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1.
Int J Cardiol Heart Vasc ; 34: 100760, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33869728

ABSTRACT

The Arrhythmia Working Group of the Austrian Society of Cardiology (ÖKG) has set the goal of systematically structuring and organizing the acute care of patients with ventricular arrhythmias (VA), i.e. ventricular tachycardia (VT) or ventricular fibrillation (VF) in Austria. Within a consensus paper, national recommendations on the basic diagnostic work-up of VA (12-lead ECG, medical history, family history, laboratory analyses, echocardiography, search for reversible causes, ICD interrogation), as well as further medical treatment and therapeutic measures (indication of coronary angiography, ablation therapy) are established. Since acute ablation of VT is indicated in the current ESC guidelines as a class IB indication for scar-associated incessant VT or electrical storm (ES; ≥ 3 ICD therapies in 24 h) as well as for ischemic cardiomyopathy (iCMP) with recurrent ICD shocks, organizational measures must be taken to ensure that these guidelines can be implemented. Therefore, a VT network will be established covering all areas in Austria, consisting of primary and secondary VT centers. Organizational aspects of an acute VT network are defined and should subsequently be implemented by the participating hospitals. All electrophysiologic centers in Austria that deal with VT ablation are to be integrated into the network in the medium-term. Centers that co-operate in the network are divided into primary and secondary VT centers according to predefined criteria.

2.
Prostate Cancer Prostatic Dis ; 19(2): 163-7, 2016 06.
Article in English | MEDLINE | ID: mdl-26810014

ABSTRACT

BACKGROUND: To assess the prognostic value of preoperative C-reactive protein (CRP) serum levels for prognostication of biochemical recurrence (BCR) after radical prostatectomy (RP) in a large multi-institutional cohort. METHODS: Data from 7205 patients treated with RP at five institutions for clinically localized prostate cancer (PCa) were retrospectively analyzed. Preoperative serum levels of CRP within 24 h before surgery were evaluated. A CRP level ⩾0.5 mg dl(-1) was considered elevated. Associations of elevated CRP with BCR were evaluated using univariable and multivariable Cox proportional hazards regression models. Harrel's C-index was used to assess prognostic accuracy (PA). RESULTS: Patients with higher Gleason score on biopsy and RP, extracapsular extension, seminal vesicle invasion, lymph node metastasis, and positive surgical margins status had a significantly elevated preoperative CRP compared to those without these features. Patients with elevated CRP had a lower 5-year BCR survival proportion as compared to those with normal CRP (55% vs 76%, respectively, P<0.0001). In pre- and postoperative multivariable models that adjusted for standard clinical and pathologic features, elevated CRP was independently associated with BCR (P<0.001). However, the addition of preoperative CRP did not improve the accuracy of the standard pre- and postoperative models for prediction of BCR (70.9% vs 71% and 78.9% vs 78.7%, respectively). CONCLUSIONS: Preoperative CRP is elevated in patients with pathological features of aggressive PCa and BCR after RP. While CRP has independent prognostic value, it does not add prognostically or clinically significant information to standard predictors of outcomes.


Subject(s)
C-Reactive Protein , Prostatic Neoplasms/blood , Prostatic Neoplasms/diagnosis , Aged , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Grading , Preoperative Period , Prognosis , Proportional Hazards Models , Prostatectomy , Prostatic Neoplasms/mortality , Prostatic Neoplasms/surgery , Recurrence
3.
Herz ; 40(1): 31-6, 2015 Feb.
Article in German | MEDLINE | ID: mdl-25687615

