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Cox Proportional Hazards Analysis (cox + proportional_hazard_analysis)
Selected AbstractsThe association of HLA-DR13 with lower graft survival rates in hepatitis B and primary sclerosing cholangitis caucasian patients receiving a liver transplantLIVER TRANSPLANTATION, Issue 4 2006Yasuro Futagawa We investigated an association of human leukocyte antigen (HLA)-DR13 to graft survival in liver transplantation among Caucasian recipients. 28,708 deceased liver transplants performed between January 1990 and December 2002 in the United States as reported to the United Network for Organ Sharing registry were utilized to compare survival rates. We utilized Caucasian adult patients (>20 years) by Kaplan-Meier curves, log-rank tests, and Cox proportional hazard analyses. HLA-DR13-negative hepatitis B virus (HBV) and primary sclerosing cholangitis (PSC) recipients yielded significantly lower graft survival rates than those of DR13-negative patients (P = 0.002, P = 0.015, respectively). This negative association was still significant after adjusting potential confounding factors. The Cox test demonstrated that HLA-DR13-positive groups have a significantly higher hazard ratio in PSC (1.40; P = 0.029; 95% confidence interval, 1.04-1.90) and HBV patients (1.78; P = 0.032; 95% confidence interval, 1.05-3.02). In conclusion, our data suggest that HLA-DR13 is a strong, positive predictor of increased risk for graft loss in HBV and PSC liver transplant recipients. Further study is needed to test the hypothesis that DR13-related immune responses may play a role in mediating graft loss in HBV and PSC liver transplantations. Liver Transpl 12:600,604, 2006. © 2006 AASLD. [source] Patterns of care for men with prostate cancer after failure of primary treatmentCANCER, Issue 2 2006Tracey L. Krupski MD Abstract BACKGROUND. This study sought to determine trends in patterns of care after failure of primary prostate cancer treatment and to determine whether nonclinical factors influenced the receipt of secondary treatment. METHODS. The authors identified individuals treated for nonmetastatic prostate cancer in the years 1991,1999 from the linked databases of Medicare and the National Cancer Institute's Surveillance, Epidemiology, and End Results registry. The outcome of interest was receipt of secondary therapy. They performed Cox proportional hazard analyses to investigate the link between demographic and clinical characteristics and the likelihood of receiving secondary treatment after either surgery or radiation. RESULTS. Of 65,716 subjects who met our inclusion criteria, 10,200 (15%) received some form of secondary therapy. For men undergoing initial surgical or radiation therapy, tumor grade, year of diagnosis, and geographic region were associated with secondary therapy. No socioeconomic factors such as education, ethnicity, or income level were associated with secondary therapy. CONCLUSIONS. Patterns of care after primary prostate cancer therapy continue to vary regionally. Standardized clinical algorithms and utilization of prostate-specific antigen testing appear to have influenced secondary therapy rates. Cancer 2006. © 2006 American Cancer Society. [source] The effect of menatetrenone, a vitamin K2 analog, on disease recurrence and survival in patients with hepatocellular carcinoma after curative treatmentCANCER, Issue 4 2006A pilot study Abstract BACKGROUND The high recurrence rate of hepatocellular carcinoma (HCC) determines the long-term prognosis for patients with HCC. In the current study, the authors tested the effects of menatetrenone, a vitamin K2 analog, on recurrent HCC and survival after curative treatment. METHODS Sixty-one patients who were diagnosed as free of HCC after surgical resection or percutaneous local ablation were assigned randomly assigned to either a menatetrenone group (n = 32 patients) or a control group (n = 29 patients). Patients in the menatetrenone group received a daily oral dose of 45 mg of menatetrenone. Disease recurrence and survival rates were analyzed in patients with HCC. RESULTS The cumulative recurrence rates in the menatetrenone group were 12.5% at 12 months, 39.0% at 24 months, and 64.3% at 36 months; and the corresponding recurrence rates in the control group were 55.2%, 83.2%, and 91.6%, respectively (P = 0.0002). Similar results were obtained even for patients who had low baseline levels of serum des-,-carboxy-prothrombin. Univariate and multivariate Cox proportional hazard analyses showed that the administration of menatetrenone was the only factor related to the recurrence rate of HCC. The cumulative survival rates for the patients who received menatetrenone were 100% at 12 months, 96.6% at 24 months, and 87.0% at 36 months; and the corresponding survival rates for patients in the control group were 96.4%, 80.9%, and 64.0%, respectively (P = 0.051). CONCLUSIONS The current study findings suggested that menatetrenone may have a suppressive effect on recurrence of HCC and a beneficial effect on survival, although a larger, placebo-controlled trial will be required to prove these effects. Cancer 2006. © 2006 American Cancer Society. [source] Prospective study on the risk of hepatocellular carcinoma among hepatitis C virus-positive blood donors focusing on demographic factors, alanine aminotransferase level at donation and interaction with hepatitis B virusINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Hideo Tanaka Abstract The risk for hepatocellular carcinoma (HCC) among asymptomatic hepatitis C virus (HCV) carriers is not well understood. A community-based prospective study was conducted for over 8 years by record linkage to the Osaka Cancer Registry. The subjects were 1,927 individuals who were