2014-01-01

To explore the correlation between serum levels of Tumor Associated Materials (TAM) and clinicopathological parameters and prognosis in patients with esophageal cancer (EC). The levels of TAM were determined by chemical colorimetry in 100 EC patients and 100 healthy controls. Serum TAM levels were significantly higher in patients with esophageal carcinoma than in the control group (p < 0.001). High levels of TAM were associated with tumor size (p = 0.004), tumor depth (p < 0.001), stage (p < 0.001), lymph node metastases (p < 0.001), tumor differentiation (p = 0.001), tumor respectability (p = 0.002) and disease progression (p < 0.001). The poor prognostic outcomes were correlated with an elevated level of TAM (p = 0.001). Kaplan-Meier analysis showed patients with increased levels of TAM after operation had an lower overall survival (p < 0.001) and disease-free survival (p < 0.001). In addition, multivariate Cox proportional hazard analyses revealed that TAM may be an independent factor affecting the overall survival and disease-free survival (p < 0.001). The detection of TAM could be used to screen for tumor and assess unfavorable prognosis in patients with EC.

Long-Term Outcome of Amyotrophic Lateral Sclerosis in Korean Subjects.

PubMed

Suh, Mi Ri; Choi, Won Ah; Choi, Young-Chul; Lee, Jang Woo; Hong, Jung Hwa; Park, Jihyun; Kang, Seong-Woong

2017-12-01

To report the latest long-term outcome of amyotrophic lateral sclerosis (ALS) and to analyze the predictors of prognosis. Subjects who were diagnosed with ALS between January 2005 and December 2009 at a single institute were followed up until death or up to December 2014. Data regarding age, sex, date of onset, date of diagnosis, presence of bulbar symptoms on onset, date of initiation of non-invasive ventilation (NIV), and the date of tracheostomy were collected. Survival was assessed using Kaplan-Meier curves and multivariate analyses of the risk of death were performed using the Cox proportional hazards model. Among 212 suspicious subjects, definite ALS was diagnosed in 182 subjects. The survival rate at 3 and 5 years from onset was 61.5% and 40.1%, respectively, and the survival rate at 3 and 5 years post-diagnosis was 49.5% and 24.2%, respectively. Further, 134 patients (134/182, 73.6%) were initiated on NIV, and among them, 90 patients (90/182, 49.5%) underwent tracheostomy. Male gender and onset age of ≥65 years were independent predictors of adverse survival. The analysis of long term survival in ALS showed excellent outcomes considering the overall poor prognosis of this disease.

Downregulation of tumor suppressor QKI in gastric cancer and its implication in cancer prognosis

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

Bian, Yongqian; Wang, Li; Lu, Huanyu

2012-05-25

Highlights: Black-Right-Pointing-Pointer QKI expression is decreased in gastric cancer samples. Black-Right-Pointing-Pointer Promoter hyper methylation contributes to the downregulation of QKI. Black-Right-Pointing-Pointer QKI inhibits the growth of gastric cancer cells. Black-Right-Pointing-Pointer Decreased QKI expression predicts poor survival. -- Abstract: Gastric cancer (GC) is the fourth most common cancer and second leading cause of cancer-related death worldwide. RNA-binding protein Quaking (QKI) is a newly identified tumor suppressor in multiple cancers, while its role in GC is largely unknown. Our study here aimed to clarify the relationship between QKI expression with the clinicopathologic characteristics and the prognosis of GC. In the 222 GCmore » patients' specimens, QKI expression was found to be significantly decreased in most of the GC tissues, which was largely due to promoter hypermethylation. QKI overexpression reduced the proliferation ability of GC cell line in vitro study. In addition, the reduced QKI expression correlated well with poor differentiation status, depth of invasion, gastric lymph node metastasis, distant metastasis, advanced TNM stage, and poor survival. Multivariate analysis showed QKI expression was an independent prognostic factor for patient survival.« less

Analysis of Exhaled Breath Volatile Organic Compounds in Inflammatory Bowel Disease: A Pilot Study.

PubMed

Hicks, Lucy C; Huang, Juzheng; Kumar, Sacheen; Powles, Sam T; Orchard, Timothy R; Hanna, George B; Williams, Horace R T

2015-09-01

Distinguishing between the inflammatory bowel diseases [IBD], Crohn's disease [CD] and ulcerative colitis [UC], is important for determining management and prognosis. Selected ion flow tube mass spectrometry [SIFT-MS] may be used to analyse volatile organic compounds [VOCs] in exhaled breath: these may be altered in disease states, and distinguishing breath VOC profiles can be identified. The aim of this pilot study was to identify, quantify, and analyse VOCs present in the breath of IBD patients and controls, potentially providing insights into disease pathogenesis and complementing current diagnostic algorithms. SIFT-MS breath profiling of 56 individuals [20 UC, 18 CD, and 18 healthy controls] was undertaken. Multivariate analysis included principal components analysis and partial least squares discriminant analysis with orthogonal signal correction [OSC-PLS-DA]. Receiver operating characteristic [ROC] analysis was performed for each comparative analysis using statistically significant VOCs. OSC-PLS-DA modelling was able to distinguish both CD and UC from healthy controls and from one other with good sensitivity and specificity. ROC analysis using combinations of statistically significant VOCs [dimethyl sulphide, hydrogen sulphide, hydrogen cyanide, ammonia, butanal, and nonanal] gave integrated areas under the curve of 0.86 [CD vs healthy controls], 0.74 [UC vs healthy controls], and 0.83 [CD vs UC]. Exhaled breath VOC profiling was able to distinguish IBD patients from controls, as well as to separate UC from CD, using both multivariate and univariate statistical techniques. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Prognostic Significance of Tumor Necrosis in Hilar Cholangiocarcinoma.

PubMed

Atanasov, Georgi; Schierle, Katrin; Hau, Hans-Michael; Dietel, Corinna; Krenzien, Felix; Brandl, Andreas; Wiltberger, Georg; Englisch, Julianna Paulina; Robson, Simon C; Reutzel-Selke, Anja; Pascher, Andreas; Jonas, Sven; Pratschke, Johann; Benzing, Christian; Schmelzle, Moritz

2017-02-01

Tumor necrosis and peritumoral fibrosis have both been suggested to have a prognostic value in selected solid tumors. However, little is known regarding their influence on tumor progression and prognosis in hilar cholangiocarcinoma (HC). Surgically resected tumor specimens of HC (n = 47) were analyzed for formation of necrosis and extent of peritumoral fibrosis. Tumor necrosis and grade of fibrosis were assessed histologically and correlated with clinicopathological characteristics, tumor recurrence, and patients' survival. Univariate Kaplan-Meier analysis and a stepwise multivariable Cox regression model were applied. Mild peritumoral fibrosis was evident in 12 tumor samples, moderate peritumoral fibrosis in 20, and high-grade fibrosis in 15. Necrosis was evident in 19 of 47 tumor samples. Patients with tumors characterized by necrosis showed a significantly decreased 5-year recurrence-free survival (37.9 vs. 25.7 %; p < .05) and a significantly decreased 5-year overall survival (42.6 vs. 12.4 %; p < .05), when compared with patients with tumors showing no necrosis. R status, tumor recurrence, and tumor necrosis were of prognostic value in the univariate analysis (all p < .05). Multivariate survival analysis confirmed tumor necrosis (p = .038) as the only independent prognostic variable. The assessment of tumor necrosis appears as a valuable additional prognostic tool in routine histopathological evaluation of HC. These observations might have implications for monitoring and more individualized multimodal therapeutic strategies.

Conditional survival estimates improve over time for patients with advanced melanoma: results from a population-based analysis.

PubMed

Xing, Yan; Chang, George J; Hu, Chung-Yuan; Askew, Robert L; Ross, Merrick I; Gershenwald, Jeffrey E; Lee, Jeffrey E; Mansfield, Paul F; Lucci, Anthony; Cormier, Janice N

2010-05-01

Conditional survival (CS) has emerged as a clinically relevant measure of prognosis for cancer survivors. The objective of this analysis was to provide melanoma-specific CS estimates to help clinicians promote more informed patient decision making. Patients with melanoma and at least 5 years of follow-up were identified from the Surveillance Epidemiology and End Results registry (1988-2000). By using the methods of Kaplan and Meier, stage-specific, 5-year CS estimates were independently calculated for survivors for each year after diagnosis. Stage-specific multivariate Cox regression models including baseline survivor functions were used to calculate adjusted melanoma-specific CS for different subgroups of patients further stratified by age, gender, race, marital status, anatomic tumor location, and tumor histology. Five-year CS estimates for patients with stage I disease remained constant at 97% annually, while for patients with stages II, III, and IV disease, 5-year CS estimates from time 0 (diagnosis) to 5 years improved from 72% to 86%, 51% to 87%, and 19% to 84%, respectively. Multivariate CS analysis revealed that differences in stages II through IV CS based on age, gender, and race decreased over time. Five-year melanoma-specific CS estimates improve dramatically over time for survivors with advanced stages of disease. These prognostic data are critical to patients for both treatment and nontreatment related life decisions. (c) 2010 American Cancer Society.

Luminal-like HER2-negative stage IA breast cancer: a multicenter retrospective study on long-term outcome with propensity score analysis

PubMed Central

De Angelis, Carmine; Di Maio, Massimo; Crispo, Anna; Giuliano, Mario; Schettini, Francesco; Bonotto, Marta; Gerratana, Lorenzo; Iacono, Donatella; Cinausero, Marika; Riccardi, Ferdinando; Ciancia, Giuseppe; De Laurentiis, Michelino; Puglisi, Fabio; De Placido, Sabino; Arpino, Grazia

2017-01-01

The benefit of adding chemotherapy (CT) to adjuvant hormone therapy (HT) in stage IA luminal-like HER2-negative breast cancer (BC) is unclear. We retrospectively evaluated predictive factors and clinical outcome of 1,222 patients from 4 oncologic centers. Three hundred and eighty patients received CT and HT (CT-cohort) and 842 received HT alone (HT-cohort). Disease-free survival (DFS) and overall survival (OS) were evaluated with univariate and multivariate analyses. We also applied the propensity score methodology. Compared with the HT-cohort, patients in the CT-cohort were more likely to be younger, have larger tumors of a higher histological grade that were Ki67-positive, and lower estrogen and progesterone receptor expression. At univariate analysis, a higher histological grade and Ki67 were significantly associated to a lower DFS. At multivariable analysis, only histological grade was predictive of DFS. The CT-cohort had a worse outcome than the HT-cohort in terms of DFS and OS, but differences disappeared when matched according to propensity score. In summary, patients with stage IA luminal-like BC had an excellent prognosis, however relapse and mortality were higher in the CT-cohort than in the HT-cohort. Longer use of adjuvant HT or other therapeutic strategies may be needed to improve outcome. PMID:29348868

Impact of triple-negative phenotype on prognosis of patients with breast cancer brain metastases.

PubMed

Xu, Zhiyuan; Schlesinger, David; Toulmin, Sushila; Rich, Tyvin; Sheehan, Jason

2012-11-01

To elucidate survival times and identify potential prognostic factors in patients with triple-negative (TN) phenotype who harbored brain metastases arising from breast cancer and who underwent stereotactic radiosurgery (SRS). A total of 103 breast cancer patients with brain metastases were treated with SRS and then studied retrospectively. Twenty-four patients (23.3%) were TN. Survival times were estimated using the Kaplan-Meier method, with a log-rank test computing the survival time difference between groups. Univariate and multivariate analyses to predict potential prognostic factors were performed using a Cox proportional hazard regression model. The presence of TN phenotype was associated with worse survival times, including overall survival after the diagnosis of primary breast cancer (43 months vs. 82 months), neurologic survival after the diagnosis of intracranial metastases, and radiosurgical survival after SRS, with median survival times being 13 months vs. 25 months and 6 months vs. 16 months, respectively (p < 0.002 in all three comparisons). On multivariate analysis, radiosurgical survival benefit was associated with non-TN status and lower recursive partitioning analysis class at the initial SRS. The TN phenotype represents a significant adverse prognostic factor with respect to overall survival, neurologic survival, and radiosurgical survival in breast cancer patients with intracranial metastasis. Recursive partitioning analysis class also served as an important and independent prognostic factor. Copyright © 2012 Elsevier Inc. All rights reserved.

Impact of age on the survival of patients with liver cancer: an analysis of 27,255 patients in the SEER database.

PubMed

Zhang, Wenjie; Sun, Beicheng

2015-01-20

The risk of liver cancer (LC) is regarded as age dependent. However, the influence of age on its prognosis is controversial. The aim of our study was to compare the long-term survival of younger versus older patients with LC. In this retrospective study, we searched Surveillance, Epidemiology, and End-RESULTS (SEER) population-based data and identified 27,255 patients diagnosed with LC between 1988 and 2003. These patients were categorized into younger (45 years and under) and older age (over 45 years of age) groups. Five-year cancer specific survival data was obtained. Kaplan-Meier methods and multivariable Cox regression models were used to analyze long-term survival outcomes and risk factors. There were significant differences between groups with regards to pathologic grading, histologic type, stage, and tumor size (p < 0.001). The 5-year liver cancer specific survival (LCSS) rates in the younger and older age groups were 14.5% and 8.4%, respectively (p < 0.001 by univariate and multivariate analysis). A stratified analysis of age on cancer survival showed only localized and regional stages to be validated as independent predictors, but not for advanced stages. Compared to older patients, younger patients with LC have a higher LCSS after surgery, despite the poorer biological behavior of this carcinoma.

Adult Acute Erythroleukemia: An Analysis of 108 patients treated at a single institution

PubMed Central

Santos, Fabio; Faderl, Stefan; Garcia-Manero, Guillermo; Koller, Charles; Beran, Miloslav; O'Brien, Susan; Pierce, Sherry; Freireich, Emil; Huang, Xuelin; Borthakur, Gautam; Bueso-Ramos, Carlos; de Lima, Marcos; Keating, Michael; Cortes, Jorge; Kantarjian, Hagop; Ravandi, Farhad

2014-01-01

Acute erythroleukemia (AML-M6) is an uncommon subtype of acute myeloid leukemia (AML); it is considered to have a poor prognosis. From January 1st, 1980 to May 21st, 2008, 108 patients with newly diagnosed AML-M6 were seen at the University of Texas – M.D. Anderson Cancer Center (UT-MDACC). Half (50%) had a history of myelodysplatic syndrome (MDS), compared to 41% in our control group (patients with other AML subtypes) (p=0.05). Poor risk cytogenetics was more common in patients with AML-M6 (69% versus 46%, p<0.001). Complete remission rates were 63% for patients with AML-M6, comparing to 58% for the control group (p = 0.285). Median disease free survival (DFS) for patients with AML-M6 was 31 weeks, versus 49 weeks for the control group (p = 0.004). Median overall survival (OS) of patients with AML-M6 was 33 weeks, compared to 42 weeks for the control group (p = 0.13). On multivariate analysis for DFS and OS, AML-M6 was not an independent risk factor. Acute erythroleukemia is commonly associated with a previous diagnosis of MDS and poor risk karyotype. The diagnosis of AML-M6 does not impart by itself a worse prognosis, and treatment decisions on this disease should be guided by well know AML prognostic factors. PMID:19741728

Worse Prognosis for Stage IA Lung Cancer Patients with Smoking History and More Severe Chronic Obstructive Pulmonary Disease.

PubMed

Yoshida, Yukihiro; Kage, Hidenori; Murakawa, Tomohiro; Sato, Yasunori; Ota, Satoshi; Fukayama, Masashi; Nakajima, Jun

2015-01-01

This retrospective study examined whether the severity of chronic obstructive lung disease (COPD) affects surgical outcomes. The subjects were 243 consecutive patients who underwent lobectomy for clinical stage IA lung cancer from 1999 to 2008 in our hospital. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading system was used to classify the severity of COPD in smokers. Among the 149 smokers, 62 were diagnosed with COPD (25 as GOLD 1, 33 as GOLD 2, and 4 as GOLD 3). In univariate analysis, postoperative pulmonary complications were associated with male sex and more severe COPD. The frequencies were 17.1% in non-COPD, 24.0% in GOLD 1-COPD, and 46.0% in GOLD 2/3-COPD smokers (p = 0.0006). In univariate analysis, older age, smoking history, higher smoking pack-years and more severe COPD were associated with poor relapse-free survival. Relapse-free survival at five years was 80.7%, 66.9%, and 61.3% in non-COPD, GOLD 1-COPD, and GOLD 2/3-COPD smokers, respectively (p = 0.0005). Multivariate analyses showed that only GOLD 2/3-COPD was associated with postoperative pulmonary complications and relapse-free survival. Inhaled bronchodilators were prescribed preoperatively to 24.3% of the GOLD 2/3-COPD group. Smokers with GOLD 2/3-COPD are at high risk for pulmonary complications and have an unfavorable long-term prognosis.

The Prevalence of CD146 Expression in Breast Cancer Subtypes and Its Relation to Outcome.

PubMed

de Kruijff, Ingeborg E; Timmermans, Anna M; den Bakker, Michael A; Trapman-Jansen, Anita M A C; Foekens, Renée; Meijer-Van Gelder, Marion E; Oomen-de Hoop, Esther; Smid, Marcel; Hollestelle, Antoinette; van Deurzen, Carolien H M; Foekens, John A; Martens, John W M; Sleijfer, Stefan

2018-05-05

CD146, involved in epithelial-to-mesenchymal transition (EMT), might affect cancer aggressiveness. We here investigated the prevalence of CD146 expression in breast cancer subtypes, its relation to prognosis, the relation between CD146 and EMT and the outcome to tamoxifen. Primary breast cancer tissues from 1342 patients were available for this retrospective study and immunohistochemically stained for CD146. For survival analyses, pure prognosis was studied by only including lymph-node negative patients who did not receive (neo)adjuvant systemic treatment ( n = 551). 11% of the tumors showed CD146 expression. CD146 expression was most prevalent in triple-negative cases (64%, p < 0.001). In univariable analysis, CD146 expression was a prognostic factor for both metastasis-free survival (MFS) ( p = 0.020) and overall survival (OS) ( p = 0.037), but not in multivariable analysis (including age, tumor size, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67). No correlation between CD146 and EMT nor difference in outcome to first-line tamoxifen was seen. In this large series, our data showed that CD146 is present in primary breast cancer and is a pure prognostic factor for MFS and OS in breast cancer patients. We did not see an association between CD146 expression and EMT nor on outcome to tamoxifen.

The impact of non-alcoholic fatty liver disease fibrosis score on cardiac prognosis in patients with chronic heart failure.

PubMed

Takahashi, Tetsuya; Watanabe, Tetsu; Shishido, Tetsuro; Watanabe, Ken; Sugai, Takayuki; Toshima, Taku; Kinoshita, Daisuke; Yokoyama, Miyuki; Tamura, Harutoshi; Nishiyama, Satoshi; Arimoto, Takanori; Takahashi, Hiroki; Yamanaka, Tamon; Miyamoto, Takuya; Kubota, Isao

2018-07-01

Liver abnormalities have a strong impact on clinical outcomes in patients with heart failure (HF), and are known as cardio-hepatic syndrome. The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has been developed to identify liver fibrosis in patients with NAFLD. It remains to be determined whether NFS is associated with cardiovascular prognosis in patients with chronic heart failure (CHF). We calculated NFS in 516 patients with CHF admitted to our hospital. The clinical endpoints were deaths due to progressive HF, myocardial infarction, stroke, and sudden cardiac death, and rehospitalization for worsening HF. There were 173 cardiovascular events noted during a median follow-up of 464 days. Patients with cardiovascular events showed a higher NFS as compared with those without. We divided the patients into four groups according to quartiles of NFS. The proportion of New York Heart Association functional class III/IV and serum brain natriuretic peptide levels were increased with increasing NFS. Kaplan-Meier analysis revealed that cardiovascular event rate was increased with increasing NFS in patients with CHF. In multivariate Cox proportional hazards analysis, NFS was independently associated with cardiovascular events after adjustment for confounding factors. Elevated NFS was associated with unfavorable outcomes in patients with CHF. Liver fibrosis assessed by NFS may provide valuable prognostic information in patients with CHF.

Urine Trefoil Factors as Prognostic Biomarkers in Chronic Kidney Disease.

PubMed

Yamanari, Toshio; Sugiyama, Hitoshi; Tanaka, Keiko; Morinaga, Hiroshi; Kitagawa, Masashi; Onishi, Akifumi; Ogawa-Akiyama, Ayu; Kano, Yuzuki; Mise, Koki; Ohmoto, Yasukazu; Shikata, Kenichi; Wada, Jun

2018-01-01

Trefoil factor family (TFF) peptides are increased in serum and urine in patients with chronic kidney disease (CKD). However, whether the levels of TFF predict the progression of CKD remains to be elucidated. We determined the TFF levels using peptide-specific ELISA in spot urine samples and performed a prospective cohort study. The association between the levels of urine TFFs and other urine biomarkers as well as the renal prognosis was analyzed in 216 CKD patients (mean age: 53.7 years, 47.7% female, 56.9% with chronic glomerulonephritis, and mean eGFR: 58.5 ml/min/1.73 m 2 ). The urine TFF1 and TFF3 levels significantly increased with the progression of CKD stages, but not the urine TFF2 levels. The TFF1 and TFF3 peptide levels predicted the progression of CKD ≥ stage 3b by ROC analysis (AUC 0.750 and 0.879, resp.); however, TFF3 alone predicted CKD progression in a multivariate logistic regression analysis (odds ratio 3.854, 95% confidence interval 1.316-11.55). The Kaplan-Meier survival curves demonstrated that patients with a higher TFF1 and TFF3 alone, or in combination with macroalbuminuria, had a significantly worse renal prognosis. The data suggested that urine TFF peptides are associated with renal progression and the outcomes in patients with CKD.

Urine Trefoil Factors as Prognostic Biomarkers in Chronic Kidney Disease

PubMed Central

Yamanari, Toshio; Tanaka, Keiko; Morinaga, Hiroshi; Kitagawa, Masashi; Onishi, Akifumi; Ogawa-Akiyama, Ayu; Kano, Yuzuki; Mise, Koki; Ohmoto, Yasukazu; Shikata, Kenichi

2018-01-01

Introduction Trefoil factor family (TFF) peptides are increased in serum and urine in patients with chronic kidney disease (CKD). However, whether the levels of TFF predict the progression of CKD remains to be elucidated. Methods We determined the TFF levels using peptide-specific ELISA in spot urine samples and performed a prospective cohort study. The association between the levels of urine TFFs and other urine biomarkers as well as the renal prognosis was analyzed in 216 CKD patients (mean age: 53.7 years, 47.7% female, 56.9% with chronic glomerulonephritis, and mean eGFR: 58.5 ml/min/1.73 m2). Results The urine TFF1 and TFF3 levels significantly increased with the progression of CKD stages, but not the urine TFF2 levels. The TFF1 and TFF3 peptide levels predicted the progression of CKD ≥ stage 3b by ROC analysis (AUC 0.750 and 0.879, resp.); however, TFF3 alone predicted CKD progression in a multivariate logistic regression analysis (odds ratio 3.854, 95% confidence interval 1.316–11.55). The Kaplan-Meier survival curves demonstrated that patients with a higher TFF1 and TFF3 alone, or in combination with macroalbuminuria, had a significantly worse renal prognosis. Conclusion The data suggested that urine TFF peptides are associated with renal progression and the outcomes in patients with CKD. PMID:29850501

[An analysis of the prognostic factors of acute myocardial infarction in different gender].

PubMed

Wang, Chun-Mei; Wu, Xue-Si; Han, Zhi-Hong; Zhang, Qian

2009-02-01

To analyse the prognostic factors of ST-elevation acute myocardial infarction men and women. The data of 904 in-hospital patients with ST-elevation myocardial infarction were collected from the database of our hospital during 2003 - 2004 and 728 of them were followed-up. The patients were divided into groups of male and female. Women had more accompanying diseases such as diabetes mellitus (DM) and hypertension than men; left ventricular ejection fraction (LVEF) was lower in female. The rate of successful reperfusion was lower in women than men (P < 0.05). Mortality rate was higher in women. 728 (202 female) patients were followed up. The use of beta-blockers were statistically different between two groups during follow-up. In the female group, LVEF was lower significantly and the rate of readmission for heart failure and myocardial infarction as well as that of mortality was higher (P < 0.05). Multivariate analysis showed that sex difference was an independent risk factor for in-hospital mortality (OR = 2.130, 95% CI 0.954 - 4.754, P = 0.045), but not for mortality in the followed-up period and readmission. There are many factors leading to the poor prognosis of ST-elevation acute myocardial infarction in women. It is essential to pay more attention to its clinical characteristics and begin intervention of the risk factors earlier so as to improve the prognosis.

The effect of surgery and radiotherapy on outcome of anaplastic thyroid carcinoma.

PubMed

Pierie, Jean-Pierre E N; Muzikansky, Alona; Gaz, Randall D; Faquin, William C; Ott, Mark J

2002-01-01

Anaplastic thyroid carcinoma (ATC) is an aggressive rare tumor. We analyzed our experience for prognosis and the effect of surgery and radiotherapy on patients with ATC. We conducted a retrospective review of all patients (n = 67) with ATC treated at a tertiary care center from 1969 to 1999. Survivor median follow-up was 51 months. Tumor and patient characteristics and therapy were assessed for effect on survival by multivariate analysis. Patients presented with a neck mass (99%), change of voice (51%), dysphagia (33%), and dyspnea (28%). Surgery was performed in 44 of 67 patients, with 12 complete resections. The 6-month and 1- and 3-year survival rates were 92%, 92%, and 83% after complete resection; 53%, 35%, and 0% after debulking; and 22%, 4%, and 0% after no resection, respectively (P < .0001). A radiation dose of >45 Gy improved survival as compared with a lower dose (P = .02). Multivariate analysis showed that age < or = 70 years, absence of dyspnea or dysphagia at presentation, a tumor size < or = 5 cm, and any surgical resection improved survival (P < .05). Candidates for surgery with curative intent for ATC are patients < or = 70 years, tumors < or = 5 cm, and no distant disease. Radiotherapy >45 Gy improves outcome.

EMMPRIN/CD147 is an independent prognostic biomarker in cutaneous melanoma.

PubMed

Caudron, Anne; Battistella, Maxime; Feugeas, Jean-Paul; Pages, Cécile; Basset-Seguin, Nicole; Mazouz Dorval, Sarra; Funck Brentano, Elisa; Sadoux, Aurélie; Podgorniak, Marie-Pierre; Menashi, Suzanne; Janin, Anne; Lebbé, Céleste; Mourah, Samia

2016-08-01

CD147 has been implicated in melanoma invasion and metastasis mainly through increasing metalloproteinase synthesis and regulating VEGF/VEGFR signalling. In this study, the prognostic value of CD147 expression was investigated in a cohort of 196 cutaneous melanomas including 136 consecutive primary malignant melanomas, 30 lymph nodes, 16 in-transit and 14 visceral metastases. A series of 10 normal skin, 10 blue nevi and 10 dermal nevi was used as control. CD147 expression was assessed by immunohistochemistry, and the association of its expression with the clinicopathological characteristics of patients and survival was evaluated using univariate and multivariate statistical analyses. Univariate analysis showed that high CD147 expression was significantly associated with metastatic potential and with a reduced overall survival (P < 0.05 for both) in primary melanoma patients. CD147 expression level was correlated with histological factors which were associated with prognosis: Clark level, ulceration status and more particularly with Breslow index (r = 0.7, P < 10(-8) ). Multivariate analysis retained CD147 expression level and ulceration status as predicting factors for metastasis and overall survival (P < 0.05 for both). CD147 emerges as an important factor in the aggressive behaviour of melanoma and deserves further evaluation as an independent prognostic biomarker. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prognostic significance of MRI findings in patients with myxoid-round cell liposarcoma.

PubMed

Tateishi, Ukihide; Hasegawa, Tadashi; Beppu, Yasuo; Kawai, Akira; Satake, Mitsuo; Moriyama, Noriyuki

2004-03-01

The aims of this study were to determine the prognostic significance of MRI findings in patients with myxoid-round cell liposarcomas and to clarify which MRI features best indicate tumors with adverse clinical behavior. The initial MRI studies of 36 pathologically confirmed myxoid-round cell liposarcomas were retrospectively reviewed, and observations from this review were correlated with the histopathologic features. MR images were evaluated by two radiologists with agreement by consensus, and both univariate and multivariate analyses were conducted to evaluate survival with a median clinical follow-up of 33 months (range, 9-276 months). Statistically significant MRI findings that favored a diagnosis of intermediate- or high-grade tumor were large tumor size (> 10 cm), deeply situated tumor, tumor possessing irregular contours, absence of lobulation, absence of thin septa, presence of thick septa, absence of tumor capsule, high-intensity signal pattern, pronounced enhancement, and globular or nodular enhancement. Of these MRI findings, thin septa (p < 0.05), a tumor capsule (p < 0.01), and pronounced enhancement (p < 0.01) were associated significantly, according to univariate analysis, with overall survival. Multivariate analysis indicated that pronounced enhancement was associated significantly with overall survival (p < 0.05). Contrast-enhanced MRI findings can indicate a good or adverse prognosis in patients with myxoid-round cell liposarcomas.

Prenatal diagnosis of prevalence of the right heart: associated anomalies and outcome predictors.

PubMed

Peng, Ruan; Xie, Hong-Ning; Zhu, Yun-Xiao; Li, Li-Juan; Du, Liu; Zheng, Ju

2014-07-01

To analyze the characteristics, associations, and outcomes of prevalence of the right heart and to evaluate the use of sonography to predict the risk of a poor prognosis in fetuses with this condition. We conducted a retrospective cohort study of 182 fetuses with prevalence of the right heart. At the initial evaluation, the left ventricle (LV) and right ventricle (RV) sizes, left atrium and right atrium sizes, great artery diameters, appearance of the aortic arch and ductus arteriosus arch, and flow direction across the foramen ovale and aortic arch were documented. Malformations were documented in fetuses with intracardiac anomalies, who were divided into groups with and without coexisting extracardiac defects. The RV-LV diameter ratio and main pulmonary artery-to-aortic root diameter ratio were calculated and compared. The following variables were analyzed: coexisting intracardiac anomalies, associated extracardiac anomalies, diagnosis before 24 gestational weeks, fetal growth restriction, reversed flow across the foramen ovale, reversed flow in the aortic arch, and RV-LV ratio greater than 2.0. Relationships between these sonographic findings and the prognosis were evaluated by multivariable logistic regression. Of the 182 fetuses, 1 (0.5%) had intrauterine death, and 25 (13.7%) had neonatal death; 1 (0.5%) had selective reduction, and 106 (58.2%) underwent termination of pregnancy; 49 (26.9%) survived at this writing. The mean RV-LV ratio was 1.67. Multivariable logistic regression revealed that only 2 sonographic parameters, coexisting intracardiac anomalies (odds ratio, 17.75; 95% confidence interval, 4.18-75.26) and diagnosis before 24 weeks (odds ratio, 17.26; 95% confidence interval, 1.80-165.39) were significantly associated with a poor prognosis. The sonographic parameters of coexisting intracardiac anomalies and diagnosis before 24 gestational weeks are significant independent predictors of a poor prognosis in fetuses with prevalence of the right heart. Combinations of these risk factors may be useful in prenatal consultation. © 2014 by the American Institute of Ultrasound in Medicine.

Analysis of the prognostic value of BMI and the difference in its impact according to age and sex in DLBCL patients.

PubMed

Kanemasa, Yusuke; Shimoyama, Tatsu; Sasaki, Yuki; Tamura, Miho; Sawada, Takeshi; Omuro, Yasushi; Hishima, Tsunekazu; Maeda, Yoshiharu

2018-02-01

Studies that have evaluated the prognostic value of body mass index (BMI) in patients with diffuse large B-cell lymphoma have recently been reported. However, the impact of BMI on survival outcomes remains controversial. We retrospectively analyzed the data of 406 diffuse large B-cell lymphoma patients treated with R-CHOP or R-CHOP-like regimens. The number (%) of patients that were categorized into 1 of 4 groups according to BMI were underweight (<18.5 kg/m 2 ), 58 (14.3%); normal weight (≥18.5 to <25 kg/m 2 ), 262 (64.5%); overweight (≥25 to <30 kg/m 2 ), 75 (18.5%); and obese (≥30.0 kg/m 2 ), 11 (2.7%). While the prognosis of overweight patients was good, being similar to that of normal weight, underweight, and obese patients had a worse prognosis (5-y overall survival [OS] was 57.9%, 74.3%, 73.4%, and 40.9% for underweight, normal weight, overweight, and obese patients, respectively; P = .004). In multivariate analysis, underweight and obesity were independent prognostic factors for OS compared with normal weight (hazard ratios 2.90 and 5.17, respectively). In elderly female patients (≥70 y), patients with a low BMI (<25 kg/m 2 ) had significantly inferior OS than those with a high BMI (≥25 kg/m 2 ) (5-y OS, 61.5% vs 85.7%; P = .039). In contrast, in young female patients (<70 years), patients with a low BMI had significantly better OS than those with a high BMI (5-y OS, 88.6% vs 46.4%; P < .001). In male patients, there were no differences in the effect of BMI on OS between young and elderly patients. In this study, we demonstrated that being underweight and obese were independent prognostic factors compared with being normal weight. In female patients, BMI had a different impact on the prognosis of young and elderly patients, whereas in male patients, there was no difference in the effect of BMI on prognosis according to age. Copyright © 2017 John Wiley & Sons, Ltd.

Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous Nephropathy

PubMed Central

Seitz-Polski, Barbara; Dolla, Guillaume; Payré, Christine; Girard, Christophe A.; Polidori, Joel; Zorzi, Kevin; Birgy-Barelli, Eléonore; Jullien, Perrine; Courivaud, Cécile; Krummel, Thierry; Benzaken, Sylvia; Bernard, Ghislaine; Burtey, Stéphane; Mariat, Christophe; Esnault, Vincent L.M.

2016-01-01

The phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy. However, the value of anti-PLA2R1 antibody titers in predicting patient outcomes is unknown. Here, we screened serum samples from 50 patients positive for PLA2R1 for immunoreactivity against a series of PLA2R1 deletion mutants covering the extracellular domains. We identified reactive epitopes in the cysteine-rich (CysR), C-type lectin domain 1 (CTLD1), and C-type lectin domain 7 (CTLD7) domains and confirmed the reactivity with soluble forms of each domain. We then used ELISAs to stratify 69 patients positive for PLA2R1 by serum reactivity to one or more of these domains: CysR (n=23), CysRC1 (n=14), and CysRC1C7 (n=32). Median ELISA titers measured using the full-length PLA2R1 antigens were not statistically different between subgroups. Patients with anti-CysR–restricted activity were younger (P=0.008), had less nephrotic range proteinuria (P=0.02), and exhibited a higher rate of spontaneous remission (P=0.03) and lower rates of renal failure progression (P=0.002) and ESRD (P=0.01) during follow-up. Overall, 31 of 69 patients had poor renal prognosis (urinary protein/creatinine ratio >4 g/g or eGFR<45 ml/min per 1.73 m2 at end of follow-up). High anti-PLA2R1 activity and epitope spreading beyond the CysR epitope were independent risk factors of poor renal prognosis in multivariable Cox regression analysis. Epitope spreading during follow-up associated with disease worsening (n=3), whereas reverse spreading from a CysRC1C7 profile back to a CysR profile associated with favorable outcome (n=1). We conclude that analysis of the PLA2R1 epitope profile and spreading is a powerful tool for monitoring disease severity and stratifying patients by renal prognosis. PMID:26567246

Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous Nephropathy.

PubMed

Seitz-Polski, Barbara; Dolla, Guillaume; Payré, Christine; Girard, Christophe A; Polidori, Joel; Zorzi, Kevin; Birgy-Barelli, Eléonore; Jullien, Perrine; Courivaud, Cécile; Krummel, Thierry; Benzaken, Sylvia; Bernard, Ghislaine; Burtey, Stéphane; Mariat, Christophe; Esnault, Vincent L M; Lambeau, Gérard

2016-05-01

The phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy. However, the value of anti-PLA2R1 antibody titers in predicting patient outcomes is unknown. Here, we screened serum samples from 50 patients positive for PLA2R1 for immunoreactivity against a series of PLA2R1 deletion mutants covering the extracellular domains. We identified reactive epitopes in the cysteine-rich (CysR), C-type lectin domain 1 (CTLD1), and C-type lectin domain 7 (CTLD7) domains and confirmed the reactivity with soluble forms of each domain. We then used ELISAs to stratify 69 patients positive for PLA2R1 by serum reactivity to one or more of these domains: CysR (n=23), CysRC1 (n=14), and CysRC1C7 (n=32). Median ELISA titers measured using the full-length PLA2R1 antigens were not statistically different between subgroups. Patients with anti-CysR-restricted activity were younger (P=0.008), had less nephrotic range proteinuria (P=0.02), and exhibited a higher rate of spontaneous remission (P=0.03) and lower rates of renal failure progression (P=0.002) and ESRD (P=0.01) during follow-up. Overall, 31 of 69 patients had poor renal prognosis (urinary protein/creatinine ratio >4 g/g or eGFR<45 ml/min per 1.73 m(2) at end of follow-up). High anti-PLA2R1 activity and epitope spreading beyond the CysR epitope were independent risk factors of poor renal prognosis in multivariable Cox regression analysis. Epitope spreading during follow-up associated with disease worsening (n=3), whereas reverse spreading from a CysRC1C7 profile back to a CysR profile associated with favorable outcome (n=1). We conclude that analysis of the PLA2R1 epitope profile and spreading is a powerful tool for monitoring disease severity and stratifying patients by renal prognosis. Copyright © 2016 by the American Society of Nephrology.

MicroRNA-211 expression is down-regulated and associated with poor prognosis in human glioma.

PubMed

Zhang, Jun; Lv, Jianguang; Zhang, Feng; Che, Hongmin; Liao, Qiwei; Huang, Wobin; Li, Shaopeng; Li, Yuqian

2017-07-01

Accumulating evidence has supported the role of microRNAs in the initiation and development of malignant tumors. MicroRNA-211 (miR-211), which was reported to involve in diverse physiological activities in several cancers, was investigated for its expression in human glioma and adjacent normal brain tissues, as well as its correlation with patient prognosis. Glioma tissues and adjacent normal brain tissues were obtained from 82 patients who underwent surgical resection, and quantitative real-time polymerase chain reaction was performed to assess the expression level of miR-211. Here, we found that miR-211 was significantly decreased in glioma tissues compared with adjacent normal brain tissues (glioma, 3.52 ± 0.14 vs. normal, 4.96 ± 0.17, p < 0.001), and inversely associated with ascending WHO classification (grade III-IV, 3.16 ± 0.21 vs. grade I-II, 4.22 ± 0.26, p < 0.001). Then, the correlation of miR-211 with clinicopathological factors was investigated by Pearson's Chi square test, indicating that miR-211 might be a potential biomarker to predict the malignant status of glioma. Further, Kaplan-Meier curves with log-rank analysis were carried out to determine the relationship between miR-211 expression level and the overall survival rate of glioma patients. Our data showed that there was a close correlation between down-regulated miR-211 and shorter survival time in 82 patients (p = 0.026). Finally, the multivariate Cox regression analysis indicated that WHO grade (HR = 2.437, 95% CI 1.251-4.966, p = 0.007), KPS (HR = 2.215, 95% CI 1.168-4.259, p = 0.016), and miR-211 expression level (HR = 3.614, 95% CI 2.152-6.748, p < 0.001) were considered as independent risk factors for glioma prognosis. These results suggested that lower miR-211 expression might be a marker for poor prognosis of glioma patients.

Clinicopathological analysis in PTCL-NOS with CADM1 expression.

