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Kaplan-Meier Analysis (kaplan-meier + analysis)
Selected AbstractsNitric Oxide Metabolites Are Associated with Survival in Older PatientsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 9 2007Toshio Hayashi MD OBJECTIVES: To assess the efficacy of various vascular endocrinological substances, such as plasma nitric oxide metabolites (NOx), as surrogate markers of survival in older patients. DESIGN: Prospective cohort, observational. SETTING: Nagoya University Hospital and related hospitals, Japan. PARTICIPANTS: One hundred fifty patients aged 70 and older, recruited consecutively from the outpatient clinics of Nagoya University Hospital and related hospitals. MEASUREMENT: Serum biochemical analyses such as albumin and total cholesterol, various prognostic markers, such as tumor necrosis factor (TNF)-,, NOx, activities of daily living (ADLs), and instrumental ADLs (IADLs) were evaluated on enrollment. ADLs, IADLs, and comorbidities, especially depression and impaired cognition, were evaluated on enrollment. The main outcome was survival rate over 2.75 years. RESULTS: Forty-nine patients died during the follow-up period. Mann-Whitney U -test showed that hemoglobin, total protein, serum albumin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high sensitive c-reactive protein, NOx, B-type natriuretic peptide, interleukin-6, and TNF-, levels; ADLs; cognitive impairment; and depressive status were significantly different for subjects who survived and those who died. Of the dependent variables in the Cox proportional hazards regression analyses, only ADLs, NOx, and albumin were significantly different. In the Kaplan-Meier analyses of mortality, the prognosis of patients in the third and fourth quartiles of NOx was significantly worse than that of patients in the first or second quartile. The prognosis of patients with impaired ADLs was worse than that of other patients for the overall period. CONCLUSION: Lower levels of NOx may be associated with survival in older patients. It may be an effective marker, like ADLs, which is a well-known marker. [source] Nephrectomy improves survival in patients with invasion of adjacent viscera and absence of nodal metastases (stage T4N0 renal cell carcinoma)BJU INTERNATIONAL, Issue 6 2009Umberto Capitanio OBJECTIVE To examine the cancer-specific mortality (CSM) of patients with T4N0,2M0 renal cell carcinoma (RCC) treated with either nephrectomy (RN) or no surgery (NS). PATIENTS AND METHODS Of 43 143 patients with RCC identified in the Surveillance, Epidemiology and End Results database, 310 had tumours involving adjacent organs with no evidence of distant metastases (T4NanyM0) and had RN (246, 79.4%) or NS (64, 20.6%). Kaplan-Meier analyses, Cox regression and competing-risks regression models were used to compare the effect of RN vs NS on CSS. RESULTS In patients with T4N0 disease the median survival benefit associated with RN vs NS was 42 months (48 vs 6 months, P < 0.001). Conversely, the median survival in patients T4N1-2 was no different between RN and NS (9.3 vs 9.1 months, P = 0.9). Multivariable analyses in T4N0 cases indicated a substantial survival disadvantage for patients having NS vs RN (hazard ratio 4.8, P < 0.001). Conversely, in patients with N1-2 stages, the CSS was virtually the same for NS and RN (hazard ratio 0.9, P = 0.9). Competing-risks regression models confirmed the benefit of RC in patients with T4N0 and the lack of benefit in those with T4N1-2 disease, after controlling for other-cause mortality. CONCLUSION Our data suggest a survival benefit in patients with T4N0 RCC treated with RC. By contrast, RN seems to have no effect on survival in patients with evidence of nodal metastases. [source] Bacillus Calmette-Guérin therapy in stage Ta/T1 bladder cancer: prognostic factors for time to recurrence and progressionBJU INTERNATIONAL, Issue 7 2004P. Andius OBJECTIVE To report prognostic factors for time to recurrence and progression after bacillus Calmette-Guérin (BCG) prophylaxis in patients with stage Ta/T1 papillary bladder cancer. PATIENTS AND METHODS The clinical records were assessed retrospectively for 236 patients with papillary stage Ta/T1 bladder cancer treated with BCG between 1986 and 2000. Patients with known carcinoma in situ were excluded. The median (range) follow-up was 44 (4,155) months. The effect of 13 variables on the time to recurrence and progression was evaluated using multivariate Cox proportional hazard regression and Kaplan-Meier analyses. RESULTS The recurrence rate was markedly reduced for all grades and stages. Patients with a negative first cystoscopy and maintenance BCG had a significantly longer time to recurrence than those treated with an induction course alone (P < 0.001). Thirty-seven patients (16%) progressed in stage. The result of the first cystoscopy (P < 0.001), tumour grade (P = 0.003) and six or fewer initial instillations (P = 0.002) had prognostic importance for the time to progression. Twenty-eight patients (12%) had a history of an upper tract tumour, which was 3,10 times the expected rate. Age, number of tumours, number of positive cystoscopies, length of tumour history before BCG, BCG strain and treatment year had no influence on time to recurrence and progression. CONCLUSIONS Maintenance treatment does not seem to be necessary among patients with TaG1-G2 disease after a negative first cystoscopy, as the progression rate was very low. One new finding was that BCG seemed to be equally effective among patients with or with no history of an upper tract tumour. Another new and surprising finding was that patients treated with fewer than six induction instillations, because of very bothersome side-effects, had an increased risk of tumour progression and of local failure. [source] Osteopontin as a molecular prognostic marker for melanomaCANCER, Issue 1 2008Javier Rangel MD Abstract BACKGROUND. Osteopontin has been suggested as a marker of disease progression in patients with melanoma because of its overexpression in recent microarray analyses. However, its prognostic role in melanoma has not been fully defined. METHODS. Osteopontin expression status was examined using immunohistochemical analysis of a tissue microarray that contained primary cutaneous melanomas from 345 patients. The correlation