positive for anti-HCV through screening for second-generation HCV antibody (passive hemagglutination assay: , 212) in voluntary blood donation. The risk factors for HCC and interaction between HCV and hepatitis B virus (HBV) infection were evaluated by including additional blood donors: 2,519 individuals positive for hepatitis B virus surface antigen (HBsAg) alone, 25 positive for both anti-HCV and HBsAg, 150,379 negative for both anti-HCV and HBsAg. The incidence of HCC (/105 person-years) among the HCV-positive individuals increased with age in both genders, ranging from 68 to 1,306 among those aged 45,74 years. In the HCV-positive individuals, the cumulative risk of developing HCC between the ages of 40 and 74 year was 21.6% among males and 8.7% among females. A stepwise increase in risk was noted as the serum alanine aminotransferase level increased or serum cholesterol level at baseline decreased in multivariate Cox proportional hazard analysis. The 9-year cumulative incidence of HCC among individuals positive for HCV alone, those positive for HBsAg alone and those positive for both was 3.0%, 2.0% and 12.0%, respectively. The age-and-sex-adjusted rate ratio was 126, 102 and 572, respectively, when those negative for both were used as a reference. The results demonstrate an increased risk for HCC among asymptomatic HCV-positive individuals in Japan. Coinfection with HBV and HCV carried a superadditive risk for HCC. © 2004 Wiley-Liss, Inc. [source] Evidence for an age-related influence of microsatellite instability on colorectal cancer survivalINTERNATIONAL JOURNAL OF CANCER, Issue 6 2002Susan M. Farrington Abstract It is well established that microsatellite instability (MSI), the hallmark of defective DNA mismatch repair (MMR), is associated with prolonged survival in colorectal cancer compared with tumours that are microsatellite stable (MSS). MSI in sporadic colorectal tumours is primarily due to epigenetic silencing of MLH1. However, there are no prospective population-based studies of survival in patients with germline MMR gene mutations who develop cancer. Although MSI is almost universal in tumours from HNPCC family members, there is a potential confounding effect of ascertainment and other biases that could explain the apparent survival benefit in HNPCC families. Resolving whether germline MMR gene mutations impact on survival is important because it potentially undermines the rationale for surveillance of mutation carriers. Here, we report an investigation of the influence of MSI on survival in cohorts of cancer patients (aged < 30 years at diagnosis, n = 118; non-age-selected, n = 181) in the context of clinicopathologic variables. There was a substantial age-related influence of tumour MSI status on survival. In young patients with tumour MSI, 65% of patients with MSI tumours had germline MSH2 or MLH1 mutations. Clinicopathologic variables and tumour MSI of the cohort were studied with respect to survival and compared with control groups. Young patients had excess MSI tumours (p < 0.000001), mucinous tumours (p < 0.01), advanced disease (p , 0.001) and poorer 5-year survival compared with older cases. Cox proportional hazard analysis identified Dukes' stage, age at diagnosis and calendar year of treatment as independent predictors of survival. There was no detectable association between tumour MSI and survival in young patients, although we confirmed previous observations that MSI is associated with better prognosis in later onset cohorts. These findings underscore the rationale for surveillance and early identification of tumours in MMR gene carriers as well as refining understanding of the influence of MSI on cancer progression. © 2002 Wiley-Liss, Inc. [source] Risk of Hip Fracture in Disabled Community-Living Older AdultsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2003Louise C. Walter MD OBJECTIVES: To determine the rate of hip fracture and risk factors associated with hip fractures in disabled older persons who enroll in the Program of All-Inclusive Care for the Elderly (PACE), a program providing comprehensive care to community-living nursing-home-eligible persons. DESIGN: Prospective cohort study between January 1990 and December 1997. SETTING: The twelve PACE demonstration sites: San Francisco, California; Columbia, South Carolina; Detroit, Michigan; Denver, Colorado; East Boston, Massachusetts; El Paso, Texas; Milwaukee, Wisconsin; Oakland, California; Portland, Oregon; Rochester, New York; Sacramento, California; and the Bronx, New York. PARTICIPANTS: Five thousand one hundred eighty-seven individuals in PACE; mean age 79, 71% female, 49% white, 47% with dementia. MEASUREMENTS: Functional status, cognitive status, demographics, and comorbid conditions were recorded on all the participants, who were tracked for occurrence of a hip fracture. The goals were to determine the rate of hip fracture and identify risk factors. RESULTS: Two hundred thirty-eight hip fractures (4.6%) occurred during follow-up. The rate of hip fracture was 2.2% per person-year. Four independent predictors of hip fracture were identified using Cox proportional hazard analysis: age of 75 and older (adjusted hazard ratio (HR) = 2.0, 95% confidence interval (CI) = 1.4,2.8); white ethnicity (HR = 2.1, 95% CI = 1.6,2.8); ability to transfer independently to and from bed, chair, and toilet (HR = 3.0, 95% CI = 1.2,7.2); and five or more Short Portable Mental Status Questionnaire errors (HR = 1.6, 95% CI = 1.3,2.1). The incidence of hip fracture ranged from 0.5% per person-year in persons with zero to one independent risk factors to 4.7% per person-year in those with all four independent risk factors. CONCLUSIONS: The rate of hip fracture in this cohort of disabled community-living