PubMed

Kato, Takeharu; Miyoshi, Hiroaki; Kobayashi, Seiichiro; Yoshida, Noriaki; Imaizumi, Yoshitaka; Seto, Masao; Uchimaru, Kaoru; Miyazaki, Yasushi; Ohshima, Koichi

2017-11-01

Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), is a heterogeneous disease with respect to clinicopathological features. Cell adhesion molecule 1 (CADM1) has been reported to be ectopically expressed in adult T cell leukaemia/lymphoma (ATLL). However, the frequency of CADM1 expression remains unknown in peripheral T cell lymphomas. In the current study, CADM1 expression was analysed in 88 PTCL-NOS patients. CADM1 was expressed in 14 of 88 (15.9%) PTCL-NOS cases, and its expression was associated with C-C chemokine receptor type 4 (CCR4) expression and nuclear atypia. CADM1-positive PTCL-NOS cases (10/74) had a significantly poorer prognosis than CADM1-negative cases (64/74) (P = 0.001). Multivariate analysis confirmed that CADM1 expression was an independent prognostic factor in PTCL-NOS. These findings suggest that CADM1 expression is a novel prognostic factor for PTCL-NOS.

Mitochondrial reactive oxygen species and complex II levels are associated with the outcome of hepatocellular carcinoma

PubMed Central

WU, JIANHUA; ZHAO, FEI; ZHAO, YUFEI; GUO, ZHANJUN

2015-01-01

In the present study, two oxidative stress parameters, reactive oxygen species (ROS) and mitochondrial respiratory complex II, were evaluated in the mitochondria of hepatocellular carcinoma (HCC) cells to determine the association between these parameters and the carcinogenesis and clinical outcome of HCC. High levels of ROS and low levels of complex II were found to be associated with reduced post-operative survival in HCC patients using the log-rank test. Furthermore, multivariate analysis confirmed that the levels of ROS [relative risk (RR)=2.867; 95% confidence interval (CI), 1.062–7.737; P=0.038] and complex II (RR=5.422; 95% CI, 1.273–23.088; P=0.022) were independent predictors for the survival of patients with HCC. Therefore, the analysis of ROS and complex II levels may provide a useful research and therapeutic tool for the prediction of HCC prognosis and treatment. PMID:26622849

Parotid adenoid cystic carcinoma: Retrospective single institute analysis.

PubMed

Mannelli, Giuditta; Cecconi, Lorenzo; Fasolati, Martina; Santoro, Roberto; Franchi, Alessandro; Gallo, Oreste

Adenoid cystic carcinoma (ACC) is a uncommon salivary malignant tumor. Our aim was to review our experience with parotid ACC, to identify clinical-pathological parameters predictive for outcome. We retrospectively reviewed 228 patients affected by parotid gland carcinomas surgically treated at our Institution. Forty-four ACC were included in this study. Multivariate analysis risk models were built to predict recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and disease free survival (DFS). Twenty-one patients (47.7%) died from ACC and 2.3% for other causes. The 41% presented local-regional recurrence, with a regional-RFP rate of 93%, and the 34% reported distant metastases (DM). The five and ten-year OS rates were 74% and 50%, respectively. Recurrences were mainly influenced by the presence of perineural invasion and nerve paralysis, whilst female gender and age<50 were predictors for good prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic value of CD44 expression in non-small cell lung cancer: a systematic review.

PubMed

Luo, Zhuang; Wu, Rong-Rong; Lv, Liang; Li, Peng; Zhang, Li-Yan; Hao, Qing-Lin; Li, Wei

2014-01-01

CD44 is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). Although the expression of CD44 has been reported to correlate with poor prognosis of NSCLC in most literatures, some controversies still exist. Since the limited patient numbers within independent studies, here we performed a meta-analysis to clarify the correlations between CD44 expression and prognosis and clinicopathological features in NSCLC. Relevant literatures were identified using PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases (up to February 2014). Data from eligible studies were extracted and included into meta-analysis using a random effects model. Studies were pooled. Summary hazard ratios (HR) and clinical parameters were calculated. We performed a final analysis of 1772 patients from 23 evaluable studies for Prognostic Value and 2167 patients from 28 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD44-V6 for overall survival in NSCLC was 1.63 [95% confidence interval (CI): 1.20-2.21] by univariate analysis and 1.29 (95% CI: 0.71-2.37) by multivariate analysis.The pooled HR of overexprssion panCD44 for overall survival in NSCLC was 1.53 (95% CI: 0.58-4.04) by univariate analysis and 3.00 (95% CI: 1.53-5.87) by multivariate analysis. Overexpression of CD44-V6 is associated with tumor differentiation (poor differentiation, OR = 1.66, 95% CI: 1.12-2.45), tumor histological type [squamous cell carcinomas (SCC), OR = 2.6, 95% CI: 1.63-5.02], clinical TMN stage (TMN stage III, OR = 2.22, 95% CI: 1.44-3.43) and lymph node metastasis (N1-3, 3.52, 95% CI: 2.08-5.93) in patients with NSCLC. However, there was no significant association between CD44-V6 and tumor size [T category, OR = 1.42, 95% CI: 0.73-2.78]. Our meta-analysis showed that CD44-V6 is an efficient prognostic factor for NSCLC. Overexpression of CD44-V6 was significantly associated with tumor differentiation, tumor histological type, clinical TMN stage and lymph node metastasis. However, there was no significant association between CD44-V6 and tumor size. Large prospective studies are now needed to confirm the clinical utility of CD44 as an independent prognostic marker.

Expression of p53, p21 and cyclin D1 in penile cancer: p53 predicts poor prognosis.

PubMed

Gunia, Sven; Kakies, Christoph; Erbersdobler, Andreas; Hakenberg, Oliver W; Koch, Stefan; May, Matthias

2012-03-01

To evaluate the role of p53, p21 and cyclin D1 expression in patients with penile cancer (PC). Paraffin-embedded tissues from PC specimens from six pathology departments were subjected to a central histopathological review performed by one pathologist. The tissue microarray technique was used for immunostaining which was evaluated by two independent pathologists and correlated with cancer-specific survival (CSS). κ-statistics were used to assess interobserver variability. Uni- and multivariable Cox proportional hazards analysis was applied to assess the independent effects of several prognostic factors on CSS over a median of 32 months (IQR 6-66 months). Specimens and clinical data from 110 men treated surgically for primary PC were collected. p53 staining was positive in 30 and negative in 62 specimens. κ-statistics showed substantial interobserver reproducibility of p53 staining evaluation (κ=0.73; p<0.001). The 5-year CSS rate for the entire study cohort was 74%. Five-year CSS was 84% in p53-negative and 51% in p53-positive PC patients (p=0.003). Multivariable analysis showed p53 (HR=3.20; p=0.041) and pT-stage (HR=4.29; p<0.001) as independent significant prognostic factors for CSS. Cyclin D1 and p21 expression were not correlated with survival. However, incorporating p21 into a multivariable Cox model did contribute to improved model quality for predicting CSS. In patients with PC, the expression of p53 in the primary tumour specimen can be reproducibly assessed and is negatively associated with cancer specific survival.

Effect of race on biochemical disease-free outcome in patients with prostate cancer treated with definitive radiation therapy in an equal-access health care system: radiation oncology report of the Department of Defense Center for Prostate Disease Research.

PubMed

Johnstone, Peter A S; Kane, Christopher J; Sun, Leon; Wu, Hongyu; Moul, Judd W; McLeod, David G; Martin, Douglas D; Kusuda, Leo; Lance, Raymond; Douglas, Robert; Donahue, Timothy; Beat, Michael G; Foley, John; Baldwin, Dalton; Soderdahl, Douglas; Do, Jason; Amling, Christopher L

2002-11-01

To report on the first collaboration of the Department of Defense Center for Prostate Disease Research concerned with the relationship between African American race and biochemical disease-free outcomes after definitive radiation therapy. Information from the medical records of 1,806 patients (1,349 white, 343 African American, 42 of "other" races, and 72 of "unknown" races) treated with definitive radiation therapy between 1973 and 2000 was reviewed. Patients receiving adjuvant hormonal therapy or postoperative adjuvant or salvage radiation therapy were excluded. Biochemical failure was calculated in over 96% of cases by using ASTRO criteria; patients with fewer than three follow-up visits were considered to have biochemical failure with a prostate-specific antigen (PSA) value more than 10-fold the previous value or with any value greater than 50.0 ng/mL. Median radiation therapy doses were similar. The median follow-up was 58.4 months. Kaplan-Meier tests, Cox proportional hazards regression analysis, and log-rank tests were used for data analysis. There was no statistically significant difference in biochemical disease-free survival according to race when patients were stratified according to T stage. African American race conferred a negative prognosis for patients with lesions of Gleason biopsy score 7 (P =.004) but not for patients with lesions of Gleason score 2-4 (P =.14), 5-6 (P =.79), or 8-10 (P =.86). Similarly, African American race conferred a negative prognosis in patients with PSA values of 20.1-50.0 ng/mL (P =.01) at presentation but not in patients with PSA values less than or equal to 4.0 ng/mL (P =.84), 4.1-10.0 ng/mL (P =.71), 10.1-20.0 ng/mL (P =.75), or above 50.0 ng/mL (P =.15) at presentation. At multivariate analysis, race was not a statistically significant predictor of outcome. In the equal-access health care system of the Department of Defense, African American race is not associated with a consistently negative prognosis in patients treated with definitive radiation therapy for prostate cancer. Race appears to confer a negative prognosis only in patients with advanced disease at presentation.

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

PubMed Central

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

2015-01-01

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

[Analysis on influencing factors of prognosis of patients with acute organophosphorus pesticide poisoning].

PubMed

Guo, C F; Wang, Y; Liu, J H; Shen, P; Wang, H; Wei, Y J; Shi, X F; Zhou, X J; Wang, W W

2016-05-20

To analyze the relationship between risk factors and prognosis of acute organophosphorus pesticide poisoning (AOPP). The clinical data including APACHEⅡ, D-dimer, C-reactive protein, procalcitonin, lactic acid of the 67 cases of acute organophosphorus pesticide poisoning which respectively divided into survival group and death group by the outcome were collected. The independent influcing factors were got by logistic regression analysis. The analysis showed that APACHEⅡ, D-dimer、C-reactive protein and Procalcitonin were influencing factors to evaluate prognosis of AOPP (P<0.05) .Meanwhile, APACHEⅡ and CRP were the independent influencing factors to evaluate prognosis of AOPP (P<0.05). APACHEⅡ26was the optimum thresholds to acess the prognosis of AOPP and its Youden index was largest. APACHEⅡ and CRP played an important role in the assessment of prognosis on AOPP. When APACHEⅡwas more than 26, it suggested the patient of AOPP will have a bad prognosis.

Elevated Levels of Dickkopf-1 Are Associated with β-Catenin Accumulation and Poor Prognosis in Patients with Chondrosarcoma

PubMed Central

Chen, Changbao; Zhou, Hua; Zhang, Xiaolin; Ma, Xinlong; Liu, Zhongjun; Liu, Xiaoguang

2014-01-01

Background Dickkopf-1 (DKK1) is an antagonist of Wnt/β-catenin signaling implicated in tumorigenesis. However, the biological role of DKK1 and β-catenin involved in chondrosarcoma has not been sufficiently investigated. This study was designed to investigate the expression profiles of DKK1 and β-catenin, and to clarify their clinical values in chondrosarcoma. Methods The mRNA and protein levels of DKK1 and β-catenin in fresh chondrosarcoma and the corresponding non-tumor tissues were analyzed by Real-time PCR and Western blot, respectively. The protein expression patterns of DKK1 and β-catenin were investigated by immunohistochemistry. The associations among DKK1 level, β-catenin accumulation, clinicopathological factors and the overall survival were separately evaluated. Results Both DKK1 and β-catenin levels were remarkably elevated in chondrosarcoma compared with the corresponding non-tumor tissues. High DKK1 level and positive β-catenin accumulation in chondrosarcoma specimens were 58.7% and 53.9%, respectively. Elevated DKK1 level significantly correlated with positive β-catenin accumulation, and they were remarkably associated with histological grade and Musculoskeletal Tumor Society stage. Furthermore, DKK1 level and β-catenin accumulation had significant impacts on the prognosis of chondrosarcoma patients. Multivariate analysis revealed that DKK1 level was an independent prognostic factor for overall survival. Conclusions Elevated DKK1 levels associated with β-catenin accumulation play a crucial role in chondrosarcoma. DKK1 can serve as a novel predictor of poor prognosis in patients with chondrosarcoma. PMID:25144498

Inverse expression of cystein-rich 61 (Cyr61/CCN1) and connective tissue growth factor (CTGF/CCN2) in borderline tumors and carcinomas of the ovary.

PubMed

Bartel, Frank; Balschun, Katharina; Gradhand, Elise; Strauss, Hans G; Dittmer, Jürgen; Hauptmann, Steffen

2012-09-01

Members of the CCN [cystein-rich 61 (Cyr61)/connective tissue growth factor (CTGF)/nephroblastoma (NOV)] protein family are involved in the regulation of cellular proliferation, apoptosis, and migration and are also assumed to play a role in carcinogenesis. Therefore, we performed a retrospective study to investigate the immunohistochemical expression of both Cyr61 and CTGF in 92 borderline tumors (BOTs) and 107 invasive carcinomas of the ovary (IOCs). To determine their diagnostic and prognostic value, we correlated protein expression with clinicopathologic factors including overall and disease-free survival. Cyr61 and CTGF were found to be inversely expressed in both BOTs and IOCs, with a stronger expression of Cyr61 in IOCs. Moreover, Cyr61 was found to be preferentially expressed in high-grade serous carcinomas, whereas CTGF was found more frequently in low-grade serous carcinomas. Weak Cyr61 levels correlated with both low estrogen receptor and p53 expression (P=0.038, P=0.04, respectively). However, no association was observed between CTGF, estrogen receptor, and p53 expression levels in IOCs. Regarding prognosis, Cyr61 was found to be of no value, but the loss of CTGF was found to be associated with a poor prognosis in multivariate analysis of overall (relative risk 2.8; P=0.050) and disease-free (relative risk 2.3; P=0.031) survival. Cyr61 and CTGF are inversely expressed in BOTs and IOCs, and loss of CTGF independently indicates poor prognosis in IOCs.

The prognostic values of tumor-infiltrating neutrophils, lymphocytes and neutrophil/lymphocyte rates in bladder urothelial cancer.

PubMed

Liu, Kangkang; Zhao, Kun; Wang, Lining; Sun, Erlin

2018-05-20

Tumor-infiltrating neutrophils (TINs) and lymphocytes (TILs) are found to play essential roles in many tumors and associate with the prognosis of patients. But, the prognostic values of TINs, TILs and NLR (neutrophils-lymphocytes ratio) in bladder cancer (BC) are still undefined. The object of our study was to systematically interrogate the associations of these immune cells with clinical outcomes of BC patients. In our study, a total of 102 patients pathologically diagnosed with BC were included. CD66b + and CD8 + antibodies were used to mark neutrophils and CD8 + lymphocytes by immunohistochemistry. The results found that TINs and NLR were significantly associated with pathological T-stages of tumors (P < 0.01), but TILs were not. And TINs were also related to pathological tumor grades (P = 0.012). Regarding the prognostic values, TINs was related to the high risk of recurrence in non-muscle invasive BC (NMIBC) patients. Elevated TINs and NLR were associated with poor overall survivals of BC patients, whereas higher TILs were related to longer survivals (P < 0.01). Multivariate analysis showed that both of TINs (HR 2.427, 1.024-5.752, P = 0.044) and NLR (HR 3.529, 1.147-10.864, P = 0.028) were independent unfavorable prognosis markers. In conclusion, Tumor infiltrating immune cells, including TINs, TILs and NLR were important markers in predicting the prognosis of bladder cancer patients. TINs and NLR were more likely to be negative predictors, but TILs were favorable in patients with BC. Copyright © 2018 Elsevier GmbH. All rights reserved.

Role of human epididymis protein 4 in chemoresistance and prognosis of epithelial ovarian cancer.

PubMed

Lee, Seungho; Choi, Seowon; Lee, Yookyung; Chung, Donghae; Hong, Suntaek; Park, Nohhyun

2017-01-01

Human epididymis protein 4 (HE4) is a novel biomarker for epithelial ovarian cancer. This study was designed to evaluate the role of HE4 in chemo-response against anti-cancer drugs and prognosis of epithelial ovarian cancer. HE4-depleted cells and HE4-overexpressing cells were generated. The effect of HE4 gene silencing and overexpression was examined using a cell viability assay after exposure to chemotherapeutic agents and the signaling pathway. We studied the expression of HE4 in ovarian cancer tissue and the prognostic significance. Cytoplasmic staining was graded for intensity and percentage of positive cells. The grades were multiplied to determine an H-score. Knockdown of HE4 in OVCAR-3 cells resulted in reduction in cell growth and increased sensitivity to paclitaxel and cisplatin compared to control cells. This effect originated from the decreased activation of cell-growth-related signaling, such as AKT and Erk mediated by epidermal growth factor (EGF), while overexpression of HE4 resulted in enhanced cell growth and suppressed the anti-tumorigenic activity of paclitaxel. Activation of AKT and Erk pathways was enhanced in HE4-overexpressing cells compared to control cells. Based on the results of multivariate analysis, the risk of death was significantly higher in patients with an H-score > 4. HE4 induces chemoresistance against anti-cancer drugs and activates the AKT and Erk pathways to enhance tumor survival. HE4 expression in ovarian cancer tissue is associated with a worse prognosis for epithelial ovarian cancer patients. © 2016 Japan Society of Obstetrics and Gynecology.

Impact of Expression of Vimentin and Axl in Breast Cancer.

PubMed

Tanaka, Kimihiro; Tokunaga, Eriko; Inoue, Yuka; Yamashita, Nami; Saeki, Hiroshi; Okano, Shinji; Kitao, Hiroyuki; Oki, Eiji; Oda, Yoshinao; Maehara, Yoshihiko

2016-12-01

The association between Axl and vimentin protein expression has been observed in several cell lines. However, the clinical importance of Axl and vimentin expression in breast cancer have not been fully determined. The expressions of Axl and vimentin were evaluated by immunohistochemistry in a total of 343 patients with invasive ductal carcinoma. The relationships between expression of Axl and vimentin and clinicopathologic characteristics and prognosis were analyzed. Axl expression was classified into high (n = 170) and low (n = 173) expression groups. Axl expression alone was not associated with any clinicopathologic factor or prognosis. Coexistence of vimentin-positive and Axl-high expression was observed in 10.5% (n = 36). Vimentin-positive and Axl-high tumors were associated with triple-negative breast cancers (P = .0396) and with poor prognosis in terms of both recurrence-free survival (P = .0126) and overall survival (P = .0005) compared to the other groups, including vimentin-positive and Axl-low tumors, vimentin-negative and Axl-high tumors, and vimentin-negative and Axl-low tumors. Multivariate analysis showed that coexistence of vimentin-positive and Axl-high expression was an independent poor prognostic factor for recurrence-free survival (hazard ratio, 2.78; 95% confidence interval, 1.23-5.68; P = .0158) and overall survival (hazard ratio, 3.72; 95% confidence interval, 1.51-8.47; P = .0059). Coexistence of vimentin-positive and Axl-high expression is a poor prognostic factor for primary breast cancer. Vimentin and Axl expression might contribute to the aggressive phenotype in breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognosis in adenocarcinomas of lower oesophagus, gastro-oesophageal junction and cardia evaluated by uPAR-immunohistochemistry.

PubMed

Laerum, Ole Didrik; Ovrebo, Kjell; Skarstein, Arne; Christensen, Ib Jarle; Alpízar-Alpízar, Warner; Helgeland, Lars; Danø, Keld; Nielsen, Boye Schnack; Illemann, Martin

2012-08-01

Adenocarcinomas of lower oesophagus, gastro-oesophageal junction and cardia in humans are highly invasive tumours with poor prognosis. The localisation of urokinase-type plasminogen activator receptor (uPAR) was determined in 66 patients; 60 with adenocarcinomas and six cases with Barrett's oesophagus. uPAR was expressed in nearly all cases of invasive adenocarcinomas by populations of cancer cells, macrophages and myofibroblasts at both the invasion front and the tumour core. In areas with high-grade dysplasia or with Barrett's metaplasia adjacent to the tumour tissue, no uPAR-immunoreactivity was found. High local expression of uPAR, therefore, appears to be a characteristic marker for invasive behaviour in this tumour, suggesting that uPAR's contribution to matrix degradation during invasive growth is a late event in carcinogenesis. Using a scoring system for semiquantitative estimation of uPAR-positivity on immmunohistochemically stained specimens, a significant association was found between poor overall survival and high uPAR-score for cancer cells in the tumour core and for macrophages peripherally at the tumour invasion zone. In multivariate analysis, these two uPAR-scores were confirmed as highly significant prognostic parameters independent of Tumour, Node, Metastasis (TNM)-stage and World Health Organization (WHO) classification. The proteolytic action of these malignant and nonmalignant accessory cells thus seemed to follow two main patterns: one dominated by uPAR positive cancer cells and one by uPAR-positive macrophages. Scoring of uPAR-positivity might be a useful parameter for onset of invasion and prognosis in these adenocarcinomas. Copyright © 2011 UICC.

Characteristics and Prognosis of Oldest Old Subjects with Amyotrophic Lateral Sclerosis.

PubMed

Dandaba, Meira; Couratier, Philippe; Labrunie, Anaïs; Nicol, Marie; Hamidou, Bello; Raymondeau, Marie; Logroscino, Giancarlo; Preux, Pierre Marie; Marin, Benoît

2017-01-01

Amyotrophic Lateral Sclerosis (ALS) is an age-related neurodegenerative disease with unclear characteristics and prognosis in the oldest old (80 years and over). The aim of this study was to compare the oldest old and younger ALS patients in terms of clinical and socio-demographic characteristics, and prognosis. ALS incident cases from the register of ALS in Limousin (FRALim), diagnosed between January 2000 and July 2013, were included. Descriptive and comparative analyses by age group were carried out. For time to event univariate analysis, Kaplan-Meier estimator and log rank test were used. Univariate and multivariate survival analyses were carried out with Cox's proportional hazard model. Out of 322 patients, 50 (15.5%) were aged 80 or over ("oldest old" ALS) at the time of diagnosis. Among them, the male:female gender-ratio was 1.27, and 32.6% had a bulbar onset (not different from subjects aged less than 80 years). With increasing age, there was a worsening of the clinical state of the patients at time of diagnosis in terms of weight loss, forced vital capacity, ALSFRS-R and manual muscular testing. Access to ALS referral centres decreased with age, and the use of riluzole tended to be lower in the oldest old group. The median survival of oldest old patients appeared to be 10 months shorter than that of subjects aged less than 80 years (7.4 vs. 17.4 months). The survival of oldest old ALS patients is particularly short. It relates to prognostic features at baseline and to an independent effect of advanced age. © 2017 S. Karger AG, Basel.

High levels of serum CA15-3 and residual invasive tumor size are associated with poor prognosis for breast cancer patients with non-pathological complete response after neoadjuvant chemotherapy.

PubMed

Fujimoto, Yukie; Higuchi, Tomoko; Nishimukai, Arisa; Miyagawa, Yoshimasa; Kira, Ayako; Ozawa, Hiromi; Bun, Ayako; Imamura, Michiko; Miyoshi, Yasuo

2018-06-24

To identify surrogate markers for prognosis of breast cancer patients with non-pathological complete response (non-pCR) to neoadjuvant chemotherapy (NAC), our investigation focused on serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA15-3) as well as clinicopathological factors both pre- and post-NAC. A total of 185 breast cancer patients treated with NAC were recruited. Serum CEA and CA15-3 were measured at baseline and at completion of NAC. Among the non-pCR cancers (n = 142), disease-free survival (DFS) of patients with CA15-3-low at baseline (3-year DFS: 0.908, n = 73) was significantly better than of those with CA15-3-high (3-year DFS: 0.681, n = 69, P = 0.0134). Multivariable analysis demonstrated that baseline CA15-3 levels (hazard ratio (HR): 3.31, 95% confidence interval (CI): 1.28-10.23; P = 0.0122) and residual invasive size (HR: 4.47, 1.26-28.39; P = 0.0171) were significant independent factors for DFS. The combination of these factors proved to be accurate predictor for DFS regardless of breast cancer subtypes. The combination of residual invasive size and serum CA15-3 levels at baseline seems to be a significant and independent surrogate marker of poor outcome for patients with non-pCR. These findings suggest that these markers may be useful for identifying patients with inferior prognosis and candidates for additional adjuvant treatments. © 2018 Wiley Periodicals, Inc.

Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD): The TRIPOD Statement.

PubMed

Collins, Gary S; Reitsma, Johannes B; Altman, Douglas G; Moons, Karel G M

2015-06-01

Prediction models are developed to aid health care providers in estimating the probability or risk that a specific disease or condition is present (diagnostic models) or that a specific event will occur in the future (prognostic models), to inform their decision making. However, the overwhelming evidence shows that the quality of reporting of prediction model studies is poor. Only with full and clear reporting of information on all aspects of a prediction model can risk of bias and potential usefulness of prediction models be adequately assessed. The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Initiative developed a set of recommendations for the reporting of studies developing, validating, or updating a prediction model, whether for diagnostic or prognostic purposes. This article describes how the TRIPOD Statement was developed. An extensive list of items based on a review of the literature was created, which was reduced after a Web-based survey and revised during a 3-day meeting in June 2011 with methodologists, health care professionals, and journal editors. The list was refined during several meetings of the steering group and in e-mail discussions with the wider group of TRIPOD contributors. The resulting TRIPOD Statement is a checklist of 22 items, deemed essential for transparent reporting of a prediction model study. The TRIPOD Statement aims to improve the transparency of the reporting of a prediction model study regardless of the study methods used. The TRIPOD Statement is best used in conjunction with the TRIPOD explanation and elaboration document. To aid the editorial process and readers of prediction model studies, it is recommended that authors include a completed checklist in their submission (also available at www.tripod-statement.org). The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Initiative developed a set of recommendations for the reporting of studies developing, validating, or updating a prediction model, whether for diagnostic or prognostic purposes. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

High expression of trimethylated histone H3 at lysine 27 predicts better prognosis in non-small cell lung cancer.

PubMed

Chen, Xiaohui; Song, Ning; Matsumoto, Keitaro; Nanashima, Atsushi; Nagayasu, Takeshi; Hayashi, Tomayoshi; Ying, Mingang; Endo, Daisuke; Wu, Zhiren; Koji, Takehiko

2013-11-01

Epigenetic parameters such as DNA methylation and histone modifications play pivotal roles in carcinogenesis. Global histone modification patterns have been implicated as possible predictors of cancer recurrence and prognoses in a great variety of tumor entities. Our study was designed to evaluate the association among trimethylated histone H3 at lysine 27 (H3K27me3), clinicopathological variables and outcome in early-stage non-small cell lung cancer (NSCLC). The expression of H3K27me3 and its methyl-transferase, enhancer of zeste homolog 2 (EZH2) together with proliferating cell nuclear antigen (PCNA) were evaluated by immunohistochemistry in normal lung tissue (n=5) and resected NSCLC patients (n=42). In addition, the specificity of antibody for H3K27me3 was tested by western blot analysis. The optimal cut-off point of H3K27me3 expression for prognosis was determined by the X-tile program. The prognostic significance was determined by means of Kaplan-Meier survival estimates and log-rank tests. As a result, enhanced trimethylation of H3K27me3 was correlated with longer overall survival (OS) and better prognosis (P<0.05). Moreover, both univariate and multivariate analyses indicated that H3K27me3 level was a significant and independent predictor of better survival (hazard ratio, 0.187; 95% confidence interval, 0.066-0.531, P=0.002). Furthermore, H3K27me3 expression was positively correlated with DNA methylation level at CCGG sites while reversely related to EZH2 expression (P<0.05). In conclusion, H3K27me3 level defines unrecognized subgroups of NSCLC patients with distinct epigenetic phenotype and clinical outcome, and can probably be used as a novel predictor for better prognosis in NSCLC patients.

Lymphocytic response to tumour and deficient DNA mismatch repair identify subtypes of stage II/III colorectal cancer associated with patient outcomes.

PubMed

Williams, David S; Mouradov, Dmitri; Jorissen, Robert N; Newman, Marsali R; Amini, Elham; Nickless, David K; Teague, Julie A; Fang, Catherine G; Palmieri, Michelle; Parsons, Marie J; Sakthianandeswaren, Anuratha; Li, Shan; Ward, Robyn L; Hawkins, Nicholas J; Faragher, Ian; Jones, Ian T; Gibbs, Peter; Sieber, Oliver M

2018-01-30

Tumour-infiltrating lymphocyte (TIL) response and deficient DNA mismatch repair (dMMR) are determinants of prognosis in colorectal cancer. Although highly correlated, evidence suggests that these are independent predictors of outcome. However, the prognostic significance of combined TIL/MMR classification and how this compares to the major genomic and transcriptomic subtypes remain unclear. A prospective cohort of 1265 patients with stage II/III cancer was examined for TIL/MMR status and BRAF / KRAS mutations. Consensus molecular subtype (CMS) status was determined for 142 cases. Associations with 5-year disease-free survival (DFS) were evaluated and validated in an independent cohort of 602 patients. Tumours were categorised into four subtypes based on TIL and MMR status: TIL-low/proficient-MMR (pMMR) (61.3% of cases), TIL-high/pMMR (14.8%), TIL-low/dMMR (8.6%) and TIL-high/dMMR (15.2%). Compared with TIL-high/dMMR tumours with the most favourable prognosis, both TIL-low/dMMR (HR=3.53; 95% CI=1.88 to 6.64; P multivariate <0.001) and TIL-low/pMMR tumours (HR=2.67; 95% CI=1.47 to 4.84; P multivariate =0.001) showed poor DFS. Outcomes of patients with TIL-low/dMMR and TIL-low/pMMR tumours were similar. TIL-high/pMMR tumours showed intermediate survival rates. These findings were validated in an independent cohort. TIL/MMR status was a more significant predictor of prognosis than National Comprehensive Cancer Network high-risk features and was a superior predictor of prognosis compared with genomic (dMMR, pMMR/ BRAF wt / KRAS wt , pMMR/ BRAF mut / KRAS wt , pMMR/ BRAF wt / KRAS mut ) and transcriptomic (CMS 1-4) subtypes. TIL/MMR classification identified subtypes of stage II/III colorectal cancer associated with different outcomes. Although dMMR status is generally considered a marker of good prognosis, we found this to be dependent on the presence of TILs. Prognostication based on TIL/MMR subtypes was superior compared with histopathological, genomic and transcriptomic subtypes. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

C-reactive protein-to-albumin ratio is a predictor of hepatitis B virus related decompensated cirrhosis: time-dependent receiver operating characteristics and decision curve analysis.

PubMed

Huang, Si-Si; Xie, Dong-Mei; Cai, Yi-Jing; Wu, Jian-Min; Chen, Rui-Chong; Wang, Xiao-Dong; Song, Mei; Zheng, Ming-Hua; Wang, Yu-Qun; Lin, Zhuo; Shi, Ke-Qing

2017-04-01

Hepatitis B virus (HBV) infection remains a major health problem and HBV-related-decompensated cirrhosis (HBV-DC) usually leads to a poor prognosis. Our aim was to determine the utility of inflammatory biomarkers in predicting mortality of HBV-DC. A total of 329 HBV-DC patients were enrolled. Survival estimates for the entire study population were generated using the Kaplan-Meier method. The prognostic values for model for end-stage liver disease (MELD) score, Child-Pugh score, and inflammatory biomarkers neutrophil/lymphocyte ratio, C-reactive protein-to-albumin ratio (CAR), and lymphocyte-to-monocyte ratio (LMR) for HBV-DC were compared using time-dependent receiver operating characteristic curves and time-dependent decision curves. The survival time was 23.1±15.8 months. Multivariate analysis identified age, CAR, LMR, and platelet count as prognostic independent risk factors. Kaplan-Meier analysis indicated that CAR of at least 1.0 (hazard ratio, 7.19; 95% confidence interval, 4.69-11.03), and LMR less than 1.9 (hazard ratio, 2.40; 95% confidence interval, 1.69-3.41) were independently associated with mortality of HBV-DC. The time-dependent receiver operating characteristic indicated that CAR showed the best performance in predicting mortality of HBV-DC compared with LMR, MELD score, and Child-Pugh score. The results were also confirmed by time-dependent decision curves. CAR and LMR were associated with the prognosis of HBV-DC. CAR was superior to LMR, MELD score, and Child-Pugh score in HBV-DC mortality prediction.

[Clinical analysis of 23 gynecologic carcinoma patients with brain metastasis].

PubMed

Zhang, J X; Wang, S Z; Li, B; Zhang, Z Y

2016-06-21

To explore the clinicopathological characteristics and treatments of brain metastasis (BM) in patients with gynecologic carcinoma. Twenty-three pathologically confirmed patients with gynecologic carcinoma who had brain metastasis between February 2008 and October 2012 were analyzed retrospectively. The primary carcinoma was cervical cancer in 5 patients, endometrial carcinoma in 8 patients and ovarian cancer in 10 patients, which accounted for 1.81% (5/276), 2.10% (8/380) and 2.67% (10/374) of patient with the same diagnosis of the same period, respectively.Among them, 91.3% (21/23) patients had heterochronous BM.Single BM was documented in 52.2% (12/23) patients.Besides, 78.2% (18/23) BM located in cerebrum.At the time of BM, 91.3% (21/23) patients had symptoms of central nervous system, in which headache ranked the top (90.4%). Altogether, thirteen patients had extracranial metastasis, in which 9 of them had metastasis of the lung.The median post-brain-metastasis survival (mPBMS) for the recursive partitioning analysis (RPA) classes Ⅰ-Ⅲ was 54 months, 9 months and 1 month, respectively (P<0.01). None of surgery, radiotherapy or chemotherapy treatment was proven to have prognosis-improving ability either in single variant or multivariate analysis.However, in patients with extracranial metastasis, chemotherapy could significantly improve their mPBMS (P<0.05). The incidence of brain metastasis in patients with cervical cancer, endometrial carcinoma, and ovarian cancer increased gradually.RPA was valuable for a prognostic assessment in gynecologic carcinoma patients with BM.Chemotherapy could significantly improve prognosis of gynecologic carcinoma patients with BM if extracranial metastasis was presented.

[Analysis of the Role of PET/CT SUVmax in Prognosis and Its Correlation with 
Clinicopathological Characteristics in Resectable Lung Squamous Cell Carcinoma].

PubMed

Ren, Hongliang; Xu, Wengui; You, Jian; Song, Xiuyu; Huang, Hui; Zhao, Ning; Ren, Xiubao; Zhang, Xinwei

2016-04-20

Lung cancer is the leading cause of cancer death in men and women in the world, more than one-half of cases are diagnosed at a advanced stage, and the overall 5-year survival rate for lung cancer is 18%. Lung cancer is divided into non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). Approximately 80%-85% of cases are NSCLC which includes three main types: adenocarcinoma (40%), squamous cell carcinoma (SCC) (20%-30%), and large cell carcinoma (10%). Although therapies that target driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related SCC. We need pay more attention to the diagnosis and treatment of SCC. 18F-FDG positron emission tomography (PET)/computed tomography (CT) has emerged as an accurate staging modality in lung cancer diagnosis. The aim of this study is to investigate the role of maximum standardized uptake value (SUVmax) on PET-CT in prognosis and its correlation with clinicopathological characteristics in resectable SCC. One hundred and eighty-two resectable SCC patients who underwent PET/CT imaging between May 2005 and October 2014 were enrolled into this retrospectively study. All the enrolled patients had underwent pulmonary resection with mediastinal lymph node dissection without preoperative chemotherapy or radiotherapy. Survival outcomes were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model. Correlation between SUVmax and clinicopathological factors was analysed using Pearson correlation analysis and Spearman rank correlation analysis. The patients were divided into two groups on the basis of SUVmax 13.0 as cutoff value, and patients with SUVmax more than 13.0 had shorter median overall survival than patients less than 13.0 in univariate analysis (56 months vs 87 months; P=0.022). There was remarkable correlation between SUVmax and gender, tumor size, tumor-node-metastasis (TNM) stage, neutrophil, NLR, hemoglobin (P<0.05). Multivariate Cox analysis demonstrated that SUVmax (HR=1.714, 95%CI: 1.021-2.876, P=0.042), TNM stage (HR=1.677, 95%CI: 1.231-2.284, P=0.001) were independent predictors for survival. Furthermore, univariate survival analysis showed significant difference by SUVmax in patients of stage I (P=0.045). SUVmax may be of importance prognostic factor independent of TNM stage, which was considerable for risk stratification in patients with TNM stage. Besides, there was correlation between SUVmax of primary tumor and clinicopathological characteristics.
.

Cardiogenic pulmonary oedema: alarmingly poor long term prognosis. Analysis of risk factors.

PubMed

Marcinkiewicz, Marta; Ponikwicka, Katarzyna; Szpakowicz, Anna; Musiał, Włodzimierz Jerzy; Kamiński, Karol Adam

2013-01-01

Acute heart failure (AHF) is a life-threatening condition associated with poor prognosis. To investigate the long term prognosis and identify prognostic factors among patients who were discharged after an episode of cardiogenic pulmonary oedema. We enrolled 84 patients (M: 56%, n = 47) who were discharged with cardiogenic pulmonary oedema as a diagnosis. Clinical, biochemical and echocardiographic variables were collected and analysed. The completeness of two- and five-year follow-up was 100% and 96%, respectively. The median (IQR) age was 74 years (64-81), left ventricular ejection fraction was 35% (27-45), blood pressure on admission was 140/90 mm Hg (115-180/70-100), estimated glomerular filtration rate was 60 mL/min/1.73 m2 (45-73). Forty per cent (n = 34) of the patients had a history of atrial fibrillation (AF), however, AF was directly involved with pulmonary oedema only in 4% (n = 3) of the cases. Acute myocardial infarction (AMI) accounted for 34% (n = 29) of all the causes of pulmonary oedema and was associated with a better two-year prognosis compared to other causes of pulmonary oedema (p = 0.018). Two- and five-year mortality was 45% (n = 38) and 72% (n = 58), respectively. Co-morbidities were common. Ischaemic heart disease and arterial hypertension were present in 83% and 70% of the patients, respectively. Multivariable analysis identified increased left ventricular mass (RR 3.609, 95% CI 1.235-10.547, p = 0.017) and treatment with long-acting vasodilator drugs (LAVDs) (RR 4.881, 95% CI 1.618-14.727, p = 0.004) as independent negative prognostic factors, whereas in-hospital therapy with beta-blockers created a distinctly protective effect (RR 0.123, 95% CI 0.033-0.457, p = 0.002) in the two-year follow-up. Five-year mortality was independently associated with older age (RR 1.08, 95% CI 1.02-1.14, p = 0.005) and treatment with LAVDs (RR 6.4, 95% CI 1.47-28.14, p = 0.012), while percutaneous coronary intervention (RR 0.17, 95% CI 0.05-0.58, p = 0.004) significantly decreased the risk. AHF is a heterogeneous syndrome with a very high remote mortality. LAVDs administered during the hospital stay as well as older age on admission correlate with higher long-term overall mortality. In the age of percutaneous coronary intervention, AMI aetiology of pulmonary oedema is no longer a negative prognostic factor for the long-term prognosis.

Immunological network analysis in HPV associated head and neck squamous cancer and implications for disease prognosis.

