Significant Predictors Of Progression Research Articles

Factors Associated with Progression of Japanese Open-Angle Glaucoma with Lower Normal Intraocular Pressure

To characterize the natural history and define the risk factors associated with the progression of normal-tension glaucoma (NTG) in Japanese patients who were followed up closely without treatment. Prospective 5-year study. Patients with NTG with intraocular pressure (IOP) consistently ≤15 mmHg without treatment at baseline. Visual field (VF) examinations were performed every 3 months, and disc/peripapillary retina photographs were taken every 6 months. Patients were followed up without treatment. Deterioration in VF was defined by reference to Guided Progression Analysis Software of the Humphrey VF Swedish Interactive Thresholding Algorithm 24-2 (Carl Zeiss Meditec, Jena, Germany) and disc/peripapillary retina deterioration as adjudged by 3 independent observers. Life table analysis was used for evaluating the time to disease progression, as defined by VF or deterioration of the optic nerve head structure. The Cox proportional hazards model was used to identify risk factors for glaucoma progression. We enrolled 90 patients (mean age, 53.9 years; baseline IOP, 12.3 mmHg; mean deviation [MD],-2.8 decibels [dB]). The MD slope averaged-0.33 dB/year (median,-0.23; 95% confidence interval [CI],-0.44 to-0.22). Glaucoma progression probability at 5 years was 66% (95% CI, 55-78), as defined by VF deterioration or disc/peripapillary retina deterioration (criterion 1): 52% (95% CI, 37-60), as defined by VF deterioration (criterion 2), and 50% (95% CI, 38-71), as defined by disc/peripapillary retina deterioration (criterion 3). Presence or history of disc hemorrhage (DH) (P < 0.001), long-term IOP fluctuation (P= 0.020), and a greater vertical cup-to-disc ratio (v-C/D) (P= 0.018) were significant predictors for progression defined by criterion 1. Long-term IOP fluctuation (P= 0.011) and a greater v-C/D (P= 0.036) were significant predictors for progression by criterion 2. Presence or history of DH (P= 0.0018) and long-term IOP fluctuation (P= 0.022) were significant predictors for progression by criterion3. In Japanese patients with NTG with mean baseline IOP of 12.3 mmHg without treatment, estimated mean MD slope for 5 years was -0.33 dB/year; probability of glaucoma progression based on VF or disc/peripapillary end points at 5 years was 66%. Presence or history of DH, long-term IOP fluctuation, and greater v-C/D significantly contributed to progression.

Single-center Experience in Treating Patients With t(4;14) Multiple Myeloma With and Without Planned Frontline Autologous Stem Cell Transplantation

BackgroundTranslocation t(4;14) has traditionally been classified as a high-risk cytogenetic feature in patients with multiple myeloma with shortened progression-free (PFS) and overall survival (OS) despite initial response to treatment. Recent data have shown an improved long-term survival in these patients treated with novel agents, such as bortezomib. Patients and MethodsWe conducted a retrospective study on our patients with t(4;14) multiple myeloma treated with bortezomib-based induction between July 1, 2006 and June 30, 2014 to assess the real-world outcomes of these patients in a tertiary center. ResultsAmong the 75 patients analyzed, the median PFS was 33.5 months, and the median OS was 69.6 months after a median follow-up of 41 months. Even in the era of novel agents, patients who received frontline autologous stem cell transplant had a better PFS than those who received chemotherapy alone (median PFS, 24.2 months vs. 41.5 months; P = .01). Hypercalcemia at the time of presentation was found to be a significant predictor of progression (hazard ratio [HR], 10.1; 95% confidence interval [CI], 4.0-26.0) and death (HR, 9.4; 95% CI, 3.2-27.8), and co-harboring of del(17p) by fluorescent in situ hybridization with t(4;14) was associated with a significantly inferior OS (HR, 4.0; 95% CI, 1.4-11.4). ConclusionEven in the era of novel agents, t(4;14) remains a negative prognostic marker. Frontline autologous stem cell transplant remains as an essential tool when treating these high-risk patients, but further prospective randomized studies are needed to determine the most effective strategy for this patient group.