older adults was similar to that reported in nursing home cohorts. Older age, white race, ability to transfer independently, and cognitive impairment were independent predictors of hip fracture. Persons with these risk factors should be targeted for preventive interventions, which should include strategies for making transferring safer. [source] Perineural invasion has a negative impact on survival of patients with gallbladder carcinomaBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 9 2002R. Yamaguchi Background: The clinical significance of perineural invasion of gallbladder carcinoma remains unclear. The aim of this study was to elucidate the incidence and mode of perineural invasion of gallbladder carcinoma and clarify its prognostic significance. Methods: A clinicopathological study was conducted on 68 patients who underwent attempted curative resection for gallbladder carcinoma. According to the pathological tumour node metastasis (pTNM) classification of the Union Internacional Contra la Cancrum, there were five (7 per cent), nine (13 per cent), 20 (29 per cent) and 34 (50 per cent) patients with pT1, pT2, pT3 and pT4 disease respectively. Twenty patients (29 per cent) had pM1 disease, including involved para-aortic nodes, liver metastases and localized dissemination. Results: The overall incidence of perineural invasion was 71 per cent (48 of 68 patients). Forty-four (96 per cent) of 46 patients with extrahepatic bile duct invasion had perineural invasion. Although several histological factors were associated with perineural invasion, multivariate analysis demonstrated that extrahepatic bile duct invasion was the only significant factor correlated with perineural invasion (odds ratio 99·0, P < 0·001). The perineural invasion index, defined as the ratio of the number of involved nerves to the total number of nerves examined, was significantly higher at the centre than in the proximal and distal parts of the tumour in the 46 patients with extrahepatic bile duct invasion (P < 0·001). The 5-year survival rate for patients with perineural invasion was significantly lower than that for patients with no invasion (7 versus 72 per cent; P < 0·001). Cox proportional hazard analysis identified perineural invasion (relative risk (RR) 5·3, P < 0·001) and lymph node metastasis (RR 2·5, P = 0·008) as significant independent prognostic factors. Conclusion: Perineural invasion is common in advanced gallbladder carcinoma and has a significant negative impact on patient survival. © 2002 British Journal of Surgery Society Ltd [source] Association between smoking during radiotherapy and prognosis in head and neck cancer: A follow-up study ,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2002George P. Browman MD Abstract Background. The study objective was to confirm a previous finding that patients with stage III/IV squamous head and neck cancer (SHNC) who smoke during radiotherapy (RT) experience reduced survival. Methods. An observational cohort study. Patients' smoking status was assessed weekly by questionnaire plus blood cotinine. Patients were assessed every 3 to 4 months for survival. Logistic regression and Cox proportional hazards analyses were used to detect the independent contribution of smoking on survival. Results. Of 148 patients, 113 smoked during RT. Blood cotinine and smoking questionnaire responses were highly correlated (Spearman R = .69; p < .0005). Abstainers and very light smokers experienced better survival than light, moderate, and heavy smokers (median, 42 vs 29 months; p = .07). Tumor and nodal status and years smoked were the most important prognostic factors. Smoking during RT was not an independent predictor of survival, but baseline smoking status was (p = .016). Conclusion. Smoking status should be documented in all future trials of RT in SHNC to allow for pooled analyses with sufficient power to address this question. © 2002 Wiley Periodicals, Inc. Head Neck 24: 1031,1037, 2002 [source] Loss of STARD10 expression identifies a group of poor prognosis breast cancers independent of HER2/Neu and triple negative statusINTERNATIONAL JOURNAL OF CANCER, Issue 6 2010Niamh C. Murphy Abstract The phospholipid transfer protein STARD10 cooperates with c-erbB signaling and is overexpressed in Neu/ErbB2 breast cancers. We investigated if STARD10 expression provides additional prognostic information to HER2/neu status in primary breast cancer. A published gene expression dataset was used to determine relationships between STARD10 and HER2 mRNA levels and patient outcome. The central findings were independently validated by immunohistochemistry in a retrospective cohort of 222 patients with breast cancer with a median follow-up of 64 months. Kaplan,Meier and Cox proportional hazards analyses were used for univariate and multivariate analyses. Patients with low STARD10 or high HER2 tumor mRNA levels formed discrete groups each associated with a poor disease-specific survival (p = 0.0001 and p = 0.0058, respectively). In the immunohistochemical study low/absent STARD10 expression i.e. ,10% positive cells was observed in 24 of 222 (11%) tumors. In a univariate model, low/absent STARD10 expression was significantly associated with decreased patient survival (p = 0.0008). In multivariate analyses incorporating tumor size, tumor grade, lymph node status, ER, PR and HER2 status, low STARD10 expression was an independent predictor of death from breast cancer (HR: 2.56 (95% CI: 1.27,5.18), p = 0.0086). Furthermore, low/absent STARD10 expression, HER2 amplification and triple negative status were independent prognostic variables. Loss of STARD10 expression may provide an additional marker of poor outcome in breast cancer identifying a subgroup of patients with a particularly