ABSTRACT

Catheter ablation is an established treatment option for patients with atrial fibrillation (AF). In paroxysmal AF ablation, pulmonary vein isolation alone is a well-defined procedural endpoint, leading to success rates of up to 80% with multiple procedures over 5 years of follow-up. The success rate in persistent AF ablation is significantly more limited. This is partly due to the rudimentary understanding of the substrate maintaining persistent AF. Three main pathophysiological concepts for this arrhythmia exist: the multiple wavelet hypothesis, the concept of focal triggers, mainly located in the pulmonary veins and the rotor hypothesis. However, the targets and endpoints of persistent AF ablation are ill-defined and there is no consensus on the optimal ablation strategy in these patients. Based on these concepts, several ablation approaches for persistent AF have emerged: pulmonary vein isolation, the stepwise approach (i.e. pulmonary vein isolation, ablation of fractionated electrograms and linear ablation), magnetic resonance imaging (MRI) and rotor-based approaches. Currently, persistent AF ablation is a second-line therapy option to restore and maintain sinus rhythm. Several factors, such as the presence of structural heart disease, duration of persistent AF and dilatation and possibly also the degree of fibrosis of the left atrium should influence the decision to perform persistent AF ablation.


Subject(s)
Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Body Surface Potential Mapping/methods , Catheter Ablation/methods , Heart Conduction System/surgery , Pulmonary Veins/surgery , Chronic Disease , Humans , Minimally Invasive Surgical Procedures/methods , Treatment Outcome
4.
Br J Cancer ; 111(2): 213-9, 2014 Jul 15.
Article in English | MEDLINE | ID: mdl-25003663

ABSTRACT

BACKGROUND: Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status. METHODS: We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes. RESULTS: In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1-6 nodes in cT1 and 6-8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively. CONCLUSIONS: Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis.


Subject(s)
Prostatic Neoplasms/pathology , Aged , Aged, 80 and over , Cohort Studies , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Prostatectomy , Prostatic Neoplasms/surgery , Risk Assessment
5.
Eur J Surg Oncol ; 40(12): 1693-9, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24780094

ABSTRACT

BACKGROUND: To test the hypothesis that perioperative blood transfusion (PBT)impacts oncologic outcomes of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: Retrospective analysis of 2492 patients with UTUC treated at 23 institutions with RNU between 1987 and 2007.Cox regression models addressed the association of PBT with disease recurrence, cancer-specific mortality and any-cause mortality. RESULTS: A total of 510 patients (20.5%) patients received PBT. Within a median follow-up of 36 months (Interquartile range: 55 months), 663 (26.6%) patients experienced disease recurrence, 545 patients (21.9%) died of UTUC and 884 (35.5%) patients died from any cause. Patients who received PBT were at significantly higher risk of disease recurrence, cancer-specific mortality and overall mortality than patients not receiving PBT in univariable Cox regression analyses. In multivariable Cox regression analyses that adjusted for the effects of standard clinicopathologic features, PBT did not remain associated with disease recurrence (HR: 1.11; 95% CI 0.92-1.33, p = 0.25), cancer-specific mortality (HR: 1.09; 95% CI 0.89-1.33, p = 0.41) or overall mortality (HR: 1.09; 95% CI 0.93-1.28, p = 0.29). CONCLUSIONS: In patients undergoing RNU for UTUC, PBT is associated with disease recurrence, cancer-specific survival or overall survival in univariable, but not in multivariable Cox regression analyses.


Subject(s)
Blood Transfusion , Carcinoma, Transitional Cell/surgery , Kidney Neoplasms/surgery , Nephrectomy , Perioperative Period , Ureter/surgery , Ureteral Neoplasms/surgery , Aged , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Female , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Laparoscopy , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Nephrectomy/methods , Retrospective Studies , Treatment Outcome , Ureteral Neoplasms/mortality , Ureteral Neoplasms/pathology , Urologic Surgical Procedures/methods , Vascular Neoplasms/secondary
6.
Eur J Surg Oncol ; 40(1): 113-20, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24113620