between osteopontin expression and several histologic markers for melanoma was assessed by using the Chi-square test and the Le directional test. The impact of osteopontin expression on recurrence-free survival (RFS) and disease-specific survival (DSS) of patients with melanoma was examined using Cox regression and Kaplan-Meier analyses. The impact of increasing osteopontin expression on sentinel lymph node (SLN) metastasis was assessed using logistic regression analysis. RESULTS. High osteopontin expression was associated with increased tumor thickness (P = .037), Clark level (P = .035), and mitotic index (P = .046). Kaplan-Meier analysis demonstrated an association between osteopontin expression and reduced RFS (P < .03) and DSS (P = .05). Multivariate Cox regression analysis demonstrated that high osteopontin immunostaining had an independent impact on the DSS of this melanoma cohort (P = .049). In addition, osteopontin expression was significantly predictive of SLN metastasis (P = .009) and SLN burden, as assessed by the mean number of SLN metastases (P = .0025). Multivariate logistic regression analysis demonstrated an independent role for osteopontin expression in predicting SLN status (P = .0062). CONCLUSIONS. The current results validated the role of osteopontin as an independent prognostic marker for melanoma and provided new evidence for its predictive role in melanoma lymph node metastasis. Cancer 2008. © 2007 American Cancer Society. [source] GRP78 expression correlates with histologic differentiation and favorable prognosis in neuroblastic tumorsINTERNATIONAL JOURNAL OF CANCER, Issue 6 2005Wen-Ming Hsu Abstract Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum protein, is essential for the differentiation of neuroblastoma cells and is selectively induced when the cells are undergoing apoptosis. These findings suggest that GRP78 may affect the tumor behavior of neuroblastoma. Our study evaluates the association of clinicopathologic factors and patient survival with the expression of GRP78 in patients with neuroblastoma. GRP78 expression in 68 neuroblastic tumors was investigated semiquantitatively by immunohistochemistry. GRP78 mRNA and protein levels in 7 tumor tissues were also quantified by real-time PCR and Western blot respectively and correlated well with the immunohistochemical results. Forty (58.8%) of the 68 neuroblastic tumors showed positive GRP78 expression. The percentage of positive GRP78 immunostaining increased as the tumor histology became differentiated (p = 0.001). Furthermore, positive GRP78 expression strongly correlated with early clinical stages (P = 0.002) but inversely correlated with MYCN amplification (p = 0.001). Kaplan-Meier analysis showed that patients with positive GRP78 expression did have better survival than those with negative expression (5-year survival rate, 72.9% and 23.4% respectively, p < 0.001). Multivariate analysis further showed that GRP78 expression was an independent prognostic factor. Moreover, GRP78 expression predicted better survival in patients with either undifferentiated or differentiated histologies. GRP78 expression still had significant prognostic value when the analysis was restricted to tumors of advanced stages or without MYCN amplification. Thus, GRP78 can serve as a novel independent favorable prognostic factor for patients with neuroblastoma. © 2004 Wiley-Liss, Inc. [source] Sustained Nonvertebral Fragility Fracture Risk Reduction After Discontinuation of Teriparatide TreatmentJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2005Richard Prince Abstract A follow-up in 1262 women was conducted after the discontinuation of teriparatide. The hazard ratio for combined teriparatide group (20 and 40 ,g) for the 50-month period after baseline was 0.57 (p = 0.002), suggesting a sustained effect in reducing the risk of nonvertebral fragility fracture. Introduction: Treatment with teriparatide {rhPTH(1-34)} 20 and 40 ,g once-daily subcutaneous dosing significantly reduced the risk of nonvertebral fragility fractures over a median exposure of 19 months. Materials and Methods: All participants in the Fracture Prevention Trial were invited to participate in a follow-up study. Prior treatment assignments were revealed, and patients were able to receive osteoporosis treatments without restriction. Results: Approximately 60% of the 1262 patients received an osteoporosis treatment at some time during follow-up, with greater use in the former placebo group than in the combined former teriparatide group (p < 0.05). The hazard ratios for nonvertebral fragility fractures in each teriparatide group relative to placebo were statistically significant for the 50-month period including treatment and follow-up (p < 0.03). In the follow-up period, the hazard ratio was significantly different between the 40 ,g and combined groups versus placebo but not for the 20 ,g group versus placebo. However, the 20 and 40 ,g groups were not different from each other. Kaplan-Meier analysis of time to fracture showed that the fracture incidence in the former placebo and teriparatide groups diverged during the 50-month period including teriparatide treatment and follow-up (p = 0.009). Total hip and femoral neck BMD decreased in teriparatide-treated patients who had no follow-up treatment; BMD remained stable or further increased in patients who received a bisphosphonate after teriparatide treatment. Conclusions: While the study design is observational, the results support a sustained effect of teriparatide in reducing the risk of nonvertebral fragility fractures up to 30 months after discontinuation of treatment. [source] Ablation of Focally Induced Atrial Fibrillation:JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2 2004Selective or Extensive? Introduction: Focally induced atrial fibrillation (AF) often is due to ectopic activity in the pulmonary veins (PV). Although initial approaches were aimed at ablating only the ectopic foci, more extensive ablation approaches have evolved that isolate all PVs empirically and/or create circumferential ablation lines in the left atrium (LA). These techniques last longer and may be associated with more risks. We retrospectively evaluated the outcome and risks of ablation for focally induced AF in a single-center patient population. Methods and Results: We