PubMed

Chen, Xiaohang; Yan, Bingqing; Lou, Huihuang; Shen, Zhenji; Tong, Fangjia; Zhai, Aixia; Wei, Lanlan; Zhang, Fengmin

2018-04-01

Human papillomavirus-positive (HPV+) head and neck squamous cell cancer (HNSCC) exhibits a better prognosis than HPV-negative (HPV-) HNSCC. This difference may in part be due to enhanced immune activation in the HPV+ HNSCC tumor microenvironment. To characterize differences in immune activation between HPV+ and HPV- HNSCC tumors, we identified and annotated differentially expressed genes based upon mRNA expression data from The Cancer Genome Atlas (TCGA). Immune network between immune cells and cytokines was constructed by using single sample Gene Set Enrichment Analysis and conditional mutual information. Multivariate Cox regression analysis was used to determine the prognostic value of immune microenvironment characterization. A total of 1673 differentially expressed genes were functionally annotated. We found that genes upregulated in HPV+ HNSCC are enriched in immune-associated processes. And the up-regulated gene sets were validated by Gene Set Enrichment Analysis. The microenvironment of HPV+ HNSCC exhibited greater numbers of infiltrating B and T cells and fewer neutrophils than HPV- HNSCC. These findings were validated by two independent datasets in the Gene Expression Omnibus (GEO) database. Further analyses of T cell subtypes revealed that cytotoxic T cell subtypes predominated in HPV+ HNSCC. In addition, the ratio of M1/M2 macrophages was much higher in HPV+ HNSCC. The infiltration of these immune cells was correlated with differentially expressed cytokine-associated genes. Enhanced infiltration of B cells and CD8+ T cells were identified as independent protective factors, while high neutrophil infiltration was a risk enhancing factor for HPV+ HNSCC patients. A schematic model of immunological network was established for HPV+ HNSCC to summarize our findings. Copyright © 2018 Elsevier Ltd. All rights reserved.

Co-expression of midkine and pleiotrophin predicts poor survival in human glioma.

PubMed

Ma, Jinyang; Lang, Bojuan; Wang, Xiongwei; Wang, Lei; Dong, Yuanxun; Hu, Huojun

2014-11-01

The aim of this study was to investigate whether co-expression of midkine (MK) and pleiotrophin (PTN) has prognostic relevance in human gliomas. Immunohistochemistry was used to investigate the expression of MK and PTN proteins in 168 patients with gliomas. The levels of MK and PTN mRNA in glioma tissues and paratumor tissues were evaluated in 45 paired cases by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival analysis was performed to assess prognostic significance. The expression levels of MK and PTN proteins in glioma tissue were both significantly higher (both p<0.001) than those in paratumor tissues on immunohistochemistry analysis, which was confirmed by qRT-PCR analysis. Additionally, the overexpression of either MK or PTN was significantly associated with the World Health Organization Grade (p=0.001 and 0.034, respectively), low Karnofsky Performance Status (KPS) score (p=0.022 and 0.001, respectively), time to recurrence (p=0.043 and 0.011, respectively) and poor overall survival (p=0.018 and 0.001, respectively). Multivariate Cox proportional-hazards regression analysis revealed that increased expressions of MK and PTN were both independent prognostic factors for poor overall survival (p=0.030 and 0.022, respectively). Furthermore, the co-expression of MK and PTN was more significantly (p=0.003) associated with adverse prognosis in patients with gliomas than the respective expression of MK or PTN alone. To our knowledge, these findings are the first to indicate that the co-expression of MK and PTN is significantly correlated with prognosis in glioma patients, suggesting that the co-expression of these proteins may be used as both an early diagnostic and independent prognostic marker. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impact of Age on the Prognosis of Operable Gastric Cancer Patients: An Analysis Based on SEER Database.

PubMed

Chen, Jie; Chen, Jinggui; Xu, Yu; Long, Ziwen; Zhou, Ye; Zhu, Huiyan; Wang, Yanong; Shi, Yingqiang

2016-06-01

To investigate the impact of age on the clinicopathological features and survival of patients with gastric cancer (GC), and hope to better define age-specific patterns of GC and possible associated risk factors.Using the surveillance, epidemiology, and end results (SEER) database to search the patients who diagnosed GC between 2007 and 2011 with a known age. The overall and 5-year gastric cancer specific survival (CSS) data were obtained using Kaplan-Meier plots. Multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors.A total of 7762 GC patients treated with surgery during the 4-year study period were included in the final study cohort. We divided into five subgroups according to the different age ranges. The overall 5-year cause-specific survival (CSS) was 60.3% in Group 1 (below 45 years), 60.3% in the Group 2 (45-55 years), 61.2% in Group 3 (56-65 years), 59.2% in Group 4 (66-75 years), and 59.2% in Group 5 (older than 76 years). Kaplan-Meier plots showed that patients older than 76 years had the worst 5-year CSS of 56.0% rate in all the subgroups. Age, tumor size, primary site, histological type, and Tumor Node Metastasis stage were identified as significant risk factors for poor survival on univariate analysis (all P < 0.001, log-rank test). Additionally, as the age increased, the risk of death for GC demonstrated a significant increase.In conclusion, our analysis of the SEER database revealed that the prognosis of GC varies with age. Patients at age 56 to 65 group have more favorable clinicopathologic characteristics and better CSS than other groups.

Short-course whole-brain radiotherapy (WBRT) for brain metastases due to small-cell lung cancer (SCLC).

PubMed

Bohlen, Guenther; Meyners, Thekla; Kieckebusch, Susanne; Lohynska, Radka; Veninga, Theo; Stalpers, Lukas J A; Schild, Steven E; Rades, Dirk

2010-04-01

Many patients with brain metastases due to SCLC have a poor survival prognosis. The most common treatment is whole-brain radiotherapy (WBRT). This retrospective study compares short-course WBRT with 5x4Gy in 1 week to standard WBRT with 10x3Gy in 2 weeks. Forty-four SCLC patients receiving WBRT with 5x4Gy were compared to 102 patients receiving 10x3Gy for survival (OS) and local (intracerebral) control (LC). Seven further potential prognostic factors were investigated: age, gender, Karnofsky Performance Score (KPS), number of brain metastases, extracerebral metastases, interval from tumor diagnosis to WBRT, RPA (Recursive Partitioning Analysis) class. After 5x4Gy, 12-month OS was 15%, versus 22% after 10x3Gy (p=0.69). On multivariate analysis, improved OS was associated with age or=70 (p<0.001), <4 brain metastases (p=0.011), and RPA class 1 (p<0.001). 12-month LC was 34% after 5x4Gy versus 25% after 10x3Gy (p=0.32). On multivariate analysis, improved LC was associated with KPS >or=70 (p<0.001), <4 brain metastases (p=0.027), and RPA class 1 (p<0.001). In patients with brain metastases due to SCLC, short-course WBRT with 5x4Gy provided similar outcomes as 10x3Gy and appears preferable, particularly for patients with poor estimated survival.

Outcomes and risk factors for cancer patients undergoing endoscopic intervention of malignant biliary obstruction.

PubMed

Haag, Georg-Martin; Herrmann, Thomas; Jaeger, Dirk; Stremmel, Wolfgang; Schemmer, Peter; Sauer, Peter; Gotthardt, Daniel Nils

2015-12-04

Malignant bile duct obstruction is a common problem among cancer patients with hepatic or lymphatic metastases. Endoscopic retrograde cholangiography (ERC) with the placement of a stent is the method of choice to improve biliary flow. Only little data exist concerning the outcome of patients with malignant biliary obstruction in relationship to microbial isolates from bile. Bile samples were taken during the ERC procedure in tumor patients with biliary obstruction. Clinical data including laboratory values, tumor-specific treatment and outcome data were prospectively collected. 206 ERC interventions in 163 patients were recorded. In 43 % of the patients, systemic treatment was (re-) initiated after successful biliary drainage. A variety of bacteria and fungi was detected in the bile samples. One-year survival was significantly worse in patients from whom multiresistant pathogens were isolated than in patients, in whom other species were detected. Increased levels of inflammatory markers were associated with a poor one-year survival. The negative impact of these two factors was confirmed in multivariate analysis. In patients with pancreatic cancer, univariate analysis showed a negative impact on one-year survival in case of detection of Candida species in the bile. Multivariate analysis confirmed the negative prognostic impact of Candida in the bile in pancreatic cancer patients. Outcome in tumor patients with malignant bile obstruction is associated with the type of microbial biliary colonization. The proof of multiresistant pathogens or Candida, as well as the level of inflammation markers, have an impact on the prognosis of the underlying tumor disease.

Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients.

PubMed

Lind, Guro E; Guriby, Marianne; Ahlquist, Terje; Hussain, Israr; Jeanmougin, Marine; Søreide, Kjetil; Kørner, Hartwig; Lothe, Ragnhild A; Nordgård, Oddmund

2017-01-01

Patients with early colorectal cancer (stages I-II) generally have a good prognosis, but a subgroup of 15-20% experiences relapse and eventually die of disease. Occult metastases have been suggested as a marker for increased risk of recurrence in patients with node-negative disease. Using a previously identified, highly accurate epigenetic biomarker panel for early detection of colorectal tumors, we aimed at evaluating the prognostic value of occult metastases in sentinel lymph nodes of colon cancer patients. The biomarker panel was analyzed by quantitative methylation-specific PCR in primary tumors and 783 sentinel lymph nodes from 201 patients. The panel status in sentinel lymph nodes showed a strong association with lymph node stage ( P  = 8.2E-17). Compared with routine lymph node diagnostics, the biomarker panel had a sensitivity of 79% (31/39). Interestingly, among 162 patients with negative lymph nodes from routine diagnostics, 13 (8%) were positive for the biomarker panel. Colon cancer patients with high sentinel lymph node methylation had an inferior prognosis (5-year overall survival P  = 3.0E-4; time to recurrence P  = 3.1E-4), although not significant. The same trend was observed in multivariate analyses ( P  = 1.4E-1 and P  = 6.7E-2, respectively). Occult sentinel lymph node metastases were not detected in early stage (I-II) colon cancer patients who experienced relapse. Colon cancer patients with high sentinel lymph node methylation of the analyzed epigenetic biomarker panel had an inferior prognosis, although not significant in multivariate analyses. Occult metastases in TNM stage II patients that experienced relapse were not detected.

Prognosticators and risk grouping in patients with lung metastasis from nasopharyngeal carcinoma: a more accurate and appropriate assessment of prognosis.

PubMed

Cao, Xun; Luo, Rong-Zhen; He, Li-Ru; Li, Yong; Lin, Wen-Qian; Chen, You-Fang; Wen, Zhe-Sheng

2011-08-26

Lung metastases arising from nasopharyngeal carcinomas (NPC) have a relatively favourable prognosis. The purpose of this study was to identify the prognostic factors and to establish a risk grouping in patients with lung metastases from NPC. A total of 198 patients who developed lung metastases from NPC after primary therapy were retrospectively recruited from January 1982 to December 2000. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Actuarial survival rates were plotted against time using the Kaplan-Meier method, and log-rank testing was used to compare the differences between the curves. The median overall survival (OS) period and the lung metastasis survival (LMS) period were 51.5 and 20.9 months, respectively. After univariate and multivariate analyses of the clinical variables, age, T classification, N classification, site of metastases, secondary metastases and disease-free interval (DFI) correlated with OS, whereas age, VCA-IgA titre, number of metastases and secondary metastases were related to LMS. The prognoses of the low- (score 0-1), intermediate- (score 2-3) and high-risk (score 4-8) subsets based on these factors were significantly different. The 3-, 5- and 10-year survival rates of the low-, intermediate- and high-risk subsets, respectively (P < 0.001) were as follows: 77.3%, 60% and 59%; 52.3%, 30% and 27.8%; and 20.5%, 7% and 0%. In this study, clinical variables provided prognostic indicators of survival in NPC patients with lung metastases. Risk subsets would help in a more accurate assessment of a patient's prognosis in the clinical setting and could facilitate the establishment of patient-tailored medical strategies and supports.

Pre-radiotherapy feeding tube identifies a poor prognostic subset of postoperative p16 positive oropharyngeal carcinoma patients.

PubMed

Verma, Vivek; Liu, Jingxia; Eschen, Laura; Danieley, Jonathan; Spencer, Christopher; Lewis, James S; Diaz, Jason; Piccirillo, Jay F; Adkins, Douglas R; Nussenbaum, Brian; Thorstad, Wade L; Gay, Hiram A

2015-01-09

This study explores variables associated with poor prognosis in postoperative p16 positive oropharyngeal squamous cell carcinoma (OPSCC) patients undergoing adjuvant radiotherapy or chemoradiotherapy. Specifically, analysis was done related to timing of feeding tube insertion relative to radiotherapy. From 1997-2009, of 376 consecutive patients with OPSCC, 220 received adjuvant IMRT, and 97 were p16 positive and eligible. Of these, 23 had feeding tube placement before IMRT (B-FT), 32 during/after IMRT (DA-FT), and 42 had no feeding tube (NO-FT). Feeding tubes were not placed prophylactically. These three groups were analyzed for differential tumor, patient, treatment, and feeding tube characteristics, as well as differences in overall survival (OS), disease free survival (DFS), and distant metastasis free survival (DMFS). Pre-RT FT insertion was associated with higher tumor size and depth, T (but not N) and overall stage, comorbidities, presence of chemotherapy, and less use of transoral laser microsurgery/transoral bovie. Additionally, time from surgery to IMRT completion was also statistically longer in the B-FT group. The feeding tube was permanent in 52% of patients in the B-FT group versus 16% in the DA-FT group (p = 0.0075). The 5-year OS for the NO-FT, DA-FT, and B-FT groups was 90%, 86%, and 50%, respectively. The 5-year DFS for the NO-FT, DA-FT, and B-FT groups was 87.6%, 83.6%, and 42.7%, respectively. Multivariate analysis showed that for OS and DFS, feeding tube placement timing and smoking history were statistically significant. Due to the poor prognosis of early FT insertion, the presence of FTs at time of radiotherapy consultation can be used as an alternate marker to identify a subset of p16 positive OPSCC patients that have a poor prognosis.

Prognosis of status epilepticus in elderly patients.

PubMed

Vilella, L; González Cuevas, M; Quintana Luque, M; Toledo, M; Sueiras Gil, M; Guzmán, L; Salas Puig, J; Santamarina Pérez, E

2018-03-01

To evaluate the clinical features and prognosis of status epilepticus (SE) in patients above 70 years old. Retrospective analysis of all patients ≥70 years old with SE registered prospectively during 4 years. Follow-up after discharge was performed. Ninety patients were evaluated. Acute symptomatic etiology was the most prevalent. The mean number of antiepileptic drugs (AEDs) used was 2.7 ± 1.2, and 21% of the patients required sedation. A poor outcome was considered when death (31.1%) or developing of new neurological impairment at discharge (32.2%) occurred. After multivariate analysis, four variables predicted a poor outcome: acute symptomatic etiology (OR: 6.320; 95% CI: 1.976-20.217; P = .002), focal motor SE type (OR: 9.089; 95% CI: 2.482-33.283; P = .001), level of consciousness (OR: 4.596; 95% CI: 1.903-11.098; P = .001), and SE duration >12 hours (OR: 3.763; 95% CI: 1.130-12.530; P = .031). Independent predictive factors of mortality were SE duration >12 hours (OR: 4.306; 95% CI: 1.044-17.757; P = .043), modified Status Epilepticus Severity Score (mSTESS) (OR: 2.216; 95% CI: 1.313-3.740; P = .003), and development of complications (OR: 3.334; 95% CI: 1.004-11.070, P = .049). Considering long-term mortality, age (HR 1.036; 95% CI 1.001-1.071; P = .044), a potentially fatal underlying cause (HR 2.609; 95% CI 1.497- 4.548; P = .001), and mSTESS score >4 (HR 1.485; 95% CI 1.158-1.903; P = .002) remained as predictive factors. There was no association between sedation and the number of AEDs used with outcome at discharge or long-term mortality (P > .05). SE above 70 years old has a high morbimortality. Prognosis is not related to treatment aggressiveness. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Down-regulation of long non-coding RNA MEG3 indicates an unfavorable prognosis in non-small cell lung cancer: Evidence from the GEO database.

PubMed

Zhang, Zichao; Liu, Tiantian; Wang, Kai; Qu, Xiao; Pang, Zhaofei; Liu, Shaorui; Liu, Qi; Du, Jiajun

2017-09-30

Long non-coding RNA (lncRNA) MEG3 (maternally expressed gene 3) is an imprinted gene that suppresses cells growth in various tumors. However, the association between MEG3 expression and prognosis in non-small cell lung cancer (NSCLC) has not been fully investigated. Seven datasets with 1144 patients were obtained from Gene Expression Omnibus (GEO) database (Affymetrix U133 Plus 2.0 platform). Association between MEG3 and other variables was tested using the chi-squared test. Kaplan-Meier survival analysis was carried out to explore the association between MEG3 expression and overall survival (OS)/progression free survival (PFS). Results of univariate and multivariate Cox regression analysis were represented in HR and 95%CI form. Summarized results and publication bias were showed by forest plots and funnel plots respectively. Differential expression of MEG3 was related to stage (GSE31210OS and GSE31210PFS), histology (GSE29013OS and GSE29013PFS) and gender (GSE29013PFS). In summary, low MEG3 expression was associated with shorter long-term survival time in several datasets (GSE3141 (p=0.039), GSE30219 (p=0.008) for OS and GSE30219 (p=0.048) for PFS). We found that MEG3 was an independent prognostic factor in GSE30219 for PFS (HR 0.666, 95%CI 0.458-0.969, p=0.033). The summarized results suggested that low MEG3 expression was a poor prognostic factor in NSCLC (HR=0.77, 95%CI 0.63-0.95). Specifically, the association between low MEG3 expression and poor prognosis was markedly significant in younger patients (≤60years old) (HR0.602, 95%CI 0.417-0.867, p=0.007). These findings indicate that MEG3 could be a novel prognostic factor for NSCLC patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Pre-S deletions of hepatitis B virus predict recurrence of hepatocellular carcinoma after curative resection

PubMed Central

Li-Shuai, Qu; Yu-Yan, Chen; Hai-Feng, Zhang; Jin-Xia, Liu; Cui-Hua, Lu

2017-01-01

Abstract The relationship between hepatitis B virus (HBV) and the prognosis of hepatocellular carcinoma (HCC) after surgery remains uncertain. A retrospective cohort study was performed to evaluate the impact of pre-S deletions, T1762/A1764, and A1896 mutations on prognosis of HCC after curative resection. A total of 113 patients with positive serum HBV DNA (>200 IU/mL) who had underwent curative resection of pathologically proven HCC were recruited to determine the risk factors affecting the prognosis. The median follow-up time was 36.5 months and recurrence was detected in 67 patients (59.3%). The cumulative recurrence rates and overall survival rates at 1-, 3-, and 5-year after curative resection were 18.0%, 49.7%, 70.3%, and 93.7%, 61.0%, 42.5%, respectively. Patients with pre-S deletions showed significantly higher recurrence rates compared with those with wild type infection (HR: 1.822, P = .018), but not related with a significantly poor survival (HR: 1.388, P = .235). Subgroup analysis indicated that the patients with type III deletion had significant higher tumor recurrence rates than other deletion types (HR: 2.211, 95% confidence intervals [CI]: 1.008–4.846, P = .048). Multivariate analysis revealed that pre-S deletion, tumor size >3 cm in diameter, and the presence of microvascular invasion were independent risk factors for tumor recurrence. HBV pre-S deletions were found to be clustered primarily in the 5′ end of pre-S2 region and were more often found between amino acids 120 and 142 of the pre-S2 domain. The domains most frequently potentially involved were the transactivator domain in pre-S2 and polymerized human serum albumin binding site. Our cohort showed that pre-S deletions at the time of resection could predict tumor recurrence in HCC patients after curative resection. PMID:29069001

Tumor Volume Is a Prognostic Factor in Non-Small-Cell Lung Cancer Treated With Chemoradiotherapy

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

Alexander, Brian M.; Othus, Megan; Caglar, Hale B.

2011-04-01

Purpose: To investigate whether primary tumor and nodal volumes defined on radiotherapy planning scans are correlated with outcome (survival and recurrence) after combined-modality treatment. Methods and Materials: A retrospective review of patients with Stage III non-small-cell lung cancer treated with chemoradiation at Brigham and Women's Hospital/Dana-Farber Cancer Institute from 2000 to 2006 was performed. Tumor and nodal volume measurements, as computed by Eclipse (Varian, Palo Alto, CA), were used as independent variables, along with existing clinical factors, in univariate and multivariate analyses for association with outcomes. Results: For patients treated with definitive chemoradiotherapy, both nodal volume (hazard ratio [HR], 1.09;more » p < 0.01) and tumor volume (HR, 1.03; p < 0.01) were associated with overall survival on multivariate analysis. Both nodal volume (HR, 1.10; p < 0.01) and tumor volume (HR, 1.04; p < 0.01) were also associated with local control but not distant metastases. Conclusions: In addition to traditional surgical staging variables, disease burden, measured by primary tumor and nodal metastases volume, provides information that may be helpful in determining prognosis and identifying groups of patients for which more aggressive local therapy is warranted.« less

[Negative prognostic impact of female gender on oncological outcomes following radical cystectomy].

PubMed

Dabi, Y; Rouscoff, Y; Delongchamps, N B; Sibony, M; Saighi, D; Zerbib, M; Peyraumore, M; Xylinas, E

2016-02-01

To confirm gender specific differences in pathologic factors and survival rates of urothelial bladder cancer patients treated with radical cystectomy. We conducted a retrospective monocentric study on 701 patients treated with radical cystectomy and pelvic lymphadenectomy for muscle invasive bladder cancer. Impact of gender on recurrence rate, specific and non-specific mortality rate were evaluated using Cox regression models in univariate and multivariate analysis. We collected data on 553 males (78.9%) and 148 females (21.1%) between 1998 and 2011. Both groups were comparable at inclusion regarding age, pathologic stage, nodal status and lymphovascular invasion. Mean follow-up time was 45 months (interquartile 23-73) and by that time, 163 patients (23.3%) had recurrence of their tumor and 127 (18.1%) died from their disease. In multivariable Cox regression analyses, female gender was independently associated with disease recurrence (RR: 1.73; 95% CI 1.22-2.47; P=0.02) and cancer-specific mortality (RR=2.50, 95% CI=1.71-3.68; P<0.001). We confirmed female gender to be an independent negative prognosis factor for patients following a radical cystectomy and lymphadenectomy for an invasive muscle bladder cancer. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Up-regulation of lncRNA SNHG1 indicates poor prognosis and promotes cell proliferation and metastasis of colorectal cancer by activation of the Wnt/β-catenin signaling pathway

PubMed Central

Zhu, Yuping; Li, Bo; Liu, Zhuo; Jiang, Lai; Wang, Gang; Lv, Min; Li, Dechuan

2017-01-01

Recently, the lncRNA small nucleolar RNA host gene (SNHG1) has been exhibited to be upregulated, which plays a crucial role in the development and prognosis of several cancers. However, the role of the biology and clinical significance of SNHG1 in the tumorigenesis of colorectal cancer (CRC) has rarely been reported. In this work, we firstly found that SNHG1 expression levels were upregulated aberrantly in colorectal cancer tissues and colorectal cancer cell lines. By Kaplan-Meier survival analysis, patients with high SNHG1 expression level had poorer overall survival (OS) and progression-free survival (PFS) than those with low SNHG1 expression. In multivariate analysis, increased SNHG1 expression was proved to be an independent unfavorable prognostic indicator for CRC. In vitro experiments revealed that SNHG1 silencing inhibited the growth and metastasis and induced apoptosis of CRC cell lines. Finally, we found that SNHG1 may induce the activation of the WNT/β-catenin pathway through regulating β-catenin expression and transcription factor-4 (TCF-4), cyclin D1 and MMP-9. Altogether, our findings demonstrated that lncRNA SNHG1, was high expressed in colorectal cancer tissues and may serve as a tumor oncogene through regulating WNT/β-catenin signal pathway, which provided a candidate diagnostic biomarker and a promising therapeutic target for patients with CRC. PMID:29340086

Clinical significance of nm23 gene expression in gastric cancer.

PubMed

Mönig, Stefan P; Nolden, Brit; Lübke, Thomas; Pohl, Alexandra; Grass, Guido; Schneider, Paul M; Dienes, Hans P; Hölscher, Arnulf H; Baldus, Stephan E

2007-01-01

The expression of the nm23 gene has been associated with the development of metastasis. Numerous studies have shown down-regulation of nm23 expression in metastatic breast and colon cancer. The expression of the putative metastasis-suppressor gene nm23 in gastric carcinoma is controversial. The aim of this study was the analysis of nm23 expression in a large series of gastric cancer patients. In a retrospective immunohistochemical study specimens obtained from 116 gastric cancer patients (mean age 64 years; range: 33-85) who had undergone gastrectomy with extended lymphadenectomy were analyzed. Nm23 expression in the tumor epithelium was studied by immunohistochemistry followed by a semi-quantitative (score 0-3) evaluation. Statistical analysis including Chi-square test, uni- and multivariate survival analyses were performed. The nm23 staining pattern was positive (score 2-3) in 100 (86.2%) specimens and negative (score 0-1) in 16 (13.8%) samples. Lymph node metastasis was found in 65% of the patients. No significant correlations could be determined between nm23 expression and other variables such as gender, age, tumor differentiation, WHO-, Laurén-, Goseki-, or Ming-classification. The intensity of nm23 staining in the tumor cells was not significantly correlated with depth of tumor infiltration (T-stage), lymph node metastasis (N-stage), distant metastasis (M-stage), UICC-stage, or prognosis. Our series did not show a correlation of nm23 expression in terms of lymph node and distant metastasis or prognosis in gastric cancer patients.

Nutritional predictors for postoperative short-term and long-term outcomes of patients with gastric cancer.

PubMed

Kanda, Mitsuro; Mizuno, Akira; Tanaka, Chie; Kobayashi, Daisuke; Fujiwara, Michitaka; Iwata, Naoki; Hayashi, Masamichi; Yamada, Suguru; Nakayama, Goro; Fujii, Tsutomu; Sugimoto, Hiroyuki; Koike, Masahiko; Takami, Hideki; Niwa, Yukiko; Murotani, Kenta; Kodera, Yasuhiro

2016-06-01

Evidence indicates that impaired immunocompetence and nutritional status adversely affect short-term and long-term outcomes of patients with cancer. We aimed to evaluate the clinical significance of preoperative immunocompetence and nutritional status according to Onodera's prognostic nutrition index (PNI) among patients who underwent curative gastrectomy for gastric cancer (GC).This study included 260 patients with stage II/III GC who underwent R0 resection. The predictive values of preoperative nutritional status for postoperative outcome (morbidity and prognosis) were evaluated. Onodera's PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × lymphocyte count (per mm).The mean preoperative PNI was 47.8. The area under the curve for predicting complications was greater for PNI compared with the serum albumin concentration or lymphocyte count. Multivariate analysis identified preoperative PNI < 47 as an independent predictor of postoperative morbidity. Moreover, patients in the PNI < 47 group experienced significantly shorter overall and disease-free survival compared with those in the PNI ≥ 47 group, notably because of a higher prevalence of hematogenous metastasis as the initial recurrence. Subgroup analysis according to disease stage and postoperative adjuvant treatment revealed that the prognostic significance of PNI was more apparent in patients with stage II GC and in those who received adjuvant chemotherapy.Preoperative PNI is easy and inexpensive to determine, and our findings indicate that PNI served as a significant predictor of postoperative morbidity, prognosis, and recurrence patterns of patients with stage II/III GC.

An epigenetic signature of adhesion molecules predicts poor prognosis of ovarian cancer patients

PubMed Central

Chang, Ping-Ying; Liao, Yu-Ping; Wang, Hui-Chen; Chen, Yu-Chih; Huang, Rui-Lan; Wang, Yu-Chi; Yuan, Chiou-Chung; Lai, Hung-Cheng

2017-01-01

DNA methylation is a promising biomarker for cancer. The epigenetic effects of cell adhesion molecules may affect the therapeutic outcome and the present study examined their effects on survival in ovarian cancer. We integrated methylomics and genomics datasets in The Cancer Genome Atlas (n = 391) and identified 106 highly methylated adhesion-related genes in ovarian cancer tissues. Univariate analysis revealed the methylation status of eight genes related to progression-free survival. In multivariate Cox regression analysis, four highly methylated genes (CD97, CTNNA1, DLC1, HAPLN2) and three genes (LAMA4, LPP, MFAP4) with low methylation were significantly associated with poor progression-free survival. Low methylation of VTN was an independent poor prognostic factor for overall survival after adjustment for age and stage. Patients who carried any two of CTNNA1, DLC1 or MFAP4 were significantly associated with poor progression-free survival (hazard ratio: 1.59; 95% confidence interval: 1.23, 2.05). This prognostic methylation signature was validated in a methylomics dataset generated in our lab (n = 37, hazard ratio: 16.64; 95% confidence interval: 2.68, 103.14) and in another from the Australian Ovarian Cancer Study (n = 91, hazard ratio: 2.43; 95% confidence interval: 1.11, 5.36). Epigenetics of cell adhesion molecules is related to ovarian cancer prognosis. A more comprehensive methylomics of cell adhesion molecules is needed and may advance personalized treatment with adhesion molecule-related drugs. PMID:28881822

The FIB-4 index is a significant prognostic factor in patients with non-B non-C hepatocellular carcinoma after curative surgery.

PubMed

Okamura, Yukiyasu; Ashida, Ryo; Yamamoto, Yusuke; Ito, Takaaki; Sugiura, Teiichi; Bekku, Emima; Aramaki, Takeshi; Uesaka, Katsuhiko

2016-03-01

The aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) index were developed as a non-invasive parameter for predicting liver fibrosis. This study aimed to validate the APRI and FIB-4 indexes in patients treated with curative therapy for non-B non-C (NBNC) hepatocellular carcinoma (HCC). Accumulated database comprising 399 patients who underwent hepatectomy was reviewed retrospectively. Analyses were performed to evaluate whether the APRI and FIB-4 indexes are predictors of liver cirrhosis and/or the prognosis in patients with NBNC-HCC. Forty-seven patients with NBNC-HCC who underwent curative radiofrequency ablation therapy (RFA) in the same period were enrolled as the validation set. The APRI and FIB-4 indexes were significantly higher in the cirrhosis group than in the no-cirrhosis group (P = 0.001 and P < 0.001, respectively). A receiver operating characteristic curve analysis showed that the FIB-4 index was more accurate in predicting background liver cirrhosis than the APRI. According to a multivariate analysis, an FIB-4 index larger than 2.7 (hazard ratio 2.11 and 2.21, 95 % confidence interval 1.06-4.18 and 1.38-3.54, P = 0.033 and P = 0.001) remained significant independent predictors of overall and recurrence-free survival, respectively. The present findings showed that the FIB-4 index is a significant predictor of background liver cirrhosis and the prognosis after curative resection for NBNB-HCC.

Mucin (MUC) expression in EUS-FNA specimens is a useful prognostic factor in pancreatic ductal adenocarcinoma

PubMed Central

Higashi, Michiyo; Yokoyama, Seiya; Yamamoto, Takafumi; Goto, Yuko; Kitazono, Ikumi; Hiraki, Tsubasa; Taguchi, Hiroki; Hashimoto, Shinichi; Fukukura, Yoshihiko; Koriyama, Chihaya; Mataki, Yuko; Maemura, Kosei; Shinchi, Hiroyuki; Jain, Maneesh; Batra, Surinder K.; Yonezawa, Suguru

2015-01-01

Objectives The aim of this study was to further examine the utility of mucin expression profiles as prognostic factors in PDAC. Methods Mucin (MUC) expression was examined by immunohistochemistry (IHC) analysis in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens obtained from 114 patients with PDAC. The rate of expression of each mucin was compared with clinicopathologic features. Results The expression rates of mucins in cancer lesions were MUC1, 87.7%; MUC2, 0.8%; MUC4, 93.0%; MUC5AC, 78.9%; MUC6, 24.6%; and MUC16, 67.5%. MUC1 and MUC4 were positive and MUC2 was negative in most PDACs. Patients with advanced stage of PDAC with MUC5AC expression had a significantly better outcome than those who were MUC5AC-negative (P=0.002).With increasing clinical stage, total MUC6 expression decreased (P for trend=0.001) and MUC16 cytoplasmic expression increased (P for trend=0.02). The prognosis of patients with MUC16 cytoplasmic expression was significantly poorer than those without this expression. Multivariate survival analysis revealed that MUC16 cytoplasmic expression was a significant independent predictor of a poor prognosis after adjusting for the effects of other prognostic factors (P=0.002). Conclusion Mucin expression profiles in EUS-FNA specimens have excellent diagnostic utility and are useful predictors of outcome in patients with PDAC. PMID:25906442

Serum CA 19-9 as a prognostic factor in patients with metastatic gastric cancer.

PubMed

Jo, Jae-Cheol; Ryu, Min-Hee; Koo, Dong-Hoe; Ryoo, Baek-Yeol; Kim, Hwa Jung; Kim, Tae Won; Choi, Kee Don; Lee, Gin Hyug; Jung, Hwoon-Yong; Yook, Jeong Hwan; Oh, Sung Tae; Kim, Byung Sik; Kim, Jin-Ho; Kang, Yoon-Koo

2013-12-01

To evaluate tumor markers as prognostic factors in patients with metastatic or recurrent gastric cancer receiving first-line chemotherapy. Between January 2000 and December 2008, 1178 patients with metastatic or recurrent gastric cancer were assayed for expression of three serum tumor markers, CA 19-9, CA 72-4 and carcinoembryonic antigen (CEA), prior to the initiation of first-line chemotherapy. Elevated serum concentrations of carbohydrate antigen (CA) 19-9 (>37 U/mL), CA 72-4 (>4 U/mL) and carcinoembryonic antigen (CEA) (>6 ng/mL) were observed in 38, 56 and 33% of patients, respectively. Univariate analysis showed that elevated serum concentration of each of the three markers, CA 19-9 (P = 0.001), CA 72-4 (P = 0.001) and CEA (P = 0.030), was significantly associated with poor patient prognosis. However, multivariate analysis showed that an elevated CA 19-9 concentration only was significantly associated with shorter survival (hazard ratio [HR] 1.22; 95% CI, 1.08-1.37, P = 0.002). In the good risk and moderate risk groups, previously defined by clinical factors alone, survival was significantly lower in patients with elevated CA 19-9 (P < 0.001 and P = 0.021, respectively), but this difference was not observed in the poor-risk group. Elevated serum CA 19-9 concentration in patients with metastatic or recurrent gastric cancer, especially in good or moderate risk groups, is an independent negative predictor of prognosis. © 2012 Wiley Publishing Asia Pty Ltd.

Primary mucosal melanoma of the head and neck in Denmark, 1982-2012: Demographic and clinical aspects. A retrospective DAHANCA study.

PubMed

Lawaetz, Mads; Birch-Johansen, Fatima; Friis, Søren; Eriksen, Jesper G; Kiss, Katalin; Gade, Søren; Møller-Madsen, Maria; Pourbordbari, Negar; von Buchwald, Christian

2016-08-01

Background The study was performed to determine the epidemiological, clinical, and histopathological characteristics and prognosis of primary mucosal melanoma of the head and neck (MMHN) in Denmark. Material and methods This was a national retrospective multicenter study of patients diagnosed with MMHN between 1982 and 2012 in Denmark. Data were retrieved from national databases and patient records. Incidence trends were examined for the entire period. We prepared survival curves and performed univariate and multivariate analysis for the period 1992-2012 to identify possible prognostic factors. Results No significant trends in incidence were found in the study period. The three-year overall and disease-free survival rates for MMHN were 46.5% and 35.5%, respectively. Negative margins was an independent predictor of disease-free survival, and age below 65, absence of distant metastases, and low overall TNM stage were predictors of overall survival. Radiotherapy did not improve survival significantly. Recurrence rates were high, even for patients with negative margins. Conclusions MMHN remains a rare disease with a poor prognosis, particularly for patients aged over 65, those with distant metastasis, and those with advanced TNM stage. Importantly, the rate of recurrence is lowest in patients with negative margins.

Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis

PubMed Central

Mitsuhashi, Kei; Nosho, Katsuhiko; Sukawa, Yasutaka; Matsunaga, Yasutaka; Ito, Miki; Kurihara, Hiroyoshi; Kanno, Shinichi; Igarashi, Hisayoshi; Naito, Takafumi; Adachi, Yasushi; Tachibana, Mami; Tanuma, Tokuma; Maguchi, Hiroyuki; Shinohara, Toshiya; Hasegawa, Tadashi; Imamura, Masafumi; Kimura, Yasutoshi; Hirata, Koichi; Maruyama, Reo; Suzuki, Hiromu; Imai, Kohzoh

2015-01-01

Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer. PMID:25797243

Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis.

PubMed

Mitsuhashi, Kei; Nosho, Katsuhiko; Sukawa, Yasutaka; Matsunaga, Yasutaka; Ito, Miki; Kurihara, Hiroyoshi; Kanno, Shinichi; Igarashi, Hisayoshi; Naito, Takafumi; Adachi, Yasushi; Tachibana, Mami; Tanuma, Tokuma; Maguchi, Hiroyuki; Shinohara, Toshiya; Hasegawa, Tadashi; Imamura, Masafumi; Kimura, Yasutoshi; Hirata, Koichi; Maruyama, Reo; Suzuki, Hiromu; Imai, Kohzoh; Yamamoto, Hiroyuki; Shinomura, Yasuhisa

2015-03-30

Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer.

Effect of actionable somatic mutations on racial/ethnic disparities in head and neck cancer prognosis.

PubMed

Wu, Evan S; Park, Jong Y; Zeitouni, Joseph A; Gomez, Carmen R; Reis, Isildinha M; Zhao, Wei; Kwon, Deukwoo; Lee, Eunkyung; Nelson, Omar L; Lin, Hui-Yi; Franzmann, Elizabeth J; Savell, Jason; McCaffrey, Thomas V; Goodwin, W Jarrard; Hu, Jennifer J

2016-08-01

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and minorities have the worst survival. However, the molecular mechanisms underlying survival disparities have not been elucidated. In a retrospective study, we assessed association between HNSCC early death (<2 years) and 208 somatic mutations of 10 cancer-related genes in 214 patients: 98 non-Hispanic whites (46%), 72 Hispanic whites (34%), and 44 African Americans (20%). Hispanic whites and African Americans had significantly higher mutation rates for EGFR, HRAS, KRAS, and TP53. HNSCC early death was significantly associated with 3+ mutations (odds ratio [OR] = 2.78, 95% confidence interval [CI] = 1.16, 6.69), NOTCH1 mutations in non-Hispanic whites (OR = 5.51; 95% CI = 1.22-24.83) and TP53 mutations in Hispanic whites (OR = 3.84; 95% CI = 1.08-13.68) in multivariable analysis adjusted for age, sex, tumor site, and tumor stage. We have provided the proof-of-principal data to link racial/ethnic-specific somatic mutations and HNSCC prognosis and pave the way for precision medicine to overcome HNSCC survival disparities. © 2016 Wiley Periodicals, Inc. Head Neck 38:1234-1241, 2016. © 2016 Wiley Periodicals, Inc.

Whole Blood mRNA Expression-Based Prognosis of Metastatic Renal Cell Carcinoma.