ABSTRACT

AIMS: Evidence suggests a detrimental effect of diabetes mellitus (DM) on cancer incidence and outcomes. To date, the effect of DM and its treatment on prognosis in upper tract urothelial carcinoma (UTUC) remains uninvestigated. We tested the hypothesis that DM and metformin use impact oncologic outcomes of patients treated with radical nephroureterectomy (RNU) for UTUC. METHODS: Retrospective analysis of 2492 patients with UTUC treated at 23 institutions with RNU without neoadjuvant therapy. Cox regression models addressed the association of DM and metformin use with disease recurrence, cancer-specific mortality and any-cause mortality. RESULTS: A total of 365 (14.3%) patients had DM and 194 (7.8%) patients used metformin. Within a median follow-up of 36 months, 663 (26.6%) patients experienced disease recurrence, 545 patients (21.9%) died of UTUC and 884 (35.5%) patients died from any cause. Diabetic patients who did not use metformin were at significantly higher risk of disease recurrence and cancer-specific death compared to non-diabetic patients and diabetic patients who used metformin. In multivariable Cox regression analyses, DM treated without metformin was associated with worse recurrence-free survival (HR: 1.44, 95% CI 1.10-1.90, p = 0.009) and cancer-specific mortality (HR: 1.49, 95% CI 1.11-2.00, p = 0.008). CONCLUSIONS: Diabetic UTUC patients without metformin use have significantly worse oncologic outcomes than diabetics who used metformin and non-diabetics. The possible mechanism behind the impact of DM on UTUC biology and the potentially protective effect of metformin need further elucidation.


Subject(s)
Carcinoma, Transitional Cell/surgery , Diabetes Mellitus/drug therapy , Hypoglycemic Agents/administration & dosage , Kidney Neoplasms/surgery , Metformin/administration & dosage , Nephrectomy , Ureteral Neoplasms/surgery , Aged , Carcinoma, Transitional Cell/complications , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/complications , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Neoplasm Staging , Proportional Hazards Models , Retrospective Studies , Treatment Outcome , Ureteral Neoplasms/complications , Ureteral Neoplasms/mortality , Ureteral Neoplasms/pathology , Ureteroscopy , Urologic Surgical Procedures
7.
Prostate Cancer Prostatic Dis ; 16(4): 367-71, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23999669

ABSTRACT

BACKGROUND: The impact of statin use on biochemical recurrence (BCR) in patients treated with radical prostatectomy (RP) remains controversial. METHODS: We retrospectively evaluated 6842 patients who underwent RP for clinically localized prostate cancer (PC) between 2000 and 2011. Uni- and multivariable cox regression models addressed the association of statin use with BCR. RESULTS: Overall, 2275 (33.3%) patients used statins. Statin users were older and had a higher rate of positive surgical margins than patients not using statins (P-values 0.05). Within a median follow-up of 25 months (interquartile range: 8-42 months), 778 (11.4%) patients experienced BCR. Actuarial estimate 5-years BCR-free survival was 82%±1 for patients without statin use and 84±1% for patients using statins (P=0.05); statin use was not associated with BCR (hazard ratio: 0.88, 95% confidence interval: 0.76-1.03, P=0.10) after adjusting for the effects of standard clinicopathologic features. CONCLUSIONS: In PC patients undergoing RP, statin use was not independently associated with lower risk of BCR.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Prostatic Neoplasms/pathology , Aged , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Proportional Hazards Models , Prostate-Specific Antigen/blood , Prostatectomy , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/mortality , Prostatic Neoplasms/surgery , Retrospective Studies
8.
Br J Cancer ; 109(6): 1460-6, 2013 Sep 17.
Article in English | MEDLINE | ID: mdl-23982601