TRANSITION PREDICTORS OF X-RAY 0 STAGE FOR KNEE OSTEOARTHRITIS INTO THE 1ST STAGE (BASED ON THE COMPLEX EVALUATION OF THE KNEE JOINT BY MRI WORMS)

Background. Osteoarthritis (OA) is the most common disease among all rheumatological diseases. Approximately 70-80% of all OA cases of are gonarthritis. Routine X-ray examination is not informative to assess non-bone structures. Magnetic resonance imaging (MRI) allows visualizing all the structural elements of a joint, such as articular soft tissue structures and subcortical parts. To achieve objective data, the researcher needs to adhere a protocol allowing to assess of all joint parts, the so-called method of evaluation of the whole body (Whole Organ Magnetic Resonance Imaging Score –WORMS). Aim. to determine predictors of OA progression for X-ray 0 stage on the basis of the knee MRI procedure byWORMS.Methods. A cohort study. The sample consisted of patients with gonarthritis in all hospitals inArkhangelsk,Northwest Russia. The main inclusion criterion was clinically confirmed with knee OA by Altman 1991 without X-ray pathological changes. X-ray examinations of the knee joints were performed during the initial diagnosis and after one year. After the first X-ray examination patients underwent an MRI provided by machines with a magnetic field strength of 1.5 Tesla. The study included 76 patients, 22 patients were lost to follow up. Altogether, 54 (71.1%) patients completed the study. MRI evaluation of the data was carried out byWORMS protocol.Results. The progression of X-ray 0 stage into the first stage by Kellgren-Lawrence after one year has occurred in 45 (8.3%) patients of the 54 patients. Clinically significant predictors of progression of OA of the knee based on MRI were: degeneration of the medial meniscus (OR = 5.0, 95% CI: 1.1-22.5), and synovitis (OR = 7.0, 95% CI: 1.5-33.1), degeneration of the medial meniscus and synovitis were included Regression model. Regression model revealed the most significant predictor of progression of knee OA was synovitis (OR = 5.49, 95% CI: 1.13-26.72). The sensitivity of model was 95,1% (95% CI: 85.8-94.9), specificity was 71,4% (95% CI: 33.3-94.4), positive predictive value was 5,6% (95% CI: 89.6-99.1), negative predictive value was 55,6% (95% CI: 25,9-73,4).The findings of this study revealed the only significant MRI predictor of the transition X-ray 0 stage into the first stage was synovitis which increased the risk of the progression in 5.5 times during one year.

Patterns of initial and intracranial failure in metastatic EGFR-mutant non-small cell lung cancer treated with erlotinib

ObjectivesPatients with metastatic EGFR-mutant (mEGFRmt) NSCLC have favorable survival when treated with erlotinib. We hypothesized that treatment failure in most patients is limited to initial sites of disease, in which case incorporating local therapy such as radiation might further delay progression. We therefore analyzed patterns and predictors of failure in a large cohort of such patients. Materials and methodsWe reviewed 189 patients treated with erlotinib for mEGFRmt NSCLC. We classified first pattern of failure as involving initial sites only (ISF), new sites only (NSF), or the combination (CSF), and used competing-risks regression to identify factors associated with ISF, progression and overall survival (OS). We also separately analyzed intracranial and intrathoracic failure. ResultsOf 171 patients who progressed, 103 (60.2%) had ISF, 30 (17.5%) had NSF, and 38 (22.2%) had CSF. Younger age and lack of initial CNS involvement independently correlated with ISF, with a trend for higher T and N stage. Higher T and N stage was also a significant predictor of progression. Factors predicting shorter OS were female gender, weight loss, initial intracranial involvement, and ≥4 extracranial metastases. Intrathoracic progression was a component of first failure in 61%, and three-year cumulative incidence of brain metastasis was 30%. ConclusionThe main pattern of progression in mEGFRmt NSCLC on erlotinib is in the initial sites of disease. Younger patients and those without brain involvement are particularly likely to develop ISF. This suggests a role for incorporating local therapy into treatment of selected patients with mEGFRmt NSCLC.

Identification of Downstream Genes of the mTOR Pathway that Predict Recurrence and Progression in Non-Muscle Invasive High-Grade Urothelial Carcinoma of the Bladder.