PubMed

Giridhar, Karthik V; Sosa, Carlos P; Hillman, David W; Sanhueza, Cristobal; Dalpiaz, Candace L; Costello, Brian A; Quevedo, Fernando J; Pitot, Henry C; Dronca, Roxana S; Ertz, Donna; Cheville, John C; Donkena, Krishna Vanaja; Kohli, Manish

2017-11-03

The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score is based on clinical parameters. We analyzed whole blood mRNA expression in metastatic clear cell renal cell carcinoma (mCCRCC) patients and compared it to the MSKCC score for predicting overall survival. In a discovery set of 19 patients with mRCC, we performed whole transcriptome RNA sequencing and selected eighteen candidate genes for further evaluation based on associations with overall survival and statistical significance. In an independent validation of set of 47 patients with mCCRCC, transcript expression of the 18 candidate genes were quantified using a customized NanoString probeset. Cox regression multivariate analysis confirmed that two of the candidate genes were significantly associated with overall survival. Higher expression of BAG1 [hazard ratio (HR) of 0.14, p < 0.0001, 95% confidence interval (CI) 0.04-0.36] and NOP56 (HR 0.13, p < 0.0001, 95% CI 0.05-0.34) were associated with better prognosis. A prognostic model incorporating expression of BAG1 and NOP56 into the MSKCC score improved prognostication significantly over a model using the MSKCC prognostic score only ( p < 0.0001). Prognostic value of using whole blood mRNA gene profiling in mCCRCC is feasible and should be prospectively confirmed in larger studies.

Whole Blood mRNA Expression-Based Prognosis of Metastatic Renal Cell Carcinoma

PubMed Central

Sosa, Carlos P.; Hillman, David W.; Sanhueza, Cristobal; Dalpiaz, Candace L.; Costello, Brian A.; Quevedo, Fernando J.; Pitot, Henry C.; Dronca, Roxana S.; Ertz, Donna; Cheville, John C.; Donkena, Krishna Vanaja; Kohli, Manish

2017-01-01

The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score is based on clinical parameters. We analyzed whole blood mRNA expression in metastatic clear cell renal cell carcinoma (mCCRCC) patients and compared it to the MSKCC score for predicting overall survival. In a discovery set of 19 patients with mRCC, we performed whole transcriptome RNA sequencing and selected eighteen candidate genes for further evaluation based on associations with overall survival and statistical significance. In an independent validation of set of 47 patients with mCCRCC, transcript expression of the 18 candidate genes were quantified using a customized NanoString probeset. Cox regression multivariate analysis confirmed that two of the candidate genes were significantly associated with overall survival. Higher expression of BAG1 [hazard ratio (HR) of 0.14, p < 0.0001, 95% confidence interval (CI) 0.04–0.36] and NOP56 (HR 0.13, p < 0.0001, 95% CI 0.05–0.34) were associated with better prognosis. A prognostic model incorporating expression of BAG1 and NOP56 into the MSKCC score improved prognostication significantly over a model using the MSKCC prognostic score only (p < 0.0001). Prognostic value of using whole blood mRNA gene profiling in mCCRCC is feasible and should be prospectively confirmed in larger studies. PMID:29099775

The NLRP3 rs10754558 Polymorphism Is Associated with the Occurrence and Prognosis of Coronary Artery Disease in the Chinese Han Population.

PubMed

Zhou, Dong; Wang, Xinhong; Chen, Tao; Wen, Wen; Liu, Yang; Wu, Yue; Yuan, Zuyi

2016-01-01

The objective of this study is to investigate the potential association of the NLRP3 rs10754558 and CARD8 rs2043211 polymorphisms with the occurrence and prognosis of CAD. Gene polymorphisms were analyzed using the ABI PRISM-Snapshot multiplex method in 515 CAD patients and 401 control subjects. The serum level of IL-1β was investigated by ELISA assays. The clinical endpoints were evaluated during a median follow-up period of 32 months. The NLRP3 rs10754558 gene polymorphism was significantly associated with the occurrence of CAD, while the CARD8 rs2043211 gene polymorphism was not involved. Patients carrying G allele of NLRP3 rs10754558 had more severe coronary artery stenosis. Multivariable analysis revealed a significant association of the G allele with major adverse cardiac event. The serum IL-1β concentrations in patients with GG genotype were significantly increased compared with those in the patients with CC genotype. Our findings for the first time show that the NLRP3 rs10754558 polymorphism is involved in the occurrence of CAD in the Chinese Han population; and G allele can effectively predict clinical outcome of CAD. The G allele susceptibility to CAD is maybe associated with the increased level of serum IL-1β.

Coexistence of chronic lymphocytic thyroiditis with papillary thyroid carcinoma: clinical manifestation and prognostic outcome.

PubMed

Jeong, Jun Soo; Kim, Hyun Ki; Lee, Cho-Rok; Park, Seulkee; Park, Jae Hyun; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Chung, Woong Youn; Park, Cheong Soo

2012-08-01

The study aimed to identify the clinical characteristics of coexisting chronic lymphocytic thyroiditis (CLT) in papillary thyroid carcinoma (PTC) and to evaluate the influence on prognosis. A total of 1,357 patients who underwent thyroid surgery for PTC were included. The clinicopathological characteristics were identified. Patients who underwent total thyroidectomy (n = 597) were studied to evaluate the influence of coexistent CLT on prognosis. Among the total 1,357 patients, 359 (26.5%) had coexistent CLT. In the CLT group, the prevalence of females was higher than in the control group without CLT (P < 0.001). Mean tumor size and mean age in the patients with CLT were smaller than without CLT (P = 0.040, P = 0.047, respectively). Extrathyroidal extension in the patients with CLT was significantly lower than without CLT (P = 0.016). Among the subset of 597 patients, disease-free survival rate in the patients with CLT was significantly higher than without CLT (P = 0.042). However, the multivariate analysis did not reveal a negative association between CLT coexistence and recurrence. Patients with CLT display a greater female preponderance, smaller size, younger and lower extrathyroidal extension. CLT is not a significant independent negative predictive factor for recurrence, although presence of CLT indicates a reduced risk of recurrence.

Coexistence of Chronic Lymphocytic Thyroiditis with Papillary Thyroid Carcinoma: Clinical Manifestation and Prognostic Outcome

PubMed Central

Jeong, Jun Soo; Kim, Hyun Ki; Lee, Cho-Rok; Park, Seulkee; Park, Jae Hyun; Kang, Sang-Wook; Nam, Kee-Hyun; Chung, Woong Youn; Park, Cheong Soo

2012-01-01

The study aimed to identify the clinical characteristics of coexisting chronic lymphocytic thyroiditis (CLT) in papillary thyroid carcinoma (PTC) and to evaluate the influence on prognosis. A total of 1,357 patients who underwent thyroid surgery for PTC were included. The clinicopathological characteristics were identified. Patients who underwent total thyroidectomy (n = 597) were studied to evaluate the influence of coexistent CLT on prognosis. Among the total 1,357 patients, 359 (26.5%) had coexistent CLT. In the CLT group, the prevalence of females was higher than in the control group without CLT (P < 0.001). Mean tumor size and mean age in the patients with CLT were smaller than without CLT (P = 0.040, P = 0.047, respectively). Extrathyroidal extension in the patients with CLT was significantly lower than without CLT (P = 0.016). Among the subset of 597 patients, disease-free survival rate in the patients with CLT was significantly higher than without CLT (P = 0.042). However, the multivariate analysis did not reveal a negative association between CLT coexistence and recurrence. Patients with CLT display a greater female preponderance, smaller size, younger and lower extrathyroidal extension. CLT is not a significant independent negative predictive factor for recurrence, although presence of CLT indicates a reduced risk of recurrence. PMID:22876054

Long-term outcome of arterial lesions in Behçet disease: a series of 101 patients.

PubMed

Saadoun, David; Asli, Bouchra; Wechsler, Bertrand; Houman, Habib; Geri, Guillaume; Desseaux, Kristel; Piette, Jean-Charles; Huong, Du Le Thi; Amoura, Zahir; Salem, Tara Ben; Cluzel, Philippe; Koskas, Fabien; Resche-Rigon, Mathieu; Cacoub, Patrice

2012-01-01

The vasculitis of Behçet disease (BD) is distinctive because of involvement of both arteries and veins of all sizes. The concept of vasculo-Behçet disease has been adopted for cases in which vascular manifestations are present and often dominate the clinical features. While venous manifestations are frequent and have been reported in many publications, data regarding arterial lesions in patients with BD are rare and often isolated. In this study, we report the main characteristics, treatment, and long-term outcome of 101 patients with arterial lesions among a cohort of 820 (12.3%) BD patients. Factors that affect prognosis were assessed by multivariate analysis. There were 93 (91.2%) male patients; the median (Q1-Q3) age at diagnosis of BD was 33 (27-41) years. Arterial lesions included aneurysms (47.3%), occlusions (36.5%), stenosis (13.5%), and aortitis (2.7%). Lesions mainly involved the aorta (n = 25) and femoral (n = 23) and pulmonary (n = 21) arteries. Patients with arterial lesions were more frequently male (91.2% vs. 62.4%, respectively; p = 0.017) and had higher rates of venous involvement (80.4% vs. 29.8%, respectively; p < 0.001) compared to patients without arterial manifestations. Thirty-nine (38.6%) patients achieved complete remission. In multivariate analysis, the presence of venous involvement (odds ratio [OR], 0.29; 95% confidence interval [CI], 0.08-1.11) and arterial occlusive lesions (OR, 0.13; 95% CI, 0.01-1.25) were negatively associated with complete remission. The use of immunosuppressants (OR, 3.38; 95% CI, 0.87-13.23) was associated with the occurrence of complete remission. The 20-year survival rate was significantly lower in BD patients with arterial involvement than in those without arterial lesions (73% vs. 89%, respectively; p < 0.0001). In conclusion, the long-term outcome of arterial lesions in BD is poor, especially in the case of occlusive lesions and associated venous involvement. The use of immunosuppressants improved the prognosis.

Clinical Significance of MLH1 Methylation and CpG Island Methylator Phenotype as Prognostic Markers in Patients with Gastric Cancer

PubMed Central

Shigeyasu, Kunitoshi; Nagasaka, Takeshi; Mori, Yoshiko; Yokomichi, Naosuke; Kawai, Takashi; Fuji, Tomokazu; Kimura, Keisuke; Umeda, Yuzo; Kagawa, Shunsuke; Goel, Ajay; Fujiwara, Toshiyoshi

2015-01-01

Background To improve the outcome of patients suffering from gastric cancer, a better understanding of underlying genetic and epigenetic events in this malignancy is required. Although CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) have been shown to play pivotal roles in gastric cancer pathogenesis, the clinical significance of these events on survival outcomes in patients with gastric cancer remains unknown. Methods This study included a patient cohort with pathologically confirmed gastric cancer who had surgical resections. A cohort of 68 gastric cancers was analyzed. CIMP and MSI statuses were determined by analyzing promoter CpG island methylation status of 28 genes/loci, and genomic instability at 10 microsatellite markers, respectively. A Cox’s proportional hazards model was performed for multivariate analysis including age, stage, tumor differentiation, KRAS mutation status, and combined CIMP/MLH1 methylation status in relation to overall survival (OS). Results By multivariate analysis, longer OS was significantly correlated with lower pathologic stage (P = 0.0088), better tumor differentiation (P = 0.0267) and CIMP-high and MLH1 3' methylated status (P = 0.0312). Stratification of CIMP status with regards to MLH1 methylation status further enabled prediction of gastric cancer prognosis. Conclusions CIMP and/or MLH1 methylation status may have a potential to be prognostic biomarkers for patients with gastric cancer. PMID:26121593

Maximum covariance analysis to identify intraseasonal oscillations over tropical Brazil

NASA Astrophysics Data System (ADS)

Barreto, Naurinete J. C.; Mesquita, Michel d. S.; Mendes, David; Spyrides, Maria H. C.; Pedra, George U.; Lucio, Paulo S.

2017-09-01

A reliable prognosis of extreme precipitation events in the tropics is arguably challenging to obtain due to the interaction of meteorological systems at various time scales. A pivotal component of the global climate variability is the so-called intraseasonal oscillations, phenomena that occur between 20 and 100 days. The Madden-Julian Oscillation (MJO), which is directly related to the modulation of convective precipitation in the equatorial belt, is considered the primary oscillation in the tropical region. The aim of this study is to diagnose the connection between the MJO signal and the regional intraseasonal rainfall variability over tropical Brazil. This is achieved through the development of an index called Multivariate Intraseasonal Index for Tropical Brazil (MITB). This index is based on Maximum Covariance Analysis (MCA) applied to the filtered daily anomalies of rainfall data over tropical Brazil against a group of covariates consisting of: outgoing longwave radiation and the zonal component u of the wind at 850 and 200 hPa. The first two MCA modes, which were used to create the { MITB}_1 and { MITB}_2 indices, represent 65 and 16 % of the explained variance, respectively. The combined multivariate index was able to satisfactorily represent the pattern of intraseasonal variability over tropical Brazil, showing that there are periods of activation and inhibition of precipitation connected with the pattern of MJO propagation. The MITB index could potentially be used as a diagnostic tool for intraseasonal forecasting.

Expression and clinical significance of PIWIL2 in hilar cholangiocarcinoma tissues and cell lines.

PubMed

Chen, Y J; Xiong, X F; Wen, S Q; Tian, L; Cheng, W L; Qi, Y Q

2015-06-26

The objective of this study was to explore the relationship between PIWI-like protein 2 (PIWIL2) and clinicopathological charac-teristics and prognosis after radical resection. To accomplish this, we analyzed PIWIL2 expression in hilar cholangiocarcinoma tissues and cell lines. PIWIL2 expression was detected by immunohistochemistry in 41 hilar cholangiocarcinoma samples and 10 control tissues. Western blotting and immunocytofluorescence were used to investigate PIWIL2 expression in the cholangiocarcinoma cell line QBC939 and the bile duct epithelial cell line HIBEpic. Univariate and multivariate surviv-al analyses were performed using the Kaplan-Meier method for hilar cholangiocarcinoma patients who underwent radical resection. PIWIL2 expression was significantly higher in the hilar cholangiocarcinoma tissues and QBC939 cells than in control tissues and HIBEpic cells, respectively (P < 0.05). Poorly and moderately differentiated cholan-giocarcinoma tissues had significantly higher PIWIL2 expression than well-differentiated tissues (P < 0.05). Univariate analysis demonstrated that high PIWIL2 expression was associated with shorter survival time after radical resection (P < 0.05). Multivariate analysis showed that PI-WIL2 expression was an independent prognostic factor after radical re-section of hilar cholangiocarcinoma (P < 0.05). PIWIL2 expression was also associated with tumor-node-metastasis stage and differentiation. PIWIL2 was an independent prognostic factor after radical resection of hilar cholangiocarcinoma.

Sensory cortex hyperexcitability predicts short survival in amyotrophic lateral sclerosis.

PubMed

Shimizu, Toshio; Bokuda, Kota; Kimura, Hideki; Kamiyama, Tsutomu; Nakayama, Yuki; Kawata, Akihiro; Isozaki, Eiji; Ugawa, Yoshikazu

2018-05-01

To investigate somatosensory cortex excitability and its relationship to survival prognosis in patients with amyotrophic lateral sclerosis (ALS). A total of 145 patients with sporadic ALS and 73 healthy control participants were studied. We recorded compound muscle action potential and sensory nerve action potential of the median nerve and the median nerve somatosensory evoked potential (SEP), and we measured parameters, including onset-to-peak amplitude of N13 and N20 and peak-to-peak amplitude between N20 and P25 (N20p-P25p). Clinical prognostic factors, including ALS Functional Rating Scale-Revised, were evaluated. We followed up patients until the endpoints (death or tracheostomy) and analyzed factors associated with survival using multivariate analysis in the Cox proportional hazard model. Compared to controls, patients with ALS showed a larger amplitude of N20p-P25p in the median nerve SEP. Median survival time after examination was shorter in patients with N20p-P25p ≥8 μV (0.82 years) than in those with N20p-P25p <8 μV (1.68 years, p = 0.0002, log-rank test). Multivariate analysis identified a larger N20p-P25p amplitude as a factor that was independently associated with shorter survival ( p = 0.002). Sensory cortex hyperexcitability predicts short survival in patients with ALS. © 2018 American Academy of Neurology.

Prognostic significance of anaplasia and angiogenesis in childhood medulloblastoma: a pediatric oncology group study.

PubMed

Ozer, Erdener; Sarialioglu, Faik; Cetingoz, Riza; Yüceer, Nurullah; Cakmakci, Handan; Ozkal, Sermin; Olgun, Nur; Uysal, Kamer; Corapcioglu, Funda; Canda, Serefettin

2004-01-01

The purpose of this study was to investigate whether quantitative assessment of cytologic anaplasia and angiogenesis may predict the clinical prognosis in medulloblastoma and stratify the patients to avoid both undertreatment and overtreatment. Medulloblastomas from 23 patients belonging to the Pediatric Oncology Group were evaluated with respect to some prognostic variables, including histologic assessment of nodularity and desmoplasia, grading of anaplasia, measurement of nuclear size, mitotic cell count, quantification of angiogenesis, including vascular surface density (VSD) and microvessel number (NVES), and immunohistochemical scoring of vascular endothelial growth factor (VEGF) expression. Univariate and multivariate analyses for prognostic indicators for survival were performed. Univariate analysis revealed that extensive nodularity was a significant favorable prognostic factor, whereas the presence of anaplasia, increased nuclear size, mitotic rate, VSD, and NVES were significant unfavorable prognostic factors. Using multivariate analysis, increased nuclear size was found to be an independent unfavorable prognostic factor for survival. Neither the presence of desmoplasia nor VEGF expression was significantly related to patient survival. Although care must be taken not to overstate the importance of the results of this single-institution preliminary report, pathologic grading of medulloblastomas with respect to grading of anaplasia and quantification of nodularity, nuclear size, and microvessel profiles may be clinically useful for the treatment of medulloblastomas. Further validation of the independent prognostic significance of nuclear size in stratifying patients is required.

Fas expression in renal cell carcinoma accurately predicts patient survival after radical nephrectomy.

PubMed

Sejima, Takehiro; Morizane, Shuichi; Hinata, Nobuyuki; Yao, Akihisa; Isoyama, Tadahiro; Saito, Motoaki; Takenaka, Atsushi

2012-01-01

To investigate Fas, Fas ligand (FasL) and Bcl-2 expression, which are considered to be important apoptotic regulatory factors in renal cell carcinomas (RCCs). mRNA quantification and immunohistochemistry allowed for the determination of the expression of these three factors in surgically resected tumors from 82 patients with RCC. The correlation of protein and gene expression with more than 10 years of survival data following nephrectomy (along with clinical and pathologic parameters) was analyzed using uni- and multivariate statistical models. A significantly poorer outcome was observed in patients with tumors expressing high levels of Fas mRNA in the multivariate analysis (p = 0.0002). In addition, patient survival was significantly worse in FasL mRNA-positive tumor cases when compared with FasL mRNA-negative cases (p = 0.0345). Ten cases relapsed more than 5 years after nephrectomy. Among them, the tumors of 8 cases (80%) did not express FasL mRNA. Analysis of Bcl-2 did not show statistical significance of Bcl-2 expression as a prognostic indicator. The data suggest that pronounced Fas expression is a surrogate biomarker of active cancer cell proliferation. Given the FasL tumor counterattack theory, FasL overexpression in RCC may be one of the host immune deficiencies, consequently leading to poor prognosis. Copyright © 2012 S. Karger AG, Basel.

Comparative study of bacteremias caused by Enterococcus spp. with and without high-level resistance to gentamicin. The Grupo Andaluz para el estudio de las Enfermedades Infecciosas.

PubMed

Caballero-Granado, F J; Cisneros, J M; Luque, R; Torres-Tortosa, M; Gamboa, F; Díez, F; Villanueva, J L; Pérez-Cano, R; Pasquau, J; Merino, D; Menchero, A; Mora, D; López-Ruz, M A; Vergara, A

1998-02-01

A prospective, multicenter study was carried out over a period of 10 months. All patients with clinically significant bacteremia caused by Enterococcus spp. were included. The epidemiological, microbiological, clinical, and prognostic features and the relationship of these features to the presence of high-level resistance to gentamicin (HLRG) were studied. Ninety-three patients with enterococcal bacteremia were included, and 31 of these cases were caused by HLRG (33%). The multivariate analysis selected chronic renal failure, intensive care unit stay, previous use of antimicrobial agents, and Enterococcus faecalis species as the independent risk factors that influenced the development of HLRG. The strains with HLRG showed lower levels of susceptibility to penicillin and ciprofloxacin. Clinical features (except for chronic renal failure) were similar in both groups of patients. HLRG did not influence the prognosis for patients with enterococcal bacteremia in terms of either the crude mortality rate (29% for patients with bacteremia caused by enterococci with HLRG and 28% for patients not infected with strains with HLRG) or the hospital stay after the acquisition of enterococcal bacteremia. Hemodynamic compromise, inappropriate antimicrobial therapy, and mechanical ventilation were revealed in the multivariate analysis to be the independent risk factors for mortality. Prolonged hospitalization was associated with the nosocomial acquisition of bacteremia and polymicrobial infections.

Outcome and prognostic factors in critically ill patients with systemic lupus erythematosus: a retrospective study.

PubMed

Hsu, Chia-Lin; Chen, Kuan-Yu; Yeh, Pu-Sheng; Hsu, Yeong-Long; Chang, Hou-Tai; Shau, Wen-Yi; Yu, Chia-Li; Yang, Pan-Chyr

2005-06-01

Systemic lupus erythematosus (SLE) is an archetypal autoimmune disease, involving multiple organ systems with varying course and prognosis. However, there is a paucity of clinical data regarding prognostic factors in SLE patients admitted to the intensive care unit (ICU). From January 1992 to December 2000, all patients admitted to the ICU with a diagnosis of SLE were included. Patients were excluded if the diagnosis of SLE was established at or after ICU admission. A multivariate logistic regression model was applied using Acute Physiology and Chronic Health Evaluation II scores and variables that were at least moderately associated (P < 0.2) with survival in the univariate analysis. A total of 51 patients meeting the criteria were included. The mortality rate was 47%. The most common cause of admission was pneumonia with acute respiratory distress syndrome. Multivariate logistic regression analysis showed that intracranial haemorrhage occurring while the patient was in the ICU (relative risk = 18.68), complicating gastrointestinal bleeding (relative risk = 6.97) and concurrent septic shock (relative risk = 77.06) were associated with greater risk of dying, whereas causes of ICU admission and Acute Physiology and Chronic Health Evaluation II score were not significantly associated with death. The mortality rate in critically ill SLE patients was high. Gastrointestinal bleeding, intracranial haemorrhage and septic shock were significant prognostic factors in SLE patients admitted to the ICU.

Prognostic value of preoperative serum CA 242 in Esophageal squamous cell carcinoma cases.

PubMed

Feng, Ji-Feng; Huang, Ying; Chen, Qi-Xun

2013-01-01

Carbohydrate antigen (CA) 242 is inversely related to prognosis in many cancers. However, few data regarding CA 242 in esophageal cancer (EC) are available. The aim of this study was to determine the prognostic value of CA 242 and propose an optimum cut-off point in predicting survival difference in patients with esophageal squamous cell carcinoma (ESCC). A retrospective analysis was conducted of 192 cases. A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimum cuf- off point. Univariate and multivariate analyses were performed to evaluate prognostic parameters for survival. The positive rate for CA 242 was 7.3% (14/192). The ROC curve for survival prediction gave an optimum cut-off of 2.15 (U/ml). Patients with CA 242 ≤ 2.15 U/ml had significantly better 5-year survival than patients with CA 242 >2.15 U/ml (45.4% versus 22.6%; P=0.003). Multivariate analysis showed that differentiation (P=0.033), CA 242 (P=0.017), T grade (P=0.004) and N staging (P<0.001) were independent prognostic factors. Preoperative CA 242 is a predictive factor for long-term survival in ESCC, especially in nodal-negative patients. We conclude that 2.15 U/ml may be the optimum cuf-off point for CA 242 in predicting survival in ESCC.

Risk factors for progression to invasive carcinoma in patients with borderline ovarian tumors.

PubMed

Song, Taejong; Lee, Yoo-Young; Choi, Chel Hun; Kim, Tae-Joong; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

2014-09-01

The aim of this study was to identify risk factors for progression to invasive carcinoma in patients with borderline ovarian tumors (BOTs). We performed a retrospective review of all patients treated and followed for BOTs between 1996 and 2011. Multivariate Cox proportional hazards model analysis was performed to identify independent risk factors for progression to invasive carcinoma. A total of 364 patients were identified. During the median follow-up of 53.8 months, 31 patients (8.5%) developed recurrent disease: 12 (3.3%) had recurrent disease with progression to invasive carcinoma, and 19 (5.2%) had recurrent disease with borderline histology. Disease-related deaths (7/364; 1.7%) were observed only in patients with progression to invasive carcinoma. The multivariate analysis showed that independent risk factors for progression to invasive carcinoma were advanced disease stage (hazard ratio [HR], 5.59; P = 0.005), age 65 years or older (HR, 5.13; P = 0.037), and the presence of microinvasion (HR, 3.71; P = 0.047). These 3 factors were also independently related to overall survival. Although patients with BOTs have an excellent prognosis, the risk of progression to invasive carcinoma and thereby death remains. Therefore, physicians should pay closer attention to BOT patients with these risk factors (ie, advanced disease stage, old age, and microinvasion), and more careful surveillance for progression to invasive carcinoma is needed.

[Multivariate analysis of factors influencing the effect of radiosynovectomy].

PubMed

Farahati, J; Schulz, G; Wendler, J; Körber, C; Geling, M; Kenn, W; Schmeider, P; Reidemeister, C; Reiners, Chr

2002-04-01

In this prospective study, the time to remission after Radiosynovectomy (RSV) was analyzed and the influence of age, sex, underlying disease, type of joint, and duration of illness on the success rate of RSV was determined. A total number of 57 patients with rheumatoid arthritis (n = 33) and arthrosis (n = 21) with a total number of 130 treated joints (36 knee, 66 small and 28 medium-size joints) were monitored using visual analogue scales (VAS) from one week before RSV up to four to six months after RSV. The patients had to answer 3 times daily for pain intensity of the treated joint. The time until remission was determined according to the Kaplan-Meier survivorship function. The influence of the prognosis parameters on outcome of RSV was determined by multivariate discriminant analysis. After six months, the probability of pain relief of more than 20% amounted to 78% and was significantly dependent on the age of the patient (p = 0.02) and the duration of illness (p = 0.05), however not on sex (p = 0.17), underlying disease (p = 0.23), and type of joint (p = 0.69). Irrespective of sex, type of joint and underlying disease, a measurable pain relief can be achieved with RSV in 78% of the patients with synovitis, whereby effectiveness is decreasing with increasing age and progress of illness.

An integrated mRNA and microRNA expression signature for glioblastoma multiforme prognosis.

PubMed

Xiong, Jie; Bing, Zhitong; Su, Yanlin; Deng, Defeng; Peng, Xiaoning

2014-01-01

Although patients with Glioblastoma multiforme (GBM) have grave prognosis, significant variability in patient outcome is observed. The objective of this study is to identify a molecular signature for GBM prognosis. We subjected 355 mRNA and microRNA expression profiles to elastic net-regulated Cox regression for identification of an integrated RNA signature for GBM prognosis. A prognostic index (PI) was generated for patient stratification. Survival comparison was conducted by Kaplan-Meier method and a general multivariate Cox regression procedure was applied to evaluate the independence of the PI. The abilities and efficiencies of signatures to predict GBM patient outcome was assessed and compared by the area under the curve (AUC) of the receiver-operator characteristic (ROC). An integrated RNA prognostic signature consisted by 4 protective mRNAs, 12 risky mRNAs, and 1 risky microRNA was identified. Decreased survival was associated with being in the high-risk group (hazard ratio = 2.864, P<0.0001). The prognostic value of the integrated signature was validated in five independent GBM expression datasets (n = 201, hazard ratio = 2.453, P<0.0001). The PI outperformed the known clinical factors, mRNA-only, and miRNA-only prognostic signatures for GBM prognosis (area under the ROC curve for the integrated RNA, mRNA-only, and miRNA-only signatures were 0.828, 0.742, and 0.757 at 3 years of overall survival, respectively, P<0.0001 by permutation test). We describe the first, to our knowledge, robust transcriptome-based integrated RNA signature that improves the current GBM prognosis based on clinical variables, mRNA-only, and miRNA-only signatures.

An Integrated mRNA and microRNA Expression Signature for Glioblastoma Multiforme Prognosis

PubMed Central

Xiong, Jie; Bing, Zhitong; Su, Yanlin; Deng, Defeng; Peng, Xiaoning

2014-01-01

Although patients with Glioblastoma multiforme (GBM) have grave prognosis, significant variability in patient outcome is observed. The objective of this study is to identify a molecular signature for GBM prognosis. We subjected 355 mRNA and microRNA expression profiles to elastic net-regulated Cox regression for identification of an integrated RNA signature for GBM prognosis. A prognostic index (PI) was generated for patient stratification. Survival comparison was conducted by Kaplan-Meier method and a general multivariate Cox regression procedure was applied to evaluate the independence of the PI. The abilities and efficiencies of signatures to predict GBM patient outcome was assessed and compared by the area under the curve (AUC) of the receiver-operator characteristic (ROC). An integrated RNA prognostic signature consisted by 4 protective mRNAs, 12 risky mRNAs, and 1 risky microRNA was identified. Decreased survival was associated with being in the high-risk group (hazard ratio = 2.864, P<0.0001). The prognostic value of the integrated signature was validated in five independent GBM expression datasets (n = 201, hazard ratio = 2.453, P<0.0001). The PI outperformed the known clinical factors, mRNA-only, and miRNA-only prognostic signatures for GBM prognosis (area under the ROC curve for the integrated RNA, mRNA-only, and miRNA-only signatures were 0.828, 0.742, and 0.757 at 3 years of overall survival, respectively, P<0.0001 by permutation test). We describe the first, to our knowledge, robust transcriptome-based integrated RNA signature that improves the current GBM prognosis based on clinical variables, mRNA-only, and miRNA-only signatures. PMID:24871302

Inhospital and Post-discharge Changes in Renal Function After Transcatheter Aortic Valve Replacement.

PubMed

Blair, John E A; Brummel, Kent; Friedman, Julie L; Atri, Prashant; Sweis, Ranya N; Russell, Hyde; Ricciardi, Mark J; Malaisrie, S Chris; Davidson, Charles J; Flaherty, James D

2016-02-15

The aim of this study was to determine the influence of inhospital and post-discharge worsening renal function (WRF) on prognosis after transcatheter aortic valve replacement (TAVR). Severe chronic kidney disease and inhospital WRF are both associated with poor outcomes after TAVR. There are no data available on post-discharge WRF and outcomes. This was a single-center study evaluating all TAVR from June 1, 2008, to June 31, 2014. WRF was defined as an increase in serum creatinine of ≥0.3 mg/dl. Inhospital WRF was measured from day 0 until discharge or day 7 if the hospitalization was >7 days. Post-discharge WRF was measured at 30 days after discharge. Descriptive statistics, Kaplan-Meier time-to-event analysis, and multivariate logistic regression were used. In a series of 208 patients who underwent TAVR, 204 with complete renal function data were used in the inhospital analysis and 168 who returned for the 30-day follow-up were used in the post-discharge analysis. Inhospital WRF was seen in 28%, whereas post-discharge WRF in 12%. Inhospital and post-discharge WRF were associated with lower rates of survival; however, after multivariate analysis, only post-discharge WRF remained a predictor of 1-year mortality (hazard ratio 1.18, p = 0.030 for every 1 mg/dl increase in serum creatinine). In conclusion, the rate of inhospital WRF is higher than the rate of post-discharge WRF after TAVR, and post-discharge WRF is more predictive of mortality than inhospital WRF. Copyright © 2016 Elsevier Inc. All rights reserved.

The preoperative plasma fibrinogen level is an independent prognostic factor for overall survival of breast cancer patients who underwent surgical treatment.

PubMed

Wen, Jiahuai; Yang, Yanning; Ye, Feng; Huang, Xiaojia; Li, Shuaijie; Wang, Qiong; Xie, Xiaoming

2015-12-01

Previous studies have suggested that plasma fibrinogen contributes to tumor cell proliferation, progression and metastasis. The current study was performed to evaluate the prognostic relevance of preoperative plasma fibrinogen in breast cancer patients. Data of 2073 consecutive breast cancer patients, who underwent surgery between January 2002 and December 2008 at the Sun Yat-sen University Cancer Center, were retrospectively evaluated. Plasma fibrinogen levels were routinely measured before surgeries. Participants were grouped by the cutoff value estimated by the receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed using Kaplan-Meier analysis, and multivariate Cox proportional hazards regression model was performed to evaluate the independent prognostic value of plasma fibrinogen level. The optimal cutoff value of preoperative plasma fibrinogen was determined to be 2.83 g/L. The Kaplan-Meier analysis showed that patients with high fibrinogen levels had shorter OS than patients with low fibrinogen levels (p < 0.001). Multivariate analysis suggested preoperative plasma fibrinogen as an independent prognostic factor for OS in breast cancer patients (HR = 1.475, 95% confidence interval (CI): 1.177-1.848, p = 0.001). Subgroup analyses revealed that plasma fibrinogen level was an unfavorable prognostic parameter in stage II-III, Luminal subtypes and triple-negative breast cancer patients. Elevated preoperative plasma fibrinogen was independently associated with poor prognosis in breast cancer patients and may serve as a valuable parameter for risk assessment in breast cancer patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Novel immunological and nutritional-based prognostic index for gastric cancer.

PubMed

Sun, Kai-Yu; Xu, Jian-Bo; Chen, Shu-Ling; Yuan, Yu-Jie; Wu, Hui; Peng, Jian-Jun; Chen, Chuang-Qi; Guo, Pi; Hao, Yuan-Tao; He, Yu-Long

2015-05-21

To assess the prognostic significance of immunological and nutritional-based indices, including the prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio in gastric cancer. We retrospectively reviewed 632 gastric cancer patients who underwent gastrectomy between 1998 and 2008. Areas under the receiver operating characteristic curve were calculated to compare the predictive ability of the indices, together with estimating the sensitivity, specificity and agreement rate. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS). Propensity score analysis was performed to adjust variables to control for selection bias. Each index could predict OS in gastric cancer patients in univariate analysis, but only PNI had independent prognostic significance in multivariate analysis before and after adjustment with propensity scoring (hazard ratio, 1.668; 95% confidence interval: 1.368-2.035). In subgroup analysis, a low PNI predicted a significantly shorter OS in patients with stage II-III disease (P = 0.019, P < 0.001), T3-T4 tumors (P < 0.001), or lymph node metastasis (P < 0.001). Canton score, a combination of PNI, NLR, and platelet, was a better indicator for OS than PNI, with the largest area under the curve for 12-, 36-, 60-mo OS and overall OS (P = 0.022, P = 0.030, P < 0.001, and P = 0.024, respectively). The maximum sensitivity, specificity, and agreement rate of Canton score for predicting prognosis were 84.6%, 34.9%, and 70.1%, respectively. PNI is an independent prognostic factor for OS in gastric cancer. Canton score can be a novel preoperative prognostic index in gastric cancer.

Lack of Thy1 (CD90) expression in neuroblastomas is correlated with impaired survival.

PubMed

Fiegel, Henning C; Kaifi, Jussuf T; Quaas, Alexander; Varol, Emine; Krickhahn, Annika; Metzger, Roman; Sauter, Guido; Till, Holger; Izbicki, Jakob R; Erttmann, Rudolf; Kluth, Dietrich

2008-01-01

Neuroblastoma (NBL) is the most common solid tumor in children. Tumors in advanced stage or with positive risk factors still have a poor prognosis. Thy1 (CD90) is a membrane glycoprotein expressed in thymus, retinal ganglionic cells, and several types of stem cells. The aim of this study was to assess Thy1 expression in NBL and analyze the correlation with clinical outcome. Sixty-three specimens of NBL were stained for Thy1 on a tissue microarray by immunohistochemistry. Fresh frozen tumor tissues were used for RNA isolation, and RT-PCR analysis for Thy1-mRNA expression was performed. Patients' survival data were correlated with Thy1 status using a log rank test and a Cox regression multivariate analysis. Thy1 was expressed on 51 (81%) of the tumors. Kaplan-Meier survival analysis showed a significantly impaired survival in patients with NBL missing Thy1 (P < 0.005 by log-rank test). A multivariate Cox regression showed an independent prognostic value of Thy1 status for overall survival (P < 0.05). In addition, the frequency of events and deaths was significantly higher in the group of patients with Thy1 negative tumors, as assessed by ANOVA analysis (P < 0.05 by F-test). The data showed that Thy1-negative NBL patients have a significantly impaired overall survival compared with Thy1-positive NBL patients. Thus, Thy1 seemed to be a marker with a specific prognostic value in NBL patients. Future studies are aiming at the biological role of this marker in the tumor cell differentiation.

Pulmonary metastasectomy in colorectal cancer patients with previously resected liver metastasis: pooled analysis.

PubMed

Salah, Samer; Ardissone, Francesco; Gonzalez, Michel; Gervaz, Pascal; Riquet, Marc; Watanabe, Kazuhiro; Zabaleta, Jon; Al-Rimawi, Dalia; Toubasi, Samar; Massad, Ehab; Lisi, Elena; Hamed, Osama H

2015-01-01

Data addressing the outcomes and patterns of recurrence after pulmonary metastasectomy (PM) in patients with colorectal cancer (CRC) and previously resected liver metastasis are limited. We searched the PubMed database for studies assessing PM in CRC and gathered individual data for patients who had PM and a previous curative liver resection. The influence of potential factors on overall survival (OS) was analyzed through univariate and multivariate analysis. Between 1983 and 2009, 146 patients from five studies underwent PM and had previous liver resection. The median interval from resection of liver metastasis until detection of lung metastasis and the median follow-up from PM were 23 and 48 months, respectively. Five-year OS and recurrence-free survival rates calculated from the date of PM were 54.4 and 29.3 %, respectively. Factors predicting inferior OS in univariate analysis included thoracic lymph node (LN) involvement and size of largest lung nodule ≥2 cm. Adjuvant chemotherapy and whether lung metastasis was detected synchronous or metachronous to liver metastasis had no influence on survival. In multivariate analysis, thoracic LN involvement emerged as the only independent factor (hazard ratio 4.86, 95 % confidence interval 1.56-15.14, p = 0.006). PM offers a chance for long-term survival in selected patients with CRC and previously resected liver metastasis. Thoracic LN involvement predicted poor prognosis; therefore, significant efforts should be undertaken for adequate staging of the mediastinum before PM. In addition, adequate intraoperative LN sampling allows proper prognostic stratification and enrollment in novel adjuvant therapy trials.

Gene expression analysis of a Helicobacter pylori-infected and high-salt diet-treated mouse gastric tumor model: identification of CD177 as a novel prognostic factor in patients with gastric cancer

PubMed Central

2013-01-01

Background Helicobacter pylori (H. pylori) infection and excessive salt intake are known as important risk factors for stomach cancer in humans. However, interactions of these two factors with gene expression profiles during gastric carcinogenesis remain unclear. In the present study, we investigated the global gene expression associated with stomach carcinogenesis and prognosis of human gastric cancer using a mouse model. Methods To find candidate genes involved in stomach carcinogenesis, we firstly constructed a carcinogen-induced mouse gastric tumor model combined with H. pylori infection and high-salt diet. C57BL/6J mice were given N-methyl-N-nitrosourea in their drinking water and sacrificed after 40 weeks. Animals of a combination group were inoculated with H. pylori and fed a high-salt diet. Gene expression profiles in glandular stomach of the mice were investigated by oligonucleotide microarray. Second, we examined an availability of the candidate gene as prognostic factor for human patients. Immunohistochemical analysis of CD177, one of the up-regulated genes, was performed in human advanced gastric cancer specimens to evaluate the association with prognosis. Results The multiplicity of gastric tumor in carcinogen-treated mice was significantly increased by combination of H. pylori infection and high-salt diet. In the microarray analysis, 35 and 31 more than two-fold up-regulated and down-regulated genes, respectively, were detected in the H. pylori-infection and high-salt diet combined group compared with the other groups. Quantitative RT-PCR confirmed significant over-expression of two candidate genes including Cd177 and Reg3g. On immunohistochemical analysis of CD177 in human advanced gastric cancer specimens, over-expression was evident in 33 (60.0%) of 55 cases, significantly correlating with a favorable prognosis (P = 0.0294). Multivariate analysis including clinicopathological factors as covariates revealed high expression of CD177 to be an independent prognostic factor for overall survival. Conclusions These results suggest that our mouse model combined with H. pylori infection and high-salt diet is useful for gene expression profiling in gastric carcinogenesis, providing evidence that CD177 is a novel prognostic factor for stomach cancer. This is the first report showing a prognostic correlation between CD177 expression and solid tumor behavior. PMID:23899160

[Risk factors on the recurrence of ischemic stroke and the establishment of a Cox's regression model].