ABSTRACT

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) risk tables and the Spanish Urological Club for Oncological Treatment (CUETO) scoring model are the two best-established predictive tools to help decision making for patients with non-muscle-invasive bladder cancer (NMIBC). The aim of the current study was to assess the performance of these predictive tools in a large multicentre cohort of NMIBC patients. METHODS: We performed a retrospective analysis of 4689 patients with NMIBC. To evaluate the discrimination of the models, we created Cox proportional hazard regression models for time to disease recurrence and progression. We incorporated the patients calculated risk score as a predictor into both of these models and then calculated their discrimination (concordance indexes). We compared the concordance index of our models with the concordance index reported for the models. RESULTS: With a median follow-up of 57 months, 2110 patients experienced disease recurrence and 591 patients experienced disease progression. Both tools exhibited a poor discrimination for disease recurrence and progression (0.597 and 0.662, and 0.523 and 0.616, respectively, for the EORTC and CUETO models). The EORTC tables overestimated the risk of disease recurrence and progression in high-risk patients. The discrimination of the EORTC tables was even lower in the subgroup of patients treated with BCG (0.554 and 0.576 for disease recurrence and progression, respectively). Conversely, the discrimination of the CUETO model increased in BCG-treated patients (0.597 and 0.645 for disease recurrence and progression, respectively). However, both models overestimated the risk of disease progression in high-risk patients. CONCLUSION: The EORTC risk tables and the CUETO scoring system exhibit a poor discrimination for both disease recurrence and progression in NMIBC patients. These models overestimated the risk of disease recurrence and progression in high-risk patients. These overestimations remained in BCG-treated patients, especially for the EORTC tables. These results underline the need for improving our current predictive tools. However, our study is limited by its retrospective and multi-institutional design.


Subject(s)
Urinary Bladder Neoplasms/pathology , Aged , Cohort Studies , Disease Progression , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local/pathology , Randomized Controlled Trials as Topic , Retrospective Studies , Risk Assessment , Risk Factors , Treatment Outcome , Urinary Bladder Neoplasms/drug therapy , Urothelium/pathology
9.
Br J Cancer ; 107(11): 1826-32, 2012 Nov 20.
Article in English | MEDLINE | ID: mdl-23169335

ABSTRACT

BACKGROUND: In pT1-T3N0 urothelial carcinoma of the bladder (UCB) patients, multi-modal therapy is inconsistently recommended. The aim of the study was to develop a prognostic tool to help decision-making regarding adjuvant therapy. METHODS: We included 2145 patients with pT1-3N0 UCB after radical cystectomy (RC), naive of neoadjuvant or adjuvant therapy. The cohort was randomly split into development cohort based on the US patients (n=1067) and validation cohort based on the Europe patients (n=1078). Predictive accuracy was quantified using the concordance index. RESULTS: With a median follow-up of 45 months, 5-year recurrence-free and cancer-specific survival estimates were 68% and 73%, respectively. pT-stage, ge, lymphovascular invasion, and positive margin were significantly associated with both disease recurrence and cancer-specific mortality (P-values ≤ 0.005). The accuracies of the multivariable models at 2, 5, and 7 years for predicting disease recurrence were 67.4%, 65%, and 64.4%, respectively. Accuracies at 2, 5, and 7 years for predicting cancer-specific mortality were 69.3%, 66.4%, and 65.5%, respectively. We developed competing-risk, conditional probability nomograms. External validation revealed minor overestimation. CONCLUSION: Despite RC, a significant number of patients with pT1-3N0 UCB experience disease recurrence and ultimately die of UCB. We developed and externally validated competing-risk, conditional probability post-RC nomograms for prediction of disease recurrence and cancer-specific mortality.


Subject(s)
Cystectomy , Urinary Bladder Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Cohort Studies , Combined Modality Therapy , Counseling , Europe , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/etiology , Neoplasm Staging , Proportional Hazards Models , Reproducibility of Results , United States , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
10.
J Urol ; 186(6): 2175-81, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22014800