Microarray analysis was used to investigate the lack of identified mammalian target of rapamycin (mTOR) pathway downstream genes to overcome cross-talk at non-muscle invasive high-grade (HG)-urothelial carcinoma (UC) of the bladder, gene expression patterns, gene ontology, and gene clustering by triple (p70S6K, S6K, and eIF4E) small interfering RNAs (siRNAs) or rapamycin in 5637 and T24 cell lines. We selected mTOR pathway downstream genes that were suppressed by siRNAs more than 2-fold, or were up-regulated or down-regulated by rapamycin more than 2-fold. We validated mTOR downstream genes with immunohistochemistry using a tissue microarray (TMA) of 125 non-muscle invasive HG-UC patients and knockout study to evaluate the synergistic effect with rapamycin. The microarray analysis selected mTOR pathway downstream genes consisting of 4 rapamycin up-regulated genes (FABP4, H19, ANXA10, and UPK3A) and 4 rapamycin down-regulated genes (FOXD3, ATP7A, plexin D1, and ADAMTS5). In the TMA, FABP4, and ATP7A were more expressed at T1 and FOXD3 was at Ta. ANXA10 and ADAMTS5 were more expressed in tumors ≤ 3 cm in diameter. In a multivariate Cox regression model, ANXA10 was a significant predictor of recurrence and ATP7A was a significant predictor of progression in non-muscle invasive HG-UC of the bladder. In an ATP7A knock-out model, rapamycin treatment synergistically inhibited cell viability, wound healing, and invasion ability compared to rapamycin only. Activity of the ANXA10 and ATP7A mTOR pathway downstream genes might predict recurrence and progression in non-muscle invasive HG-UC of the bladder. ATP7A knockout overcomes rapamycin cross-talk.

Visit-to-visit blood pressure variability, average BP level and carotid arterial stiffness in the elderly: a prospective study.

In a cross-sectional study, visit-to-visit blood pressure (BP) variability was shown to be associated with artery remodelling. Here, we investigated the impact of visit-to-visit BP variability and average BP on the carotid artery remodelling progression in high-risk elderly according to different classes of antihypertension medication use/non-use. BP measurements and carotid ultrasound were performed in the common carotid artery in 164 subjects (mean age 79.7 years at baseline, 74.7% females) with one or more cardiovascular risk factors. Based on 12 visits (1 × /month for 1 year), we calculated visit-to-visit BP variability expressed as the standard deviation (s.d.), coefficient of variation (CV), maximum BP, minimum BP and delta (maximum-minimum) BP. We measured mean intima-media thickness (IMT) as well as stiffness parameter β were measured at baseline and at the mean 4.2-year follow-up. In a multiple regression analysis, the maximum, minimum, s.d. and average of systolic BP (SBP) were significantly associated with a change in β-values between the baseline and follow-up after adjustment for age, smoking, lower high-density lipoprotein level, baseline β-value and follow-up period. There were no significant associations between the visit-to-visit BP variability measures and the change in mean IMT. Significant associations of maximum, minimum, s.d. and average SBP were found with increased β-values in the subjects without calcium channel blocker (CCB) use and in the subjects using renin-angiotensin system inhibitors (RASIs). Thus, exaggerated visit-to-visit SBP variability and a high average SBP level were significant predictors of progression in carotid arterial stiffness in high-risk elderly without CCBs use and in those using a RASI.

The natural history of corneal topographic progression of keratoconus after age 30 years in non-contact lens wearers

Background/aimsTo determine if significant progression of disease occurs in older, non-contact lens wearing, subjects with keratoconus and to identify potential predictive factors.MethodsClinical and computerised corneal topography records of subjects with...

Baseline Fourier-Domain Optical Coherence Tomography Structural Risk Factors for Visual Field Progression in the Advanced Imaging for Glaucoma Study