adverse prognosis, which is independent of HER2 amplification and the triple negative phenotype. [source] Original Article: Clinical Investigation: Anterior perirectal fat tissue thickness is a strong predictor of recurrence after high-intensity focused ultrasound for prostate cancerINTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2010Makoto Sumitomo Objective: To evaluate if and why obesity affects the clinical outcome in patients undergoing high-intensity focused ultrasound (HIFU) treatment for prostate cancer (CaP). Methods: 115 patients who underwent HIFU treatment for localized CaP were categorized as obese, overweight or normal according to body mass index (BMI). The thickness of the anterior perirectal fat tissue (APFT) was measured by transrectal ultrasonography. Treatment was considered to have failed in the case of biochemical failure according to the Phoenix definition, positive follow-up biopsy or initiation of salvage therapy. Cox proportional hazards analyses were used to identify possible predictors for disease free survival (DFS), and an experimental fat tissue model was made to evaluate the ablation effect at the target tissue. Results: According to the classification by the Western Pacific Regional Office of WHO, 43 patients were of normal weight, 24 were overweight and 48 were obese. The BMI groups did not differ in Gleason score, prostate-specific antigen level at diagnosis or clinical stage. There were, however, significant correlations between BMI and prostate-specific antigen nadir (P < 0.001), and BMI and APFT thickness (P < 0.01). Multivariate analyses showed that BMI fails to be an independent predictor of DFS when APFT (P < 0.0001) is included as a variable. Conclusions: Our results suggest that APFT thickness, for which obesity could be a useful surrogate, might represent the causative factor for poor clinical outcome after transrectal HIFU treatment for CaP. [source] N-terminal pro B-type natriuretic peptide and left ventricular diameter independently predict mortality in dogs with mitral valve diseaseJOURNAL OF SMALL ANIMAL PRACTICE, Issue 2 2010W. Moonarmart Objectives: To determine whether natriuretic peptide concentrations would predict all cause mortality in dogs with degenerative mitral valve disease. Methods: One hundred dogs with naturally occurring degenerative mitral valve disease were prospectively recruited for this longitudinal study. Analysis of outcome was undertaken for 73 dogs for which the outcome was known. Dogs underwent physical examination, electrocardiography and echocardiography. Natriuretic peptide concentrations were measured by Enzyme-linked immunosorbent assay. The ability of natriuretic peptide concentrations, clinical, electrocardiographic and echocardiographic data, to predict all cause mortality was determined using univariable and multivariable Cox proportional hazards analyses. Results: Thirty dogs died during the period of follow-up. Two variables were independently predictive of all cause mortality; these were the normalised left ventricular end-diastolic diameter and the N-terminal pro B-type natriuretic peptide concentration. An increase of the left ventricular end-diastolic diameter by 0.1 increased the hazard of all cause mortality by 20% (95% confidence interval: 4 to 37%, P=0.01) and a 100 pmol/l increase in N-terminal pro B-type natriuretic peptide increased the hazard by 7% (95 confidence interval: 2 to 11%, P=0.003). Clinical Significance: N-terminal pro B-type natriuretic peptide concentration and left ventricular end-diastolic diameter are significantly and independently predictive of all cause mortality in dogs with degenerative mitral valve disease. [source] Predicting Coronary Heart Disease after Kidney Transplantation: Patient Outcomes in Renal Transplantation (PORT) StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010A. K. Israni Traditional risk factors do not adequately explain coronary heart disease (CHD) risk after kidney transplantation. We used a large, multicenter database to compare traditional and nontraditional CHD risk factors, and to develop risk-prediction equations for kidney transplant patients in standard clinical practice. We retrospectively assessed risk factors for CHD (acute myocardial infarction, coronary artery revascularization or sudden death) in 23 575 adult kidney transplant patients from 14 transplant centers worldwide. The CHD cumulative incidence was 3.1%, 5.2% and 7.6%, at 1, 3 and 5 years posttransplant, respectively. In separate Cox proportional hazards analyses of CHD in the first posttransplant year (predicted at time of transplant), and predicted within 3 years after a clinic visit occurring in posttransplant years 1,5, important risk factors included pretransplant diabetes, new onset posttransplant diabetes, prior pre- and posttransplant cardiovascular disease events, estimated glomerular filtration rate, delayed graft function, acute rejection, age, sex, race and duration of pretransplant end-stage kidney disease. The risk-prediction equations performed well, with the time-dependent c-statistic greater than 0.75. Traditional risk factors (e.g. hypertension, dyslipidemia and cigarette smoking) added little additional predictive value. Thus, transplant-related risk factors, particularly those linked to graft function, explain much of the variation in CHD after kidney transplantation. [source] Perioperative Outcome and Long-Term Mortality for Heart Failure Patients Undergoing Intermediate- and High-Risk Noncardiac Surgery: Impact of Left Ventricular Ejection FractionCONGESTIVE HEART FAILURE, Issue 2 2010Kirsten O. Healy MD The impact of left ventricular ejection fraction (LVEF) on outcome in patients with heart failure (HF) undergoing noncardiac surgery has