ABSTRACT

PURPOSE: The 7th edition of TNM for renal cell carcinoma introduced a subdivision of pT2 tumors at a 10 cm cutoff. In the present multicenter study the influence of tumor size as well as further clinical and histopathological parameters on cancer specific survival in patients with pT2 tumors was evaluated. MATERIALS AND METHODS: A total of 670 consecutive patients with pT2 tumors (10.4%) of 6,442 surgically treated patients with all tumor stages were pooled (mean followup 71.4 months). Tumors were reclassified according to the current TNM classification, and subdivided in stages pT2a and pT2b. Cancer specific survival was analyzed using the Kaplan-Meier method, and univariable and multivariable analyses were used to assess the influence of several parameters on survival. RESULTS: Tumor size continuously applied and subdivided at 10 cm or alternative cutoffs did not significantly influence cancer specific survival. In addition to N/M stage, Fuhrman grade and collecting system invasion also had an independent influence on survival. Integration of a dichotomous variable subsuming Fuhrman grade and collecting system invasion (grade 3/4 and/or collecting system invasion present vs grade 1/2 and collecting system invasion absent) into multivariate models including established prognostic parameters resulted in improvement of predictive abilities by 11% (HR 2.3, p <0.001) for all pT2 cases and 151% (HR 3.1, p <0.001) for stage pT2N0M0 cases. CONCLUSIONS: Tumor size did not have a significant influence on cancer specific survival in pT2 tumors, neither continuously applied nor based on various cutoff values. To enhance prognostic discrimination, multifactorial staging systems including pathological features should be implemented. The prognostic relevance of the variable subsuming Fuhrman grade and collecting system invasion should be considered for future evaluation.


Subject(s)
Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Kidney Tubules, Collecting , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Survival Rate , Tumor Burden , Young Adult
11.
Minerva Urol Nefrol ; 63(4): 293-308, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21996985

ABSTRACT

Since the introduction of targeted therapies in renal cell carcinoma (RCC), more individualized treatment options have become available. Molecular markers might support treatment planning due to more accurate individual risk stratification. Current molecular markers in RCC were reviewed to elucidate clinical impact and future perspectives. An English-language literature review of the Medline database (1990 to September 2010) of published data on tissue-based molecular markers and RCC was undertaken. Histological types, clinical and oncological behaviour are variable in renal masses. Molecular markers offer potential for additional information in tumour detection and diagnosis, prognostic and predictive values, as well as determination of therapeutic targets. Investigations on molecular biomarkers in RCC include hypoxia inducible factor (HIF-α), vascular endothelial growth factor (VEGF), carbonic anhydrase IX (CAIX), mammalian target of rapamycin (mTOR), survivin, B7-H1, p53, matrix metalloproteinases (MMP), Insulin-like growth factor II mRNA-binding protein 3 (IMP3), Ki-67, C-reactive protein (CRP), Vimentin, Fascin, platelet count, hemoglobin level and combinations of these factors. Although some markers offer promising results, utilization in daily practice is compromised due to limited specificity, predictive accuracy and tumour histology variablity. There is an imminent need for novel molecular markers that allow accurate histologic and biologic classification of RCC to improve upon current outcomes. It is very likely that a panel of molecular markers will be used to achieve a sufficient degree of certainty in order to guide clinical decisions. A large concerted effort is required to advance the field of RCC molecular marker through systematic discovery, verification, and validation.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/metabolism , Kidney Neoplasms/diagnosis , Kidney Neoplasms/metabolism , B7-H1 Antigen/metabolism , C-Reactive Protein/metabolism , Carbonic Anhydrases/metabolism , Carcinoma, Renal Cell/enzymology , Carrier Proteins/metabolism , Cysteine Proteinase Inhibitors/metabolism , Hemoglobins/metabolism , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Inhibitor of Apoptosis Proteins/metabolism , Insulin-Like Growth Factor II/metabolism , Ki-67 Antigen/metabolism , Kidney Neoplasms/enzymology , Matrix Metalloproteinase 1/metabolism , Microfilament Proteins/metabolism , Platelet Count , Prognosis , RNA-Binding Proteins/metabolism , Survivin , TOR Serine-Threonine Kinases/metabolism , Tumor Suppressor Protein p53/metabolism , Vascular Endothelial Growth Factor A/metabolism , Vimentin/metabolism
12.
Appl Clin Inform ; 2(4): 481-98, 2011.
Article in English | MEDLINE | ID: mdl-23616890