report on 47 patients (32 men and 15 women; age 47 ± 10 years) in whom 52 ablations were performed. In 19 patients (22 sessions), ablation was directed at the site(s) of overt ectopic activity ("selective" group), whereas in 28 patients (30 sessions) without sufficient ectopy to determine the culprit PV a mean of 3.5 PVs were empirically targeted for bidirectional disconnection from the LA ("extensive" group). On a preprocedural Holter recording, the "selective" group had significantly more isolated atrial ectopy (3,276 ± 2,933 vs 620 ± 937 beats/24 hours) and runs of atrial tachycardia (330 ± 202 vs 53 ± 87 runs/24 hours) than the "extensive" group (P < 0.01 for both). Only 11% had persistent AF before ablation. Acute procedural success was 81% (elimination of all ectopy) and 83%, respectively (bidirectional and fully circumferential isolation of all targeted PVs). Procedure and fluoroscopy times were significantly shorter in the "selective" group. There were no major complications, but 7 minor complications and 2 acute PV stenoses > 50% in the 30 "extensive" procedures were observed. Mean follow-up was 8.4 ± 8.5 months (median 6.9). Kaplan-Meier analysis, excluding recurrences during only the first month ("delayed cure"), showed AF recurrence in 45% after 6 months and in 55% after 1 year. Outcome was not dependent on ablation approach ("selective" or "extensive") nor was time to first AF (22 ± 64 days and 30 ± 69 days). AF recurrence tended to be higher in patients with larger LA (P = 0.08), underlying heart disease or hypertension (P = 0.08), and those "extensive" patients in whom not all 4 PVs were targeted (P = 0.07). Conclusion: Trigger-directed ablation for focally induced AF is associated with a relatively high recurrence rate during follow-up. Apart from recurrence of the ectopic trigger, this may point to underlying structural changes in the atrial substrate not addressed by the ablation. Prospective evaluation of the risk-to-benefit profile of any technique (selective, extensive, including linear lines) is required. (J Cardiovasc Electrophysiol, Vol. 15, pp. 200-205, February 2004) [source] Influence of methylated p15 INK4b and p16 INK4a genes on clinicopathological features in colorectal cancerJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2006Atsushi Ishiguro Abstract Background and Aim:, Genetic silencing by promoter methylation has attracted attention in the carcinogenesis of colorectal cancer. Methylation of the p16INK4a gene has been found in primary colorectal cancer. Although the p15INK4b gene displays high homology to the p16INK4a gene in the amino acid sequence, methylation of p15INK4b has not been fully studied. We investigated p15INK4b methylation status in patients with colorectal cancer to verify the association between the methylation of p15INK4b and clinicopathological features compared with p16INK4a. Methods:, DNA samples from the tissues of primary colorectal cancer and corresponding adjacent normal colon mucosa were obtained from surgical resections of 88 patients (47 males and 41 females, aged 29,83 years). Methylation-specific polymerase chain reaction was used to analyze p15INK4b and p16INK4a methylation status after bisulfite modification. Cumulative survival rates (mean follow-up period: 53.2 months) were calculated by the Kaplan-Meier analysis. Results:, Methylations of p15INK4b and p16INK4a genes were detected in 23 (26.1%) and 20 (22.7%) colorectal cancers, respectively. Methylation of p15INK4b was not associated with any clinicopathological features. Compared with normal mucosa, the methylation of p15INK4b was more prominent in tumor tissue (P < 0.001). Reverse transcription-polymerase chain reaction (RT-PCR) revealed that p15INK4b methylaton decreased mRNA expression. Kaplan-Meier analysis showed that patients with stage I-II had a significant difference in survival rate between those with and without methylated p15INK4b (P = 0.018). Conclusions:, Our results suggest that methylation of the p15INK4b gene contributes to the process of carcinogenesis in colorectal cancer as well as p16INK4a and is useful as a prognostic factor in the early stage. [source] Predictors of clinical outcome in children undergoing orthotopic liver transplantation for acute and chronic liver diseaseLIVER TRANSPLANTATION, Issue 9 2006Chris Rhee The current United Network for Organ Sharing (UNOS) policy is to allocate liver grafts to pediatric patients with chronic liver disease based on the pediatric end-stage liver disease (PELD) scoring system, while children with fulminant hepatic failure may be urgently listed as Status 1a. The objective of this study was to identify pre-transplant variables that influence patient and graft survival in those children undergoing LTx (liver transplantion) for FHF (fulminant hepatic failure) compared to those patients transplanted for extrahepatic biliary atresia (EHBA), a chronic form of liver disease. The UNOS Liver Transplant Registry was examined for pediatric liver transplants performed for FHF and EHBA from 1987 to 2002. Variables that influenced patient and graft survival were assessed using univariate and multivariate analysis. Kaplan-Meier analysis of FHF and EHBA groups revealed that 5 year patient and graft survival were both significantly worse (P < 0.0001) in those patients who underwent transplantation for FHF. Multivariate analysis of 29 variables subsequently revealed distinct sets of factors that influenced patient and graft survival for both FHF and EHBA. These results confirm that separate prioritizing systems for LTx are needed for children with chronic liver disease and FHF; additionally, our findings illustrate that there are unique sets of variables which predict survival following LTx for these two groups. Liver Transpl 12:1347-1356, 2006. © 2006 AASLD. [source] Graft and patient survival after adult live donor liver transplantation compared to a matched cohort who received a deceased donor transplantationLIVER TRANSPLANTATION, Issue 10 2004Paul J. Thuluvath Live donor liver transplantation (LDLT) has become increasingly common in the United States and around the world. In this study, we compared the outcome of 764 patients who received LDLT in the United States and compared the results with a matched population that received deceased donor transplantation (DDLT) using