not been extensively evaluated. In this study, 174 patients (mean age, 75±12 years, 47% male, mean LVEF (47%±18%) underwent intermediate- or high-risk noncardiac surgery. Patients were stratified by LVEF, and adverse perioperative complications were identified and compared. Adverse perioperative events occurred in 53 patients (30.5%), including 14 (8.1%) deaths within 30 days, 26 (14.9%) myocardial infarctions, and 44 (25.3%) HF exacerbations. Among the factors associated with adverse perioperative outcomes in the first 30 days were advanced age (>80 years), diabetes, and a severely decreased LVEF (<30%). Long-term mortality was high, and Cox proportional hazards analysis demonstrated that LVEF was an independent risk factor for long-term mortality. Congest Heart Fail. 2010;16:45,49. © 2009 Wiley Periodicals, Inc. [source] GENETIC STUDY: BclI glucocorticoid receptor polymorphism and smoking in the general populationADDICTION BIOLOGY, Issue 3 2009Satu J. Siiskonen ABSTRACT We studied the hypothesis that the BclI polymorphism of the glucocorticoid receptor gene is associated with an increased probability of being a (heavy) smoker and a decreased ability to quit smoking. The study cohort consisted of all subjects in the Rotterdam Study, a Dutch population-based cohort of people aged 55 years and older, for whom BclI genotyping and smoking status at baseline were available. In prospective analyses, the smoking status was reassessed during three additional examination rounds. Logistic regression analysis was used to study the association between BclI polymorphism and being a smoker or a heavy smoker at baseline. Furthermore, the relationship between BclI polymorphism and incident smoking cessation was tested with Cox proportional hazards analysis within those who smoked at baseline. In total, 6358 subjects were included in the study. The presence of a G-allele was not associated with current smoking at baseline [odds ratio (OR) = 0.96, 95%confidence interval (CI): 0.85,1.09] or with the incidence of smoking cessation during follow-up [hazard ratio (HR) = 0.98, 95%CI: 0.80,1.19]. Within current smokers, having a G-allele was not significantly associated with the risk of being a heavy smoker when measured by pack-years smoked (OR = 1.07, 95%CI: 0.85,1.35) or daily consumption of tobacco (OR = 1.10, 95%CI: 0.88,1.37). We were not able to replicate the earlier findings indicating that the proportion of current smokers is lower among carriers of the CC-genotype of the BclI glucocorticoid receptor. Furthermore, the BclI glucocorticoid receptor polymorphism did not predict the incidence of smoking cessation in the general elderly population. [source] Potential role for Interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection,HEPATOLOGY, Issue 4 2010Jason Grebely Polymorphisms in the IL28B (interleukin-28B) gene region are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. We evaluated the role of IL28B in spontaneous and treatment-induced clearance following recent HCV infection. The Australian Trial in Acute Hepatitis C (ATAHC) was a study of the natural history and treatment of recent HCV, as defined by positive anti-HCV antibody, preceded by either acute clinical HCV infection within the prior 12 months or seroconversion within the prior 24 months. Factors associated with spontaneous and treatment-induced HCV clearance, including variations in IL28B, were assessed. Among 163 participants, 132 were untreated (n = 52) or had persistent infection (infection duration ,26 weeks) at treatment initiation (n = 80). Spontaneous clearance was observed in 23% (30 of 132 participants). In Cox proportional hazards analysis (without IL28B), HCV seroconversion illness with jaundice was the only factor predicting spontaneous clearance (adjusted hazards ratio = 2.86; 95% confidence interval = 1.24, 6.59; P = 0.014). Among participants with IL28B genotyping (n = 102 of 163 overall and 79 of 132 for the spontaneous clearance population), rs8099917 TT homozygosity (versus GT/GG) was the only factor independently predicting time to spontaneous clearance (adjusted hazard ratio = 3.78; 95% confidence interval = 1.04, 13.76; P = 0.044). Participants with seroconversion illness with jaundice were more frequently rs8099917 TT homozygotes than other (GG/GT) genotypes (32% versus 5%, P = 0.047). Among participants adherent to treatment and who had IL28B genotyping (n = 54), sustained virologic response was similar among TT homozygotes (18 of 29 participants, 62%) and those with GG/GT genotype (16 of 25, 64%, P = 0.884). Conclusion: During recent HCV infection, genetic variations in IL28B region were associated with spontaneous but not treatment-induced clearance. Early therapeutic intervention could be recommended for individuals with unfavorable IL28B genotypes. (HEPATOLOGY 2010;) [source] Comparative performances of staging systems for early hepatocellular carcinomaHPB, Issue 5 2009Hari Nathan Abstract Background:, Several staging systems for patients with hepatocellular carcinoma (HCC) have been proposed, but studies of their prognostic accuracy have yielded conflicting conclusions. Stratifying patients with early HCC is of particular interest because these patients may derive the greatest benefit from intervention, yet no studies have evaluated the comparative performances of staging systems in patients with early HCC. Methods:, A retrospective cohort study was performed using data on 379 patients who underwent liver resection or liver transplantation for HCC at six major hepatobiliary centres in the USA and Europe. The staging systems evaluated were: the Okuda staging system, the International Hepato-Pancreato-Biliary Association (IHPBA) staging system, the Cancer of the Liver Italian Programme (CLIP) score, the Barcelona Clinic Liver Cancer (BCLC) staging system, the Japanese Integrated Staging (JIS) score and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system, 6th edition. A recently proposed early HCC prognostic score was also evaluated. The discriminative abilities of the staging systems were evaluated using Cox proportional hazards models and the bootstrap-corrected concordance index (c). Results:, Overall survival of the cohort was 74% at 3 years and 52% at 5 years, with a median survival of 62 months. Most systems demonstrated poor discriminatory ability (P > 0.05 on Cox proportional hazards analysis, c, 0.5). However, the AJCC/UICC system clearly stratified patients (P < 0.001, c= 0.59), albeit only into two groups. The early HCC prognostic score also clearly stratified patients (P < 0.001, c= 0.60) and identified three distinct prognostic groups. Discussion:, The early HCC prognostic score is superior to the AJCC/UICC staging system (6th edition) for predicting the survival of patients with early HCC after liver resection or liver transplantation. Other major HCC staging systems perform poorly in patients with early HCC. [source] Prognostic factors of tracheobronchial mucoepidermoid carcinoma,15 years experienceRESPIROLOGY, Issue 2 2008Chien-Hung CHIN Background and objectives: Mucoepidermoid carcinoma of the tracheobronchial tree is a rare tumour which displays a variable degree of clinical aggressiveness and malignancy. The relationship between the patient's prognosis and the tumour's histological features and clinical behaviour is uncertain. The aim of this study was to identify the clinicopathological features and analyse the outcomes of patients with this type of cancer. Methods: A retrospective analysis of the medical records of patients diagnosed with mucoepidermoid carcinoma of the lung between 1991 and 2006 was conducted. Results: The study comprised 15 patients. Higher histological grade tumours had a higher proportion of squamoid cells (P = 0.019); the tumours of patients with lymph node metastases also had a higher proportion of squamoid cells than did the tumours of patients without lymph node metastases (P = 0.015). Patients with early stage tumours (stage IA, IB, IIB) had better outcomes (10-year survival rate = 87.5%), than did patients with late-stage tumours (stage IIIB, IV) (1-year survival rate = 28.6%; 2-year survival rate = 0%, P = 0.001). Patients with lower-grade tumours (grade 1 and grade 2) had better outcomes (1-year survival rate = 80%; 5-year survival rate = 57.1%) than did patients with higher-grade tumours (grade 3) (1-year survival rate = 20%, P = 0.035). Tumour staging was a significant independent predictor of survival on Cox proportional hazards analysis. Conclusions: The proportion of squamoid cells on tumour histology may be an indicator of the level of tumour malignancy. Tumour, node, metastasis staging is a significant determinant of prognosis in patients with tracheobronchial mucoepidermoid carcinoma. [source] Immunosuppressant Therapy Adherence and Graft Failure Among Pediatric Renal Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009M. A. Chisholm-Burns The study objective was to determine the association between immunosuppressant therapy (IST) adherence and graft failure among pediatric renal transplant recipients (RTRs) using data reported in the United States Renal Data System (USRDS), which contains Medicare prescription claims. RTRs (,18 years) who received their only transplant during 1995,2000, experienced graft survival more than 6 months posttransplant, had 36 months of USRDS data (or had data until graft failure or death), utilized Medicare IST coverage, and were prescribed cyclosporine/tacrolimus were included. IST adherence was measured by medication possession ratio (MPR). Cox proportional hazards analysis was used to assess the relationship between time to graft failure and continuous MPR. MPR quartiles were used to examine MPR as a categorical variable (Quartile 4 = adherent group, Quartiles 1,3 = nonadherent group). Kaplan,Meier estimates of time to graft failure were compared between adherent and nonadherent groups. 877 RTRs met inclusion criteria. Cox proportional hazards modeling suggested that greater adherence was significantly associated with longer time to graft failure (p = 0.009), after adjusting for relevant clinical factors. Kaplan,Meier analysis found a difference between adherent and nonadherent groups in graft survival by time (,2= 5.68, p = 0.017). Interventions promoting adherence should be implemented among pediatric RTRs and parents/guardians to optimize graft survival. [source] Racial Disparity Trends for Graft Failure in the US Pediatric Kidney Transplant Population, 1980,2004AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009B. M. Chavers Graft survival among adult African American kidney transplant patients remains low compared to whites, but little information is available for children and adolescents. We examined trends in graft failure among US incident primary kidney transplant patients aged <19 years (n = 13 692), 1980,2004. Trends in 1-year and 2- to 5-year graft failure (for patients whose grafts survived the first year) were analyzed in 5-year intervals. One-year graft failure declined 70% for white and 77% for African American patients over the 25-year period, and 1-year graft failure rates improved at a slightly higher rate for African American compared to white patients (p = 0.02). In contrast, the graft failure rates for years 2,5 declined 53% for white and only 41% for African American patients over the 25 years (p = 0.29). In fully adjusted Cox proportional hazards analysis, the rate of graft failure among African Americans was approximately 2-fold higher than