To identify baseline structural parameters that predict the progression of visual field (VF) loss in patients with open-angle glaucoma. Multicenter cohort study. Participants from the Advanced Imaging for Glaucoma (AIG) study were enrolled and followed up. VF progression is defined as either a confirmed progression event on Humphrey Progression Analysis or a significant (P < .05) negative slope for VF index (VFI). Fourier-domain optical coherence tomography (FDOCT) was used to measure optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) thickness parameters. A total of 277 eyes of 188 participants were followed up for 3.7 ± 2.1 years. VF progression was observed in 83 eyes (30%). Several baseline NFL and GCC parameters, but not disc parameters, were found to be significant predictors of progression on univariate Cox regression analysis. The most accurate single predictors were the GCC focal loss volume (FLV), followed closely by NFL-FLV. An abnormal GCC-FLV at baseline increased risk of progression by a hazard ratio of 3.1. Multivariate Cox analysis showed that combining age and central corneal thickness with GCC-FLV in a composite index called "Glaucoma Composite Progression Index" (GCPI) further improved the accuracy of progression prediction. GCC-FLV and GCPI were both found to be significantly correlated with the annual rate of change in VFI. Focal GCC and NFL loss as measured by FDOCT are the strongest predictors for VF progression among the measurements considered. Older age and thinner central corneal thickness can enhance the predictive power using the composite risk model.

Prognostic value of posttreatment neutrophil-lymphocyte ratio in head and neck squamous cell carcinoma treated by chemoradiotherapy.

An inflammatory-immunological marker, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), was evaluated as a predictive marker of advanced head and neck cancer patients receiving chemoradiotherapy. This study included 104 patients with treatment-naïve head and neck cancer who underwent definitive chemoradiotherapy. An inflammatory marker was measured at baseline and after 1 month of treatment. Univariate and multivariate analyses using Cox proportional hazards model were used to identify predictors of progression-free survival (PFS) and overall survival (OS). A univariate analysis revealed that T,N-stage, the pre- and posttreatment NLRs were significant predictors of progression after the chemoradiotherapy. However, the posttreatment NLR remained an independent predictor of PFS in the multivariate analysis (HR=2.23, 95% CI 1.15-2.321; P=0.001). A high posttreatment NLR was significantly associated with an increased risk of death (HR=1.87, 95% CI 0.89-3.31; P=0.037). A high posttreatment NLR is associated with poor prognostic factor. An early reduction in the NLR after treatment may indicate survival improvement in the patients.

3:18 PMAbstract No. 338 - Pre and post-procedural evaluation of imaging biomarkers after radioembolization for hepatocellular carcinoma as an indicator of progression

The purpose of this study is to evaluate possible imaging biomarkers on contrast-enhanced CT and MRI exams that predict local progression per modified Response Evaluation Criteria in solid tumors (mRECIST) criteria post radioembolization of hepatocellular carcinoma (HCC). Among patients who underwent radioembolization for HCC between May 1, 2005 and May 1, 2015 at a single institution, 34 patients had adequate pre and at least 2 post-procedural exams. Local response to treatment was classified as progressive (PD) or stable disease (SD) using mRECIST. Imaging markers, including portal venous phase enhancement (PVE), lobulated enhancement (LE), presence of arterioportal shunting (APS), and portal vein thrombosis (PVT) were assessed in each imaging examination. Wilcoxen Rank-Sum (WRS) and log-rank analyses were performed to establish statistically significant differences in local progression free survival (LPFS). The mean imaging follow-up time was 12.64 months. Local progression was seen in 25 patients (73.5%) following radioembolization. Average time to progression was 2.9 months. PVT, APS, and PVE seen on pre or post-procedural imaging were not significant predictors of LPFS. LE on immediate post-procedural imaging was a significant predictor of progression by WRS (p=0.039) and log-rank analysis (p=0.037), however LE on pre-procedural imaging was not a significant predictor. 9 patients with and 0 patients without progression showed LE on pre or post-procedural imaging, respectively. PVT, APS, and portal venous enhancement were not statistically significant predictors of local progression, whereas immediate post-procedural LE demonstrated a statistically significant decrease in LPFS in patients with hepatocellular carcinoma treated with radioembolization.

Plasma Cytokine Levels in Chronic Asymptomatic HIV-1 Subtype C Infection as an Indicator of Disease Progression in Botswana: A Retrospective Case Control Study.