ABSTRACT

OBJECTIVES: Telemonitoring of vital signs is an established option in treatment of patients with chronic heart failure (CHF). In order to allow for early detection of atrial fibrillation (AF) which is highly prevalent in the CHF population telemonitoring programs should include electrocardiogram (ECG) signals. It was therefore the aim to extend our current home monitoring system based on mobile phones and Near Field Communication technology (NFC) to enable patients acquiring their ECG signals autonomously in an easy-to-use way. METHODS: We prototypically developed a sensing device for the concurrent acquisition of blood pressure and ECG signals. The design of the device equipped with NFC technology and Bluetooth allowed for intuitive interaction with a mobile phone based patient terminal. This ECG monitoring system was evaluated in the course of a clinical pilot trial to assess the system's technical feasibility, usability and patient's adherence to twice daily usage. RESULTS: 21 patients (4f, 54 ± 14 years) suffering from CHF were included in the study and were asked to transmit two ECG recordings per day via the telemonitoring system autonomously over a monitoring period of seven days. One patient dropped out from the study. 211 data sets were transmitted over a cumulative monitoring period of 140 days (overall adherence rate 82.2%). 55% and 8% of the transmitted ECG signals were sufficient for ventricular and atrial rhythm assessment, respectively. CONCLUSIONS: Although ECG signal quality has to be improved for better AF detection the developed communication design of joining Bluetooth and NFC technology in our telemonitoring system allows for ambulatory ECG acquisition with high adherence rates and system usability in heart failure patients.

13.
Minerva Urol Nefrol ; 62(3): 241-58, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20940694

ABSTRACT

Bladder cancer is the second most common genitourinary malignancy in the United States, and is a major cause of morbidity and mortality. Despite aggressive treatment, survival for patients with muscle-invasive urothelial carcinoma of the bladder remains poor. Cancer stage, grade, and other clinical and pathological characteristics provide only limited prognostic information, and there is significant heterogeneity in patient outcomes using current risk stratification. Recent research into the profiling of bladder cancer at the molecular level has begun to shed light on important mechanisms of pathogenesis, as well as providing a number of potential tissue markers. These may provide useful prognostic information and guide patient selection for therapeutic strategies. This review explores recent advances in tissue-based molecular markers in bladder cancer and their potential utility. We also discuss design and statistical consideration for development and validation of molecular markers. A combination of complementary and yet independent molecular markers will likely better capture the biologic potential of each individual bladder tumor resulting in improved clinical decision-making.


Subject(s)
Urinary Bladder Neoplasms/diagnosis , Cyclin-Dependent Kinase Inhibitor p21/biosynthesis , Humans , Tumor Suppressor Protein p53/biosynthesis , Urinary Bladder Neoplasms/metabolism
14.
J Urol ; 181(5): 2305-11, 2009 May.
Article in English | MEDLINE | ID: mdl-19303095

ABSTRACT

PURPOSE: The similar appearance of renal tumor histological subtypes can complicate differential diagnoses. This problem is most notable for the chromophobe subtype of renal cell carcinoma, which can be histologically indistinguishable from oncocytoma with investigational molecular markers failing to provide reliable differentiation. KAI1 is a metastasis suppressor gene whose expression correlates inversely with the metastatic potential of most solid tumor cancer types. We tested the hypothesis that KAI1 is differentially expressed among renal tumor histological subtypes. MATERIALS AND METHODS: Immunohistochemical staining for KAI1 protein was performed in 152 nephrectomy specimens, including 48 clear cell, 35 papillary and 31 chromophobe renal cell carcinoma samples, 28 oncocytomas and 10 tumor-free kidneys. Staining was scored as none/minimal, low, moderate or high. KAI1 mRNA levels were compared by quantitative reverse transcriptase-polymerase chain reaction in an additional 22 chromophobe renal cell carcinoma and oncocytoma samples. RESULTS: In all 10 tumor-free kidneys KAI1 protein was detected exclusively in distal tubule cell membranes. Of the tumor specimens KAI1 protein was absent in all papillary renal cell carcinoma specimens. It was present in only 1 of 48 clear cell renal cell carcinomas (2%) and 2 of 28 oncocytomas (7%) but only at low levels. In contrast, 27 of 31 chromophobe renal cell carcinoma specimens (87%) expressed KAI1 protein, most at moderate or high levels. The diagnostic accuracy of KAI1 immunostaining for discerning chromophobe renal cell carcinoma from oncocytoma was 90% with similar results observed at the RNA level. CONCLUSIONS: KAI1 is an accurate biomarker for chromophobe renal cell carcinoma that may aid in the diagnostic differentiation of chromophobe renal cell carcinoma from oncocytoma. It remains to be determined whether KAI1 expression contributes to the low metastatic potential of chromophobe renal cell carcinoma.