the United Network for Organ Sharing (UNOS) database. For each LDLT recipient (n = 764), two DDLT recipients (n = 1,470), matched for age, gender, race, diagnosis, and year of transplantation, were selected from the UNOS data after excluding multiple organ transplantation or retransplantation, children, and those with incomplete data. Despite our matching, recipients of LDLT had more stable liver disease, as shown by fewer patients with UNOS status 1 or 2A, in an intensive care unit, or on life support. Creatinine and cold ischemia time were also lower in the LDLT group. Primary graft nonfunction, hyperacute rejection rates, and patient survival by Kaplan-Meier analysis were similar in both groups (2-year survival was 79.0% in LDLT vs. 80.7% in case-controls; P = .5), but graft survival was significantly lower in LDLT (2-year graft survival was 64.4% vs. 73.3%; P < .001). Cox regression (after adjusting for confounding variables) analysis showed that LDLT recipients were 60% more likely to lose their graft compared to DDLT recipients (hazard ratio [HR] 1.6; confidence interval 1.1-2.5). Among hepatitis C virus (HCV) patients, LDLT recipients showed lower graft survival when compared to those who received DDLT. In conclusion, short-term patient survival in LDLT is similar to that in the DDLT group, but graft survival is significantly lower in LDLT recipients. LDLT is a reasonable option for patients who are unlikely to receive DDLT in a timely fashion. (Liver Transpl 2004;10:1263,1268.) [source] Relationship between the Duration of the Basal QRS Complex and Electrical Therapies for Ventricular Tachycardias among ICD PatientsPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2010JAVIER JIMÉNEZ-CANDIL M.D., Ph.D. Background:,In implantable cardioverter-defibrillators (ICD) patients, the duration of the basal QRS complex (QRSd) is not associated with a greater risk of developing ventricular tachyarrhythmias. QRSd could be inversely related to the effectiveness of antitachycardia pacing (ATP) because it may be associated with longer conduction times of the paced-impulses and hence, with a greater propensity to require shocks to terminate ventricular tachycardias (VTs). Methods:,We followed 216 ICD patients (pacing site: right ventricular apex; QRSd , 100: 34%) for 21 ± 12 months. ICD programming was standardized. QRSd was determined on the electrocardiogram (50 mm/s) at device implantation. Results:,Five hundred and fifty-one VTs (cycle length: 329 ± 35 ms) occurred in 67 patients (36% had a QRSd , 100 ms). ATP terminated 86% of VTs and 11% needed shocks. Mean ATP efficiency per patient was 83%. QRSd was significantly correlated with the probability of successful ATP (C-coefficient: 0.66), the best cut-off point being 100 (sensitivity and specificity of 91% and 49%). Patients with QRSd , 100 had a higher ATP effectiveness (98% vs 75%; P = 0.003) and fewer VTs terminated by shocks (1% vs 23%; P = 0.003). By logistic regression, QRSd > 100 remained as an independent predictor of receiving shocks to terminate VTs (P = 0.01). According to Kaplan-Meier analysis, the occurrence of VTs was similar regardless of the QRSd (30% vs 38%; P = 0.2), but the incidence of shock due to VTs was higher in patients with a QRSd > 100 (19% vs 7%; P = 0.01). Conclusion:,Since QRSd is a negative and independent predictor of effective ATP, ICD patients with QRSd > 100 ms require shocks more frequently to terminate VTs. (PACE 2010; 596,604) [source] Persistence with cholinesterase inhibitor therapy in a population-based cohort of patients with Alzheimer's diseasePHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2010Joseph E. Amuah PhD Abstract Purpose To estimate the risk (and determinants) of discontinuing cholinesterase inhibitors (ChEIs) in a population-based sample of Alzheimer's disease (AD) patients. Methods This is a retrospective cohort study based on linked de-identified administrative health data from the province of Saskatchewan, Canada. The cohort included all AD patients receiving a ChEI prescription during the first year of provincial coverage (2000,2001). Persistence was defined as no gap of 60+ days between depletion and subsequent refill of a ChEI prescription. Kaplan-Meier analysis was used to estimate the risk of discontinuation over 40 months. Cox regression with time-varying covariates was used to assess risk factors for ChEI discontinuation. Results The sample included 1080 patients (64% female, average age 80,±,7 years). Baseline mean (SD) Mini-Mental State Examination (MMSE) and Functional Activities Questionnaire (FAQ) scores were 20.8 (4.4) and 17.5 (7.7), respectively. Over 40 months, 84% discontinued therapy. The 1-year risk of discontinuation was 66.4% (95%CI 63.5,69.3%). Discontinuation was significantly more likely for females (adjusted HR 1.34, 95%CI 1.16,1.55) and among those with lower MMSE scores (2.52, 2.01,3.17 if <15), not receiving social assistance (1.25, 1.07,1.45), and paying at least 65% of total prescription costs (1.51, 1.30,1.74). It was significantly less likely for patients with frequent physician visits (0.78, 0.66,0.93, for 7,19 vs. <7 visits), higher Chronic Disease Scores (0.74, 0.61,0.89, for 7+ vs. <4), and FAQ scores of 9+ (0.82, 0.69,0.99). Conclusion The likelihood of discontinuing ChEI therapy was high in this real-world sample of AD patients. Significant predictors included clinical, socioeconomic, and practice factors. Copyright © 2010 John Wiley & Sons, Ltd. [source] Osteopontin stimulates invasion of NCI-h295 cells but is not associated with survival in adrenocortical carcinoma,THE JOURNAL OF PATHOLOGY, Issue 2 2009Dirk Weismann Abstract Gene array studies indicated that osteopontin (OPN) mRNA is highly expressed in adrenocortical carcinomas (ACCs). OPN enhances invasiveness, proliferation, and metastasis formation, and is associated with poor survival in some malignant diseases. Integrin ,v,3 has been shown to mediate OPN effects on invasion. In this study, we demonstrated OPN and integrin ,v,3 expression in normal adrenal glands and benign adenomas, with staining seen exclusively in adrenocortical cells as well as even stronger staining in ACC. Western blot analysis confirmed overexpression of OPN in ACC (p < 0.01). With Matrigel invasion assays, we have shown that OPN greatly stimulates the invasiveness of NCI-h295 cells (>six-fold increase, p < 0.001). Transfection with integrin ,v,3 further increased invasiveness after OPN stimulation (p < 0.001). This increase was reversed by the addition of an anti-integrin ,3 antibody, indicating a functional relationship of OPN and integrin ,v,3 in ACC. With tissue arrays, we confirmed high OPN expression in 147 ACC samples. However, no association with survival was seen in Kaplan-Meier analysis including 111 patients with primary tumours graded for OPN staining and follow-up data available. In conclusion, our in vitro data indicate that OPN and integrin ,v,3 may act as a functional complex facilitating the invasiveness of adrenocortical tumours. This relationship remains of relevance to our understanding of carcinogenesis, but further studies are needed to address the physiological and pathological function of OPN in adrenal tissue. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Second Malignant Neoplasms in Patients Under 40 Years of Age With Laryngeal Cancer,THE LARYNGOSCOPE, Issue 4 2001James T. Albright MD Abstract Objectives/Hypothesis To determine the incidence of second malignant neoplasms (SMN) in patients under 40 years of age with invasive squamous cell carcinoma (SCC) of the larynx. Study Design Retrospective. Methods Using a National Cancer Institute tumor registry database encompassing 1973,1996, the incidence of SMN in patients under 40 years of age with laryngeal cancer was determined and compared with that of the registry's older, more traditional laryngeal cancer population. Median follow-up was 136 months. Results Among the 364 patients under the age of 40 years with laryngeal cancer, 30 (8.2%) had developed a secondary malignancy to date. In comparison, 4876 (21.4%) of 22,786 patients 40 years or older with laryngeal cancer were affected by an SMN. Kaplan-Meier analysis of the younger cohort projected 3.0%, 6.8%, and 10.7% relative risk of developing a SMN at any site over 5-, 10-, and 15-year periods, respectively, after index tumor diagnosis. Similar results for the older cohort were 14.2%, 28.1%, and 39.4% at 5, 10, and 15 years, respectively. Further Kaplan-Meier analysis demonstrated at least a fourfold increased risk for the development of secondary upper aerodigestive tract malignancies among older compared with younger patients. Conclusion Patients under 40 years of age with invasive SCC of the larynx are significantly less likely to develop a second malignancy than their older counterparts. [source] Baseline 6-Min Walk Distance Predicts Survival in Lung Transplant CandidatesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2008T. Martinu In a large, prospectively followed, two-center cohort of patients listed for lung transplantation (n = 376), we used Cox proportional hazards models to determine the importance of baseline 6-min walk distance (6MWD) in predicting patient survival. 6MWD used as a continuous variable was a significant predictor of survival after adjusting for other important covariates when transplant was considered as a time-varying covariate (HR for each 500 ft increase in 6MWD = 0.57, 95% CI: 0.43,0.77, p = 0.0002). 6MWD remained an important predictor of survival in models that considered only survival to transplant (HR for each 500 ft increase in 6MWD = 0.41, 95% CI: 0.27,0.62, p < 0.0001) or survival only after transplant (HR for each 500 ft increase in 6MWD = 0.40, 95% CI: 0.22,0.72, p = 0.002). Unadjusted Kaplan-Meier analysis demonstrates significantly different survival by 6MWD tertiles (<900, 900,1200, or >1200 ft, p-value = 0.0001). In the overall model, 6MWD prediction of survival was relatively homogeneous across disease category (6MWD by disease interaction term, p-value = 0.63). Our results demonstrate a significant relationship between baseline 6MWD and survival among patients listed for lung transplantation that exists across all native disease categories and extends through transplantation. The 6MWD is thus a useful measure of both urgency and utility among patients awaiting lung transplantation. [source] Successful Long-Term Outcomes Using Pediatric En Bloc Kidneys for TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2002Jade S. Hiramoto Goal: The objective of our study was to determine whether acceptable long-term graft survival and function can be achieved using pediatric en bloc renal transplants by employing specific immunologic and selection strategies. Materials and Methods: A retrospective analysis of pediatric en bloc kidney transplants at a single institution was performed. A Kaplan-Meier analysis was used to evaluate graft survival. Findings: Fifty-seven adult recipients with at least a 1-year follow-up period were successfully transplanted using pediatric en bloc kidneys between 1993 and 1998. Complete data regarding immunosuppression were available for 53 patients. All patients had a cyclosporine (CsA)- or tacrolimus (TAC)-based regimen with either azathioprine (Aza) or mycophenolate mofetil (MMF) and corticosteroids. All but two received induction with OKT3. One-, 3-, 4-, 5- and 7-year graft survival was calculated to be 88%, 86%, 83%, 68% and 68%, respectively. The mean serum creatinine value at 3 years was 1.0 ± 0.4 mg/dL. Thirteen patients (23%) had biopsy-proven rejection. Ten of 19 (53%) patients treated with CsA/Aza had rejection, whereas 2/15 (13%) on CsA/MMF and 1/19 (5%) of patients on TAC/MMF had rejection. Nine patients (16%) had surgical complications. Conclusion: Excellent long-term results can be achieved in pediatric en bloc kidney transplantation using OKT3, TAC and MMF in carefully selected adult recipients. [source] High N-terminal pro,brain natriuretic peptide levels and low diffusing capacity for carbon monoxide as independent predictors of the occurrence of precapillary pulmonary arterial hypertension in patients with systemic sclerosisARTHRITIS & RHEUMATISM, Issue 1 2008Y. Allanore Objective To evaluate predictors of pulmonary arterial hypertension (PAH) in a prospective cohort of patients with systemic sclerosis (SSc). Methods Routine clinical assessments as well as measurements of the diffusing capacity for carbon monoxide/alveolar volume (DLCO/VA) ratio and N-terminal pro,brain natriuretic peptide (NT-proBNP) level were performed in a prospective cohort of 101 SSc patients who did