PubMed

An, Ya-chen; Chen, Yun-xia; Wang, Yu-xun; Zhao, Xiao-jing; Wang, Yan; Zhang, Jiang; Li, Chun-ling; Peng, Yan-bo; Gao, Su-ling; Chang, Li-sha; Zhang, Li; Xue, Xin-hong; Chen, Rui-ying; Wang, Da-li

2011-08-01

To investigate the risk factors and establish the Cox's regression model on the recurrence of ischemic stroke. We retrospectively reviewed consecutive patients with ischemic stroke admitted to the Neurology Department of the Hebei United University Affiliated Hospital between January 1, 2008 and December 31, 2009. Cases had been followed since the onset of ischemic stroke. The follow-up program was finished in June 30, 2010. Kaplan-Meier methods were used to describe the recurrence rate. Monovariant and multivariate Cox's proportional hazard regression model were used to analyze the risk factors associated to the episodes of recurrence. And then, a recurrence model was set up. During the period of follow-up program, 79 cases were relapsed, with the recurrence rates as 12.75% in one year and 18.87% in two years. Monovariant and multivariate Cox's proportional hazard regression model showed that the independent risk factors that were associated with the recurrence appeared to be age (X₁) (RR = 1.025, 95%CI: 1.003 - 1.048), history of hypertension (X₂) (RR = 1.976, 95%CI: 1.014 - 3.851), history of family strokes (X₃) (RR = 2.647, 95%CI: 1.175 - 5.961), total cholesterol amount (X₄) (RR = 1.485, 95%CI: 1.214 - 1.817), ESRS total scores (X₅) (RR = 1.327, 95%CI: 1.057 - 1.666) and progression of the disease (X₆) (RR = 1.889, 95%CI: 1.123 - 3.178). Personal prognosis index (PI) of the recurrence model was as follows: PI = 0.025X₁ + 0.681X₂ + 0.973X₃ + 0.395X₄ + 0.283X₅ + 0.636X₆. The smaller the personal prognosis index was, the lower the recurrence risk appeared, while the bigger the personal prognosis index was, the higher the recurrence risk appeared. Age, history of hypertension, total cholesterol amount, total scores of ESRS, together with the disease progression were the independent risk factors associated with the recurrence episodes of ischemic stroke. Both recurrence model and the personal prognosis index equation were successful constructed.

PTEN Loss Increases PD-L1 Protein Expression and Affects the Correlation between PD-L1 Expression and Clinical Parameters in Colorectal Cancer

PubMed Central

Lu, Biyan; Wang, Chenliang; Zhang, Junxiao; Huang, Lanlan; Wang, Xiaoyan; Timmons, Christine L.; Hu, Jun; Liu, Bindong; Wu, Xiaojian; Wang, Lei; Wang, Jianping; Liu, Huanliang

2013-01-01

Background Programmed death ligand-1 (PD-L1) has been identified as a factor associated with poor prognosis in a range of cancers, and was reported to be mainly induced by PTEN loss in gliomas. However, the clinical effect of PD-L1 and its regulation by PTEN has not yet been determined in colorectal cancer (CRC). In the present study, we verified the regulation of PTEN on PD-L1 and further determined the effect of PTEN on the correlation between PD-L1 expression and clinical parameters in CRC. Methods/Results RNA interference approach was used to down-regulate PTEN expression in SW480, SW620 and HCT116 cells. It was showed that PD-L1 protein, but not mRNA, was significantly increased in cells transfected with siRNA PTEN compared with the negative control. Moreover, the capacity of PTEN to regulate PD-L1 expression was not obviously affected by IFN-γ, the main inducer of PD-L1. Tissue microarray immunohistochemistry was used to detect PD-L1 and PTEN in 404 CRC patient samples. Overexpression of PD-L1 was significantly correlated with distant metastasis (P<0.001), TNM stage (P<0.01), metastatic progression (P<0.01) and PTEN expression (P<0.001). Univariate analysis revealed that patients with high PD-L1 expression had a poor overall survival (P<0.001). However, multivariate analysis did not support PD-L1 as an independent prognostic factor (P = 0.548). Univariate (P<0.001) and multivariate survival (P<0.001) analysis of 310 located CRC patients revealed that high level of PD-L1 expression was associated with increased risks of metastatic progression. Furthermore, the clinical effect of PD-L1 on CRC was not statistically significant in a subset of 39 patients with no PTEN expression (distant metastasis: P = 0.102; TNM stage: P = 0.634, overall survival: P = 0.482). Conclusions PD-L1 can be used to identify CRC patients with high risk of metastasis and poor prognosis. This clinical manifestation may be partly associated with PTEN expression. PMID:23785454

Appraising stroke risk in maintenance hemodialysis patients: a large single-center cohort study.

PubMed

Power, Albert; Chan, Kakit; Singh, Seema K; Taube, David; Duncan, Neill

2012-02-01

Stroke incidence in hemodialysis patients is up to 10 times greater than in the general population and is associated with a worse prognosis. Factors influencing stroke risk by subtype and subsequent prognosis are poorly described in the literature. Retrospective single-center cohort study. 2,384 established maintenance hemodialysis patients at a single center from January 1, 2002, to June 1, 2009. Patient demographics, comorbid conditions. Incidence of acute stroke (International Classification of Diseases, 9th Revision codes 430, 431, 432.9, 433.1, and 434.1 with evidence of compatible neuroimaging), patient survival. Cumulative patient survival, incidence of acute fatal and nonfatal stroke. 127 strokes occurred during 9,541 total patient-years of follow-up. First (incident) stroke occurred at a rate of 14.9/1,000 patient years (95% CI, 12.2-17.9) with a predominance of ischemic compared with hemorrhagic subtypes (11.2 vs 3.7/1,000 patient-years). 54% of hemorrhagic strokes occurred in patients of South Asian ethnicity compared with ischemic strokes, which occurred predominantly in white patients (45% of events). Diabetes mellitus (HR, 1.92; 95% CI, 1.29-2.85; P = 0.001) and prior cerebrovascular disease (HR, 4.54; 95% CI, 3.07-6.72; P < 0.001) were independently associated with incident cerebrovascular accident on multivariate analysis. Acute stroke was associated with worse patient survival (HR, 3.26; 95% CI, 2.47-4.30; P < 0.001) and overall 1-year mortality of 24%, which was significantly worse in patients with hemorrhagic events (39% vs 19% mortality for ischemic subtypes). Serum albumin level >3.5 g/L (HR, 0.38; 95% CI, 0.19-0.76; P = 0.007) and C-reactive protein level >3.0 mg/l (HR, 1.36; 95% CI, 1.12-1.64; P = 0.002) influenced survival after stroke on multivariate analysis. Retrospective analysis of data cannot prove causality. The high incidence of stroke in hemodialysis patients is associated with high mortality, especially hemorrhagic subtypes. Strict management of hypertension, better appreciation of hemodialysis anticoagulation, and large-scale interventional studies are urgently required to direct prevention and treatment of this significant disease. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Clinical significance of preoperative carcinoembryonic antigen level in patients with clinical stage IA non-small cell lung cancer.

PubMed

Maeda, Ryo; Suda, Takashi; Hachimaru, Ayumi; Tochii, Daisuke; Tochii, Sachiko; Takagi, Yasushi

2017-01-01

The objective of this study was to assess the preoperative serum carcinoembryonic antigen (CEA) level in patients with clinical stage IA non-small cell lung cancer (NSCLC) and to evaluate its clinical significance. Between January 2005 and December 2014, a total of 378 patients with clinical stage IA NSCLC underwent complete resection with systematic node dissection. The survival rate was estimated starting from the date of surgery to the date of either death or the last follow-up by the Kaplan-Meier method. Univariate analyses by log-rank tests were used to determine prognostic factors. Cox proportional hazards ratios were used to identify independent predictors of poor prognosis. Clinicopathological predictors of lymph node metastases were evaluated by logistic regression analyses. The 5-year survival rate of patients with an elevated preoperative serum CEA level was significantly lower than that of patients with a normal CEA level (75.5% vs. 87.7%; P=0.02). However, multivariate analysis did not show the preoperative serum CEA level to be an independent predictor of poor prognosis. Postoperative pathological factors, including lymphatic permeation, visceral pleural invasion, and lymph node metastases, tended to be positive in patients with an elevated preoperative serum CEA level. In addition, the CEA level was a statistically significant independent clinical predictor of lymph node metastases. The preoperative serum CEA level was not an independent predictor of poor prognosis in patients with pathological stage IA NSCLC but was an important clinical predictor of tumor invasiveness and lymph node metastases in patients with clinical stage IA NSCLC. Therefore, measurement of the preoperative serum CEA level should be considered even for patients with early-stage NSCLC.

Suppression of p53-inducible gene 3 is significant for glioblastoma progression and predicts poor patient prognosis.

PubMed

Quan, Jishu; Li, Yong; Jin, Meihua; Chen, Dunfu; Yin, Xuezhe; Jin, Ming

2017-03-01

Glioblastoma is the most malignant and invasive brain tumor with extremely poor prognosis. p53-inducible gene 3, a downstream molecule of the tumor suppressor p53, has been found involved in apoptosis and oxidative stress response. However, the functions of p53-inducible gene 3(PIG3) in cancer are far from clear including glioblastoma. In this study, we found that p53-inducible gene 3 expression was suppressed in glioblastoma tissues compared with normal tissues. And the expression of p53-inducible gene 3 was significantly associated with the World Health Organization grade. Patients with high p53-inducible gene 3 expression have a significantly longer median survival time (15 months) than those with low p53-inducible gene 3 expression (8 months). According to Cox regression analysis, p53-inducible gene 3 was an independent prognostic factor with multivariate hazard ratio of 0.578 (95% confidence interval, 0.352-0.947; p = 0.030) for overall survival. Additionally, gain and loss of function experiments showed that knockdown of p53-inducible gene 3 significantly increased the proliferation and invasion ability of glioblastoma cells while overexpression of p53-inducible gene 3 inhibited the proliferation and invasion ability. The results of in vivo glioblastoma models further confirmed that p53-inducible gene 3 suppression promoted glioblastoma progression. Altogether, our data suggest that high expression of p53-inducible gene 3 is significant for glioblastoma inhibition and p53-inducible gene 3 independently indicates good prognosis in patients, which might be a novel prognostic biomarker or potential therapeutic target in glioblastoma.

Symptomatic and Asymptomatic Neurological Complications of Infective Endocarditis: Impact on Surgical Management and Prognosis

PubMed Central

Delahaye, François; Tattevin, Pierre; Federspiel, Claire; Le Moing, Vincent; Chirouze, Catherine; Nazeyrollas, Pierre; Vernet-Garnier, Véronique; Bernard, Yvette; Chocron, Sidney; Obadia, Jean-François; Alla, François; Hoen, Bruno; Duval, Xavier

2016-01-01

Objectives Symptomatic neurological complications (NC) are a major cause of mortality in infective endocarditis (IE) but the impact of asymptomatic complications is unknown. We aimed to assess the impact of asymptomatic NC (AsNC) on the management and prognosis of IE. Methods From the database of cases collected for a population-based study on IE, we selected 283 patients with definite left-sided IE who had undergone at least one neuroimaging procedure (cerebral CT scan and/or MRI) performed as part of initial evaluation. Results Among those 283 patients, 100 had symptomatic neurological complications (SNC) prior to the investigation, 35 had an asymptomatic neurological complications (AsNC), and 148 had a normal cerebral imaging (NoNC). The rate of valve surgery was 43% in the 100 patients with SNC, 77% in the 35 with AsNC, and 54% in the 148 with NoNC (p<0.001). In-hospital mortality was 42% in patients with SNC, 8.6% in patients with AsNC, and 16.9% in patients with NoNC (p<0.001). Among the 135 patients with NC, 95 had an indication for valve surgery (71%), which was performed in 70 of them (mortality 20%) and not performed in 25 (mortality 68%). In a multivariate adjusted analysis of the 135 patients with NC, age, renal failure, septic shock, and IE caused by S. aureus were independently associated with in-hospital and 1-year mortality. In addition SNC was an independent predictor of 1-year mortality. Conclusions The presence of NC was associated with a poorer prognosis when symptomatic. Patients with AsNC had the highest rate of valve surgery and the lowest mortality rate, which suggests a protective role of surgery guided by systematic neuroimaging results. PMID:27400273

Prognostic value of tripartite motif containing 29 expression in patients with gastric cancer following surgical resection.

PubMed

Wang, Chenghu; Zhou, Yi; Chen, Beibei; Yuan, Weiwei; Huang, Jinxi

2018-04-01

Tripartite motif containing 29 (TRIM29) dysregulation serves an important function in the progression of numerous types of cancer, but its function in the prognosis of patients with gastric cancer remains unknown. The present study assessed the prognostic value of TRIM29 in patients with gastric cancer following surgical resection. A total of 243 fresh gastric adenocarcinoma and adjacent normal tissues were continuously retrieved from patients who underwent curative surgery for gastric cancer at the Cancer Hospital of Henan Province (Zhengzhou, China) between January 2005 and December 2011. The reverse transcription-quantitative polymerase chain reaction was performed to assess TRIM29 expression. The association between TRIM29 expression and clinicopathological features and prognosis was subsequently evaluated. The results of the present study revealed that the expression of TRIM29 was increased in the gastric cancer tissues compared with the normal adjacent tissues, and that upregulated expression of TRIM29 was associated with tumor cell differentiation, tumor stage, lymph node metastasis, and tumor-node-metastasis (TNM) stage. In the training and validation data, high TRIM29 expression was associated with poor overall survival in patients with gastric cancer. Furthermore, multivariate analysis identified that TRIM29 expression was an independent prognostic factor for overall survival, in addition to TNM stage and Lauren classification. Combining TRIM29 expression with the TNM staging system generated a novel predictive model that exhibited improved prognostic accuracy for overall survival in patients with gastric cancer. The present study revealed that TRIM29 was an independent adverse prognostic factor in patients with gastric cancer. Incorporating TRIM29 expression level into the TNM staging system may improve risk stratification and render prognosis more accurate in patients with gastric cancer.

Long-term follow-up of HBsAg-positive patients in Germany.

PubMed

Niederau, Claus; Amani, Asef; Thiel, Andreas

2016-01-01

Little is known about the prognosis and complications of chronic hepatitis B in countries with low disease prevalence including Germany. This retrospective/prospective study analyzes the course of 608 HBsAg-positive patients between 2002 and 2012 in Germany. The follow-up duration was 5.2±2.9 years (mean±SD) and the age of the patients was 40.4±13.8 years. Of the total cohort, 59.9% were men; 34.9% had been born in Germany, 30.4% in Turkey, and 34.7% in other countries. In 78.3% of women, diagnosis was made during pregnancy screening, which is the only reinforced screening procedure in Germany. During follow-up, 21 patients died, five had a LTX, and 20 developed a hepatocellular carcinoma. Of the total cohort, 15% developed at least one severe liver-associated complication. By multivariate analysis, prognosis was associated with high age and cirrhosis, but not with sex, HBV-DNA, alanine aminotransferase, and ethnic origin. Of the 608 patients, 211 (34.7%) had at least one antiviral therapy. Of the 178 patients who were treated with nucleot(s)ides at the last visit 88.8% had an HBV-DNA less than 20 IU/ml. Today, in Germany, hepatitis B is a disease of migrants. The present data show that mandatory screening is effective and needs to include more high-risk groups. Mortality and complications including hepatocellular carcinoma are associated primarily with cirrhosis and age, but not with HBeAg status or viral load probably because modern therapies considerably reduce viral replication in almost all patients. The prognosis is exclusively determined by the risk for hepatocellular carcinoma.

Liver fibrosis score predicts mortality in heart failure patients with preserved ejection fraction.

PubMed

Yoshihisa, Akiomi; Sato, Yu; Yokokawa, Tetsuro; Sato, Takamasa; Suzuki, Satoshi; Oikawa, Masayoshi; Kobayashi, Atsushi; Yamaki, Takayoshi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Saitoh, Shu-Ichi; Takeishi, Yasuchika

2018-04-01

Heart failure with preserved ejection fraction (HFpEF) has several pathophysiological aspects, including stiffness and/or congestion of multiple organs. Poor prognosis is expected in heart failure patients with liver stiffness, which has recently been assessed by non-alcoholic fatty liver disease fibrosis score (NFS; based on aspartate aminotransferase to alanine aminotransferase ratio, platelet counts, and albumin). We aimed to investigate the impact of NFS on prognosis of HFpEF patients, with consideration for the peripheral collagen markers such as procollagen type III peptide (PIIIP), type IV collagen 7S, and hyaluronic acid. We performed a prospective observational study. Consecutive 492 hospitalized HFpEF patients were divided into four groups based on their NFS: first-fourth quartiles (n = 123). The fourth quartile group had the highest levels of PIIIP, type IV collagen 7S, hyaluronic acid, and B-type natriuretic peptide (P<0.001 each). In addition, there were significant positive correlations between PIIIP, type IV collagen 7S, hyaluronic acid, B-type natriuretic peptide, and NFS (P < 0.001 each). In the follow-up period (mean 1107 days), 93 deaths occurred. All-cause mortality increased in all four quartiles (8.1%, 12.2%, 23.6%, and 31.7%, P < 0.001). In the multivariable Cox proportional hazard analysis, NFS was an independent predictor of all-cause mortality in the HFpEF patients. NFS, a novel indicator of liver fibrosis, correlates with circulating systemic markers of fibrosis and congestion and is associated with higher all-cause mortality in HFpEF patients. NFS can be calculated simply and may be a useful tool to assess liver stiffness and prognosis in HFpEF patients. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

COX-2 overexpression in resected pancreatic head adenocarcinomas correlates with favourable prognosis

PubMed Central

2014-01-01

Background Overexpression of cyclooxygenase-2 (COX-2) has been implicated in oncogenesis and progression of adenocarcinomas of the pancreatic head. The data on the prognostic importance of COX expression in these tumours is inconsistent and conflicting. We evaluated how COX-2 overexpression affected overall postoperative survival in pancreatic head adenocarcinomas. Methods The study included 230 consecutive pancreatoduodenectomies for pancreatic cancer (PC, n = 92), ampullary cancer (AC, n = 62) and distal bile duct cancer (DBC, n = 76). COX-2 expression was assessed by immunohistochemistry. Associations between COX-2 expression and histopathologic variables including degree of differentiation, histopathologic type of differentiation (pancreatobiliary vs. intestinal) and lymph node ratio (LNR) were evaluated. Unadjusted and adjusted survival analysis was performed. Results COX-2 staining was positive in 71% of PC, 77% in AC and 72% in DBC. Irrespective of tumour origin, overall patient survival was more favourable in patients with COX-2 positive tumours than COX-2 negative (p = 0.043 in PC, p = 0.011 in AC, p = 0.06 in DBC). In tumours of pancreatobiliary type of histopathological differentiation, COX-2 expression did not significantly affect overall patient survival. In AC with intestinal differentiation COX-2 expression significantly predicted favourable survival (p = 0.003). In PC, COX-2 expression was significantly associated with high degree of differentiation (p = 0.002). COX-2 and LNR independently predicted good prognosis in a multivariate model. Conclusions COX-2 is overexpressed in pancreatic cancer, ampullary cancer and distal bile duct cancer and confers a survival benefit in all three cancer types. In pancreatic cancer, COX-2 overexpression is significantly associated with the degree of differentiation and independently predicts a favourable prognosis. PMID:24950702

Clinical Prognosis of Superior Versus Basal Segment Stage I Non-Small Cell Lung Cancer.

PubMed

Handa, Yoshinori; Tsutani, Yasuhiro; Tsubokawa, Norifumi; Misumi, Keizo; Hanaki, Hideaki; Miyata, Yoshihiro; Okada, Morihito

2017-12-01

Despite its extensive size, variations in the clinicopathologic features of tumors in the lower lobe have been little studied. The present study investigated the prognostic differences in tumors originating from the superior and basal segments of the lower lobe in patients with non-small cell lung cancer. Data of 134 patients who underwent lobectomy or segmentectomy with systematic nodal dissection for clinical stage I, radiologically solid-dominant, non-small cell lung cancer in the superior segment (n = 60) or basal segment (n = 74) between April 2007 and December 2015 were retrospectively reviewed. Factors affecting survival were assessed by the Kaplan-Meier method and Cox regression analyses. Prognosis in the superior segment group was worse than that in the basal segment group (5-year overall survival rates 62.6% versus 89.9%, p = 0.0072; and 5-year recurrence-free survival rates 54.4% versus 75.7%, p = 0.032). In multivariable Cox regression analysis, a superior segment tumor was an independent factor for poor overall survival (hazard ratio 3.33, 95% confidence interval: 1.22 to 13.5, p = 0.010) and recurrence-free survival (hazard ratio 2.90, 95% confidence interval: 1.20 to 7.00, p = 0.008). The superior segment group tended to have more pathologic mediastinal lymph node metastases than the basal segment group (15.0% versus 5.4%, p = 0.080). Tumor location was a prognostic factor for clinical stage I non-small cell lung cancer in the lower lobe. Patients with superior segment tumors had worse prognosis than patients with basal segment tumors, with more metastases in mediastinal lymph nodes. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Mortality in bullous pemphigoid and prognostic factors in 1st and 3rd year of follow-up in specialized centre in Poland.

PubMed

Kalinska-Bienias, Agnieszka; Lukowska-Smorawska, Katarzyna; Jagielski, Pawel; Kowalewski, Cezary; Wozniak, Katarzyna

2017-11-01

Bullous pemphigoid (BP) is associated with higher mortality and coexisting comorbidities, some of them affecting poor prognosis. The aim of the study was to identify prognostic factors causing greater mortality both in the 1st and 3rd year of follow-up and to determine the 1-, 2-, 3-year mortality rates, standardized mortality ratio (SMR) in Polish BP patients. All patients with BP (a cohort of 205 patients, mean age 76.2 years) diagnosed between 5 January 2000 and 10 December 2013 in a referral unit for autoimmune bullous diseases at the university hospital in Poland were included retrospectively. Mortality data were obtained from the Centre for Document Personalization at the Minister of Interior and Administration. Our original observation was that prednisone in moderate dose (0.5 mg kg -1 ) in monotherapy was an independent risk factor of fatal prognosis in the 1st year of follow-up, assessed using multivariate analysis. We confirmed the strong correlation between neurological diseases and greater mortality. Both in the 1st and 3rd year of follow-up, dementia and Parkinson disease resulted in increased mortality. We also found that arrhythmias significantly increased mortality in the 1st and 3rd year of follow-up. The prognostic factors in BP changed over time of follow-up. In the 3rd year of observation, the age above 77, longer hospitalization and BP severity were associated with greater mortality. We observed poorer prognosis in BP patients than age-matched general Polish population. The 1-, 2-, 3-year mortality rates were 22.4, 31.2, 39.5% and SMR was 3.8 (95% CI 3.4-3.7).

Neutrophil infiltration is a favorable prognostic factor in early stages of colon cancer.

PubMed

Wikberg, Maria L; Ling, Agnes; Li, Xingru; Öberg, Åke; Edin, Sofia; Palmqvist, Richard

2017-10-01

The tumor immune response has been proven critical to prognosis in colorectal cancer (CRC), but studies on the prognostic role of neutrophil infiltration have shown contradictory results. The aim of this study was to elucidate the prognostic role of infiltrating neutrophils at different intratumoral subsites and in different molecular subgroups of CRC. The relations between neutrophil infiltration and infiltration of other immune cells (T-cell and macrophage subsets) were also addressed. Expression of the neutrophil marker CD66b was assessed by immunohistochemistry in 448 archival human tumor tissue samples from patients surgically resected for CRC. The infiltration of CD66b-positive cells was semi-quantitatively evaluated along the tumor invasive front, in the tumor center, and within the tumor epithelium (intraepithelial expression). We found that poor infiltration of CD66b-positive cells in the tumor front indicated a worse patient prognosis. The prognostic significance of CD66b infiltration was found to be mainly independent of tumor molecular characteristics and maintained significance in multivariable analysis of stage I-II colon cancers. We further analyzed the prognostic impact of CD66b-positive cells in relation to other immune markers (NOS2, CD163, Tbet, FOXP3, and CD8) and found that neutrophil infiltration, even though strongly correlated to infiltration of other immune cell subsets, had additional prognostic value. In conclusion, we find that low infiltration of neutrophils in the tumor front is an independent prognostic factor for a poorer patient prognosis in early stages of colon cancers. Further studies are needed to elucidate the biological role of neutrophils in colorectal carcinogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic impact of number of resected and involved lymph nodes at complete resection on survival in non-small cell lung cancer.

PubMed

Saji, Hisashi; Tsuboi, Masahiro; Yoshida, Koichi; Kato, Yasufumi; Nomura, Masaharu; Matsubayashi, Jun; Nagao, Toshitaka; Kakihana, Masatoshi; Usuda, Jitsuo; Kajiwara, Naohiro; Ohira, Tatsuo; Ikeda, Norihiko

2011-11-01

Lymph node (LN) status is a major determinant of stage and survival in patients with lung cancer. In the 7th edition of the TNM Classification of Malignant Tumors, the number of involved LNs is included in the definition of pN factors in breast, stomach, esophageal, and colorectal cancer, and the pN status significantly correlates with prognosis. We retrospectively investigated the prognostic impact of the number of resected LNs (RLNs) and involved LNs in the context of other established clinical prognostic factors, in a series of 928 consecutive patients with non-small cell lung cancer (NSCLC) who underwent complete resection at our institution between 2000 and 2007. The mean number of RLNs was 15. There was a significant difference in the total number of RLNs categorized between less than 10 and ≥10 (p = 0.0129). Although the incidence of LN involvement was statistically associated with poor prognosis, the largest statistically significant increase in overall survival was observed between 0 to 3 and ≥4 involved LNs (hazard ratio = 7.680; 95% confidence interval = 5.051-11.655, p < 0.0001). On multivariate analysis, we used the ratio between the number of involved LNs and RLNs. The number of RLNs was found to be a strong independent prognostic factor for NSCLC (hazard ratio = 6.803; 95% confidence interval = 4.137-11.186, p < 0.0001). Complete resection including 10 or more LNs influenced survival at complete NSCLC resection. Four involved LNs seemed to be a benchmark for NSCLC prognosis. The number of involved LNs is a strong independent prognostic factor in NSCLC, and the results of this study may provide new information for determining the N category in the next tumor, node, metastasis classification.

Pretreatment dietary patterns, weight status, and head and neck squamous cell carcinoma prognosis123

PubMed Central

Arthur, Anna E; Peterson, Karen E; Rozek, Laura S; Taylor, Jeremy MG; Light, Emily; Chepeha, Douglas B; Hébert, James R; Terrell, Jeffrey E; Wolf, Gregory T

2013-01-01

Background: Few studies have evaluated the association of diet and weight status with head and neck cancer outcomes. Objective: The purpose of this study was to determine whether pretreatment dietary patterns and weight status are associated with head and neck cancer prognosis. Design: This was a longitudinal study of 542 patients with newly diagnosed head and neck cancer who completed food-frequency questionnaires and health surveys before treatment. Clinical data were abstracted from medical records and the Social Security Death Index. Dietary patterns were identified by using principal component analysis. Cox proportional hazard models were used to examine the association of derived dietary patterns (fit by quintiles of exposure) and weight status with time to recurrence and survival, with control for covariates. Results: During the study period, there were 229 deaths and 184 recurrences. Two dietary patterns were identified: a whole-foods pattern (characterized by high intakes of vegetables, fruit, fish, poultry, and whole grains) and a Western pattern (characterized by high intakes of red and processed meats, refined grains, potatoes, and French fries). In multivariable analyses, significantly fewer deaths were observed in subjects most adherent to the whole-foods pattern (HR: 0.56; 95% CI: 0.34, 0.92; P-trend = 0.01). Subjects classified as overweight or obese had significantly fewer deaths (HR: 0.65; 95% CI: 0.49, 0.85; P = 0.001) and recurrences (HR: 0.70; 95% CI: 0.52, 0.95; P = 0.02) than did normal-weight or underweight subjects. Conclusion: Consumption of a diet rich in vegetables, fruit, fish, poultry, and whole grains and being overweight before diagnosis with head and neck cancer are associated with a better prognosis. PMID:23269814

Pretreatment dietary patterns, weight status, and head and neck squamous cell carcinoma prognosis.

PubMed

Arthur, Anna E; Peterson, Karen E; Rozek, Laura S; Taylor, Jeremy M G; Light, Emily; Chepeha, Douglas B; Hébert, James R; Terrell, Jeffrey E; Wolf, Gregory T; Duffy, Sonia A

2013-02-01

Few studies have evaluated the association of diet and weight status with head and neck cancer outcomes. The purpose of this study was to determine whether pretreatment dietary patterns and weight status are associated with head and neck cancer prognosis. This was a longitudinal study of 542 patients with newly diagnosed head and neck cancer who completed food-frequency questionnaires and health surveys before treatment. Clinical data were abstracted from medical records and the Social Security Death Index. Dietary patterns were identified by using principal component analysis. Cox proportional hazard models were used to examine the association of derived dietary patterns (fit by quintiles of exposure) and weight status with time to recurrence and survival, with control for covariates. During the study period, there were 229 deaths and 184 recurrences. Two dietary patterns were identified: a whole-foods pattern (characterized by high intakes of vegetables, fruit, fish, poultry, and whole grains) and a Western pattern (characterized by high intakes of red and processed meats, refined grains, potatoes, and French fries). In multivariable analyses, significantly fewer deaths were observed in subjects most adherent to the whole-foods pattern (HR: 0.56; 95% CI: 0.34, 0.92; P-trend = 0.01). Subjects classified as overweight or obese had significantly fewer deaths (HR: 0.65; 95% CI: 0.49, 0.85; P = 0.001) and recurrences (HR: 0.70; 95% CI: 0.52, 0.95; P = 0.02) than did normal-weight or underweight subjects. Consumption of a diet rich in vegetables, fruit, fish, poultry, and whole grains and being overweight before diagnosis with head and neck cancer are associated with a better prognosis.

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

PubMed

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

2018-01-10

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

[Clinical characteristics and medium-term prognosis of patients with heart failure and preserved systolic function. Do they differ in systolic dysfunction?].

PubMed

Ojeda, Soledad; Anguita, Manuel; Muñoz, Juan F; Rodríguez, Marcos T; Mesa, Dolores; Franco, Manuel; Ureña, Isabel; Vallés, Federico

2003-11-01

To assess the prevalence, clinical profile and medium-term prognosis in patients with heart failure and preserved systolic ventricular function compared to those with systolic dysfunction. 153 patients were included, 62 with preserved systolic ventricular function (left ventricular ejection fraction > or = 45%) and 91 with impaired systolic ventricular function (left ventricular ejection fraction < 45%). The mean follow-up period was 25 10 months. Mean age was similar (66 10 vs. 65 10; p = 0.54). There was a higher proportion of women among patients with preserved systolic function (53% vs. 28%; p < 0.01). Ischemic and idiopathic cardiomyopathy were the most common causes of heart failure in patients with systolic dysfunction, whereas valvular disease and hypertensive cardiopathy were the most common in patients with preserved systolic function. Angiotensin-converting enzyme inhibitors and beta-blockers were more often prescribed in patients with impaired systolic ventricular function (86% vs. 52%; p < 0.01 and 33% vs. 11%; p < 0.01, respectively). There were no differences between the groups in terms of mortality rate (37% vs. 29%), readmission rate for other causes (29% vs. 23%), readmission rate for heart failure (45% vs. 45%), cumulative survival (51% vs. 62%) and the likelihood of not being readmitted for heart failure (50% vs. 52%). In the multivariate analysis, left ventricular ejection fraction was not a predictor of death or readmission because of heart failure. In a large proportion of patients with heart failure, systolic ventricular function is preserved. Despite the clinical differences between patients with preserved and impaired systolic ventricular function, the medium-term prognosis was similar in both groups.

Macroscopic appearance of Type IV and giant Type III is a high risk for a poor prognosis in pathological stage II/III advanced gastric cancer with postoperative adjuvant chemotherapy

PubMed Central

Yamashita, Keishi; Ema, Akira; Hosoda, Kei; Mieno, Hiroaki; Moriya, Hiromitsu; Katada, Natsuya; Watanabe, Masahiko

2017-01-01

AIM To evaluate whether a high risk macroscopic appearance (Type IV and giant Type III) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage II/III (pStage II/III) gastric cancer. METHODS One hundred and seventy-two advanced gastric cancer (defined as pT2 or beyond) patients with pStage II/III who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival (RFS) (35.7%) and overall survival (OS) (34%) than an average risk appearance (P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13th Japanese Gastric Cancer Association (JGCA) pT (P = 0.01), but not with the 13th JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13th JGCA pStage (P < 0.0001) and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified high-risk macroscopic appearance (P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13th JGCA stage in pStage II/III advanced gastric cancer. PMID:28451064

[Factors influencing the prognosis of patent ductus arteriosus in very low birth weight infants].

PubMed

Wang, Chen-Hong; Shi, Li-Ping; Ma, Xiao-Lu; Luo, Fang; Chen, Zheng; Lin, Hui-Jia; DU, Li-Zhong

2016-08-01

To investigate the factors influencing the prognosis of patent ductus arteriosus (PDA) in very low birth weight (VLBW) infants. A total of 194 VLBW infants who were admitted from January 2012 to December 2014 were enrolled as study subjects. According to cardiac ultrasound findings and treatment outcome, these infants were divided into non-PDA group, spontaneous closure group, pharmaceutical closure group, and surgical closure group. Their clinical and echocardiographic characteristics were analyzed. The spontaneous closure rate of PDA was 58.7%. The spontaneous closure group showed significantly higher gestational age, birth weight, and proportion of small-for-gestational-age infants than the pharmaceutical and surgical closure groups (P<0.05). The pharmaceutical and surgical closure groups had a significantly higher incidence rate of neonatal respiratory distress syndrome and a significantly higher proportion of infants who were given pulmonary surfactant (PS) than the spontaneous closure group (P<0.05). During different periods of time, the spontaneous closure group had a significantly smaller ductus arteriosus diameter than the pharmaceutical and surgical closure groups (P<0.05). The multivariate logistic regression analysis showed that gestational age, application of PS, and ductus arteriosus diameter at 48 hours were significantly associated with the prognosis of PDA. The major transductal flow pattern in the spontaneous closure group was closing pattern, while in the pharmaceutical and surgical closure groups, the main flow patterns were pulmonary hypertension and growing patterns within 48 hours and growing pattern on days 4 and 7. The VLBW infants have a high spontaneous closure rate of PDA. A decreased closure rate of PDA is associated with the lower gestational age and the application of PS. PDA with a large ductus arteriosus diameter and a growing or pulsatile flow pattern cannot easily achieve spontaneous closure.

Clinical impact of sarcopenia on prognosis in pancreatic ductal adenocarcinoma: A retrospective cohort study.

PubMed

Ninomiya, Go; Fujii, Tsutomu; Yamada, Suguru; Yabusaki, Norimitsu; Suzuki, Kojiro; Iwata, Naoki; Kanda, Mitsuro; Hayashi, Masamichi; Tanaka, Chie; Nakayama, Goro; Sugimoto, Hiroyuki; Koike, Masahiko; Fujiwara, Michitaka; Kodera, Yasuhiro

2017-03-01

To investigate the impact of the body composition such as skeletal muscle, visceral fat and body mass index (BMI) on patients with resected pancreatic ductal adenocarcinoma (PDAC). A total of 265 patients who underwent curative surgery for PDAC were examined in this study. The total skeletal muscle and fat tissue areas were evaluated in a single image obtained at the third lumber vertebra during a preoperative computed tomography (CT) scan. The patients were assigned to either the sarcopenia or non-sarcopenia group based on their skeletal muscle index (SMI) and classified into high visceral fat area (H-VFA) or low VFA (L-VFA) groups. The association of clinicopathological features and prognosis with the body composition were statistically analyzed. There were 170 patients (64.2%) with sarcopenia. The median survival time (MST) was 23.7 months for sarcopenia patients and 25.8 months for patients without sarcopenia. The MST was 24.4 months for H-VFA patients and 25.8 months for L-VFA patients. However, sarcopenia patients with BMI ≥22 exhibited significantly poorer survival than patients without sarcopenia (MST: 19.2 vs. 35.4 months, P = 0.025). There was a significant difference between patients with and without sarcopenia who did not receive chemotherapy (5-year survival rate: 0% vs. 68.3%, P = 0.003). The multivariate analysis revealed that tumor size, positive dissected peripancreatic tissue margin, and sarcopenia were independent prognostic factors. Sarcopenia is an independent prognostic factor in PDAC patients with a BMI ≥22. Therefore, evaluating skeletal muscle mass may be a simple and useful approach for predicting patient prognosis. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

[Effect of educational level on the prognosis of acute myocardial infarction].

PubMed

Nazzal, Carolina; Corbalán, Ramón; Díaz, Claudia; Sepúlveda, Pablo; Schacht, Eliana

2015-07-01

Socioeconomic status is associated with cardiovascular mortality. To evaluate the effect of educational level, on the prognosis of patients with acute myocardial infarction in Chile. Cohort study of 3,636 patients aged 63.1 ± 13.2 years, 27% women, hospitalized in 16 centers participating in the Chilean Myocardial Infarction Registry (GEMI) between 2009 and 2012. Vital status was obtained from the National Mortality Database. Patients were divided, according to educational level, in four groups, namely none (no formal education), basic (< 8 years), secondary (8-12 years) and tertiary (> 12 years). Crude and adjusted (age, sex, cardiovascular risk factors and treatments) hazard ratios (HR) were estimated using Cox regression models. The distribution by educational level was 3.2% none, 31.8% basic, 43.0% secondary and 22.0% tertiary. During a median follow-up period of 22 months (interquartile range 11-37 years), 631 patients died (17.3%), of whom 198 died during hospitalization (5.5%). The 30 day case-fatality rate according to educational level was 3.4% in tertiary, 4.7% in secondary, 11.9% in basic, 19.1% in none (p < 0.0001). Among patients surviving the first 30 days, the case-fatality rate was 4.4%, 8.6%, 14.6% and 27.0%, respectively (p < 0.0001). The increased risk of death for groups with lower education compared with individuals with tertiary education, persisted in the multivariate analysis with a hazard ratio for secondary education 1.58 (95% confidence intervals (CI), 1.18-2.10); for basic education 1.90 (95% CI, 1.41-2.47) and for none 3.50 (95% CI, 2.35-5.21). A lower educational level was associated with a worse prognosis in patients with myocardial infarction, even after controlling for potential confounding factors.

Sleep, mental health status, and medical errors among hospital nurses in Japan.