Subject(s)
Adenoma, Oxyphilic/genetics , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Extracellular Matrix Proteins/metabolism , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Nerve Tissue Proteins/metabolism , Adenoma, Oxyphilic/pathology , Adenoma, Oxyphilic/surgery , Biomarkers, Tumor/genetics , Biopsy, Needle , Carcinoma, Renal Cell/surgery , Case-Control Studies , Diagnosis, Differential , Extracellular Matrix Proteins/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Kidney Neoplasms/surgery , Male , Nephrectomy , Nerve Tissue Proteins/genetics , Prognosis , Reference Values , Risk Assessment , Sampling Studies , Sensitivity and Specificity
15.
J Urol ; 176(5): 1957-62, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17070218

ABSTRACT

PURPOSE: We diagnosed the subtypes of renal cell carcinoma on needle core biopsies using a combination of histopathology and a molecular diagnostic algorithm. MATERIALS AND METHODS: Core biopsies were taken of renal tumors following nephrectomy. RNA was extracted and quantitative real-time polymerase chain reaction was performed for 4 gene products to differentiate among renal cell carcinoma subtypes. Histopathological diagnosis was achieved on a second core before and after obtaining the molecular diagnostic algorithm results. RESULTS: Based on the nephrectomy diagnosis 6 of 77 renal masses were nonneoplastic and 71 were tumors, including 65 renal cell carcinoma/oncocytomas. The overall diagnostic accuracy using histology and our molecular diagnostic algorithm combined was 90.0% (70 of 77). Side by side comparison of histology vs molecular diagnostic algorithm was feasible for 60 classifiable renal cell carcinoma/oncocytomas (31 clear cell, 14 papillary renal cell carcinoma, 6 chromophobe renal cell carcinoma, 2 mucinous tubular and spindle cell carcinoma, and 7 oncocytoma). In this group histology correctly predicted the final histological subtype in 83.3% (50 of 60) of cores. Addition of the molecular diagnostic algorithm to histology improved the subtyping accuracy to 95% (57 of 60), whereas the molecular diagnostic algorithm alone was accurate in 50 of 60 cases (83.3%). Dividing these 60 specimens into clear cell and nonclear cell neoplasms, the addition of the molecular diagnostic algorithm improved the sensitivity for the diagnosis of clear cell carcinoma from 87.1% (27 of 31) to 100% and the negative predictive value from 87.5% to 100%. CONCLUSIONS: Core biopsies of renal tumors provide adequate material for diagnosing and subtyping renal cell carcinoma. The addition of our molecular diagnostic algorithm to histology improved the diagnostic accuracy of core biopsies of renal masses.