HIV infects cells of the immune system causing immune activation and proliferation of immune cells, leading to alteration of production and activity of a number of cytokines. These changes in cytokine levels can affect the immune function, and have the potential to directly impact the course of HIV disease. We characterized plasma cytokine concentration profiles in HIV-1 subtype C chronically infected, antiretroviral therapy (ART)-naive participants to establish their influence on disease progression and viremia. Plasma levels of interleukin (IL)-1α, IL-7, IL-12p40, granulocyte macrophage-colony-stimulating factor (GM-CSF), and interferon (IFN)-γ were quantified in samples from 60 treatment-naive participants in the placebo arm of the completed Micronutrient-HIV disease progressions study, "Dikotlana" (2004-2009) in Gaborone, Botswana. Participants were stratified into progressors (P) and nonprogressors (NP) based on their rates of CD4(+) T cell depletion during the study period. Nonprogressors were those who had <1% CD4(+) T cell depletion at 24 months postenrollment. Progressors were defined as those with CD4(+) T cell depletion of >15% at 24 months postenrollment. Cytokine levels were compared between P and NP using the Mann-Whitney U-test. Logistic regression analysis was used to determine if cytokines predicted disease progression. Correlations of cytokines with CD4(+) T cell counts and viral loads were determined by the Spearman rank test. Median baseline CD4(+) T cell counts were 453 (Q1, Q3; 401, 592) and 479 (Q1, Q3; 401-592) for nonprogressors and progressors, respectively. Nonprogressors had a higher viral set point than progressors. IL-12p40 levels were significantly higher in the P than in NP at enrollment and 24 months (p < 0.05). Levels of IL-1α, IL-7, IFN-γ, and GM-CSF did not differ significantly between the two groups. Except for IL-12p40, which displayed an inverse correlation with CD4(+) T cell counts and a direct correlation with viral load, all other cytokines showed no correlations. IL-12p40 was found to be the most significant predictor of progression and its production was most likely driven by HIV replication products as evidenced by its direct correlation with viral load. In chronic HIV-1 subtype C infection, CD4(+) T cell counts and plasma cytokine levels may not necessarily evolve in parallel, suggesting the involvement of other factors in determining the rates of CD4(+) T cell depletion.

Molecular and clinical support for a four-tiered grading system for bladder cancer based on the WHO 1973 and 2004 classifications

Currently, the use of two classification systems for bladder cancer grade is advocated in clinical guidelines because the WHO2004 classification has not been sufficiently validated with biological markers and follow-up. The slides of 325 primary non-muscle invasive bladder cancers from three hospitals were reviewed by one uro-pathologist in two separate sessions for the WHO1973 (G1, G2 and G3) and 2004 (papillary urothelial neoplasm of low malignant potential (LMP), low-grade (LG) and high-grade (HG)) classifications. FGFR3 status was examined with PCR-SNaPshot analysis. Expression of Ki-67, P53 and P27 was analyzed by immuno-histochemistry. Clinical recurrence and progression were determined. We performed validation and cross-validation of the two systems for grade with molecular markers and clinical outcome. Multivariable analyses were done to predict prognosis and pT1 bladder cancer. Grade review resulted in 88 G1, 149 G2 and 88 G3 lesions (WHO1973) and 79 LMP, 101 LG and 145 HG lesions (WHO2004). Molecular validation of both grading systems showed that FGFR3 mutations were associated with lower grades whereas altered expression (Ki-67, P53 and P27) was found in higher grades. Clinical validation showed that the two classification systems were both significant predictors for progression but not for recurrence. Cross-validation of both WHO systems showed a significant stepwise increase in biological (molecular markers) and clinical (progression) potential along the line: G1—LG—G2—HG—G3. The LMP and G1 categories had a similar clinical and molecular profile. On the basis of molecular biology and multivariable clinical data, our results support a four-tiered grading system using the 1973 and 2004 WHO classifications with one low-grade (LMP/LG/G1) category that includes LMP, two intermediate grade (LG/G2 and HG/G2) categories and one high-grade (HG/G3) category.

Abstract 495: Body Mass Index is Associated with Progression of Carotid Intima-Media Thickness in Black, but not in White Young Adults: The Bogalusa Heart Study.