not have PAH or severe comorbidities. After a planned 36-month followup, we evaluated the predictive value of these parameters for the development of precapillary PAH, as demonstrated by cardiac catheterization, disease progression, and death. Criteria for cardiac catheterization were a systolic pulmonary artery pressure (PAP) of >40 mm Hg on echocardiography, a DLCO value of <50% without pulmonary fibrosis, and unexplained dyspnea. Results Eight patients developed PAH, 29 had disease progression, and 10 died during a median followup of 29 months. Kaplan-Meier analysis identified the following baseline parameters as being predictors of PAH: DLCO/VA ratio <70% or <60% (P < 0.01 for each comparison), elevated plasma NT-proBNP level (>97th percentile of normal; P = 0.005), echocardiographically estimated systolic PAP >40 mm Hg (P = 0.08), and erythrocyte sedimentation rate >28 mm/hour (P = 0.015). In multivariate analyses, an elevated baseline NT-proBNP level (hazard ratio [HR] 9.97 [95% confidence interval (95% CI) 1.69,62.42]) and a DLCO/VA ratio <60% (HR 36.66 [95% CI 3.45,387.6]) were predictors of the occurrence of PAH during followup. An increased NT-proBNP level together with a decreased DLCO/VA ratio of <70% was highly predictive of the occurrence of PAH during followup (HR 47.20 [95% CI 4.90,450.33]). Conclusion This prospective study identified a decreased DLCO/VA ratio and an increased NT-proBNP as predictors of PAH in SSc. Use of these markers should result in improved PAH risk stratification and allow earlier initiation of therapy. [source] Outcomes of dental implants placed in a surgical training programmeAUSTRALIAN DENTAL JOURNAL, Issue 4 2009LP Smith Abstract Background:, This study evaluates surgical outcomes and survival rates of implants placed in a multidisciplinary implant teaching programme. Methods:, A retrospective review of all implant surgery performed over a 6-year period by accredited oral and maxillofacial surgery trainees at the Royal Dental Hospital of Melbourne was undertaken. Patients were reviewed for a minimum of 6 months post-implant placement. Implant survival was defined as those implants which were not removed, were clinically integrated as assessed by torque testing and in an appropriate position to receive a subsequent prosthesis. Kaplan-Meier analysis was used to assess overall survival and univariate factors affecting survival. Multivariate analysis used Cox proportional hazards models. Results:, Over 6 years, 127 patients were treated. Follow-up data were present for 105 patients with 236 implants placed. Survival of implants at 1 and 5 years was 94 per cent and 92.8 per cent, respectively. The only univariate and multivariate factor which affected implant survival was perioperative bone grafting. All failed implants were single stage. Other factors such as patient age, smoking status, implant site, anaesthetic type, immediate or delayed placement, implant length and diameter, and medical comorbidities did not significantly affect implant survival. Conclusions:, A satisfactory implant survival rate was found in a tertiary teaching centre. Perioperative bone grafting significantly increased the risk of implant failure. [source] A 10-year follow-up after transurethral resection of the prostate, contact laser prostatectomy and electrovaporization in men with benign prostatic hyperplasia; long-term results of a randomized controlled trialBJU INTERNATIONAL, Issue 6 2010Robert J. Hoekstra Study Type , Therapy (RCT) Level of Evidence 1b OBJECTIVE To compare long-term results of transurethral resection of the prostate (TURP), contact laser prostatectomy (CLP) and electrovaporization of the prostate (EVAP) in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS Between 1996 and 2001, a prospective, randomized controlled trial was conducted in 150 men with LUTS suggestive of BPH, who had a prostate volume of 20,65 mL and a Schäfer's obstruction grade of ,2. Outcome variables were the International Prostate Symptom Score (IPSS), Quality of Life (QoL) question, Symptom Problem Index (SPI), BPH Impact Index (BII), maximum urinary flow rate (Qmax), prostate volume, prostate specific antigen (PSA) level, morbidity and mortality. In 2008 we carried out a long-term follow-up in these patients. Long-term values were compared with preoperative values for each treatment group (Wilcoxon signed-rank test), differences among groups were analysed (Kruskal,Wallis test) and actuarial failure-rates of the interventions were determined (Kaplan-Meier analysis). RESULTS Although we could account for 91% of the initial participants in 2008, 66 (44%) patients (29 TURP, 20 CLP and 17 EVAP) were available for follow-up measurements after a mean (range) of 10.1(6.9,12.7) years Among the three treatment groups, there were no significant differences in IPSS, QoL, SPI, BII, Qmax, PSA level and prostate volume. The IPSS, QoL, SPI and BII were still improved (P < 0.05) from values before treatment for all treatments. Only in the TURP group were the long-term results of Qmax still improved (P < 0.05). The mortality rate was comparable among the treatments. The 10-year actuarial failure rates (95% confidence interval) were 0.11 (0.03,0.20), 0.22 (0.10,0.35) and 0.23 (0.11,0.35) for TURP, CLP and EVAP, respectively. CONCLUSIONS After a mean follow-up of 10.1 years, there were similar and durable improvements in IPSS, QoL, SPI and BII for patients with LUTS suggestive of BPH after TURP, CLP and EVAP. Between the treatment groups there were no statistically significant differences in Qmax, PSA levels and prostate volume at any time during the follow-up. However, only patients treated with TURP showed minimal durable improvements in Qmax. There was no statistically significant difference in success rate and mortality rate among the three treatments. [source] The independent value of tumour volume in a contemporary cohort of men treated with radical prostatectomy for clinically localized diseaseBJU INTERNATIONAL, Issue 4 2010Sima P. Porten Study Type , Prognosis (case series) Level of Evidence 4 OBJECTIVE To determine if prostate tumour volume is an independent prognostic factor in a contemporary cohort of men who had a radical prostatectomy (RP) for clinically localized disease, as the effect of tumour volume on prostate cancer outcomes has not