for white patients over the entire study period. Graft survival has improved slightly more for African American than white pediatric patients over the past 25 years. However, graft survival for African American pediatric patients remains poor compared with white patients. [source] Defining the Risk of Elective Cyclosporine Withdrawal in Stable Kidney Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2002Shakeel Anjum Although it is known that elective cyclosporine (CsA) withdrawal increases the risk for acute rejection, few studies have been large enough to identify risk factors for acute rejection after CsA withdrawal. We examined risk factors for acute rejection in 464 kidney transplant recipients who underwent elective CsA withdrawal. The incidence of acute rejection within 6 months of CsA withdrawal was 20/141 (14.2%) in the period January 1986 to May 1989, but only 14/323 (4.5%) since May 1989 (p =,0.0002). Among those transplanted since May 1989, the incidence was 5/20 (25%) for those with both 2 HLA-B and 2 HLA-DR mismatches, compared with only 9/298 (3.0%) for those with fewer mismatches (p <,0.0001). In Cox proportional hazards analysis, risk factors for acute rejection within 6 months, or at any time after elective CsA withdrawal, were date of transplant January 1986 to May 1989 (compared with more recently May 1989 to March 1999), younger age, obesity, as well as B and DR mismatches. Recipient race (83% were white), acute rejection during the first year before withdrawal (31%), mycophenolate mofetil (17%), and other variables failed to predict postwithdrawal acute rejection. We concluded that avoiding CsA withdrawal in the relatively small number of recipients with both 2 HLA-B and 2 HLA-DR mismatches could further reduce our already low incidence of acute rejection following elective CsA withdrawal. [source] Long-Term Follow-Up of Patients with Syncope Evaluated by Head-Up Tilt TestANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2010Giulia Domenichini M.D. Background: Clinicians may be tempted to consider a positive head-up tilt test (HUTT) an unfavorable prognostic indicator. We investigated whether results of routine HUTT predict long-term recurrence of syncope. Methods: We analyzed syncope recurrence at long-term among 107 patients (mean age 51 ± 20 years) receiving HUTT for diagnostic evaluation of unexplained/suspected neurocardiogenic syncope in our Institute. Results: HUTT was positive in 76 patients (vasodepressive response, n = 58; cardioinhibitory, n = 5; mixed, n = 13). During a median follow-up of 113 months (range, 7,161), 34 (32%) patients experienced recurrence (24 [32%] with positive HUTT during 110 months (7,159); 10 [32%] with negative HUTT during 120 [22,161] months). Actuarial freedom from recurrence at 10 years did not significantly differ for patients with positive/negative test results (after passive/active phases) or with different positive response patterns (vasodepressive, cardioinhibitory, mixed). By contrast, history of >4 syncopes in the 12 months preceding HUTT stratified risk of recurrence, irrespective of HUTT positivity/negativity. At Cox proportional hazards analysis, history of >4 syncopes in the 12 months preceding HUTT was the single independent risk factor for recurrence both in the overall study population (HR, 1.7; 95% CI, 1.07,2.69) and within the subset of patients who tested positive (HR, 1.83; 95% CI, 1.07,3.17). Conclusions: This long-term follow-up study reinforces the concept that a positive HUTT should not be considered an unfavorable prognostic indicator; frequency of recent occurrences may be a more valid predictor. Ann Noninvasive Electrocardiol 2010;15(2):101,106 [source] Cytoplasmic mislocalization of the orphan nuclear receptor Nurr1 is a prognostic factor in bladder cancerCANCER, Issue 2 2010Teruo Inamoto MD Abstract BACKGROUND: Nurr1 belongs to a novel class of orphan nuclear receptors (the NR4A family). The authors have previously shown that Nurr1 is important in carcinogenesis. In the current study, they examined the clinicopathologic relevance of expression patterns of Nurr1 in bladder tumors. METHODS: Nurr1 expression was determined using immunohistochemical staining in a bladder cancer tissue array (145 tumors). Tumors were classified according to Nurr1 protein levels in both cytoplasm and nucleus. Disease-specific survival and recurrence-free survival were investigated by Kaplan-Meier analysis and Cox proportional hazards analysis in multivariate models and correlated with variables such as tumor stage, growth pattern, and clinical outcome (recurrence and survival). In vitro, Nurr1 was examined for its role in bladder cancer cell proliferation and migration using small interfering RNA silencing. RESULTS: Nurr1 expression in tumor cells correlated with increasing tumor stage and invasive growth pattern. Disease-specific survival was significantly shorter in patients whose tumors demonstrated a high level of cytoplasmic Nurr1 compared with those with lower levels of cytoplasmic Nurr1 expression. Furthermore, cytoplasmic Nurr1 expression level was found to be an independent predictor of disease-specific survival (odds ratio, 4.894; P < .001). In vitro, silencing of endogenous Nurr1 attenuated the migration of bladder cancer cells. CONCLUSIONS: The expression of Nurr1 in the cytoplasm correlates with adverse outcome and is an independent prognostic marker for tumor progression and survival in patients with bladder cancer. This might represent a novel target in bladder cancer therapy. Cancer 2010. © 2010 American Cancer Society. [source] Prognosis for patients with thin cutaneous melanomaCANCER, Issue 6 2003Long-term survival data from the New South Wales Central Cancer Registry, the Sydney Melanoma