Introduction: Increased Carotid intima-media thickness (CIMT) has been shown to be predictive of future cardiovascular events in middle-age and older adults, with this outcome being detrimentally enhanced by increased body adiposity -as measured by Body Mass Index (BMI). Hypothesis: We assessed the hypothesis that the association between BMI and CIMT varies among race (black/white) and gender groups. Methods: B-mode ultrasound images of the far walls for both carotid arteries were obtained from 676 community-based subjects, aged 24 to 43 years, enrolled in the Bogalusa Heart Study (70% white and 43% male). CIMT, BMI and traditional cardio metabolic (CM) risk factors were measured at baseline, and a second set of CIMT imaging was performed at follow-up after an average of 6.9 years. Composite CIMT was considered for the analyses. Progression of IMT was defined as an increase of IMT between examinations, that was greater than the upper endpoint of the 95% confidence interval of the mean difference between the baseline samples and their blind duplicates. Results: BMI was the only significant predictor of progression of CIMT within the general population (Odds Ratio [OR]= 1.062 p=0.0031), after controlling for age, race, sex and traditional CM risk factors. In race-specific analyses, BMI significantly influenced the odds of CIMT progression only in the black subpopulation (OR= 1.092 p&lt;0.0001). Gender-specific analyses showed independent association of these parameters in females only (OR= 1.063 p=0.0179). Conclusions: In conclusion, these findings help support the proposed hypothesis of racial and gender divergences in the association between BMI and progression of CIMT, which suggest that race (black-white) and gender-specific mechanistic differences exist in the impact of increased body adiposity on carotid artery disease. Further, these observations may help strengthen individualized race and gender approaches to cardio-metabolic risk prevention in the community.

MP50-14 CLINICAL STAGE I RENAL MASS UPSTAGING TO PATHOLOGICAL T3A DISEASE PORTENDS A WORSE PROGNOSIS ONLY WHEN SINUS FAT INVASION IS PRESENT

You have accessJournal of UrologyKidney Cancer: Evaluation and Staging III1 Apr 2015MP50-14 CLINICAL STAGE I RENAL MASS UPSTAGING TO PATHOLOGICAL T3A DISEASE PORTENDS A WORSE PROGNOSIS ONLY WHEN SINUS FAT INVASION IS PRESENT Sumit De, Robert Uzzo, Elizabeth Handorf, David Chen, Rosalia Viterbo, Richard Greenberg, Nikhil Waingankar, Mohammed Haseebuddin, Marc Smaldone, and Alexander Kutikov Sumit DeSumit De More articles by this author , Robert UzzoRobert Uzzo More articles by this author , Elizabeth HandorfElizabeth Handorf More articles by this author , David ChenDavid Chen More articles by this author , Rosalia ViterboRosalia Viterbo More articles by this author , Richard GreenbergRichard Greenberg More articles by this author , Nikhil WaingankarNikhil Waingankar More articles by this author , Mohammed HaseebuddinMohammed Haseebuddin More articles by this author , Marc SmaldoneMarc Smaldone More articles by this author , and Alexander KutikovAlexander Kutikov More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2925AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Invasion of intrarenal or perirenal adipose tissue carries a pT3a designation in the AJCC 7 Staging System for Renal Cell Carcinoma and thus implies an inferior prognosis. We sought to reevaluate in a large prospectively maintained dataset the association between oncologic outcomes and pT3a upstaging due to adipose invasion in patients undergoing surgery for a cT1 renal mass. METHODS Patients with cT1N0M0 renal masses who were surgically treated between February 2001 and July 2014 were identified in our prospectively maintained institutional registry. We used Kaplan-Meier survival curves with log rank statistic to evaluate overall and progression free survival. Univariable and multivariable Cox regression analyses were used to assess prognostic roles of perirenal and sinus fat invasion, controlling for age, sex, tumor size, histology, and grade. RESULTS A total of 792 of 3240 patients met inclusion criteria. Median follow-up was 2.4 years for the cohort with 92 (11.6%) patients demonstrating disease progression. Upstaging to T3a disease was noted in 52 (6.6%) patients. Of these, 21 (40.4%) patients exhibited invasion of sinus fat. Perinephric fat invasion was not a significant predictor of progression on univariable analysis (HR 0.69, 95% CI 0.17-2.84, p=0.613). Meanwhile, on both univariable (HR 4.05, 95% CI 1.87-8.81, p=<0.001) and multivariable analyses (HR 2.83, 95% CI 1.23-6.53, p=.01) sinus fat invasion was strongly associated with disease progression. CONCLUSIONS Not all T3a disease is the same. Only invasion of sinus fat in patients undergoing surgery for clinical stage I renal mass was associated with disease recurrence. Perirenal fat invasion, on the other hand, was not linked with worse oncologic outcomes when compared with patients without tumor upstaging. If validated in other datasets, these data may help inform decision-making when formulating future AJCC staging criteria. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e616 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sumit De More articles by this author Robert Uzzo More articles by this author Elizabeth Handorf More articles by this author David Chen More articles by this author Rosalia Viterbo More articles by this author Richard Greenberg More articles by this author Nikhil Waingankar More articles by this author Mohammed Haseebuddin More articles by this author Marc Smaldone More articles by this author Alexander Kutikov More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Visual rating and volumetric measurement of medial temporal atrophy in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort: baseline diagnosis and the prediction of MCI outcome.