been consistently shown in the era of widespread screening with prostate-specific antigen (PSA). PATIENTS AND METHODS The study included 856 men who had RP from 1998 to 2007 for localized prostate cancer. Tumour volume based on pathology was analysed as a continuous and categorized (<0.26, 0.26,0.50, 0.51,1.00, 1.01,2.00, 2.01,4.00, >4.00 mL) variable using Cox proportional hazards regression and Kaplan-Meier analysis. A multivariable analysis was also conducted controlling for PSA level, Gleason grade, surgical margins, and pathological stage. RESULTS Tumour volume had a positive association with grade and stage, but did not correlate with biochemical recurrence-free survival on univariate analysis as a continuous variable (hazard ratio 1.00, P = 0.09), and was only statistically significant for volumes of >4 mL as a categorical variable. No tumour volume was an independent predictor of prostate cancer recurrence on multivariate analysis. There was no difference between tumour volume and time to cancer recurrence for organ-confined tumours using Kaplan-Meier analysis. In low-risk patients (PSA level <10 ng/mL, Gleason score ,6, clinical stage T1c/T2a) tumour volume did not correlate with biochemical recurrence-free survival in univariate or multivariable analysis. CONCLUSIONS There is no evidence that tumour volume is an independent predictor of prostate cancer outcome and it should not be considered as a marker of tumour risk, behaviour or prognosis. [source] Invasion of renal sinus fat is not an independent predictor of survival in pT3a renal cell carcinomaBJU INTERNATIONAL, Issue 12 2009Stephen A. Poon OBJECTIVE To clarify the significance of the location of extrarenal tumour extension of renal cell carcinoma (RCC) as in the 2002 Tumour-Nodes-Metastasis classification. Renal cortical tumours with perirenal fat invasion (PFI) or sinus fat invasion (SFI) are consolidated within the pT3a grouping; tumours with SFI are close to the renal veins, lymphatics and the collecting system. This might carry a worse prognosis for disease-specific survival (DSS), but reports are limited and contradictory. PATIENTS AND METHODS We retrospectively reviewed 1244 patients treated with nephrectomy from 1988 to 2007, to identify patients with pT3a renal tumours. They were classified as having PFI or SFI. Kaplan-Meier analysis and Cox proportional hazards regression models were used to assess predictors of survival. RESULTS The 230 patients who met the inclusion criteria had a median follow-up of 24 months. SFI was found in 63 (27.4%) patients and was associated with a worse 5-year DSS than the 167 (72.6%) with PFI (62.5% vs 75.0%; log rank P = 0.022). On univariate analysis, diameter (hazard ratio, HR 1.1), nuclear grade (HR 4.5), margin status (HR 5.8), lymph node metastases (HR 6.4), and systemic metastases (HR 15.4) were significant for DSS. In a multivariate model, only nuclear grade (HR 3.1), margin status (HR 8.9) and systemic metastases (HR 9.8) were independent predictors. CONCLUSION Patients with renal tumours with SFI are more likely to die from RCC than those with PFI. However, in the present patients the presence of SFI was not an independent predictor of DSS. [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] Human papillomaviruses are identified in a subgroup of sinonasal squamous cell carcinomas with favorable outcomeCANCER, Issue 12 2009Llucia Alos MD Abstract BACKGROUND: The role of human papillomavirus (HPV) in the pathogenesis of squamous cell carcinomas (SCCs) of the sinonasal tract and its clinicopathological implications were evaluated. METHODS: All SCCs of the sinonasal tract diagnosed in the Hospital Clinic of Barcelona from 1981 to 2006 were retrospectively evaluated (N = 60). Clinical and pathological data were reviewed. HPV infection was determined and typed by amplification of HPV DNA by polymerase chain reaction using the SPF-10 primers. p16INK4a expression was determined by immunohistochemistry. Overall and progression-free survival for HPV-positive and -negative patients was estimated by Kaplan-Meier analysis and by the use of a multivariate Cox proportional hazards model. RESULTS: HPV DNA was detected in tumor tissue of 12 of 60 (20%) patients. HPV16 was identified in 11 tumors and HPV35 in 1. Immunohistochemistry for p16INK4a stained all HPV-positive and no HPV-negative tumors (P < .001). No differences were observed in terms of site and histological grade or stage at presentation between HPV-positive and -negative tumors. However, HPV-positive patients had a significantly better 5-year progression-free survival (62%; 95% confidence interval [CI], 23%-86% vs 20%; 95% CI, 9%-34%; P = .0043, log-rank test) and overall survival (80%; 95% CI, 20%-96% vs 31%; 95% CI, 15%-47%; P = .036, log-rank test) than patients with HPV-negative tumors. In multivariate analysis, HPV-positive tumors were associated with improved progression-free survival (hazard ratio, 0.21; 95% CI, 0.17-0.98; P = .012). CONCLUSIONS: A subgroup of sinonasal SCCs is associated with HPV infection. These tumors have a significantly better prognosis. Cancer 2009. © 2009 American Cancer Society. [source] Osteopontin as a molecular prognostic marker for melanomaCANCER, Issue 1 2008Javier Rangel MD Abstract BACKGROUND. Osteopontin has been suggested as a marker of disease progression in patients with melanoma because of its overexpression in recent microarray analyses. However, its prognostic role in melanoma has not been fully defined. METHODS. Osteopontin expression status was examined using immunohistochemical analysis of a tissue microarray that contained primary cutaneous melanomas from 345 patients. The correlation between osteopontin expression and several histologic markers for melanoma was assessed by using the Chi-square test and the Le directional test. The impact of osteopontin expression on recurrence-free survival (RFS) and disease-specific survival (DSS) of patients with melanoma was examined using Cox regression and Kaplan-Meier analyses. The impact of increasing osteopontin expression on sentinel lymph node (SLN) metastasis was assessed using logistic regression analysis. RESULTS. High osteopontin expression was associated with increased tumor thickness (P = .037), Clark level (P = .035), and mitotic index (P = .046). Kaplan-Meier analysis demonstrated