Biomedical subjects

Felix K-H Chun

Publications and source records attributed to Felix K-H Chun.

29 records · Page 2Linked to original sources

PubMed2006

Validation of a nomogram predicting the probability of lymph node invasion among patients undergoing radical prostatectomy and an extended pelvic lymphadenectomy.

INTRODUCTION: Our goal was to develop and internally validate a nomogram for prediction of lymph node invasion (LNI) in patients with clinically localized prostate cancer undergoing extended pelvic lymphadenectomy (ePLND). METHODS: 602 consecutive patients (mean age 65.8 years) underwent an ePLND, where 10 or more nodes were removed. PSA was 1.1-49.9 (median 7.2). Clinical stages were: T1c in 55.6%, T2 in 41.4% and T3 in 3%. Biopsy Gleason sums were: 6 or less in 66%, 7 in 25.4%, 8-10 in 8.6%. Multivariate logistic regression models tested the association between all of the above predictors and LNI. Regression-based coefficients were used to develop a nomogram predicting LNI and 200 bootstrap resamples were used for internal validation. RESULTS: Mean number of lymph nodes removed was 17.1 (range 10-40). LNI was detected in 66 patients (11.0%). Univariate predictive accuracy for total PSA, clinical stage and biopsy Gleason sum was 63%, 58% and 73%, respectively. A nomogram based on clinical stage, PSA and Biopsy Gleason sum demonstrated bootstrap-corrected predictive accuracy of 76%. CONCLUSIONS: A nomogram based on pre-treatment PSA, clinical stage and biopsy Gleason sum can highly accurately predict LNI at ePLND.

Aged↗

PubMed2006

The 2002 AJCC pT2 substages confer no prognostic information on the rate of biochemical recurrence after radical prostatectomy.

INTRODUCTION: We examined the prognostic value of AJCC pT2 substages in prediction of biochemical recurrence (BCR) after radical prostatectomy (RP), in European patients. METHODS: A cohort of 1726 RP patients with pT2N0 prostate cancer (PCa) was studied. Multivariate Cox regression models addressed the association between either the 1997 or 1992/2002 pT2 substages after controlling for total PSA, primary and secondary pathologic Gleason scores and surgical margin status and time to PSA recurrence (PSA >0.1 and rising) after RP. Regression coefficients were then used to test the predictive accuracy of multivariate models in a nomogram setting. RESULTS: PSA recurrence occurred in 80 (4.6%) patients. Mean and median times to recurrence were respectively 28.9 and 24.4 months. In univariate analyses, neither the 1997 (p = 0.48) nor the 1992/2002 pT2 substages (p = 0.054) were predictive of recurrence. In multivariate analyses the lack of significance persisted (1997 p = 0.709; 1992/2002 p = 0.124). When either the 1997 or 1992/2002 pT2 substages were added to a multivariate nomogram without pT2 substage information, its accuracy respectively decreased by 0.8% and 1.1%. CONCLUSION: Our data indicate that pT2 substages offer no incremental value relative to pre-treatment total PSA, surgical margin status and pathologic Gleason scores. Therefore, it might be postulated that it is sufficient to confirm organ confinement according to Partin's pathologic staging.

Analysis of Variance↗

PubMed2006

25-year prostate cancer control and survival outcomes: a 40-year radical prostatectomy single institution series.

PURPOSE: We report on 25-year cancer control and survival outcomes after radical prostatectomy in a single center series of patients treated during a 40-year period. MATERIALS AND METHODS: Between 1954 and 1994, 787 consecutive patients underwent radical prostatectomy at Virginia Mason Medical Center in Seattle, Washington. Kaplan-Meier 25-year probabilities of prostate cancer specific, overall, prostate specific antigen progression-free, local and distant progression-free survival were determined. Multivariate Cox regression models addressed prostate cancer specific mortality. RESULTS: Prostate cancer specific survival, overall survival, prostate specific antigen progression-free survival, local and distant progression-free survival ranged from 99.0% to 81.5%, 93.5% to 19.3%, 84.8% to 54.5%, 95.3% to 87.8% and 95.9% to 78.2%, respectively. In univariate analyses pathological stage, surgical margin status, pathological Gleason sum, delivery of hormonal therapy and radiotherapy represented statistically significant predictors of prostate cancer specific mortality (all p < or =0.001). In multivariate analyses only Gleason sum (p = 0.03) and delivery of hormonal therapy (p < 0.001) remained significant. CONCLUSIONS: This is one of the most mature radical prostatectomy series. It demonstrates that long-term biochemical cancer control outcomes after radical prostatectomy might be suboptimal. However, local and distant control outcomes are excellent, and cancer specific mortality is minimal even 25 years after surgery.