This study aims to determine the clinical utility of visual ratings and volumetric measurements of medial temporal atrophy among subjects from the Alzheimer's Disease Neurorimaging Initiative (ADNI) cohort. A sample of 189 subjects from the ADNI, Phase 1 (ADNI-1), was chosen as follows: 49 cognitively normal (CN), 89 with mild cognitive impairment (MCI), and 50 with Alzheimer's disease (AD). Structural MRI images were downloaded from the ADNI website, and a visual rating system (VRS) was used to obtain semi-quantitative ratings of the hippocampus (HPC) and entorhinal cortex (ERC). VRS ratings and FreeSurfer measures of the HPC and ERC were used to predict (i) baseline diagnosis and (ii) progression to AD among subjects with MCI at baseline. VRS and FreeSurfer measures of ERC were equivalent in classifying subjects at baseline, but FreeSurfer measures of HPC were superior to VRS measures for classifying CN versus MCI subjects. VRS and FreeSurfer measures of both HPC and ERC were significant predictors of progression from MCI to AD. However, VRS ratings of ERC were superior to other MRI measures. MCI subjects with minimal ERC atrophy by VRS had a threefold lower progression rate to AD at 3.2 years compared with those with mild, moderate, or severe atrophy (23% vs 63%, 69%, and 87%, respectively). Visual ratings of HPC and ERC provide useful information to a physician in a clinical setting. Visual ratings of ERC may be especially useful in following patients with MCI.

Prognostic factors for salvage radiotherapy with an analysis of post-prostatectomy PSA kinetics

Objectives: To identify prognostic factors for biochemical control including post-prostatectomy prostate-specific antigen(PSA) kinetics in prostate cancer patients undergoing salvage radiotherapy (SRT). Methods and Materials: Ninety patients who received SRT following radical prostatectomy (RP) were retrospectivelyanalyzed to determine factors associated with biochemical failure. Results: Median follow-up was 30 months (range 6-120). The projected 3-year biochemical freedom from progression(bFFP) was 70%. Factors significantly associated with biochemical failure on univariate analysis included Gleason score(GS), seminal vesicle invasion (SVI), a length of time from prostatectomy to SRT of less than 12 months, pre-RT PSAgreater than 1.0 ng/mL, a persistently detectable PSA following RP, PSA doubling time (PSADT) of 6 months or less,PSA velocity (PSAV) of 1.0 ng/mL/y or greater, and a rising PSA trend during treatment. There was a trend towarddecreased bFFP among patients with pathologic tumor stage of T3-T4 ( p =0.136) and positive surgical margins (p=0.301).Pre-RT PSA was found to be a significant predictor of progression with a HR of 3.659 (CI 1.981-8.755) for each increasein PSA of 1.0 ng/mL. Conclusion: Early consideration of SRT should be given for patients with high-risk features and rising PSA. Clinical trialsevaluating systemic therapy should be considered for patients with persistently detectable PSA after RP or a rising PSAtrend during SRT.

Management of secondary immune deficiencies

Management of secondary immune deficiencies

Impact of bladder neck involvement on progression in patients with primary non–muscle invasive bladder cancer: A prospective validation study