an association between osteopontin expression and reduced RFS (P < .03) and DSS (P = .05). Multivariate Cox regression analysis demonstrated that high osteopontin immunostaining had an independent impact on the DSS of this melanoma cohort (P = .049). In addition, osteopontin expression was significantly predictive of SLN metastasis (P = .009) and SLN burden, as assessed by the mean number of SLN metastases (P = .0025). Multivariate logistic regression analysis demonstrated an independent role for osteopontin expression in predicting SLN status (P = .0062). CONCLUSIONS. The current results validated the role of osteopontin as an independent prognostic marker for melanoma and provided new evidence for its predictive role in melanoma lymph node metastasis. Cancer 2008. © 2007 American Cancer Society. [source] Revisiting the value of assessing the mitotic rate of choroidal melanomaACTA OPHTHALMOLOGICA, Issue 2009SE COUPLAND Purpose To re-evaluate mitotic rate (MR) as an indicator of malignancy grade in uveal melanoma (UM) and as a predictor for UM-related mortality. Methods UM patients treated 1993-2006 by local resection or enucleation were included. Data on largest basal diameter (LBD), ciliary body involvement, extraocular extension, cell type, closed loops, MR per 40/HPF, cytogenetics were collected. Mortality data were obtained from NHS Cancer Registry. Results 918 patients (520 M; 398 F) had median age of 64.6 yrs with a median follow-up of 3.46 yrs (range 0.02-13). The UM had mean diameter of 14.9 mm with ciliary body involvement in 43.0%, epithelioid cells in 63.3%, closed loops in 41.2%, extraocular spread in 11.3%. Cytogenetics in 337 patients showed disomy 3 and 8 in 27%, monosomy 3 in 10.7%, chromosome 8 gains in 24.0%, both these abnormalities in 38.3%. The median MR was 3(range 0-61, SD 6). High MR correlated with ciliary body involvement (p = 0.001), epithelioid cells(p = 0.009), closed loops(p<0.0001), extraocular spread(p=0.027) & monosomy 3(p<0.0001;Mann-Whitney). MR also correlated with LBD(p=0.0001; t-test). Metastatic death occurred in 243 patients (26.7%). Kaplan-Meier analysis showed MR >4/40 HPF to be associated with increased 10-year metastatic mortality from 32.5 (95% confidence intervals [CI] 25.7-39.3) to 65.5 (95% CI 55-7-75.4; log rank statistic 53.28, p<0.0001). Cox multivariate analysis showed MR to be an independent predictive factor for metastatic death (p<0.0001). MR was predictive of metastatic death also in patients without detectable monosomy 3 (Log rank statistic 10.38, p = 0.002). Conclusion MR correlates with other known risk factors for metastatic death and independently predicts mortality even when cytogenetics show disomy 3. [source] Neural networks compared with Cox regressionACTA OPHTHALMOLOGICA, Issue 2008B DAMATO Purpose Survival prediction is useful in patient care and research. Most studies rely on Cox analysis and Kaplan-Meier curves whereas we have preferred neural networks. The aim of this presentation is to compare these methods and to discuss the advantages and limitations of each. Methods This presentation will be based on our experience with uveal melanoma. A neural network was trained with data from 1780 patients and evaluated with data from another 874 patients. Clinical, histopathological and cytogenetic data were included in the model. All cause mortality was reported, both for patients and for the matched general population. Results Cox analysis assumes linear correlations between variables and proportional hazards throughout the follow-up period. Kaplan-Meier analysis requires large patient categories, so that the precision of any prognostication is reduced. Neural networks overcome these limitations. Our model does censor non-metastatic deaths so that melanoma-related mortality is not exaggerated in groups of patients with significant competing risks. Conclusion Neural networks allow large numbers of variables to be included in predictive models with relatively small numbers of patients, thereby improving prognostication. Nevertheless, care must be taken when interpreting survival results to avoid serious misconceptions about the natural history of a disease and the impact of treatment. [source] L/I-7 Comparison of HCV outcomes in recipients of expanded-criteria, living donor, and standard liver graftsCLINICAL TRANSPLANTATION, Issue 2006M. Kinkhabwala Introduction:, Living donor (LD) and expanded-criteria donor (ECD) livers are important sources of organ transplants in some regions. Hepatitis C virus (HCV) remains the most common reason for end-stage liver disease in the United States. It is unclear whether ECD and LD grafts are associated with poorer outcomes in hepatitis C recipients, as compared with non-ECD (standard [STD]) MELD-allocated livers. The aim of this retrospective study was to compare long-term hepatitis C recurrence rates and outcomes in recipients of ECD, LD, and STD grafts. Methods:, The cohort of patients analyzed comprised all adult hepatitis C transplant recipients between 1/1/01 and 11/1/04 (minimum follow-up, 1 year). Recipients not surviving the immediate perioperative period (90 days) were excluded. Censored events were defined by disease-free graft survival. Disease recurrence was defined by histologically confirmed hepatitis C and at least stage II fibrosis. ECDs were identified according to accepted criteria (e.g., age, steatosis, ischemia, donation after cardiac death, abnormal biopsy). Results:, In all, 120 patients formed the study cohort, with 79 ECD, 27 LD, and 14 STD grafts. The mean recipient MELD was 19.8 overall (range, 6 to 43), 20.1 (ECD), 14.1 (LD), and 24.7 (STD). The mean time to censored event was 709 days overall, 631 (ECD), 884 (STD), and 846 (LD). The 2-year disease-free survival rate was 44% (ECD), 55.6% (LD), and 70.7% (STD), by Kaplan-Meier analysis. Comparison of the curves indicated a significant difference between ECD and STD recipients, but no difference between ECD and LD recipients. Conclusions:, Recipients with hepatitis C who received ECD grafts had poorer outcomes in our experience, as compared with those receiving STD grafts. LD grafts, which can be viewed as a subset of ECD grafts, also had poorer outcomes than STD whole grafts, but this difference was not statistically significant. [source] | |||||||||||||||||||||||||