PubMed

Arimura, Mayumi; Imai, Makoto; Okawa, Masako; Fujimura, Toshimasa; Yamada, Naoto

2010-01-01

Medical error involving nurses is a critical issue since nurses' actions will have a direct and often significant effect on the prognosis of their patients. To investigate the significance of nurse health in Japan and its potential impact on patient services, a questionnaire-based survey amongst nurses working in hospitals was conducted, with the specific purpose of examining the relationship between shift work, mental health and self-reported medical errors. Multivariate analysis revealed significant associations between the shift work system, General Health Questionnaire (GHQ) scores and nurse errors: the odds ratios for shift system and GHQ were 2.1 and 1.1, respectively. It was confirmed that both sleep and mental health status among hospital nurses were relatively poor, and that shift work and poor mental health were significant factors contributing to medical errors.

Prognostic factors of Bell's palsy and Ramsay Hunt syndrome

PubMed Central

Cai, Zhengyi; Li, Huijing; Wang, Xun; Niu, Xiaoting; Ni, Peiqi; Zhang, Wanli; Shao, Bei

2017-01-01

Abstract The aim of this study was to compare clinical characteristics, electroneurography (ENoG) results, and functional outcomes of patients with Bell's palsy (BP) and Ramsay Hunt syndrome (RHS). Around 57 patients with BP and 23 patients with RHS were enrolled in this study from January 2010 and September 2015. Both clinical characteristics and ENoG results were recorded at hospital admission. The evaluations of functional outcomes were conducted with House–Brackmann (H-B) grading system at 6-month follow-up. There were no significant differences in age, gender proportion, initial H-B grades, time before commencement of treatment and the presence of comorbid disease in 2 groups. However, the final H-B grades at 6-month follow-up were significantly better in BP patients than RHS patients. The results of ENoG showed that degeneration index (DI) was significantly higher in the RHS group than the BP group. But no significant difference was found in the value of prolonged latency time (PLT) between the 2 groups. In multivariate analysis, age and ENoG DI were independently associated with functional outcome of recovery in the BP group (OR 0.167, 95% CI 0.038–0.622, P = 0.009 and OR 0.289 95% CI 0.107–0.998, P = 0.050, respectively). However, in the RHS group, only ENoG DI was related to the final H-B grades (OR 0.067, 95% CI 0.005–0.882, P = 0.040). Spearman's rank correlation analysis showed that higher age and ENoG DI were related to poorer prognosis in 2 groups (P < 0.05). PLT was related to functional outcomes only in the BP group (rs = 0.460, P < 0.001). The receiver operating characteristic (ROC) of ENoG DI analysis revealed that the cutoff value was 67.0% for BP prognosis and 64.5% for RHS prognosis. What's more, patients with hypertension or diabetes mellitus had both higher final H-B grade and ENoG DI than those without the same comorbidity. Patients with RHS had poorer prognosis than those with BP. Some factors including age, ENoG DI, and the presence of disease influenced recovery from BP and RHS. The present study demonstrated that BP patients with ENoG DI < 67.0% and RHS patients with ENoG DI < 65.5% had a greater opportunity for recovery within half a year. PMID:28079835

Spindle cell carcinoma of the esophagus

PubMed Central

Zhang, Baihua; Xiao, Qin; Yang, Desong; Li, Xu; Hu, Jun; Wang, Yonggang; Wang, Wenxiang

2016-01-01

Abstract This study conducted a retrospective multicenter analysis to investigate the clinicopathological features, optimal therapeutic strategy, and prognosis of spindle cell carcinoma (SpCC) of the esophagus. A total of 71 patients with esophageal SpCC from 3 large cancer centers in China were systematically analyzed. All patients received curative resection, 13 patients received adjuvant radiotherapy and 15 patients received adjuvant combination chemotherapy. Additionally, a total of 1852 patients with typical esophageal SCC (SCC) were selected as controls in this study. SpCC mostly presented as a polypoid appearance (66.2%), and the surrounding mucosa showed high-grade hyperplasia or superficial SCC in 31 cases (43.7%). Two patients even had extensive carcinoma in situ that spread to the resection margins. Patients in the SpCC group were more likely to present with stage I lesions compared with those in the typical SCC group (33.8% vs 8.0%, P < 0.001). Although the percentage of T1/2 lesions was higher in the SpCC group than in the typical SCC group (67.6% vs 29.7%, P < 0.001), both groups had similar rates of locoregional lymphatic metastases (45.1% vs 48.4%, P = 0.578). The median survival time and 5-year overall survival of the SpCC group was 43 months and 44.8%, respectively, higher than 37.5 months and 38.3%, respectively, for the typical SCC group (P = 0.044). In univariate analysis, the macroscopical type and pathological T, N, and TNM stages had a statistically significant impact on the prognosis of SpCC after curative resection. However, only the TNM stage (hazard ratio, 2.708; 95% confidence interval, 1.786–4.105, P < 0.001) was identified as an independent prognostic factor in multivariate analysis. The 5-year OS of SpCC in stages I (79.8%) and II (39.7%) were significantly longer than that of stages III/IV (16.2%) (P < 0.001 and P = 0.012). As those SpCC cases that received chemoradiotherapy were in more advanced stages, their prognosis was still worse than SpCC patients who did not receive chemoradiotherapy even after such treatment (P = 0.042, 0.010, respectively). SpCC shows a highly aggressive tendency of lymphatic spread, although it does not tend to infiltrate deeply into the esophageal wall. Compared with typical SCC that also underwent esophagectomy with extended lymphadenectomy, SpCC may achieve a better survival rate. Further investigation is warranted to examine the effect of postoperative chemoradiotherapy on the prognosis of SpCC. PMID:27631227

Clinical correlates and prognostic value of different metastatic sites in patients with malignant melanoma of the skin: a SEER database analysis.

PubMed

Abdel-Rahman, Omar

2018-03-01

Population-based data on the clinical correlates and prognostic value of the pattern of metastases among patients with cutaneous melanoma are needed. Surveillance, Epidemiology and End Results (SEER) database (2010-2013) has been explored through SEER*Stat program. For each of six distant metastatic sites (bone, brain, liver, lung, distant lymph nodes, and skin/subcutaneous), relevant correlation with baseline characteristics were reported. Survival analysis has been conducted through Kaplan-Meier analysis, and multivariate analysis has been conducted through a Cox proportional hazard model. A total of 2691 patients with metastatic cutaneous melanoma were identified in the period from 2010 to 2013. Patients with isolated skin/subcutaneous metastases have the best overall and melanoma-specific survival (MSS) followed by patients with isolated distant lymph node metastases followed by patients with isolated lung metastases. Patients with isolated liver, bone, or brain metastases have the worst overall and MSS (p < .0001 for both end points). Multivariate analysis revealed that age more than 70 at diagnosis (p = .012); multiple sites of metastases (p <.0001), no surgery to the primary tumor (p <.0001), and no surgery to the metastatic disease (p < .0001) were associated with worse overall survival (OS). For MSS, nodal positivity (p = .038), multiple sites of metastases (p < .0001), no surgery to the primary tumor (p < .0001), and no surgery to the metastatic disease (p < .0001) were associated with worse survival. The prognosis of metastatic cutaneous melanoma patients differs considerably according to the site of distant metastases. Further prospective studies are required to evaluate the role of local treatment in the management of metastatic disease.

Tumour location within the breast: Does tumour site have prognostic ability?

PubMed

Rummel, Seth; Hueman, Matthew T; Costantino, Nick; Shriver, Craig D; Ellsworth, Rachel E

2015-01-01

Tumour location within the breast varies with the highest frequency in the upper outer quadrant (UOQ) and lowest frequency in the lower inner quadrant (LIQ). Whether tumour location is prognostic is unclear. To determine whether tumour location is prognostic, associations between tumour site and clinicopathological characteristics were evaluated. All patients enrolled in the Clinical Breast Care Project whose tumour site-UOQ, upper inner quadrant (UIQ), central, LIQ, lower outer quadrant (LOQ)-was determined by a single, dedicated breast pathologist were included in this study. Patients with multicentric disease (n = 122) or tumours spanning multiple quadrants (n = 381) were excluded from further analysis. Clinicopathological characteristics were analysed using chi-square tests for univariate analysis with multivariate analysis performed using principal components analysis (PCA) and multiple logistic regression. Significance was defined as P < 0.05. Of the 980 patients with defined tumour location, 30 had bilateral disease. Tumour location in the UOQ (51.5%) was significantly higher than in the UIQ (15.6%), LOQ (14.2%), central (10.6%), or LIQ (8.1%). Tumours in the central quadrant were significantly more likely to have higher tumour stage (P = 0.003) and size (P < 0.001), metastatic lymph nodes (P < 0.001), and mortality (P = 0.011). After multivariate analysis, only tumour size and lymph node status remained significantly associated with survival. Evaluation of tumour location as a prognostic factor revealed that although tumours in the central region are associated with less favourable outcome, these associations are not independent of location but rather driven by larger tumour size. Tumours in the central region are more difficult to detect mammographically, resulting in larger tumour size at diagnosis and thus less favourable prognosis. Together, these data demonstrate that tumour location is not an independent prognostic factor.

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

Morganti, Alessio G.; Unit of Radiotherapy, Unit of General Oncology, Fondazione Giovanni Paolo II, Campobasso; Falconi, Massimo

Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462more » patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.« less

Computer-aided prognosis on breast cancer with hematoxylin and eosin histopathology images: A review.

PubMed

Chen, Jia-Mei; Li, Yan; Xu, Jun; Gong, Lei; Wang, Lin-Wei; Liu, Wen-Lou; Liu, Juan

2017-03-01

With the advance of digital pathology, image analysis has begun to show its advantages in information analysis of hematoxylin and eosin histopathology images. Generally, histological features in hematoxylin and eosin images are measured to evaluate tumor grade and prognosis for breast cancer. This review summarized recent works in image analysis of hematoxylin and eosin histopathology images for breast cancer prognosis. First, prognostic factors for breast cancer based on hematoxylin and eosin histopathology images were summarized. Then, usual procedures of image analysis for breast cancer prognosis were systematically reviewed, including image acquisition, image preprocessing, image detection and segmentation, and feature extraction. Finally, the prognostic value of image features and image feature-based prognostic models was evaluated. Moreover, we discussed the issues of current analysis, and some directions for future research.

The effect of molecular subtype and body mass index on neo-adjuvant chemotherapy in breast cancer patients.

PubMed

Iwase, Toshiaki; Nakamura, Rikiya; Yamamoto, Naohito; Yoshi, Atushi; Itami, Makiko; Miyazaki, Masaru

2014-06-01

The aim of the present study was to analyze the effect of subtype and body mass index (BMI) on neo-adjuvant chemotherapy (NAC) and postoperative prognosis. Two-hundred and forty nine patients who underwent surgery after NAC were included. A multivariate analysis and survival analysis were used to clarify the relationship between BMI, subtype, and NAC. In the logistic regression model, the pCR rate had a significant relationship with the subtype and tumor stage. In the non-pCR group, more overweight patients had significantly a worse disease-free survival (DFS) compared to normal range patients (Log lank test, p < 0.05). In the Cox proportional hazards model, subtype and tumor stage were significantly associated with decreased DFS. In conclusion, patients with the ER (+), HER (-) type and a high BMI had a high risk for recurrence when they achieved non-pCR after NAC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Plasma serotonin level is a predictor for recurrence and poor prognosis in colorectal cancer patients.

PubMed

Xia, Yan; Wang, Dawei; Zhang, Nan; Wang, Zhihao; Pang, Li

2018-02-01

To investigate the prognostic value of plasma serotonin levels in colorectal cancer (CRC). Preoperative plasma serotonin levels of 150 healthy control (HC) cases, 150 benign colorectal polyp (BCP) cases, and 176 CRC cases were determined using radioimmunoassay assay. Serotonin levels were compared between HC, BCP, and CRC cases, and those in CRC patients were related to 5-year outcome. Plasma serotonin levels were markedly higher in CRC patients than in either HCs or BCP cases. An elevated serotonin level was significantly associated with advanced tumor node metastasis. Receiver operating characteristic curve analysis showed that the level of serotonin had a high predictive value for disease recurrence and mortality. Multivariate analysis revealed that high serotonin level was significantly associated with poor recurrence-free survival and overall survival. Our results suggest that a high peri-operative plasma serotonin level is useful as a prognostic biomarker for CRC recurrence and poor survival. © 2017 Wiley Periodicals, Inc.

{sup 1}H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis

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

Zhang, Ying; Lin, Lianjie; Xu, Yanbin

2013-04-19

Highlights: •Twenty ulcerative colitis patients and nineteen healthy controls were enrolled. •Increased 3-hydroxybutyrate, glucose, phenylalanine, and decreased lipid were found. •We report early stage diagnosis of ulcerative colitis using NMR-based metabolomics. -- Abstract: Ulcerative colitis (UC) has seriously impaired the health of citizens. Accurate diagnosis of UC at an early stage is crucial to improve the efficiency of treatment and prognosis. In this study, proton nuclear magnetic resonance ({sup 1}H NMR)-based metabolomic analysis was performed on serum samples collected from active UC patients (n = 20) and healthy controls (n = 19), respectively. The obtained spectral profiles were subjected tomore » multivariate data analysis. Our results showed that consistent metabolic alterations were present between the two groups. Compared to healthy controls, UC patients displayed increased 3-hydroxybutyrate, β-glucose, α-glucose, and phenylalanine, but decreased lipid in serum. These findings highlight the possibilities of NMR-based metabolomics as a non-invasive diagnostic tool for UC.« less

Multifactorial analysis of factors affecting recurrence of stroke in Japan.

PubMed

Omori, Toyonori; Kawagoe, Masahiro; Moriyama, Michiko; Yasuda, Takeshi; Ito, Yasuhiro; Hyakuta, Takeshi; Nagatsuka, Kazuyuki; Matsumoto, Masayasu

2015-03-01

Data on factors affecting stroke recurrence are relatively limited. The authors examined potential factors affecting stroke recurrence, retrospectively. The study participants were 1087 patients who were admitted to stroke centers suffering from first-ever ischemic stroke and returned questionnaires with usable information after discharge. The authors analyzed the association between clinical parameters of the patients and their prognosis. Recurrence rate of during an average of 2 years after discharge was 21.3%, and there were differences among stroke subtypes. It was found that the disability level of the patients after discharge correlated well with the level at discharge (r s = 0.66). Multivariate logistic regression analysis of the data shows that modified Rankin Scale score, National Institute of Health Stroke Scale score, gender, age, and family history had statistically significant impacts on stroke recurrence, and the impact was different depending on subtypes. These findings suggest that aggressive and persistent health education for poststroke patients and management of risk factors are essential to reduce stroke recurrence. © 2012 APJPH.

Epidermal growth factor (EGF) receptor-ligand based molecular staging predicts prognosis in head and neck squamous cell carcinoma partly due to deregulated EGF- induced amphiregulin expression.

PubMed

Gao, Jian; Ulekleiv, Camilla H; Halstensen, Trond S

2016-09-26

Increased expression of epidermal growth factor receptor (EGFR) and its ligands is associated with poor prognosis and chemoresistance in many carcinoma types, but its role in head and neck squamous cell carcinoma (HNSCC) is unclear. Our aim was to clarify whether mRNA expression of EGFR-ligands was linked to prognosis and cisplatin resistance, and if so, which ligand was most important and how was the expression regulated. To examine the prognostic effect of EGFR-ligand expression, we analyzed tumorous mRNA expression in 399 HNSCC patients. The intracellular signaling pathways controlling epidermal growth factor (EGF)-induced amphiregulin (AREG) expression were examined in three oral squamous cell carcinoma (OSCC) cell lines. Effect of AREG on cisplatin resistance was examined by viability assays in four-, and by association in 11 OSCC cell lines. The patients were divided into five groups according to the median mRNA expression levels of four EGFR ligands, i.e. AREG, EGF, heparin-binding EGF-like growth factor (HBEGF) and beta-cellulin (BTC). The number of increased-expressed EGFR-ligands were progressively correlated to five-year survival, even in advanced TNM-stage IV patients, where five-year mortality increased from 26 % if tumor expressed none to one EGFR-ligand, to 45 % in three to four ligand expressing tumors. Thus, staging the tumor according to these EGFR-ligand mRNA expression pattern completely out performed TNM staging in predicting prognosis. Multivariate analysis identified AREG as the dominating predictor, and AREG was overexpressed in OSCC compared to tumors from other sites. Both EGF and HBEGF stimulation induced strong AREG increase in OSCC cell lines, which was partially mediated by the extracellular signal-regulated kinase 1/2 pathway, and negatively regulated by p38, c-Jun N-terminal kinase, and phosphoinositide-3 kinase. Although increased AREG mRNA expression predicted unfavorable prognosis in platinum treated HNSCC patients, AREG did not mediate cisplatin resistance in the OSCC cell lines. Increased tumorous mRNA expression of four EGFR ligands was progressively associated with poor prognosis in HNSCC. Thus, EGFR-ligands mRNA expression pattern may be a new prognostic biomarker. The tightly regulated EGF-induced AREG mRNA expression was partly lost in the OSCC cell lines and restoring its regulation may be a new target in cancer treatment. Not applicable as the clinical data of the 498 HNSCC patients and their mRNA expression profiles were collected from the open TCGA database: http://cancergenome.nih.gov/cancersselected/headandneck .

Prognostic significance of the allelic loss of the BRCA1 gene in colorectal cancer

PubMed Central

Garcia, J M; Rodriguez, R; Dominguez, G; Silva, J M; Provencio, M; Silva, J; Colmenarejo, A; Millan, I; Muñoz, C; Salas, C; Coca, S; España, P; Bonilla, F

2003-01-01

Background: Survival at the intermediate stage of colorectal cancer (CRC) is less predictable than in the early and advanced stages. Several genetic markers possibly involved in growth and progression of CRC can be used for prognosis. Aims: This study investigated the proportion of allelic loss (loss of heterozygosity (LOH)) at the BRCA1 locus in sporadic CRC and its value in patient prognosis. Patients and methods: A total of 314 patients were investigated for LOH at the BRCA1 locus using polymerase chain reaction by means of three intragenic polymorphic microsatellite markers. Allelic losses were compared with clinicopathological characteristics of patients, recurrence rate, disease free survival (DFS), and overall survival. Results: Twenty six patients were excluded because of microsatellite instability. Of the remaining 288 cases, 244 (84.7%) were informative, with 97 (39.8%) patients bearing BRCA1 LOH. Recurrence rate was higher in patients with LOH (p = 0.0003), and DFS was 73.3% (SEM 5.7) at five years in patients without LOH, and 49.2% (7.1) in cases with positive allelic loss (p = 0.0004). Retention of alleles at the BRCA1 locus was associated with a favourable DFS in stages I and II (p<0.05). The presence of LOH was also significantly associated with short overall survival (p = 0.02). Multivariate analysis in the complete series showed that stage (p = 0.006) and lymph node metastases (⩾4 nodes, p = 0.0001; 1–3 nodes, p = 0.038) were independent prognostic factors. However, multivariate study by stages revealed that BRCA1 LOH was an independent prognostic factor in stages I and II (p = 0.001). Conclusions: BRCA1 LOH is a molecular alteration present in CRC, with unfavourable repercussions for overall survival, that could be considered as an outstanding independent prognostic factor in stages I and II. PMID:14633957

Prognostic value of cancer stem cell marker CD133 expression in pancreatic ductal adenocarcinoma (PDAC): a systematic review and meta-analysis.

PubMed

Li, Xiaoping; Zhao, Haojie; Gu, Jianchun; Zheng, Leizhen

2015-01-01

CD133 is one of the most commonly used markers of pancreatic cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. Although the expression of CD133 has been reported to correlate with poor prognosis of PDAC in most literatures, some controversies still exist. In this study, we aimed to investigate the correlation between CD133 expression and prognosis and clinicopathological features in PDAC. A search in the Medline, EMBASE and Chinese CNKI (China National Knowledge Infrastructure) database (up to 1 March 2015) was performed using the following keywords pancreatic cancer, CD133, AC133, prominin-1 etc. Data from eligible studies were extracted and included into meta-analysis using a random effects model. Outcomes included overall survival and various clinicopathological features. We performed a final analysis of 723 patients from 11 evaluable studies for prognostic value and 687 patients from 12 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD133 for overall survival in PDAC was 0.58 (95% confidence interval (CI): 0.49-0.67) by univariate analysis and 0.73 (95% CI: 0.52-1.03) by multivariate analysis. With respect to clinicopathological features, CD133 overexpression by immunohistochemistry (IHC) method was closely correlated with clinical TNM stage (TNM stage III+IV, OR=0.32, 95% CI: 0.19-0.54), tumor differentiation (poor differentiation, OR=0.56, 95% CI: 0.37-0.83), and lymph node metastasis (N1, 3.15, 95% CI: 1.56-6.36) in patients with PDAC. Our meta-analysis results suggest that CD133 is an efficient prognostic factor in PDAC. Overexpression of CD133 was significantly associated with clinical TNM stage, tumor differentiation and lymph node metastasis.

Clinical Characteristics of Malignant Melanoma in Southwest China: A Single-Center Series of 82 Consecutive Cases and a Meta-Analysis of 958 Reported Cases

PubMed Central

Huang, Hui; Zhai, Zhifang; Shen, Zhu; Lin, Hui

2016-01-01

Purpose The present study determined the clinical characteristics and prognostic factors in patients with malignant melanoma based on a series of 82 cases from January 2009 to December 2014 in Southwest Hospital and a meta-analysis (including 12 articles) involving 958 patients in China. Materials and methods The database elements included basic demographic data and prognosticators which were extracted from medical records. Statistical analyses of survival, and multivariate analyses of factors associated with survival were performed using the Kaplan—Meier method, and the Cox proportional hazard model, respectively. Literatures were identified through systematic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and Weipu database (VIP) database for the period from inception to December 2015. The meta-analysis was conducted using R 3.1.1 meta-analysis software Results In this series of 82 cases, the median age of the patients was 57.50 years. Melanoma was located in the foot in 79% of patients. Sixty-one patients (74.4%) were classified as stage II-III. Thirty-two patients (39.0%) had acral malignant melanoma, and 31 patients (37.8%) had nodular malignant melanoma. The clinical characteristics of melanoma were similar to those in areas outside southwest China (from results of the meta-analysis). The median survival time was 29.50 months. The 1-year, 3-year, and 5-year survival rates were 84.1%, 39.0% and 10.9%, respectively. COX regression following multi-factor analysis showed that ulcer, tumor boundary and lymph node metastasis were associated with prognosis. Conclusions The clinical characteristics of melanoma in Chinese were different from those in Caucasians. Ulcer, tumor margins, and lymph node metastasis were significantly associated with prognosis. Immune therapy may prolong the median survival time of patients with acral melanoma, nodular melanoma, or stage I-III disease, although these differences were not statistically significant. PMID:27861496

Astrocyte elevated gene-1: a novel independent prognostic biomarker for metastatic ovarian tumors.

PubMed

Li, Cong; Chen, Kexin; Cai, Jianping; Shi, Qing-Tao; Li, Yinghong; Li, Lejing; Song, Hongtao; Qiu, Huilei; Qin, Yu; Geng, Jing-Shu

2014-04-01

Astrocyte elevated gene-1 (AEG-1), a novel tumor-associated gene, was found overexpressed in many tumors. Therefore, our purpose is to estimate whether AEG-1 overexpression is a novel predictor of prognostic marker in metastatic ovarian tumors. Immunohistochemistry was used to estimate AEG-1 overexpression in metastatic ovarian tumors from 102 samples. The association between AEG-1 expression and prognosis was estimated by univariate and multivariate survival analyses with Cox regression. The log-rank test was used to identify any differences in the prognosis between the two groups. The median overall and progression-free survival rates of patients with tumors from gastrointestinal tract origin were 0.97 and 0.51 years, respectively. Similarly, survival rates of patients with tumors of breast origin were 2.68 and 1.96 years (P < 0.0001). Of 102 patients, 77 had high expression, and AEG-1 overexpression had a significant link of prognosis in metastatic ovarian patients (P < 0.01). On the other hand, medians of overall survival and progression-free survival of patients with tumors of gastrointestinal tract origin were significantly lower than those of patients with tumors of breast origin (P < 0.0001). Patients with metastatic ovarian tumors of breast origin had significantly better prognosis than those with the tumors from gastrointestinal tract primary malignancies. It is suggested that AEG-1 overexpression might be an independent prognostic marker of metastatic ovarian tumors.

Prognostic significance of B7-H4 expression in matched primary pancreatic cancer and liver metastases.

PubMed

Qian, Yun; Sang, Yiwen; Wang, Frederick X C; Hong, Bo; Wang, Qi; Zhou, Xinhui; Weng, Tianhao; Wu, Zhigang; Zheng, Min; Zhang, Hong; Yao, Hangping

2016-11-01

Liver metastasis development in pancreatic cancer patients is common and confers a poor prognosis. Clinical relevance of biomarker analysis in metastatic tissue is necessary. B7-H4 has an inhibitory effect on T cell mediated response and may be involved in tumor development. Although B7-H4 expression has been detected in pancreatic cancer, its expression in liver metastases from pancreatic cancer is still unknown. In this study, overall 43 pancreatic cancer liver metastases (with matched primaries in 15/43 cases) and 57 pancreatic cancer cases without liver metastases or other distant metastases were analyzed for their expression of B7-H4 by immunohistochemistry. Survival curves and log-rank tests were used to test the association of B7-H4 expression with survival. B7-H4 was highly expressed in 28 (65.1%) of the 43 liver metastases and 9 (60.0%) of the 15 matched primary tumors. The expression of B7-H4 in liver metastases was significantly higher than in the matched primary tumors (p < 0.05). Patients with high B7-H4 expression in their primary pancreatic cancer had higher risk of developing liver metastases (p < 0.05). In univariate analysis, B7-H4 expression was significantly associated with the risk of death (p < 0.05). And the multivariate analysis identified that B7-H4 was an independent prognostic indicator (p < 0.05). Our results revealed B7-H4 to be associated with poor prognosis in patients with pancreatic cancer liver metastasis. B7-H4 may promote pancreatic cancer metastasis and was promising to be a potential prognostic indicator of pancreatic cancer.

Osteoporosis Self-Assessment Tool for Asians Can Predict Neurologic Prognosis in Patients with Isolated Moderate Traumatic Brain Injury

PubMed Central

Chan, Hon-Man; Huang, Shiuh-Lin; Lin, Chih-Lung; Kwan, Aij-Lie; Lou, Yun-Ting; Chen, Chao-Wen

2015-01-01

Objectives Osteoporosis Self-Assessment Tool for Asians (OSTA) has been proved to be a simple and effective tool for recognizing osteoporosis risk. Our previous study has demonstrated that the preoperative OSTA index was a good prognostic predictor for stage II and III colon cancer patients after surgery. We aim to evaluate the value of OSTA index in prognostication of isolated traumatic brain injury with moderate severity (GCS 9-13). Methods We retrospectively reviewed all patients visiting Kaohsiung Medical University Hospital emergency department due to isolated moderate traumatic brain injury from Jan. 2010 to Dec. 2012. Background data (including the OSTA index), clinical presentations, management and outcomes (ICU admission days, total admission days, complications, Glasgow outcome score (GOS) at discharge, mortality) of the patients were recorded for further analysis. Our major outcome was good neurologic recovery defined as GOS of 5. Pearson chi-square test and the Mann-Whitney U test were used to compare demographic features. Multiple logistic regression was used to identify independent risk factors. Results 107 isolated moderate TBI patients were studied. 40 patients (37.4%) showed good recovery and 10 (9.3%) died at discharge. The univariate analysis revealed that younger age, higher OSTA index, lower ISS, lower AIS-H, and avoidance to neurosurgery were associated with better neurologic outcome for all moderate TBI patients. Multivariate analysis revealed that lower ISS, higher OSTA, and the avoidance of neurosurgery were independent risk factors predicting good neurologic recovery. Conclusion Higher ISS, lower OSTA index and exposure to neurosurgery were the independent risk factors for poorer recovery from isolated moderate TBI. In addition to labeling the cohort harboring osteoporotic risk, OSTA index could predict neurologic prognosis in patients with isolated moderate traumatic brain injury. PMID:26186582

Administration of tissue plasminogen activator without coagulation results in a Chinese population.

PubMed

Qin, Xiaoming; Zhao, Songyao; Yin, Liujie; Dou, Hailing; Chen, Jie; Wang, Yifan; Li, Mingzhe; Chen, Ruifang; Fu, Jing; Liu, Wei; Liu, Xin; Yang, Gaiqing; Wang, Runqing; Jia, Xinzhou; Bu, Shufang; Ma, Dongpu; Wang, Baoyu; Li, Shize

2018-03-01

Routine coagulation test before intravenous tissue plasminogen activator (tPA) use increases the door to needle time (DNT). We sought to evaluate the safety of tPA use without coagulation results and its impact on prognosis. In our stroke registry, tPA was delivered with coagulation results from December 2015 to April 2016 and without coagulation results from May 2016 to December 2016. Differences of demographics, clinical characteristic, and prognosis between these two groups were analyzed. In addition, logistic regression analysis was conducted to identify predictors for DNT of over 60 min. A total of 201 stroke patients were included in the final analysis. Of these, 81 patients received tPA with coagulation results and 120 patients without coagulation results. Only one (0.8%) patient with abnormal coagulation results met the exclusion criteria of tPA use in patients without coagulation results. The difference of DNT between groups with (mean, 61.7 min) and without (mean, 41.9 min) coagulation results was significant (P = 0.00). The group without coagulation results had a higher rate of favorable 90-day outcome (74.2 vs 70.4%) and lower rates of symptomatic intracranial hemorrhage/nonintracranial hemorrhage (4.9 and 22.2% vs 1.7 and 19.2%) than the group with coagulation results did; these differences were not statistically significant. In multivariate analysis, only tPA use with coagulation results was the predictor for DNT of over 60 min (P = 0.0030, OR = 2.44, 95% CI 1.28-4.65). The present study suggests that tPA could be delivered safely without coagulation results in patients without suspected coagulopathy, and avoiding coagulation tests reduces significantly the DNT interval.

Prognostic implications of 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) PET/CT in patients with glioma.

PubMed

Toriihara, Akira; Ohtake, Makoto; Tateishi, Kensuke; Hino-Shishikura, Ayako; Yoneyama, Tomohiro; Kitazume, Yoshio; Inoue, Tomio; Kawahara, Nobutaka; Tateishi, Ukihide

2018-05-01

The potential of positron emission tomography/computed tomography using 62 Cu-diacetyl-bis (N 4 -methylthiosemicarbazone) ( 62 Cu-ATSM PET/CT), which was originally developed as a hypoxic tracer, to predict therapeutic resistance and prognosis has been reported in various cancers. Our purpose was to investigate prognostic value of 62 Cu-ATSM PET/CT in patients with glioma, compared to PET/CT using 2-deoxy-2-[ 18 F]fluoro-D-glucose ( 18 F-FDG). 56 patients with glioma of World Health Organization grade 2-4 were enrolled. All participants had undergone both 62 Cu-ATSM PET/CT and 18 F-FDG PET/CT within mean 33.5 days prior to treatment. Maximum standardized uptake value and tumor/background ratio were calculated within areas of increased radiotracer uptake. The prognostic significance for progression-free survival and overall survival were assessed by log-rank test and Cox's proportional hazards model. Disease progression and death were confirmed in 37 and 27 patients in follow-up periods, respectively. In univariate analysis, there was significant difference of both progression-free survival and overall survival in age, tumor grade, history of chemoradiotherapy, maximum standardized uptake value and tumor/background ratio calculated using 62 Cu-ATSM PET/CT. Multivariate analysis revealed that maximum standardized uptake value calculated using 62 Cu-ATSM PET/CT was an independent predictor of both progression-free survival and overall survival (p < 0.05). In a subgroup analysis including patients of grade 4 glioma, only the maximum standardized uptake values calculated using 62 Cu-ATSM PET/CT showed significant difference of progression-free survival (p < 0.05). 62 Cu-ATSM PET/CT is a more promising imaging method to predict prognosis of patients with glioma compared to 18 F-FDG PET/CT.

The Preoperative Composite Physiologic Index May Predict Mortality in Lung Cancer Patients with Combined Pulmonary Fibrosis and Emphysema.

PubMed

Ueno, Fumika; Kitaguchi, Yoshiaki; Shiina, Takayuki; Asaka, Shiho; Miura, Kentaro; Yasuo, Masanori; Wada, Yosuke; Yoshizawa, Akihiko; Hanaoka, Masayuki

2017-01-01

It remains unclear whether the preoperative pulmonary function parameters and prognostic indices that are indicative of nutritional and immunological status are associated with prognosis in lung cancer patients with combined pulmonary fibrosis and emphysema (CPFE) who have undergone surgery. The aim of this study is to identify prognostic determinants in these patients. The medical records of all patients with lung cancer associated with CPFE who had undergone surgery at Shinshu University Hospital were retrospectively reviewed to obtain clinical data, including the results of preoperative pulmonary function tests and laboratory examinations, chest high-resolution computed tomography (HRCT), and survival. Univariate Cox proportional hazards regression analysis showed that a high pathological stage of the lung cancer, a higher preoperative serum carcinoembryonic antigen level, and a higher preoperative composite physiologic index (CPI) were associated with a high risk of death. Multivariate analysis showed that a high pathological stage of the lung cancer (HR: 1.579; p = 0.0305) and a higher preoperative CPI (HR: 1.034; p = 0.0174) were independently associated with a high risk of death. In contrast, the severity of fibrosis or emphysema on chest HRCT, the individual pulmonary function parameters, the prognostic nutritional index, the neutrophil-to-lymphocyte ratio, and the platelet-to-lymphocyte ratio were not associated with prognosis. In the Kaplan-Meier analysis, the log-rank test showed significant differences in survival between the high-CPI and the low-CPI group (p = 0.0234). The preoperative CPI may predict mortality and provide more powerful prognostic information than individual pulmonary function parameters in lung cancer patients with CPFE who have undergone surgery. © 2017 S. Karger AG, Basel.

KPS/LDH index: a simple tool for identifying patients with metastatic melanoma who are unlikely to benefit from palliative whole brain radiotherapy.

PubMed

Partl, Richard; Fastner, Gerd; Kaiser, Julia; Kronhuber, Elisabeth; Cetin-Strohmer, Klaudia; Steffal, Claudia; Böhmer-Breitfelder, Barbara; Mayer, Johannes; Avian, Alexander; Berghold, Andrea

2016-02-01

Low Karnofsky performance status (KPS) and elevated lactate dehydrogenases (LDHs) as a surrogate marker for tumor load and cell turnover may depict patients with a very short life expectancy. To validate this finding and compare it to other indices, namely, the recursive partitioning analysis (RPA) and diagnosis-specific graded prognostic assessment (DS-GPA), a multicenter analysis was undertaken. A retrospective analysis of 234 metastatic melanoma patients uniformly treated with palliative whole brain radiotherapy (WBRT) was done. Univariate and multivariate analyses were used to determine the impact of patient-, tumor-, and treatment-related parameters on overall survival (OS). KPS and LDH emerged as independent factors predicting OS. By combining KPS and LDH values (KPS/LDH index), groups of patients with statistically significant differences in median OS (days; 95 % CI) after onset of WBRT were identified: group 1 (KPS ≥ 70/normal LDH) 234 (96-372), group 2 (KPS ≥ 70/elevated LDH) 112 (69-155), group 3 (KPS <70/normal LDH) 43 (12-74), and group 4 (KPS <70/elevated LDH) 29 (17-41). Between all four groups, statistically significant differences were observed. The RPA and DS-GPA indices failed to distinguish significantly between good and moderate prognosis and were inferior in predicting a very unfavorable prognosis. The parameters KPS and LDH independently impacted on OS. The combination of both (KPS/LDH index) identified patients with a very short life expectancy, who might be better served by recommending best supportive care instead of WBRT. The KPS/LDH index is simple and effective in terms of time and cost as compared to other prognostic indices.

Permeability Surface Area Product Using Perfusion Computed Tomography Is a Valuable Prognostic Factor in Glioblastomas Treated with Radiotherapy Plus Concomitant and Adjuvant Temozolomide.

PubMed

Saito, Taiichi; Sugiyama, Kazuhiko; Ikawa, Fusao; Yamasaki, Fumiyuki; Ishifuro, Minoru; Takayasu, Takeshi; Nosaka, Ryo; Nishibuchi, Ikuno; Muragaki, Yoshihiro; Kawamata, Takakazu; Kurisu, Kaoru

2017-01-01

The current standard treatment protocol for patients with newly diagnosed glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). We hypothesized that the permeability surface area product (PS) from a perfusion computed tomography (PCT) study is associated with sensitivity to TMZ. The aim of this study was to determine whether PS values were correlated with prognosis of GBM patients who received the standard treatment protocol. This study included 36 patients with GBM that were newly diagnosed between October 2005 and September 2014 and who underwent preoperative PCT study and the standard treatment protocol. We measured the maximum value of relative cerebral blood volume (rCBVmax) and the maximum PS value (PSmax). We statistically examined the relationship between PSmax and prognosis using survival analysis, including other clinicopathologic factors (age, Karnofsky performance status [KPS], extent of resection, O6-methylguanine-DNA methyltransferase [MGMT] status, second-line use of bevacizumab, and rCBVmax). Log-rank tests revealed that age, KPS, MGMT status, and PSmax were significantly correlated with overall survival. Multivariate analysis using the Cox regression model showed that PSmax was the most significant prognostic factor. Receiver operating characteristic curve analysis showed that PSmax had the highest accuracy in differentiating longtime survivors (LTSs) (surviving more than 2 years) from non-LTSs. At a cutoff point of 8.26 mL/100 g/min, sensitivity and specificity were 90% and 70%, respectively. PSmax from PCT study can help predict survival time in patients with GBM receiving the standard treatment protocol. Survival may be related to sensitivity to TMZ. Copyright © 2016 Elsevier Inc. All rights reserved.

Glioblastoma: does the pre-treatment geometry matter? A postcontrast T1 MRI-based study.

PubMed

Pérez-Beteta, Julián; Martínez-González, Alicia; Molina, David; Amo-Salas, Mariano; Luque, Belén; Arregui, Elena; Calvo, Manuel; Borrás, José M; López, Carlos; Claramonte, Marta; Barcia, Juan A; Iglesias, Lidia; Avecillas, Josué; Albillo, David; Navarro, Miguel; Villanueva, José M; Paniagua, Juan C; Martino, Juan; Velásquez, Carlos; Asenjo, Beatriz; Benavides, Manuel; Herruzo, Ismael; Delgado, María Del Carmen; Del Valle, Ana; Falkov, Anthony; Schucht, Philippe; Arana, Estanislao; Pérez-Romasanta, Luis; Pérez-García, Víctor M

2017-03-01

The potential of a tumour's volumetric measures obtained from pretreatment MRI sequences of glioblastoma (GBM) patients as predictors of clinical outcome has been controversial. Mathematical models of GBM growth have suggested a relation between a tumour's geometry and its aggressiveness. A multicenter retrospective clinical study was designed to study volumetric and geometrical measures on pretreatment postcontrast T1 MRIs of 117 GBM patients. Clinical variables were collected, tumours segmented, and measures computed including: contrast enhancing (CE), necrotic, and total volumes; maximal tumour diameter; equivalent spherical CE width and several geometric measures of the CE "rim". The significance of the measures was studied using proportional hazards analysis and Kaplan-Meier curves. Kaplan-Meier and univariate Cox survival analysis showed that total volume [p = 0.034, Hazard ratio (HR) = 1.574], CE volume (p = 0.017, HR = 1.659), spherical rim width (p = 0.007, HR = 1.749), and geometric heterogeneity (p = 0.015, HR = 1.646) were significant parameters in terms of overall survival (OS). Multivariable Cox analysis for OS provided the later two parameters as age-adjusted predictors of OS (p = 0.043, HR = 1.536 and p = 0.032, HR = 1.570, respectively). Patients with tumours having small geometric heterogeneity and/or spherical rim widths had significantly better prognosis. These novel imaging biomarkers have a strong individual and combined prognostic value for GBM patients. • Three-dimensional segmentation on magnetic resonance images allows the study of geometric measures. • Patients with small width of contrast enhancing areas have better prognosis. • The irregularity of contrast enhancing areas predicts survival in glioblastoma patients.