Unit Abstract BACKGROUND Estimates of long-term survival for patients with thin (, 1 mm) primary cutaneous melanomas vary widely. Two separate methods were used to study the survival of patients with melanoma from New South Wales (NSW), Australia, and from the Sydney Melanoma Unit (SMU). METHODS The NSW Central Cancer Registry (NSWCCR) provided data on all patients who were diagnosed with cutaneous melanomas that measured , 1 mm thick between 1983 and 1998, inclusive. Patients with metastases at the time of diagnosis were not included, leaving 18,088 patients for analysis. The SMU data base was analyzed to extract data for all patients with thin melanomas who met the same criteria from 1979 to 1998, inclusive. All patients who had their primary tumors treated definitively elsewhere were excluded, leaving 2746 patients for analysis. Ten-year Kaplan,Meier survival rates were calculated, and significant differences were determined using log-rank analysis. Prognostic factors were evaluated with Cox proportional hazards analysis. RESULTS The NSWCCR analysis revealed a 10-year survival rate of 96.4%. The 10-year survival rate for patients at SMU was 92.7%. Among the patients at SMU who died, the median time to recurrence was 49.8 months, and the median time to death was 65.9 months. The 10-year survival for patients at SMU who had lesions that measured , 0.75 mm was 96.9% compared with 84.3% for patients who had lesions that measured 0.76,1.0 mm. For patients who had ulcerated melanomas measuring , 1 mm thick, the 10-year survival rate was 83%, compared with 92.3% for patients who had nonulcerated melanomas. CONCLUSIONS The results of the current study confirmed the excellent survival rate for patients with thin melanomas. Higher-risk subsets of patients who may warrant consideration for aggressive investigation and treatment are identifiable. Cancer 2003;98:1223,31. © 2003 American Cancer Society. DOI 10.1002/cncr.11624 [source] Prospective assessment of hemodialysis access patency after percutaneous intervention: Cox proportional hazards analysisCATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 3 2005John A. Bittl MD Abstract Vascular access failure is the greatest limitation of successful hemodialysis, but the factors associated with long-term patency have not been fully elucidated. Outcomes in a consecutive series of 294 thrombosed or failing accesses [128 fistulas (43.5%) and 166 grafts (56.5%) in 179 patients] were analyzed with life table and multivariable Cox proportional hazards analysis. Initial success was achieved in 275 of 294 accesses (95.6%). The median patency after intervention was 206 days (interquartile range, 79,457 days). Fistulas had longer median patency after intervention than grafts (286 vs. 170 days). Nonthrombosed accesses had longer median patency than thrombosed accesses (238 vs. 136 days), but thrombosed fistulas had similar median patency as thrombosed grafts (140 vs. 136 days). The selective use of stents as a bailout for failed balloon dilatation did not significantly reduce long-term patency (196 days for stented accesses vs. 210 days for unstented accesses). Long-term patency was inversely related to final access pressure, but access patency was not related to the presence of central venous occlusions, graft age, patient age, sex, or diabetes. Catheter-based intervention of thrombosed and failing dialysis accesses significantly prolongs patency and usefulness of dialysis accesses. The expanding use of fistulas, improved detection of early access failure, and selective use of bailout stents should enhance long-term access patency. © 2005 Wiley-Liss, Inc. [source] HMG-CoA reductase expression in breast cancer is associated with a less aggressive phenotype and influenced by anthropometric factorsINTERNATIONAL JOURNAL OF CANCER, Issue 5 2008Signe Borgquist Abstract Although several studies have reported on the anti-tumoural properties exerted by 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) inhibitors (statins), the in vivo expression of HMG-CoAR in human cancer has been considerably less investigated. In our study, we examined the immunohistochemical expression of HMG-CoAR in 511 incident breast cancers within the Malmö Diet and Cancer Study in order to explore its relationship to established clinicopathological and tumour biological parameters. Furthermore, the potential influence of estrogen exposure on HMG-CoAR expression was assessed by performing Cox's proportional hazards analyses of the relationship between the use of hormone replacement therapy (HRT), obesity (waist circumference) and tumour-cell specific HMG-CoAR expression. We found that HMG-CoAR was present in various fractions and intensities in the cytoplasm, sometimes with a membranous pattern, but not in the tumour cell nuclei. The expression of HMG-CoAR was associated with a smaller tumour size (p = 0.02), low histological grade (p = 0.001), low Ki67 index (p = 0.004), ER,+ (p = 0.02), ER,+ (p = 0.005), and high p27 expression (p = <0.001). The incidence of tumours with a high HMG-CoAR-expression was increased among HRT-users, although this was not statistically significant in a heterogeneity analysis. Obesity was significantly associated with a high HMG-CoAR expression assessed both as a high (>50%) fraction of positive cells (relative risk: 2.06; 95% confidence interval: 1.20,3.51), and a strong staining intensity (2.33: 1.08,5.02). In summary, we demonstrate that HMG-CoAR is differentially expressed in breast cancer and that a high expression is associated with prognostically favourable tumour parameters. Moreover, estrogen related life-style and anthropometric factors might indeed regulate HMG-CoAR expression. © 2008 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||