Subject(s)
Algorithms , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biopsy, Needle , Female , Humans , Male , Middle Aged
16.
J Telemed Telecare ; 12(5): 255-61, 2006.
Article in English | MEDLINE | ID: mdl-16848939

ABSTRACT

We tested the reliability, acceptability and feasibility of a home-monitoring system for cardiac patients. Each participant was equipped with a mobile phone, an automatic blood pressure device and a digital weight scale. In total, 20 patients (14 patients with chronic heart failure, six patients with hypertension; mean age 50 years, standard deviation [SD] 14) were monitored for 90 days each. They were asked to measure their blood pressure, pulse and body weight every day, and to transfer the data together with the dosage of medication to the telemonitoring server using wireless Internet technology in the mobile phone. The physician in charge received email alerts when reported data fell outside pre-defined limits. The patients' compliance with the system was high. During a cumulative monitoring period of 1,735 days, there were 2,040 data transfer sessions, a mean of 102 per patient (SD 43). The mean percentage of successful data transfers was 83% (SD 22). The stability of the telemonitoring system was 98%, meaning that patient data transfer was almost always possible. The accessibility of the secure web server for physicians was above 99%. The web-based home-monitoring system was reliable and easy to handle for both patients and health care professionals. It may be a useful tool for patients with heart failure as well as hypertensive patients.


Subject(s)
Cell Phone , Heart Failure , Hypertension , Telemedicine/methods , Telemetry/methods , Feasibility Studies , Female , Humans , Male , Patient Compliance/statistics & numerical data , Patient Satisfaction , Reproducibility of Results , Telemedicine/instrumentation , Telemetry/instrumentation
17.
Article in English | MEDLINE | ID: mdl-17271607

ABSTRACT

According to international standards, cardiac pacemakers have to indicate the status of their batteries upon magnet application by specific stimulation patterns. The purpose of this study has been to assess whether this concept can be used as a basis for automated and manufacturer independent examination of the depletion level of pacemakers in the framework of a collaborative telemedical pacemaker follow-up system. A prototype of such a system was developed and tested in a real clinical environment. Electrocardiograms (ECGs) were recorded during magnet application and automatically processed to extract the specific stimulation patterns. The results were used to assign each signal a corresponding pacemaker status: "ok," "replace" or "undefined," based on the expected behavior of the devices as specified by the manufacturer. The outcome of this procedure was compared to the result of an expert examination, resulting in a positive predictive value of 100% for the detection of ECGs indicating pacemaker status "ok." The method can, therefore, be utilized to quickly, safely and manufacturer neutrally classify cases into the categories "ok" and "needs further checking," which - in a telemedical setting - may be used to increase the efficiency of pacemaker follow-up procedures in the future.

18.
Intensive Care Med ; 28(6): 789-92, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12107687

ABSTRACT

We report a 37-year-old man with documented aborted sudden death. After resuscitation, the patient showed no structural heart disease but the ECG showed a right bundle-branch block with a descending ST segment elevation in leads V(1) and V(2). After transient normalization of the ECG, the administration of ajmaline led to spontaneous development of the distinct descending ST segment elevation in the right precordial leads and therefore to the diagnosis of Brugada syndrome. The incidence of sudden cardiac death among these patients is high. The only treatment is an implantable cardioverter-defibrillator (ICD). The Brugada syndrome should therefore be borne in mind in the differential diagnosis of sudden death.


Subject(s)
Ajmaline , Anti-Arrhythmia Agents , Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable , Electrocardiography , Myocardial Infarction/diagnosis , Adult , Diagnosis, Differential , Humans , Male , Myocardial Infarction/physiopathology , Myocardial Infarction/therapy , Resuscitation
20.
Surg Technol Int ; 9: 33-41, 2000.
Article in English | MEDLINE | ID: mdl-21136385

ABSTRACT

Laser tissue welding is a relatively new technique, which was initially described only about 30 years ago. Over the past 10 years, the implementation of protein solders has redefined the field. Alternative methods of wound closure and of tissue approximation have been quickly accepted in clinical medicine. The techniques and theory involved in performing laser tissue welding may soon be essential knowledge for all surgeons. Just as laparoscopy has become a mainstay for general surgeons and urologists, novel mechanisms of tissue approximation will continue to replace older, less efficacious techniques.

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