FDG-PET/CT and diffusion-weighted imaging for resected lung cancer: correlation of maximum standardized uptake value and apparent diffusion coefficient value with prognostic factors.

PubMed

Usuda, Katsuo; Funasaki, Aika; Sekimura, Atsushi; Motono, Nozomu; Matoba, Munetaka; Doai, Mariko; Yamada, Sohsuke; Ueda, Yoshimichi; Uramoto, Hidetaka

2018-04-09

Diffusion-weighted magnetic resonance imaging (DWI) is useful for detecting malignant tumors and the assessment of lymph nodes, as FDG-PET/CT is. But it is not clear how DWI influences the prognosis of lung cancer patients. The focus of this study is to evaluate the correlations between maximum standardized uptake value (SUVmax) of FDG-PET/CT and apparent diffusion coefficient (ADC) value of DWI with known prognostic factors in resected lung cancer. A total of 227 patients with resected lung cancers were enrolled in this study. FEG-PET/CT and DWI were performed in each patient before surgery. There were 168 patients with adenocarcinoma, 44 patients with squamous cell carcinoma, and 15 patients with other cell types. SUVmax was a factor that was correlated to T factor, N factor, or cell differentiation. ADC of lung cancer was a factor that was not correlated to T factor, or N factor. There was a significantly weak inverse relationship between SUVmax and ADC (Correlation coefficient r = - 0.227). In analysis of survival, there were significant differences between the categories of sex, age, pT factor, pN factor, cell differentiation, cell type, and SUVmax. Univariate analysis revealed that SUVmax, pN factor, age, cell differentiation, cell type, sex, and pT factor were significant factors. Multivariate analysis revealed that SUVmax and pN factor were independent significant prognostic factors. SUVmax was a significant prognostic factor that is correlated to T factor, N factor, or cell differentiation, but ADC was not. SUVmax may be more useful for predicting the prognosis of lung cancer than ADC values.

Prognostic Value of High-Sensitivity C-Reactive Protein, Procalcitonin and Pancreatic Stone Protein in Pediatric Sepsis.

PubMed

Wu, Qiong; Nie, Jun; Wu, Fu-Xia; Zou, Xiu-Lan; Chen, Feng-Yi

2017-03-30

BACKGROUND To investigate the prognostic value of procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), and pancreatic stone protein (PSP) in children with sepsis. MATERIAL AND METHODS A total of 214 patients with sepsis during hospitalization were enrolled. Serum levels of PCT, hs-CRP, and PSP were measured on day 1 of hospitalization and the survival rates of children were recorded after a follow-up of 28 days. Pearson's correlation analysis was conducted to test the association of PCT, hs-CRP, and PSP with pediatric critical illness score (PCIS). Logistic regression models were used to analyze the risk factors contributing to patients' death. The AUC was used to determine the value of PCT, hs-CRP, and PSP in the prognosis of patients with sepsis. RESULTS The expression of PCT, hs-CRP, and PSP in the dying patients was higher than in the surviving patients (p<0.001). Pearson's correlation analysis showed that serum PCT, hs-CRP, and PSP levels were negatively correlated with PCIS (p<0.001). Multivariate logistic regression revealed that PCT, hs-CRP, and PSP were independent risk factors for the prognosis of patients with sepsis (p<0.001). ROC analysis showed the AUC values of PCT, hs-CRP, and PSP were 0.83 (95% CI, 0.77-0.88), 0.76 (95% CI, 0.70-0.82), and 0.73 (95% CI, 0.67-0.79), respectively. The combined AUC value of PCT, hs-CRP, and PSP, was 0.92 (95% CI, 0.87-0.95), which was significantly increased compared with PCT, hs-CRP, or PSP (p<0.001). CONCLUSIONS The combination of serum PCT, hs-CRP, and PSP represents a promising biomarker of risk, and is a useful clinical tool for risk stratification of children with sepsis.

FBXW7 expression affects the response to chemoradiotherapy and overall survival among patients with oral squamous cell carcinoma: A single-center retrospective study.

PubMed

Arita, Hidetaka; Nagata, Masashi; Yoshida, Ryoji; Matsuoka, Yuichiro; Hirosue, Akiyuki; Kawahara, Kenta; Sakata, Junki; Nakashima, Hikaru; Kojima, Taku; Toya, Ryo; Murakami, Ryuji; Hiraki, Akimitsu; Shinohara, Masanori; Nakayama, Hideki

2017-10-01

FBXW7 (F-box and WD repeat domain containing-7) is a tumor suppressor protein that regulates the degradation of various oncoproteins in several malignancies. However, limited information is available regarding FBXW7 expression in oral squamous cell carcinoma. Therefore, this study aimed to determine the clinical significance of FBXW7 expression in oral squamous cell carcinoma. The FBXW7 expression patterns in oral squamous cell carcinoma and adjacent normal tissues from 15 patients who underwent radical resection were evaluated using quantitative real-time polymerase chain reaction and immunohistochemical staining. In addition, immunohistochemistry was performed using paraffin-embedded sections from biopsy specimens obtained from 110 patients with oral squamous cell carcinoma who underwent surgery after 5 fluorouracil-based chemoradiotherapy. The associations of FBXW7 expression with various clinicopathological features and prognosis were evaluated in these patients. As a results, in the 15 matched samples, the FBXW7 expression was significantly decreased in the oral squamous cell carcinoma tissues compared to that in the adjacent normal tissues. In the clinicopathological analysis, compared to high protein expression, low FBXW7 expression was found to significantly associate with a poor histological response to preoperative chemoradiotherapy. Kaplan-Meier curve analysis revealed that low FBXW7 expression was significantly associated with a poor prognosis, and FBXW7 expression was found to be an independent predictor of overall survival in the multivariate analysis. Our results suggest that FBXW7 may function as a tumor suppressor protein in oral squamous cell carcinoma. In addition, FBXW7 could be a potential biomarker for predicting not only the clinical response to chemoradiotherapy but also overall survival in patients with oral squamous cell carcinoma.

Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer.

PubMed

Feng, Xiaolan; Li, Haocheng; Kornaga, Elizabeth N; Dean, Michelle; Lees-Miller, Susan P; Riabowol, Karl; Magliocco, Anthony M; Morris, Don; Watson, Peter H; Enwere, Emeka K; Bebb, Gwyn; Paterson, Alexander

2016-12-27

This study was designed to investigate the combined influence of ATM and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (< 4 cm) and fewer than four positive lymph nodes. 532 formalin-fixed paraffin-embedded specimens of resected primary breast tumors were used to construct a tissue microarray. Samples from 297 patients were suitable for final statistical analysis. We detected ATM and Ki67 proteins using fluorescence and brightfield immunohistochemistry respectively, and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome. Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up (p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively (p = 0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status (p = 0.02). These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC.

Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer

PubMed Central

Feng, Xiaolan; Li, Haocheng; Kornaga, Elizabeth N.; Dean, Michelle; Lees-Miller, Susan P.; Riabowol, Karl; Magliocco, Anthony M.; Morris, Don; Watson, Peter H.; Enwere, Emeka K.; Bebb, Gwyn; Paterson, Alexander

2016-01-01

Introduction This study was designed to investigate the combined influence of ATM and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (< 4 cm) and fewer than four positive lymph nodes. Methods 532 formalin-fixed paraffin-embedded specimens of resected primary breast tumors were used to construct a tissue microarray. Samples from 297 patients were suitable for final statistical analysis. We detected ATM and Ki67 proteins using fluorescence and brightfield immunohistochemistry respectively, and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome. Results Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up (p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively (p = 0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status (p = 0.02). Conclusions These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC. PMID:27741524

Prognostic value of stromal decorin expression in patients with breast cancer: a meta-analysis.

PubMed

Li, Shuang-Jiang; Chen, Da-Li; Zhang, Wen-Biao; Shen, Cheng; Che, Guo-Wei

2015-11-01

Numbers of studies have investigated the biological functions of decorin (DCN) in oncogenesis, tumor progression, angiogenesis and metastasis. Although many of them aim to highlight the prognostic value of stromal DCN expression in breast cancer, some controversial results still exist and a consensus has not been reached until now. Therefore, our meta-analysis aims to determine the prognostic significance of stromal DCN expression in breast cancer patients. PubMed, EMBASE, the Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for full-text literatures met out inclusion criteria. We applied the hazard ratio (HR) with 95% confidence interval (CI) as the appropriate summarized statistics. Q-test and I(2) statistic were employed to estimate the level of heterogeneity across the included studies. Sensitivity analysis was conducted to further identify the possible origins of heterogeneity. The publication bias was detected by Begg's test and Egger's test. There were three English literatures (involving 6 studies) included into our meta-analysis. On the one hand, both the summarized outcomes based on univariate analysis (HR: 0.513; 95% CI: 0.406-0.648; P<0.001) and multivariate analysis (HR: 0.544; 95% CI: 0.388-0.763; P<0.001) indicated that stromal DCN expression could promise the high cancer-specific survival (CSS) of breast cancer patients. On the other hand, both the summarized outcomes based on univariate analysis (HR: 0.504; 95% CI: 0.389-0.651; P<0.001) and multivariate analysis (HR: 0.568; 95% CI: 0.400-0.806; P=0.002) also indicated that stromal DCN expression was positively associated with high disease-free survival (DFS) of breast cancer patients. No significant heterogeneity or publication bias was observed within this meta-analysis. The present evidences indicate that high stromal DCN expression can significantly predict the good prognosis in patients with breast cancer. The discoveries from our meta-analysis have better be confirmed in the updated review pooling more relevant investigations in the future.

Clinical relevance of TRKA expression on neuroblastoma: comparison with N-MYC amplification and CD44 expression.

PubMed Central

Combaret, V.; Gross, N.; Lasset, C.; Balmas, K.; Bouvier, R.; Frappaz, D.; Beretta-Brognara, C.; Philip, T.; Favrot, M. C.; Coll, J. L.

1997-01-01

TRKA expression was evaluated on 122 untreated neuroblastomas by immunohistochemistry using an antibody with predetermined specificity. This procedure is simple and reliable for protein detection at cellular level in a routine clinical setting. Fourteen tumours were classified as benign ganglioneuroma with a restricted expression of TRKA on ganglion cells; these patients were excluded from the following analysis. A total of 108 tumours were classified as neuroblastoma or ganglioneuroblastoma; 74 expressed TRKA protein, which strongly correlated with low stage, absence of N-MYC amplification, age (<1 year), CD44 expression and favourable clinical outcome. In a univariate analysis including tumour stage, age, histology, N-MYC amplification, CD44 and TRKA expression, all parameters had significant prognostic value. The absence of TRKA expression on CD44-positive or N-MYC non-amplified tumours permits the characterization of a subgroup of patients with intermediate prognosis. However, in a multivariate analysis taking into consideration the prognostic factors mentioned above, CD44 and tumour stage were the only independent prognostic factors for the prediction of patients' event-free survival. PMID:9099963

Integrative Analysis of Prognosis Data on Multiple Cancer Subtypes

PubMed Central

Liu, Jin; Huang, Jian; Zhang, Yawei; Lan, Qing; Rothman, Nathaniel; Zheng, Tongzhang; Ma, Shuangge

2014-01-01

Summary In cancer research, profiling studies have been extensively conducted, searching for genes/SNPs associated with prognosis. Cancer is diverse. Examining the similarity and difference in the genetic basis of multiple subtypes of the same cancer can lead to a better understanding of their connections and distinctions. Classic meta-analysis methods analyze each subtype separately and then compare analysis results across subtypes. Integrative analysis methods, in contrast, analyze the raw data on multiple subtypes simultaneously and can outperform meta-analysis methods. In this study, prognosis data on multiple subtypes of the same cancer are analyzed. An AFT (accelerated failure time) model is adopted to describe survival. The genetic basis of multiple subtypes is described using the heterogeneity model, which allows a gene/SNP to be associated with prognosis of some subtypes but not others. A compound penalization method is developed to identify genes that contain important SNPs associated with prognosis. The proposed method has an intuitive formulation and is realized using an iterative algorithm. Asymptotic properties are rigorously established. Simulation shows that the proposed method has satisfactory performance and outperforms a penalization-based meta-analysis method and a regularized thresholding method. An NHL (non-Hodgkin lymphoma) prognosis study with SNP measurements is analyzed. Genes associated with the three major subtypes, namely DLBCL, FL, and CLL/SLL, are identified. The proposed method identifies genes that are different from alternatives and have important implications and satisfactory prediction performance. PMID:24766212

Quantitative gene expression deregulation in mantle-cell lymphoma: correlation with clinical and biologic factors.

PubMed

Kienle, Dirk; Katzenberger, Tiemo; Ott, German; Saupe, Doreen; Benner, Axel; Kohlhammer, Holger; Barth, Thomas F E; Höller, Sylvia; Kalla, Jörg; Rosenwald, Andreas; Müller-Hermelink, Hans Konrad; Möller, Peter; Lichter, Peter; Döhner, Hartmut; Stilgenbauer, Stephan

2007-07-01

There is evidence for a direct role of quantitative gene expression deregulation in mantle-cell lymphoma (MCL) pathogenesis. Our aim was to investigate gene expression associations with other pathogenic factors and the significance of gene expression in a multivariate survival analysis. Quantitative expression of 20 genes of potential relevance for MCL prognosis and pathogenesis were analyzed using real-time reverse transcriptase polymerase chain reaction and correlated with clinical and genetic factors, tumor morphology, and Ki-67 index in 65 MCL samples. Genomic losses at the loci of TP53, RB1, and P16 were associated with reduced transcript levels of the respective genes, indicating a gene-dosage effect as the pathomechanism. Analysis of gene expression correlations between the candidate genes revealed a separation into two clusters, one dominated by proliferation activators, another by proliferation inhibitors and regulators of apoptosis. Whereas only weak associations were identified between gene expression and clinical parameters or blastoid morphology, several genes were correlated closely with the Ki-67 index, including the short CCND1 variant (positive correlation) and RB1, ATM, P27, and BMI (negative correlation). In multivariate survival analysis, expression levels of MYC, MDM2, EZH2, and CCND1 were the strongest prognostic factors independently of tumor proliferation and clinical factors. These results indicate a pathogenic contribution of several gene transcript levels to the biology and clinical course of MCL. Genes can be differentiated into factors contributing to proliferation deregulation, either by enhancement or loss of inhibition, and proliferation-independent factors potentially contributing to MCL pathogenesis by apoptosis impairment.

Factors predicting survival following complete surgical remission of pulmonary metastasis in osteosarcoma

PubMed Central

SALAH, SAMER; TOUBASI, SAMAR

2015-01-01

Pulmonary metastasectomy (PM) is associated with improved survival of patients with metastatic osteosarcoma; however, the factors affecting survival following achievement of complete surgical remission remain controversial. The main objective of this study was to report the outcomes and prognostic factors of osteosarcoma patients who achieved complete remission (CR) following PM. We analyzed the effect of demographic and disease-related characteristics on the overall survival (OS) of consecutive patients with metastatic osteosarcoma who were treated at a single institution and achieved CR following PM, through univariate and multivariate analyses. Between January, 2000 and August, 2013, 62 patients with metastatic osteosarcoma were treated and followed up at our institution. A total of 25 patients achieved CR following PM and were included in this analysis. The 5-year OS and disease-free survival following PM were 30 and 21%, respectively. The factors correlated with inferior OS in the univariate analysis included chondroblastic subtype, post-chemotherapy necrosis <90% in the primary tumor, metastasis detected during neoadjuvant or adjuvant chemotherapy and pathological identification of tumor cells reaching the visceral pleural surface of any of the resected nodules. In the multivariate analysis, the chondroblastic subtype was the sole independent adverse prognostic factor (HR=4.6, 95% CI: 1.0–21.3, P=0.044). Therefore, factors associated with tumor biology, including poor tumor necrosis in the primary tumor and detection of metastasis during primary chemotherapy, are associated with poor post-metastasectomy survival. In addition, chondroblastic subtype and visceral pleural involvement predicted poor prognosis in our series. PMID:25469287

Glycated hemoglobin level is an independent predictor of major adverse cardiac events after nonfatal acute myocardial infarction in nondiabetic patients: A retrospective observational study.

PubMed

Chen, Chin-Lan; Yen, David H-T; Lin, Chin-Sheng; Tsai, Shih-Hung; Chen, Sy-Jou; Sheu, Wayne H-H; Hsu, Chin-Wang

2017-05-01

The effect of glycemic control on the prognosis of nondiabetic patients after acute myocardial infarction (AMI) remains uncertain. We investigated whether glycated hemoglobin (HbA1c) is associated with adverse outcomes after AMI in nondiabetic patients. In this observational study, we enrolled nondiabetic patients with AMI in the emergency department of 2 medical centers from January 2011 to September 2014. All patients received primary percutaneous coronary intervention and were divided into 4 groups according to the interquartile range of average HbA1c level (Group I, ≤5.6%; Group II, 5.6%-5.8%; Group III, 5.8%-6.0%; and Group IV, >6.0%). Multivariate logistic analysis was performed to estimate the correlation of HbA1c with major adverse cardiac events (MACEs) after AMI. In total, 267 eligible patients were enrolled; 48 patients (18%) developed MACEs within a median follow-up of 178 days. Univariate analysis showed HbA1c > 6.0%, with a higher risk of MACEs in Group IV than in Group I (odds ratio [OR]: 2.733; 95% confidence interval [CI]: 1.123-6.651 vs OR: 1.511; 95% CI: 0.595-3.835). Multivariate analysis revealed an approximately 3.8 times higher risk of MACEs in Group IV than in Group I (OR: 3.769; 95% CI: 1.30-10.86). The HbA1 level is a significant predictor of MACEs after AMI in nondiabetic patients.

Retrospective Analysis of 255 Papillary Thyroid Carcinomas ≤2 cm: Clinicohistological Features and Prognostic Factors.

PubMed

Marques, Pedro; Leite, Valeriano; Bugalho, Maria João

2014-12-01

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. The widespread use of neck ultrasound (US) and US-guided fine-needle aspiration cytology is triggering an overdiagnosis of PTC. To evaluate clinical behavior and outcomes of patients with PTCs ≤2 cm, seeking for possible prognostic factors. Clinical records of cases with histological diagnosis of PTC ≤2 cm followed at the Endocrine Department of Instituto Português de Oncologia, Lisbon between 2002 and 2006 were analyzed retrospectively. We identified 255 PTCs, 111 were microcarcinomas. Most patients underwent near-total thyroidectomy, with lymph node dissections in 55 cases (21.6%). Radioiodine therapy was administered in 184 patients. At the last evaluation, 38 (14.9%) had evidence of disease. Two deaths were attributed to PTC. Median (±SD) follow-up was 74 (±23) months. Multivariate analysis identified vascular invasion, lymph node and systemic metastases significantly associated with recurrence/persistence of disease. In addition, lymph node involvement was significantly associated with extrathyroidal extension and angioinvasion. Median (±SD) disease-free survival (DFS) was estimated as 106 (±3) months and the 5-year DFS rate was 87.5%. Univariate Cox analysis identified some relevant parameters for DFS, but multivariate regression only identified lymph node and systemic metastases as significant independent factors. The median DFS estimated for lymph node and systemic metastases was 75 and 0 months, respectively. In the setting of small PTCs, vascular invasion, extrathyroidal extension and lymph node and/or systemic metastases may confer worse prognosis, perhaps justifying more aggressive therapeutic and follow-up approaches in such cases.

Radical Surgery Improves Survival in Patients with Stage 4 Neuroblastoma.

PubMed

Vollmer, Katherin; Gfroerer, Stefan; Theilen, Till-Martin; Bochennek, Konrad; Klingebiel, Thomas; Rolle, Udo; Fiegel, Henning

2018-06-01

Neuroblastoma (NBL) is the most common extracranial solid tumor in children. Despite a good overall prognosis in NBL patients, the outcome of children with stage 4 disease, even with multimodal intensive therapy, remains poor. The role of extended surgical resection of the primary tumor is in numerous studies controversial. The aim of this study was to retrospectively analyze the impact of radical surgical resection on the overall- and event-free survival of stage 4 NBL patients. We retrospectively analyzed patient charts of 40 patients with stage 4 NBL treated in our institution between January 1990 and May 2012. All clinical and pathological findings of stage 4 NBL patients were included. Extent of surgery was assessed from the operation records and was classified as non-radical (tumor biopsy, partial 50-90% resection) or radical (near-complete >90% resection, complete resection). Overall- (OS) and event-free (EFS) survival was assessed using the Kaplan-Meier analysis and log-rank test. A multivariate Cox regression analysis was used to demonstrate independency. In total, 29/40 patients were operated radically (>90% resection), whereas 11 patients received subtotal resection or biopsy only. OS and EFS were significantly increased in patients with radical operation compared with non-radical resection (p = 0.0003 for OS, p = 0.004 for EFS; log-rank test). A multivariate Cox regression analysis revealed radical operation as a significant and independent parameter for OS and EFS. Our data indicate that radical (over 90% resection) surgery improves OS and EFS in stage 4 NBL patients.

LGE Provides Incremental Prognostic Information Over Serum Biomarkers in AL Cardiac Amyloidosis.

PubMed

Boynton, Samuel J; Geske, Jeffrey B; Dispenzieri, Angela; Syed, Imran S; Hanson, Theodore J; Grogan, Martha; Araoz, Philip A

2016-06-01

This study sought to determine the prognostic value of cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) in amyloid light chain (AL) cardiac amyloidosis. Cardiac involvement is the major determinant of mortality in AL amyloidosis. CMR LGE is a marker of amyloid infiltration of the myocardium. The purpose of this study was to evaluate retrospectively the prognostic value of CMR LGE for determining all-cause mortality in AL amyloidosis and to compare the prognostic power with the biomarker stage. Seventy-six patients with histologically proven AL amyloidosis underwent CMR LGE imaging. LGE was categorized as global, focal patchy, or none. Global LGE was considered present if it was visualized on LGE images or if the myocardium nulled before the blood pool on a cine multiple inversion time (TI) sequence. CMR morphologic and functional evaluation, echocardiographic diastolic evaluation, and cardiac biomarker staging were also performed. Subjects' charts were reviewed for all-cause mortality. Cox proportional hazards analysis was used to evaluate survival in univariate and multivariate analysis. There were 40 deaths, and the median study follow-up period was 34.4 months. Global LGE was associated with all-cause mortality in univariate analysis (hazard ratio = 2.93; p < 0.001). In multivariate modeling with biomarker stage, global LGE remained prognostic (hazard ratio = 2.43; p = 0.01). Diffuse LGE provides incremental prognosis over cardiac biomarker stage in patients with AL cardiac amyloidosis. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Does shear wave ultrasound independently predict axillary lymph node metastasis in women with invasive breast cancer?

PubMed

Evans, Andrew; Rauchhaus, Petra; Whelehan, Patsy; Thomson, Kim; Purdie, Colin A; Jordan, Lee B; Michie, Caroline O; Thompson, Alastair; Vinnicombe, Sarah

2014-01-01

Shear wave elastography (SWE) shows promise as an adjunct to greyscale ultrasound examination in assessing breast masses. In breast cancer, higher lesion stiffness on SWE has been shown to be associated with features of poor prognosis. The purpose of this study was to assess whether lesion stiffness at SWE is an independent predictor of lymph node involvement. Patients with invasive breast cancer treated by primary surgery, who had undergone SWE examination were eligible. Data were retrospectively analysed from 396 consecutive patients. The mean stiffness values were obtained using the Aixplorer® ultrasound machine from SuperSonic Imagine Ltd. Measurements were taken from a region of interest positioned over the stiffest part of the abnormality. The average of the mean stiffness value obtained from each of two orthogonal image planes was used for analysis. Associations between lymph node involvement and mean lesion stiffness, invasive cancer size, histologic grade, tumour type, ER expression, HER-2 status and vascular invasion were assessed using univariate and multivariate logistic regression. At univariate analysis, invasive size, histologic grade, HER-2 status, vascular invasion, tumour type and mean stiffness were significantly associated with nodal involvement. Nodal involvement rates ranged from 7 % for tumours with mean stiffness <50 kPa to 41 % for tumours with a mean stiffness of >150 kPa. At multivariate analysis, invasive size, tumour type, vascular invasion, and mean stiffness maintained independent significance. Mean stiffness at SWE is an independent predictor of lymph node metastasis and thus can confer prognostic information additional to that provided by conventional preoperative tumour assessment and staging.

Pathologic response after preoperative therapy predicts prognosis of Chinese colorectal cancer patients with liver metastases.

PubMed

Wang, Yun; Yuan, Yun-Fei; Lin, Hao-Cheng; Li, Bin-Kui; Wang, Feng-Hua; Wang, Zhi-Qiang; Ding, Pei-Rong; Chen, Gong; Wu, Xiao-Jun; Lu, Zhen-Hai; Pan, Zhi-Zhong; Wan, De-Sen; Sun, Peng; Yan, Shu-Mei; Xu, Rui-Hua; Li, Yu-Hong

2017-10-02

Pathologic response is evaluated according to the extent of tumor regression and is used to estimate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorectal cancer patients with liver metastases who underwent hepatectomy. However, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the association between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese patients. In this retrospective study, we analyzed the data of 380 liver metastases in 159 patients. The pathologic response was evaluated according to the tumor regression grade (TRG). The prognostic role of pathologic response in recurrence-free survival (RFS) and overall survival (OS) was assessed using Kaplan-Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests. Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy (median RFS: 9.9 vs. 6.5 months, P = 0.009; median OS: 40.7 vs. 28.1 months, P = 0.040). Multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests showed that metastases with small diameter, metastases from the left-side primary tumors, and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases (all P < 0.05). A decrease in the serum carcinoembryonic antigen (CEA) level after preoperative chemotherapy predicted an increased pathologic response rate (P < 0.05). Although the application of targeted therapy did not significantly influence TRG scores of all cases of metastases, the addition of cetuximab to chemotherapy resulted in a higher pathologic response rate when combined with irinotecan-based regimens rather than with oxaliplatin-based regimens. We found that the evaluation of pathologic response may predict the prognosis of Chinese colorectal cancer patients with liver metastases after preoperative chemotherapy. Small tumor diameter, long-duration chemotherapy, left primary tumor, and decreased serum CEA level after chemotherapy are associated with increased pathologic response rates.

Radiomics-based Prognosis Analysis for Non-Small Cell Lung Cancer

NASA Astrophysics Data System (ADS)

Zhang, Yucheng; Oikonomou, Anastasia; Wong, Alexander; Haider, Masoom A.; Khalvati, Farzad

2017-04-01

Radiomics characterizes tumor phenotypes by extracting large numbers of quantitative features from radiological images. Radiomic features have been shown to provide prognostic value in predicting clinical outcomes in several studies. However, several challenges including feature redundancy, unbalanced data, and small sample sizes have led to relatively low predictive accuracy. In this study, we explore different strategies for overcoming these challenges and improving predictive performance of radiomics-based prognosis for non-small cell lung cancer (NSCLC). CT images of 112 patients (mean age 75 years) with NSCLC who underwent stereotactic body radiotherapy were used to predict recurrence, death, and recurrence-free survival using a comprehensive radiomics analysis. Different feature selection and predictive modeling techniques were used to determine the optimal configuration of prognosis analysis. To address feature redundancy, comprehensive analysis indicated that Random Forest models and Principal Component Analysis were optimum predictive modeling and feature selection methods, respectively, for achieving high prognosis performance. To address unbalanced data, Synthetic Minority Over-sampling technique was found to significantly increase predictive accuracy. A full analysis of variance showed that data endpoints, feature selection techniques, and classifiers were significant factors in affecting predictive accuracy, suggesting that these factors must be investigated when building radiomics-based predictive models for cancer prognosis.

LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia.

PubMed

Kaderi, Mohd Arifin; Kanduri, Meena; Buhl, Anne Mette; Sevov, Marie; Cahill, Nicola; Gunnarsson, Rebeqa; Jansson, Mattias; Smedby, Karin Ekström; Hjalgrim, Henrik; Jurlander, Jesper; Juliusson, Gunnar; Mansouri, Larry; Rosenquist, Richard

2011-08-01

The expression levels of LPL, ZAP70, TCL1A, CLLU1 and MCL1 have recently been proposed as prognostic factors in chronic lymphocytic leukemia. However, few studies have systematically compared these different RNA-based markers. Using real-time quantitative PCR, we measured the mRNA expression levels of these genes in unsorted samples from 252 newly diagnosed chronic lymphocytic leukemia patients and correlated our data with established prognostic markers (for example Binet stage, CD38, IGHV gene mutational status and genomic aberrations) and clinical outcome. High expression levels of all RNA-based markers, except MCL1, predicted shorter overall survival and time to treatment, with LPL being the most significant. In multivariate analysis including the RNA-based markers, LPL expression was the only independent prognostic marker for overall survival and time to treatment. When studying LPL expression and the established markers, LPL expression retained its independent prognostic strength for overall survival. All of the RNA-based markers, albeit with varying ability, added prognostic information to established markers, with LPL expression giving the most significant results. Notably, high LPL expression predicted a worse outcome in good-prognosis subgroups, such as patients with mutated IGHV genes, Binet stage A, CD38 negativity or favorable cytogenetics. In particular, the combination of LPL expression and CD38 could further stratify Binet stage A patients. LPL expression is the strongest RNA-based prognostic marker in chronic lymphocytic leukemia that could potentially be applied to predict outcome in the clinical setting, particularly in the large group of patients with favorable prognosis.

Both high and low body mass indexes are prognostic risks in Japanese patients with chronic heart failure: implications from the CHART study.

PubMed

Nochioka, Kotaro; Shiba, Nobuyuki; Kohno, Haruka; Miura, Masanobu; Shimokawa, Hiroaki

2010-11-01

Prognostic impact of body mass index (BMI) in Japanese patients with chronic heart failure (HF) remains unclear. We examined the relationship between BMI and the prognosis of Japanese HF patients in the Chronic Heart Failure Analysis and Registry in the Tohoku District (CHART) study. The study sample was 972 Japanese chronic HF patients (mean age, 68.2 ± 13.5; male 65.2%). We categorized them into 5 groups; BMI <18.5, 18.5 to 22.9, 23.0 to 24.9 (reference), 25.0 to 29.9, and ≥ 30.0. Using a Cox hazards model, the relationships between BMI and deaths or admission for worsening HF were studied in detail. Mean follow-up period was 3.4 ± 1.7 years. Multivariate analysis showed that, as compared with reference group (BMI 23.0 to 24.9), hazard ratios (HR) for all-cause death showed a U-shaped association with 1.70 (95% confidence interval; 1.04-2.76), 1.23 (0.85-1.78), 1.26 (0.84-1.90), and 2.75 (1.51-5.00) among those with BMI<18.5, 18.5 to 22.9, 25.0 to 29.9, and ≥ 30.0, respectively. There were significant and suggestive U-shaped associations between BMI and cardiac-cause death or admission for worsening HF. Both high and low BMIs were associated with increased outcomes, suggesting that extreme obesity is not beneficial in improving the prognosis of Japanese chronic HF patients. Copyright © 2010 Elsevier Inc. All rights reserved.

[Clinical significance of detection of cathepsin X and cystatin C in the sera of patients with lung cancer].

PubMed

Zhang, Xuede; Hou, Yanli; Niu, Zequn; Li, Wei; Meng, Xia; Zhang, Na; Yang, Shuanying

2013-08-20

Cathepsin X (Cat X) has been identified as a member of cathepsin family. Studies have shown that Cat X is involved in tumorigenesis and tumor development of various cancers. The aim of this study is to investigate the relationship between the clinicopathological prognosis and the levels of Cat X and cystatin C in the serum of patients with lung cancer. Blood samples were collected from 84 patients with lung cancer and 36 healthy control subjects. Cat X and cystatin C were determined by quantitative ELISA. Cat X and cystatin C levels were significantly higher in the patients with lung cancer than that in the healthy control subjects (P<0.01). Cat X level was correlated with the pathological types of lung cancer (P=0.076). Cystatin C was positively correlated with TNM stage (P=0.01). Furthermore, cystatin C/Cat X was correlated with lymph node metastasis (P=0.058). The patients with high Cat X levels experienced significantly shorter overall survival rates compared with those with low Cat X. Univariate analysis indicated that Cat X and TNM stage were related to overall survival. Multivariate Cox analysis indicated that TNM stage may be used as an independent prognostic variable in patients with lung cancer. Cat X and cystatin C levels were significantly higher in patients with lung cancer. Cat X and cystatin C detection in the sera may contribute to the diagnosis of lung cancer and may be used to evaluate the prognosis of patients with NSCLC.

Local Recurrence After Uveal Melanoma Proton Beam Therapy: Recurrence Types and Prognostic Consequences

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

Caujolle, Jean-Pierre, E-mail: ncaujolle@aol.com; Paoli, Vincent; Chamorey, Emmanuel

Purpose: To study the prognosis of the different types of uveal melanoma recurrences treated by proton beam therapy (PBT). Methods and Materials: This retrospective study analyzed 61 cases of uveal melanoma local recurrences on a total of 1102 patients treated by PBT between June 1991 and December 2010. Survival rates have been determined by using Kaplan-Meier curves. Prognostic factors have been evaluated by using log-rank test or Cox model. Results: Our local recurrence rate was 6.1% at 5 years. These recurrences were divided into 25 patients with marginal recurrences, 18 global recurrences, 12 distant recurrences, and 6 extrascleral extensions. Fivemore » factors have been identified as statistically significant risk factors of local recurrence in the univariate analysis: large tumoral diameter, small tumoral volume, low ratio of tumoral volume over eyeball volume, iris root involvement, and safety margin inferior to 1 mm. In the local recurrence-free population, the overall survival rate was 68.7% at 10 years and the specific survival rate was 83.6% at 10 years. In the local recurrence population, the overall survival rate was 43.1% at 10 years and the specific survival rate was 55% at 10 years. The multivariate analysis of death risk factors has shown a better prognosis for marginal recurrences. Conclusion: Survival rate of marginal recurrences is superior to that of the other recurrences. The type of recurrence is a clinical prognostic value to take into account. The influence of local recurrence retreatment by proton beam therapy should be evaluated by novel studies.« less

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

PubMed

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

2018-01-01

To explore new biomarkers for indicating the recurrence and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after tumor resection, we investigated the expression and prognostic value of c-kit(CD117) in HBV-related HCC. Immunohistochemistry was used to estimate the expression of c-kit(CD117) and CD34 in the liver cancer tissues. The correlations between the expression of these biomarkers and the clinicopathologic characteristics were analyzed. The positive rate of c-kit(CD117) expression in 206 HCC cases was 48.1%, and c-kit expression was significantly related with CD34-positive microvessel density. CD34-microvessel density numbers were much higher in c-kit(+) HCC tissues than in c-kit(-) HCC tissues (44.13±17.01 vs 26.87±13.16, P =0.003). The expression of c-kit was significantly higher in patients with Edmondson grade III-IV ( P <0.001) and TNM stage III ( P <0.001). Moreover, Kaplan-Meier survival analysis showed that c-kit ( P <0.001) expression was correlated with reduced disease-free survival (DFS). Multivariate analysis identified c-kit as an independent poor prognostic factor of DFS in HCC patients ( P <0.001). Increased c-kit expression could be considered as an independent unfavorable prognostic factor for predicting DFS in HBV-related HCC patients after surgery. These results could be used to identify patients at a higher risk of early tumor recurrence and poor prognosis.

Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Stroke: South Asian Experience.

PubMed

Kamran, Saadat; Akhtar, Naveed; Salam, Abdul; Alboudi, Ayman; Rashid, Hiba; Kamran, Kainat; Khan, Rabia Ali; Mirza, Mohsin Khalid; Ahmed, Arsalan; Own, Ahmed M A; Al Rukun, Sohail; Inshasi, Jihad; Deleu, Dirk; Al Sulaiti, Ghanim; Shuaib, Ashfaq

2017-10-01

The randomized trials showed improved outcome and reduced mortality in malignant middle cerebral artery (MMCA) undergoing Decompressive hemicraniectomy (DHC) within 48 hours of stroke onset. Despite high prevalence of stroke, especially in younger individuals, high and short-term mortality from stroke in South Asian and Middle East, there is little published data on DHC in patients with MMCA stroke. This is a retrospective, multicenter cross-sectional study to measure outcome following DHC using the modified Rankin Scale (mRS) and dichotomized as favorable (mRS ≤ 4) or unfavorable (mRS > 4), at 3 months. In total, 137 patients underwent DHC. At 90 days, mortality was 16.8%; 61.3% of patients survived with an mRS of 4 or less and 38.7% had an mRS greater than 4. Age (55 years), diabetes (P = .004), hypertension (P = .021), pupillary abnormality (P = .048), uncal herniation (P = .007), temporal lobe involvement (P = .016), additional infarction (MCA + anterior cerebral artery, posterior cerebral artery) (P = .001), and infarction growth rates (P = .025) were significantly higher in patients with unfavorable prognosis in univariate analysis. Multivariate analysis showed age, additional infarction, septum pellucidum deviation greater than 1 cm, and uncal herniation to be associated with a significantly poor prognosis. Time to surgery had no impact on outcome (P = .109). Similar to the results of the studies from the West, DHC Improves functional outcome in predominantly South Asian patients with MMCA Stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

An analysis of the clinical features of lung cancer in patients with connective tissue diseases.

PubMed

Saijo, Atsuro; Hanibuchi, Masaki; Goto, Hisatsugu; Toyoda, Yuko; Tezuka, Toshifumi; Nishioka, Yasuhiko

2017-03-01

Patients with connective tissue diseases (CTDs) are at increased risk for lung cancer (LC); interstitial lung disease (ILD) is a common form of organ dysfunction in cases of CTD. However, the influence of ILD on the treatment and prognosis in LC patients with CTD is unclear. Between January 2010 and December 2014, 27 patients among all patients with CTD at our institution were diagnosed with primary LC. We retrospectively analyzed the clinical features, treatment modalities, and outcomes of these patients, and evaluated the potential prognostic factors. Forty-four LC patients without CTD were also analyzed as a control cohort. LC patients with CTD had a significantly higher incidence of ILD as a complication compared with those without CTD (52% and 14%, respectively). CTD-associated ILD (CTD-ILD) at diagnosis was associated with significantly worse survival in LC patients with CTD. Multivariate analysis demonstrated that the complication of CTD-ILD was an independent poor prognostic factor in LC patients with CTD. The incidence of acute exacerbation (AE) of CTD-ILD was 21% among LC patients with CTD, and all of these patients died despite intensive treatment including high-dose corticosteroids. The restrictions in curative therapy for LC due to the presence of ILD and AE of CTD-ILD were thought to be the major reasons for the poor outcome. LC patients with CTD had a high prevalence of ILD, and the presence of CTD-ILD was significantly associated with poor prognosis. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

"Double-hit" chronic lymphocytic leukemia: An aggressive subgroup with 17p deletion and 8q24 gain.