PurposeOur previous retrospective study reported that bladder neck involvement (BNI), as well as tumor grade and stage, was a significant risk factor for progression in primary non–muscle invasive bladder cancer (NMIBC). We prospectively validated BNI as a significant predictor for progression using a new cohort of patients with primary NMIBC. Patients and methodsA total of 297 new Japanese patients who underwent transurethral resection and were pathologically diagnosed with Ta or T1 urothelial carcinoma were enrolled in this prospective study. Clinicopathologic data were collected at study entry. Multivariate Cox proportional hazards regression models were performed to identify the independent predictors for progression. A predictive scoring model for progression was developed using the regression coefficients (RCs) from the final multivariate model. The predictive ability of the model was assessed using Harrell's c-index. ResultsWith a median follow-up of 37 months, 16 patients (5.4%) progressed. Progression probability at 1 and 5 years were 1.5% and 8.0%, respectively. Multivariate analysis revealed that histologic grade 3 (hazard ratio [HR] 9.45, P = 0.0004, RC 2.25), pathologic T1 stage (HR 6.91, P = 0.0014, RC 1.93), and BNI (HR 11.75, P = 0.0009, RC 2.46) were all independent predictors of progression. When all 3 variables were scored as 1 point and the patients were divided into 3 groups, progression rates were clearly discriminated (P<0.0001). The c-index was 0.80. ConclusionsThis prospective validation study has shown that BNI is a significant prognostic factor for progression in primary NMIBC. The scoring model including BNI enables the physician to classify patients with primary NMIBC into 3 groups with clearly different progression rates.

The role of VEGF/mTOR/AKT pathway in patients with advanced urothelial carcinoma of the bladder cancer.

264 Background: Activation of the mTOR pathway can be observed in various tumor entities. In advanced urothelial carcinoma of the bladder (BCA) its role still is unclear. The aim of our study was to examine activation of the mTOR cascade in BCA and its correlation with survival data. Methods: Tissues from 268 patients undergoing radical cystektomy were collected to assess the diagnostic and prognostic value of mTOR, HIF1-alpha, p4EB-P1, pAKT and VEGF using tissue microarray-based immunohistochemistry. Results: Overexpression of mTOR pathway enzymes is frequently detected for HIF1-alpha (29.8%), pAKT (53.2%), mTOR (43.3%), p4EB-P1 (28.4%) and VEGF (58.5%). Overexpression of pAKT was a significant predictor of progression (PFS) in pT1 (p=0.026) and pT2 (p=0.018) tumors. Overall survival (OAS) was significantly shorter for patients with pT1 (p=0.021) and pT2 (p=0.026) tumors in this subgroup. HIF1-alpha overexpression leads to significant earlier recurrence of BCA following radical cystektomie in the subgroup of pT3 tumors (p=0.046). High levels of mTOR were predictive for cancer related death (p=0.021) in pT2-tumors. Conclusions: Activation of mTOR-pathway, especially pAKT is of prognostic value in patients with advanced BCA and might be useful as a target for future therapies.

Three-year's changes in glucose tolerance status in the Bellville South cohort: Rates and phenotypes associated with progression

AimsTo determine the phenotypes associated with progression to type 2 diabetes or worsening in glucose tolerance during a 3-year follow-up of a community-based cohort in Cape Town, South Africa. MethodsA total of 198 eligible subjects (72.3% women) aged 55.2 years, from the Bellville-South community were followed-up between 2008 and 2011. Baseline and follow-up data collections included glucose tolerance status, anthropometric, blood pressure, lipids, insulin, γ-glutamyltransferase, cotinine, creatinine and HbA1c. Progression in glucose tolerance status at 3-year was the composite of new-onset diabetes and any worsening in glucose tolerance status. ResultsThe cumulative incidence of progression in glucose tolerance status was: 16.2% (32 participants including 11 with new-onset diabetes), and increased in a stepwise fashion with the number of components of metabolic syndrome (MetS). In age and sex-adjusted logistic regression analyses, MetS [odd ratio: 3.08 (95% CI: 1.34–7.10)], HbA1c [5.26 (1.94–14.24)], HDL-cholesterol [0.05 (0.01–0.33)], γ-glutamyltransferase [1.99 (1.07–3.67)], triglycerides [1.71 (1.13–2.58)] and total/HDL-cholesterol [1.45 (1.08–1.93)] were significant predictors of progression, while borderline effects were observed for baseline glucose and diastolic blood pressure. Markers of adiposity were mostly stable or improved among non-progressors during follow-up, but deteriorated significantly among progressors, resulting in significant statistical interactions. ConclusionsHigh rates of deterioration of glucose status over time were found in our population, with nearly one-fifth of them acquiring a glucose tolerance worse status within a very short follow-up. Our study extends to this setting the well-known utility of phenotypes of MetS single or in combination, in predicting worsening in glucose tolerance status.