PubMed

Chapiro, Elise; Lesty, Claude; Gabillaud, Clémentine; Durot, Eric; Bouzy, Simon; Armand, Marine; Le Garff-Tavernier, Magali; Bougacha, Nadia; Struski, Stéphanie; Bidet, Audrey; Laharanne, Elodie; Barin, Carole; Veronese, Lauren; Prié, Nolwen; Eclache, Virginie; Gaillard, Baptiste; Michaux, Lucienne; Lefebvre, Christine; Gaillard, Jean-Baptiste; Terré, Christine; Penther, Dominique; Bastard, Christian; Nadal, Nathalie; Fert-Ferrer, Sandra; Auger, Nathalie; Godon, Catherine; Sutton, Laurent; Tournilhac, Olivier; Susin, Santos A; Nguyen-Khac, Florence

2018-03-01

Chronic lymphocytic leukemia (CLL) with 17p deletion (17p-) is associated with a lack of response to standard treatment and thus the worst possible clinical outcome. Various chromosomal abnormalities (including unbalanced translocations, deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one copy of the TP53 gene. The objective of the present study was to determine whether the type of chromosomal abnormality leading to 17p- and the additional aberrations influenced the prognosis in a series of 195 patients with 17p-CLL. Loss of 17p resulted primarily from an unbalanced translocation (70%) with several chromosome partners (the most frequent being chromosome 18q), followed by deletion 17p (23%), monosomy 17 (8%), isochromosome 17q [i(17q)] (5%) and a ring chromosome 17 (2%). In a univariate analysis, monosomy 17, a highly complex karyotype (≥5 abnormalities), and 8q24 gain were associated with poor treatment-free survival, and i(17q) (P = .04), unbalanced translocations (P = .03) and 8q24 gain (P = .001) were significantly associated with poor overall survival. In a multivariate analysis, 8q24 gain remained a significant predictor of poor overall survival. We conclude that 17p deletion and 8q24 gain have a synergistic impact on outcome, and so patients with this "double-hit" CLL have a particularly poor prognosis. Systematic, targeting screening for 8q24 gain should therefore be considered in cases of 17p- CLL. © 2017 Wiley Periodicals, Inc.

Clinical impact of endometrial cancer stratified by genetic mutational profiles, POLE mutation, and microsatellite instability.

PubMed

Haruma, Tomoko; Nagasaka, Takeshi; Nakamura, Keiichiro; Haraga, Junko; Nyuya, Akihiro; Nishida, Takeshi; Goel, Ajay; Masuyama, Hisashi; Hiramatsu, Yuji

2018-01-01

The molecular characterization of endometrial cancer (EC) can facilitate identification of various tumor subtypes. Although EC patients with POLE mutations reproducibly demonstrate better prognosis, the outcome of patients with microsatellite instability (MSI) remains controversial. This study attempted to interrogate whether genetic stratification of EC can identify distinct subsets with prognostic significance. A cohort of 138 EC patients who underwent surgical resection with curative intent was enrolled. Sanger sequencing was used to evaluate mutations in the POLE and KRAS genes. MSI analysis was performed using four mononucleotide repeat markers and methylation status of the MLH1 promoter was measured by a fluorescent bisulfite polymerase chain reaction (PCR). Protein expression for mismatch repair (MMR) proteins was evaluated by immunohistochemistry (IHC). Extensive hypermethylation of the MLH1 promoter was observed in 69.6% ECs with MLH1 deficiency and 3.5% with MMR proficiency, but in none of the ECs with loss of other MMR genes (P < .0001). MSI-positive and POLE mutations were found in 29.0% and 8.7% EC patients, respectively. Our MSI analysis showed a sensitivity of 92.7% for EC patients with MMR deficiency, and a specificity of 97.9% for EC patients with MMR proficiency. In univariate and multivariate analyses, POLE mutations and MSI status was significantly associated with progression-free survival (P = 0.0129 and 0.0064, respectively) but not with endometrial cancer-specific survival. This study provides significant evidence that analyses of proofreading POLE mutations and MSI status based on mononucleotide repeat markers are potentially useful biomarkers to identify EC patients with better prognosis.

Prognostic value of fluorine-18 fludeoxyglucose positron emission tomography parameters differs according to primary tumour location in small-cell lung cancer.

PubMed

Nobashi, Tomomi; Koyasu, Sho; Nakamoto, Yuji; Kubo, Takeshi; Ishimori, Takayoshi; Kim, Young H; Yoshizawa, Akihiko; Togashi, Kaori

2016-01-01

To investigate the prognostic value of fluorine-18 fludeoxyglucose (FDG) positron emission tomography (PET) parameters for small-cell lung cancer (SCLC), according to the primary tumour location, adjusted by conventional prognostic factors. From 2008 to 2013, we enrolled consecutive patients with histologically proven SCLC, who had undergone FDG-PET/CT prior to initial therapy. The primary tumour location was categorized into central or peripheral types. PET parameters and clinical variables were evaluated using univariate and multivariate analysis. A total of 69 patients were enrolled in this study; 28 of these patients were categorized as having the central type and 41 patients as having the peripheral type. In univariate analysis, stage, serum neuron-specific enolase, whole-body metabolic tumour volume (WB-MTV) and whole-body total lesion glycolysis (WB-TLG) were found to be significant in both types of patients. In multivariate analysis, the independent prognostic factor was found to be stage in the central type, but WB-MTV and WB-TLG in the peripheral type. Kaplan-Meier analysis demonstrated that patients with peripheral type with limited disease and low WB-MTV or WB-TLG showed significantly better overall survival than all of the other groups (p < 0.0083). The FDG-PET volumetric parameters were demonstrated to be significant and independent prognostic factors in patients with peripheral type of SCLC, while stage was the only independent prognostic factor in patients with central type of SCLC. FDG-PET is a non-invasive method that could potentially be used to estimate the prognosis of patients, especially those with peripheral-type SCLC.

Evaluation of radiological and pathological prognostic factors in surgically-treated patients with bronchoalveolar carcinoma.

PubMed

Carretta, A; Canneto, B; Calori, G; Ceresoli, G L; Campagnoli, E; Arrigoni, G; Vagani, A; Zannini, P

2001-08-01

The incidence of adenocarcinoma and bronchoalveolar carcinoma has increased in recent years. The aim of this study was to retrospectively evaluate radiological and pathological factors affecting survival in patients with bronchoalveolar carcinoma (BAC) or BAC associated with adenocarcinoma who underwent surgical treatment. From May 1988 to September 1999, 49 patients with BAC or BAC and adenocarcinoma underwent surgical treatment. Complete resection was performed in 42 patients. In these patients the impact of the following factors on survival was evaluated: stage, TNM status, radiological and pathological findings (percentage of bronchoalveolar carcinoma in the tumour, presence or absence of sclerosing and mucinous patterns, vascular invasion and lymphocytic infiltration). Twenty-nine patients were male and 20 female. Mean age was 63 years. Five-year survival was 54%. Univariate analysis of the patients who underwent complete resection demonstrated a favourable impact on survival in stages Ia and Ib (P = 0.01) and in the absence of nodal involvement (P = 0.02) and mucinous patterns (P = 0.02). Mucinous pattern was also prognostically relevant at multivariate analysis (P = 0.02). In the 27 patients with stage Ia and Ib disease, univariate analysis demonstrated that the absence of mucinous pattern (P = 0.006) and a higher percentage of BAC (P = 0.01) favourably influenced survival. The latter data were also confirmed by multivariate analysis (P = 0.01). Surgical treatment of early-stage BAC and combined BAC and adenocarcinoma is associated with favourable results. However, the definition of prognostic factors is of utmost importance to improve the results of the treatment. In our series tumours of the mucinous subtype and with a lower percentage of BAC had a worse prognosis.

Magnetic resonance metabolic profiling of estrogen receptor-positive breast cancer: correlation with currently used molecular markers

PubMed Central

Koo, Ja Seung; Kim, Siwon; Park, Vivian Youngjean; Kim, Eun-Kyung; Kim, Suhkmann; Kim, Min Jung

2017-01-01

Estrogen receptor (ER)-positive breast cancers overall have a good prognosis, however, some patients suffer relapses and do not respond to endocrine therapy. The purpose of this study was to determine whether there are any correlations between high-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) metabolic profiles of core needle biopsy (CNB) specimens and the molecular markers currently used in patients with ER-positive breast cancers. The metabolic profiling of CNB samples from 62 ER-positive cancers was performed by HR-MAS MRS. Metabolic profiles were compared according to human epidermal growth factor receptor 2 (HER2) and Ki-67 status, and luminal type, using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). In univariate analysis, the HER2-positive group was shown to have higher levels of glycine and glutamate, compared to the HER2-negative group (P<0.01, and P <0.01, respectively). The high Ki-67 group showed higher levels of glutamate than the low Ki-67 group without statistical significance. Luminal B cancers showed higher levels of glycine (P=0.01) than luminal A cancers. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the subgroups according to HER2 and Ki-67 status, and luminal type. This study showed that the metabolic profiles of CNB samples assessed by HR-MAS MRS can be used to detect potential prognostic biomarkers as well as to understand the difference in metabolic mechanism among subtypes of ER-positive breast cancer. PMID:28969000

Long-term outcomes and prognostic factors for patients with esophageal cancer following radiotherapy

PubMed Central

Chen, Chuang-Zhen; Chen, Jian-Zhou; Li, De-Rui; Lin, Zhi-Xiong; Zhou, Ming-Zhen; Li, Dong-Sheng; Chen, Zhi-Jian

2013-01-01

AIM: To evaluate long-term outcomes and prognostic factors for esophageal squamous cell carcinoma (SCC) treated with three dimensional conformal radiotherapy (3D-CRT). METHODS: Between January 2005 and December 2006, 153 patients (120 males, 33 females) with pathologically confirmed esophageal SCC and treated with 3D-CRT in Cancer Hospital of Shantou University were included in this retrospective analysis. Median age was 60 years (range: 37-84 years). The proportion of tumor location was as follows: upper thorax (including the cervical region), 73 (48%); middle thorax, 73 (48%); lower thorax, 7 (5%), respectively. The median radiation dose was 64 Gy (range: 50-74 Gy). Fifty four cases (35%) received cisplatin-based concurrent chemotherapy. Univariate and multivariate analysis were performed to determine the association between the correlative factors and prognosis. RESULTS: The five-year overall survival rate was 26.3%, with a median follow-up of 49 mo (range: 3-66 mo) for patients who were still alive. On univariate analysis, lesion location, lesion length by barium esophagogram, computed tomography imaging characteristics including Y diameter (anterior-posterior, AP, extent of tumor), gross tumor volume of primary lesion (GTV-E), volume of positive lymph nodes (GTV-LN), and the total target volume (GTV-T = GTV-E + GTV-LN) were prognostic for overall survival. By multivariate analysis, only the Y diameter [hazard ratio (HR) 2.219, 95%CI 1.141-4.316, P = 0.019] and the GTV-T (HR 1.372, 95%CI 1.044-1.803, P = 0.023) were independent prognostic factors for survival. CONCLUSION: The overall survival of esophageal carcinoma patients undergoing 3D-CRT was promising. The best predictors for survival were GTV-T and Y diameter. PMID:23539205

Long-term outcomes and prognostic factors for patients with esophageal cancer following radiotherapy.

PubMed

Chen, Chuang-Zhen; Chen, Jian-Zhou; Li, De-Rui; Lin, Zhi-Xiong; Zhou, Ming-Zhen; Li, Dong-Sheng; Chen, Zhi-Jian

2013-03-14

To evaluate long-term outcomes and prognostic factors for esophageal squamous cell carcinoma (SCC) treated with three dimensional conformal radiotherapy (3D-CRT). Between January 2005 and December 2006, 153 patients (120 males, 33 females) with pathologically confirmed esophageal SCC and treated with 3D-CRT in Cancer Hospital of Shantou University were included in this retrospective analysis. Median age was 60 years (range: 37-84 years). The proportion of tumor location was as follows: upper thorax (including the cervical region), 73 (48%); middle thorax, 73 (48%); lower thorax, 7 (5%), respectively. The median radiation dose was 64 Gy (range: 50-74 Gy). Fifty four cases (35%) received cisplatin-based concurrent chemotherapy. Univariate and multivariate analysis were performed to determine the association between the correlative factors and prognosis. The five-year overall survival rate was 26.3%, with a median follow-up of 49 mo (range: 3-66 mo) for patients who were still alive. On univariate analysis, lesion location, lesion length by barium esophagogram, computed tomography imaging characteristics including Y diameter (anterior-posterior, AP, extent of tumor), gross tumor volume of primary lesion (GTV-E), volume of positive lymph nodes (GTV-LN), and the total target volume (GTV-T = GTV-E + GTV-LN) were prognostic for overall survival. By multivariate analysis, only the Y diameter [hazard ratio (HR) 2.219, 95%CI 1.141-4.316, P = 0.019] and the GTV-T (HR 1.372, 95%CI 1.044-1.803, P = 0.023) were independent prognostic factors for survival. The overall survival of esophageal carcinoma patients undergoing 3D-CRT was promising. The best predictors for survival were GTV-T and Y diameter.

Endometrial Carcinomas with POLE Exonuclease Domain Mutations Have a Favorable Prognosis.

PubMed

McConechy, Melissa K; Talhouk, Aline; Leung, Samuel; Chiu, Derek; Yang, Winnie; Senz, Janine; Reha-Krantz, Linda J; Lee, Cheng-Han; Huntsman, David G; Gilks, C Blake; McAlpine, Jessica N

2016-06-15

The aim of this study was to confirm the prognostic significance of POLE exonuclease domain mutations (EDM) in endometrial carcinoma patients. In addition, the effect of treatment on POLE-mutated tumors was assessed. A retrospective patient cohort of 496 endometrial carcinoma patients was identified for targeted sequencing of the POLE exonuclease domain, yielding 406 evaluable tumors. Univariable and multivariable analyses were performed to determine the effect of POLE mutation status on progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). Combining results from eight studies in a meta-analysis, we computed pooled HR for PFS, DSS, and OS. POLE EDMs were identified in 39 of 406 (9.6%) endometrial carcinomas. Women with POLE-mutated endometrial carcinomas were younger, with stage I (92%) tumors, grade 3 (62%), endometrioid histology (82%), and frequent (49%) lymphovascular invasion. In univariable analysis, POLE-mutated endometrial carcinomas had significantly improved outcomes compared with patients with no EDMs for PFS, DSS, and OS. In multivariable analysis, POLE EDMs were only significantly associated with improved PFS. The effect of adjuvant treatment on POLE-mutated cases could not be determined conclusively; however, both treated and untreated patients with POLE EDMs had good outcomes. Meta-analysis revealed an association between POLE EDMs and improved PFS and DSS with pooled HRs 0.34 [95% confidence interval (CI), 0.15-0.73] and 0.35 (95% CI, 0.13-0.92), respectively. POLE EDMs are prognostic markers associated with excellent outcomes for endometrial carcinoma patients. Further investigation is needed to conclusively determine if treatment is necessary for this group of women. Clin Cancer Res; 22(12); 2865-73. ©2016 AACR. ©2016 American Association for Cancer Research.

Prognostic value of tumor suppressors in osteosarcoma before and after neoadjuvant chemotherapy.

PubMed

Robl, Bernhard; Pauli, Chantal; Botter, Sander Martijn; Bode-Lesniewska, Beata; Fuchs, Bruno

2015-05-09

Primary bone cancers are among the deadliest cancer types in adolescents, with osteosarcomas being the most prevalent form. Osteosarcomas are commonly treated with multi-drug neoadjuvant chemotherapy and therapy success as well as patient survival is affected by the presence of tumor suppressors. In order to assess the prognostic value of tumor-suppressive biomarkers, primary osteosarcoma tissues were analyzed prior to and after neoadjuvant chemotherapy. We constructed a tissue microarray from high grade osteosarcoma samples, consisting of 48 chemotherapy naïve biopsies (BXs) and 47 tumor resections (RXs) after neoadjuvant chemotherapy. We performed immunohistochemical stainings of P53, P16, maspin, PTEN, BMI1 and Ki67, characterized the subcellular localization and related staining outcome with chemotherapy response and overall survival. Binary logistic regression analysis was used to analyze chemotherapy response and Kaplan-Meier-analysis as well as the Cox proportional hazards model was applied for analysis of patient survival. No significant associations between biomarker expression in BXs and patient survival or chemotherapy response were detected. In univariate analysis, positive immunohistochemistry of P53 (P = 0.008) and P16 (P16; P = 0.033) in RXs was significantly associated with poor survival prognosis. In addition, presence of P16 in RXs was associated with poor survival in multivariate regression analysis (P = 0.003; HR = 0.067) while absence of P16 was associated with good chemotherapy response (P = 0.004; OR = 74.076). Presence of PTEN on tumor RXs was significantly associated with an improved survival prognosis (P = 0.022). Positive immunohistochemistry (IHC) of P16 and P53 in RXs was indicative for poor overall patient survival whereas positive IHC of PTEN was prognostic for good overall patient survival. In addition, we found that P16 might be a marker of osteosarcoma chemotherapy resistance. Therefore, our study supports the use of tumor RXs to assess the prognostic value of biomarkers.

Impact of IGF-1, IGF-1R, and IGFBP-3 promoter methylation on the risk and prognosis of esophageal carcinoma.

PubMed

Ye, Peng; Qu, Chang-Fa; Hu, Xue-Lin

2016-05-01

The aim of this study is to investigate IGF-1, IGF-1R, and IGFBP-3 methylations in esophageal carcinoma (EC) patients and their relationship with the development and prognosis of EC. This study population consisted of 264 patients (case group) whom EC radical resection was performed and 283 healthy individuals (control group). Methylation-specific PCR (MSP) detected the methylation status of IGF-1, IGF-1R, and IGFBP-3 in the peripheral blood in both groups. The expressions of IGF-1, IGF-1R, and IGFBP-3 in EC and adjacent normal tissues were detected by immunohistochemistry (IHC). The methylation rates of IGF-1, IGF-1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 in the case group were higher than those in the control group (all P < 0.05). Additionally, there were statistical significances for the methylation rates of IGF-1, IGF-1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 IGF-1 among patients of different clinicopathological features (all P < 0.05). The positive expression rates of IGF-1 and IGF-1R in EC were significantly higher than those in adjacent normal tissues (both P < 0.001), and the rate of IGFBP-3 in EC was significantly lower than that in adjacent normal tissues (P < 0.05). Correlation analysis showed that IGF-1 and IGF1R gene promoter methylation was positively correlated with the positive expressions of IGF-1 (r = 0.139, P = 0.024) and IGF-1R (r = 0.135, P = 0.028), while the IGFBP3 methylation was negatively correlated with the positive expression of IGFBP3 (r = -0.133, P = 0.031). The positive expressions of IGF-1, IGF-1R, and IGFBP-3 were related to different clinicopathological features (all P < 0.05). Cox multivariate analysis results showed that methylation status of IGF-1, IGF-1R, and IGF-1 + IGF1R + IGFBP3 ; expressions of IGF-1 and IGF-1R protein; infiltration depth; and lymph node metastasis (LNM) were independent factors of EC prognosis. Our study demonstrated that methylation of IGF-1, IGF1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 was closely linked with the occurrence of EC and patients' clinicopathological features. Besides, the methylation status of the target genes and the expressions of IGF-1 and IGF-1R protein were independent factors of EC prognosis, which could provide a direction for the prognosis and treatment of EC.

Prognostic value of inflammation-based markers in patients with pancreatic cancer administered gemcitabine and erlotinib.

PubMed

Lee, Jae Min; Lee, Hong Sik; Hyun, Jong Jin; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Chun, Hoon Jai; Um, Soon Ho; Kim, Chang Duck

2016-07-15

To evaluate the value of systemic inflammation-based markers as prognostic factors for advanced pancreatic cancer (PC). Data from 82 patients who underwent combination chemotherapy with gemcitabine and erlotinib for PC from 2011 to 2014 were collected retrospectively. Data that included the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio, and the C-reactive protein (CRP)-to-albumin (CRP/Alb) ratio were analyzed. Kaplan-Meier curves, and univariate and multivariate Cox proportional hazards regression analyses were used to identify the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). The univariate analysis demonstrated the prognostic value of the NLR (P = 0.049) and the CRP/Alb ratio (P = 0.047) in relation to PFS, and a positive relationship between an increase in inflammation-based markers and a poor prognosis in relation to OS. The multivariate analysis determined that an increased NLR (hazard ratio = 2.76, 95%CI: 1.33-5.75, P = 0.007) is an independent prognostic factor for poor OS. There was no association between the PLR and the patients' prognoses in those who had received chemotherapy that comprised gemcitabine and erlotinib in combination. The Kaplan-Meier method and the log-rank test determined significantly worse outcomes in relation to PFS and OS in patients with an NLR > 5 or a CRP/Alb ratio > 5. Systemic inflammation-based markers, including increases in the NLR and the CRP/Alb ratio, may be useful for predicting PC prognoses.

High Pretreatment Plasma D-dimer Levels Are Associated With Poor Prognosis in Patients With Ovarian Cancer Independently of Venous Thromboembolism and Tumor Extension.

PubMed

Sakurai, Manabu; Satoh, Toyomi; Matsumoto, Koji; Michikami, Hiroo; Nakamura, Yuko; Nakao, Sari; Ochi, Hiroyuki; Onuki, Mamiko; Minaguchi, Takeo; Yoshikawa, Hiroyuki

2015-05-01

Elevated plasma D-dimer (DD) is associated with decreased survival among patients with breast, lung, and colon cancers. The present study clarifies the prognostic significance of pretreatment plasma DD levels in patients with epithelial ovarian cancer (EOC). We investigated pretreatment DD levels and other variables for overall survival using univariate and multivariate analyses in 134 consecutive patients with EOC stages II to IV who were initially treated between November 2004 and December 2010. The median follow-up period was 53 (7-106) months. Univariate analysis significantly associated elevated pretreatment DD (≥2.0 μg/mL) levels to poor 5-year overall survival rates irrespective of previously treated venous thromboembolism (72.2% vs 52.6%, P = 0.039). Cancer antigen 125 levels of 200 U/mL or higher (P = 0.011), distant metastases (P = 0.0004), residual tumors (P < 0.0001), and International Federation of Gynecology and Obstetrics stage III/IV (P = 0.0033) were also poor prognostic factors. Multivariate analysis independently associated DD levels of 2.0 μg/mL or higher (P = 0.041), distant metastases (P = 0.013), and residual tumors (P < 0.0001) with poor overall survival. High pretreatment DD levels are associated with poor overall survival in patients with EOC independently of venous thromboembolism and tumor extension and might comprise a promising prognostic biomarker for patients with EOC.

Percentage of positive prostate biopsies independently predicts biochemical outcome following radiation therapy for prostate cancer.

PubMed

Gabriele, Domenico; Garibaldi, Monica; Girelli, Giuseppe; Taraglio, Stefano; Duregon, Eleonora; Gabriele, Pietro; Guiot, Caterina; Bollito, Enrico

2016-06-01

This work aims to definitely show the ability of percentage of positive biopsy cores (%PC) to independently predict biochemical outcome beyond traditional pretreatment risk-factors in prostate cancer (PCa) patients treated with radiotherapy. A cohort of 2493 men belonging to the EUREKA-2 retrospective multicentric database on (PCa) and treated with external-beam radiation therapy (EBRT) as primary treatment comprised the study population (median follow-up 50 months). A Cox regression time to prostate-specific antigen (PSA) failure analysis was performed to evaluate the predictive power of %PC, both in univariate and multivariate settings, with age, pretreatment PSA, clinical-radiological staging, bioptic Gleason Score (bGS), RT dose and RT +/- ADT as covariates. P statistics for %PC is lower than 0.001 both in univariate and multivariate models. %PC as a continuous variable yields an AUC of 69% in ROC curve analysis for biochemical relapse. Four classes of %PC (1-20%, 21-50%, 51-80% and 81-100%) distinctly split patients for risk of biochemical relapse (overall log-rank test P<0.0001), with biochemical progression free survival (bPFS) at 5-years ranging from 88% to 58% and 10-years bPFS ranging from 80% to 38%. We strongly affirm the usefulness of %PC information beyond main risk factors (PSA, staging and bGS) in predicting biochemical recurrence after EBRT for PCa. The stratification of patients according to %PC may be valuable to further discriminate cases with favourable or adverse prognosis.

Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis.

PubMed

Janjigian, Y Y; Werner, D; Pauligk, C; Steinmetz, K; Kelsen, D P; Jäger, E; Altmannsberger, H-M; Robinson, E; Tafe, L J; Tang, L H; Shah, M A; Al-Batran, S-E

2012-10-01

To determine whether human epidermal growth factor receptor 2 (HER2) status is an independent prognostic factor in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma. Formalin-fixed paraffin-embedded tumor samples from 381 metastatic gastric/GEJ cancer patients enrolled at Krankenhaus Nordwest and Memorial Sloan-Kettering Cancer Centers on six first-line trials of chemotherapy without trastuzumab were examined for HER2 by immunohistochemistry (IHC) and in situ hybridization (ISH). IHC 3+ or ISH-positive tumors were considered HER2 positive. Seventy-eight of 381 patients (20%) had HER2-positive disease. In the multivariate logistic model, there were significantly higher rates of HER2 positivity in patients with liver metastasis (liver metastasis 31%; no liver metastasis 11%; P = 0.025) and intestinal histology (intestinal 33%; diffuse/mixed 8%; P = 0.001). No significant differences in HER2 positivity were found between resections and biopsies or primaries and metastases. Patients with HER2-positive gastric cancer had longer median overall survival compared with HER2-negative gastric cancer patients (13.9 versus 11.4 months, P = 0.047), but multivariate analysis indicated that HER2 status was not an independent prognostic factor (hazard ratio 0.79; 0.44-1.14; P = 0.194). Approximately 20% of Western patients with metastatic gastric cancer are HER2 positive. Unlike breast cancer, HER2 positivity is not independently prognostic of patient outcome in metastatic gastric or GEJ.

Spironolactone in patients with heart failure and preserved ejection fraction.

PubMed

Sánchez-Sánchez, C; Mendoza-Ruiz de Zuazu, H F; Formiga, F; Manzano, L; Ceresuela, L M; Carrera-Izquierdo, M; González Franco, Á; Epelde-Gonzalo, F; Cerqueiro-González, J M; Montero-Pérez-Barquero, M

2015-01-01

Aldosterone inhibitors have been shown to be beneficial for patients with systolic heart failure. However, the evidence from patients with heart failure and preserved ejection fraction (HFPEF) is limited. We evaluated the role of spironolactone in the prognosis of a cohort of patients with HFPEF. We analyzed the outcomes of patients hospitalized for HFPEF in 52 departments of internal medicine of the Spanish RICA registry according to those who did and did not take spironolactone. We recorded the posthospital mortality rate and readmissions at 1 year and performed a multivariate survival analysis. We included 1212 patients with HFPEF, with a mean age of 79 years (standard deviation, 7.9), (64.1% women), the majority of whom had hypertensive heart disease (50.7%). The patients treated with spironolactone, compared with those who were not treated with this diuretic, had a more advanced functional class, a higher number of readmissions (44.3 vs. 29.1%; p<0.001) and a higher rate in the combined variable of readmissions/mortality (39.0 vs. 29.0%; p=0.001). In the multivariate analysis, the administration of spironolactone was associated with an increase in readmissions (RR, 1.4; 95% CI, 1.16-1.78; p=0.001). For patients with HFPEF, the administration of spironolactone was associated with an increase in all-cause readmission, perhaps due to the higher rate of hyperpotassemia. Copyright © 2015. Published by Elsevier España, S.L.U.

The Parameters Affecting the Success of Irrigation and Debridement with Component Retention in the Treatment of Acutely Infected Total Knee Arthroplasty

PubMed Central

Kim, Jae Gyoon; Bae, Ji Hoon; Lee, Seung Yup; Cho, Won Tae

2015-01-01

Background The aims of our study were to evaluate the success rate of irrigation and debridement with component retention (IDCR) for acutely infected total knee arthroplasty (TKA) (< 4 weeks of symptom duration) and to analyze the factors affecting prognosis of IDCR. Methods We retrospectively reviewed 28 knees treated by IDCR for acutely infected TKA from 2003 to 2012. We evaluated the success rate of IDCR. All variables were compared between the success and failure groups. Multivariable logistic regression analysis was also used to examine the relative contribution of these parameters to the success of IDCR. Results Seventeen knees (60.7%) were successfully treated. Between the success and failure groups, there were significant differences in the time from primary TKA to IDCR (p = 0.021), the preoperative erythrocyte sedimentation rate (ESR; p = 0.021), microorganism (p = 0.006), and polyethylene liner exchange (p = 0.017). Multivariable logistic regression analysis of parameters affecting the success of IDCR demonstrated that preoperative ESR (odds ratio [OR], 1.02; p = 0.041), microorganism (OR, 12.4; p = 0.006), and polyethylene liner exchange (OR, 0.07; p = 0.021) were significant parameters. Conclusions The results show that 60.7% of the cases were successfully treated by IDCR for acutely infected TKA. The preoperative ESR, microorganism, and polyethylene liner exchange were factors that affected the success of IDCR in acutely infected TKA. PMID:25729521

Central nervous system relapse in peripheral T-cell lymphomas: a Swedish Lymphoma Registry study.

PubMed

Ellin, Fredrik; Landström, Jenny; Jerkeman, Mats; Relander, Thomas

2015-07-02

Central nervous system (CNS) relapse in non-Hodgkin lymphoma (NHL) carries a very poor prognosis. Risk factors and outcome have been studied in aggressive B-cell lymphomas, but very little is known about the risk in peripheral T-cell lymphoma (PTCL). We aimed at analyzing risk factors for CNS involvement at first relapse or progression, as well as the outcome of these patients, in a large population-based cohort of patients with PTCL. Twenty-eight out of 625 patients (4.5%) developed CNS disease over time. In multivariable analysis, disease characteristics at diagnosis independently associated with an increased risk for later CNS involvement were involvement of more than 1 extranodal site (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.07-6.29; P = .035) and skin (HR, 3.51; 95% CI, 1.26-9.74; P = .016) and gastrointestinal involvement (HR, 3.06; 95% CI, 1.30-7.18; P = .010). The outcome of relapsed/refractory patients was very poor, and CNS involvement was not associated with a significantly worse outcome compared with relapsed/refractory patients without CNS involvement in multivariable analysis (HR, 1.6; 95% CI, 0.96-2.6; P = .074). The results from the present study indicate that CNS relapse in PTCL occurs at a frequency similar to what is seen in aggressive B-cell lymphomas, but the poor outcomes in relapse are largely driven by systemic rather than CNS disease. © 2015 by The American Society of Hematology.

Clinicopathological characteristics and prognostic factors of primary gastrointestinal lymphoma: a 22-year experience from South China.

PubMed

Li, Minrui; Zhang, Shenghong; Gu, Fang; Xiao, Weiwei; Yao, Jiayan; Chao, Kang; Chen, Minhu; Li, Juan; Zhong, Bihui

2014-01-01

Primary gastrointestinal lymphoma (PGIL) is a kind of relatively rare cancer and easily misdiagnosed due to its unspecific signs in digestive tract. Data including 216 patients histologically diagnosed as PGIL between January 1991 and October 2012 from The First Affiliated Hospital of Sun Yat-sen University were reviewed. This study was to investigate the clinicopathological features and prognosis, and make the comparison between the different sites of PGIL. Abdominal pain (75.9%) was the most frequent symptom and intermediate-grade lymphoma (53.7%) presented as the most common histological type. Intestine (55.1%) was the most common site involved, followed by stomach (38.5%), both intestine and stomach (6.4%). PGIL of different original site showed distinguished clinicopathological characteristics that patients in Stomach and GI group were older than Intestine group (Mean age: 54 and 53 vs. 43 years, p<0.001); diarrhea, B symptom, abdominal mass and complication occurred more in intestine group. Histologically, high-grade lymphoma (especially T-cell type) almost located in Intestine group (82.5%). Five-year overall survival (OS) and event-free survival (EFS) for all PGIL patients were 56.4% and 49.3%, respectively. Stomach group had better OS (72.3%) and EFS (48.4%) than Intestine group (43.1% and 23.6% respectively), but it lost the significance in the multivariate analysis. Univariate and multivariate analysis revealed that performance status, lactate dehydrogenase (LDH) level and histological type were independent prognostic factors for PGIL.

Predictive factors of mortality in pediatric patients with acute renal injury associated with sepsis.

PubMed

Riyuzo, Marcia C; Silveira, Liciana V de A; Macedo, Célia S; Fioretto, José R

To evaluate the prognosis factors of children with sepsis and acute kidney injury. This was a retrospective study of children with sepsis and acute kidney injury that were admitted to the pediatric intensive care unit (PICU) of a tertiary hospital. A multivariate analysis was performed to compare risk factors for mortality. Seventy-seven children (47 males) were retrospectively studied, median age of 4 months. Mean length of hospital stay was 7.33±0.16 days, 68.9% of patients received mechanical ventilation, 25.9% had oligo-anuria, and peritoneal dialysis was performed in 42.8%. The pRIFLE criteria were: injury (5.2%) and failure (94.8%), and the staging system criteria were: stage 1 (14.3%), stage 2 (29.9%), and stage 3 (55.8%). The mortality rate was 33.7%. In the multivariate analysis, the risk factors for mortality were PICU length of stay (OR=0.615, SE=0.1377, 95% CI=0.469-0.805, p=0.0004); invasive mechanical ventilation (OR=14.599, SE=1.1178, 95% CI=1.673-133.7564, p=0.0155); need for dialysis (OR=9.714, SE=0.8088, 95% CI=1.990-47.410, p=0.0049), and hypoalbuminemia (OR=10.484, SE=1.1147, 95% CI=1.179-93.200, p=0.035). The risk factors for mortality in children with acute kidney injury were associated with sepsis severity. Copyright © 2016. Published by Elsevier Editora Ltda.

Associations between ABO blood groups and biochemical recurrence after radical prostatectomy.

PubMed

Ohno, Yoshio; Ohori, Makoto; Nakashima, Jun; Okubo, Hidenori; Satake, Naoya; Takizawa, Issei; Hashimoto, Takeshi; Hamada, Riu; Nakagami, Yoshihiro; Yoshioka, Kunihiko; Tachibana, Masaaki

2015-01-01

Recent studies have demonstrated associations between ABO blood groups and prognosis in various types of cancers. The aim of this study was to investigate the association between ABO blood groups and biochemical recurrence (BCR) after radical prostatectomy (RP). A total of 555 patients with prostate cancer who underwent RP were included in the study. No patients received neoadjuvant and/or adjuvant therapy. The effect of ABO blood groups on BCR was examined using univariate and multivariate analyses. During the follow-up period (mean, 52.0 months), 166 patients (29.9%) experienced BCR, with a 5-year BCR-free rate of 67.3%. Although the ABO blood group was not a significantly associated with BCR in the univariate analysis, it was an independent predictor of BCR in the multivariate analysis: blood type O patients had a significantly lower risk of BCR compared to type A patients (Hazard ratio, 0.608; 95% confidence interval, 0.410-0.902; P = 0.014). Further analyses revealed that surgical margin status confounded the assessment of the association between the ABO blood group and BCR. In the analyses of patients with a negative surgical margin, the 5-year BCR-free rate in blood type O patients was a significantly higher than that in type A patients (91.2% vs. 71.0%; P = 0.026). Blood type O is significantly associated with a decreased risk of biochemical recurrence after radical prostatectomy. Further studies are needed to clarify the nature of this association.

Effects of Preoperative Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios on Survival in Patients with Extrahepatic Cholangiocarcinoma.

PubMed

Kitano, Yuki; Yamashita, Yo-Ichi; Yamamura, Kensuke; Arima, Kota; Kaida, Takayoshi; Miyata, Tatsunori; Nakagawa, Shigeki; Mima, Kosuke; Imai, Katsunori; Hashimoto, Daisuke; Chikamoto, Akira; Baba, Hideo

2017-06-01

As indicators of systemic inflammatory response, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict prognoses for various cancers. This study investigated their prognostic significance in extrahepatic cholangiocarcinoma (ECC). We analyzed 120 patients who underwent surgery for ECC between 2000 and 2014. We calculated preoperative NLR and PLR and evaluated their correlations with patients' clinicopathological features and prognosis. Although high NLR was not associated with worse recurrence-free survival (RFS) (hazard ratio (HR)=1.32, p=0.26), cancer-specific survival (CSS) (HR=1.35, p=0.31) and overall survival (OS) (HR=1.19, p=0.52), high PLR was significantly associated with worse RFS (HR=1.85, p=0.01), CSS (HR=2.38, p=0.002) and OS (HR=1.98, p=0.008). In multivariate analysis, high PLR (HR=1.89, p=0.02) and lymph node metastasis (HR=1.78, p=0.03) were independent prognostic factors for OS. A high PLR had more liver recurrences (p=0.04) and recurrences within 1 year (HR=2.38, p=0.02) than low PLR. High preoperative PLR was an independent predictor of poor prognosis for patients with ECC who underwent resections. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Effect of circulatory assistance on premature death and long-term prognosis.

PubMed

Sánchez Lázaro, I J; Almenar Bonet, L; Martínez-Dolz, L; Moro López, J; Rueda Soriano, J; Arnau Vives, M A; Buendía Fuentes, F; Ortiz Martínez, V; Cano Pérez, O; Sánchez Soriano, R; Salvador Sanz, A

2008-11-01

Patients undergoing urgent heart transplantation (HT) have a poorer prognosis and more long-term complications. The objective of this study was to compare the preoperative course in patients undergoing urgent HT according to the need for preoperative intra-aortic balloon counterpulsation (IABP). We studied 102 consecutive patients including 23 patients with IABP who underwent urgent HT between January 2000 and September 2006. We excluded patients who received combination transplants, those who underwent repeat HT, and pediatric patients who underwent HT. The statistical methods used were the t test for quantitative variables and the chi(2) test for qualitative variables. A logistic regression model was constructed to assess the possible relationship between IABP and other variables on premature death within 30 days after HT. Mean (SD) patient-age was 50 (10) years. No significant differences were observed in baseline characteristics between the IABP and the non-IAPB groups. The IABP patient group had higher rates of acute graft failure (45.5% vs 35.4%; P = .46) and premature death (18.8% vs 14.8%; P = .67) and shorter long-term survival (40.6 [34.9] vs 54.5 [43.7] mo; P = .30). Multivariate analysis demonstrated no association between the need for IABP and increased frequency of premature death. Use of IABP is not associated with premature or late death. We recommend use of IABP in patients with acute decompensated heart failure to stabilize them before HT.

Low Platelet to White Blood Cell Ratio Indicates Poor Prognosis for Acute-On-Chronic Liver Failure.

PubMed

Jie, Yusheng; Gong, Jiao; Xiao, Cuicui; Zhu, Shuguang; Zhou, Wenying; Luo, Juan; Chong, Yutian; Hu, Bo

2018-01-01

Background. Platelet to white blood cell ratio (PWR) was an independent prognostic predictor for outcomes in some diseases. However, the prognostic role of PWR is still unclear in patients with hepatitis B related acute-on-chronic liver failure (ACLF). In this study, we evaluated the clinical performances of PWR in predicting prognosis in HBV-related ACLF. Methods. A total of 530 subjects were recruited, including 97 healthy controls and 433 with HBV-related ACLF. Liver function, prothrombin time activity (PTA), international normalized ratio (INR), HBV DNA measurement, and routine hematological testing were performed at admission. Results . At baseline, PWR in patients with HBV-related ACLF (14.03 ± 7.17) was significantly decreased compared to those in healthy controls (39.16 ± 9.80). Reduced PWR values were clinically associated with the severity of liver disease and the increased mortality rate. Furthermore, PWR may be an inexpensive, easily accessible, and significant independent prognostic index for mortality on multivariate analysis (HR = 0.660, 95% CI: 0.438-0.996, p = 0.048) as well as model for end-stage liver disease (MELD) score. Conclusions . The PWR values were markedly decreased in ACLF patients compared with healthy controls and associated with severe liver disease. Moreover, PWR was an independent prognostic indicator for the mortality rate in patients with ACLF. This investigation highlights that PWR comprised a useful biomarker for prediction of liver severity.