Adult↗

PubMed2006

Validation of a nomogram for prediction of side specific extracapsular extension at radical prostatectomy.

PURPOSE: We have previously have reported a tree structured regression model for predicting SS-ECE. Others recently reported a logistic regression based SS-ECE nomogram. We developed a nomogram and compared the performance and discriminant properties of the tree regression and the nomogram in a contemporary cohort of European patients treated with radical retropubic prostatectomy. MATERIALS AND METHODS: The cohort consisted of 1,118 patients with pretreatment prostate specific antigen 0.1 to 73.2 ng/ml (median 6.6). Each of the 2,236 prostate lobes was considered separately. Clinical stage, pretreatment PSA, biopsy Gleason sum, percent positive cores and percent cancer in the biopsy specimen were used as predictors in a logistic regression model predicting SS-ECE. Regression coefficients were then used to generate an SS-ECE nomogram. Performance characteristics and discriminant properties of the previously published tree regression were also tested in the same cohort. For internal validation and to decrease overfit bias 200 bootstrap re-samples were applied to accuracy estimates for each method. RESULTS: ECE was present in 303 of 1,118 radical retropubic prostatectomy specimens (27%) and in 385 lobes (17%). In logistic regression models all variables were statistically significant multivariate predictors of SS-ECE except the percent of positive biopsy cores (p = 0.7). Bootstrap corrected predictive accuracy of the SS-ECE nomogram was 0.840 vs 0.700 for the tree regression model. CONCLUSIONS: Logistic regression based nomogram predictions of SS-ECE are highly accurate and represent a valuable aid for assessing the risk of ECE prior to surgery.

Calibration↗

PubMed2006

Prostate specific-antigen distribution in asymptomatic Canadian men with no clinical evidence of prostate cancer.

OBJECTIVE: To examine prostate specific-antigen (PSA) levels and percentage free/total PSA (f/tPSA) distributions as well as digital rectal examination (DRE) profiles in asymptomatic Canadian men with no established prostate cancer diagnosis, as recent data indicate that a man's risk of developing prostate cancer is higher if his baseline PSA level is above the median for his age group. SUBJECTS AND METHODS: We used data obtained during an early prostate cancer-detection event. An invitation to an onsite DRE, PSA level and f/tPSA assessment was accepted by 313 men. Serum PSA level and f/tPSA were measured before the DRE. A suspicious DRE and/or PSA level of > or = 2.5 ng/mL or f/tPSA of < or = 15% represented indications for a systematic 12-core ultrasonography-guided prostate biopsy. RESULTS: Of all the 313 men, most (235, 75%) had PSA levels of 0.01-1.53 ng/mL and an f/tPSA of >15% (285, 91.1%). The median (range) PSA level was 0.8 (0-34.2) ng/mL and f/tPSA was 27.4 (6.7-100)%. Age-specific median PSA levels and f/tPSA were, respectively, 0.7, 0.9, 1.0, 1.5 ng/mL and 31%, 27%, 26%, 25% for men aged 40-49, 50-59, 60-69 and 70-79 years. A suspicious DRE was recorded in 55 (17.6%) men, with eight (8.8%), 26 (20.0%), 14 (20.6%), and seven (28.9%) having suspicious DRE findings according to above age categories. Overall, seven (2.2%) prostate cancers were detected. CONCLUSION: The median age-specific baseline PSA levels and f/tPSA represent valuable indicators of prostate cancer risk. The population-specific baseline median PSA level should not be >1.0 ng/mL and the baseline f/tPSA should be >30%. Men with values outside of these ranges should be considered at greater risk of prostate cancer.

Adult↗

PubMed2006

Significant upgrading affects a third of men diagnosed with prostate cancer: predictive nomogram and internal validation.

OBJECTIVE: To explore the rate of significant upgrading from biopsy to radical prostatectomy (RP) specimens in a contemporary cohort, and to develop a prognostic model capable of predicting the probability of significant upgrading, as previous reports indicate that up to 43% of men with low-grade prostate cancer at biopsy will be diagnosed with high-grade cancer at RP. PATIENTS AND METHODS: The study cohort comprised 4789 men (median age 63 years, range 39-82) treated with RP, with available clinical stage, prostate-specific antigen levels, biopsy and RP Gleason sum values. These variables were used as predictors in multivariate logistic regression models (LRMs) addressing the rate of significant Gleason sum upgrading, defined as a Gleason sum increase either from < or = 6 to > or = 7 or from 7 to > or = 8 between the biopsy and RP specimens. Regression coefficients were used to develop and validate (200 bootstrap re-samples) a nomogram predicting significant biopsy Gleason sum upgrading. RESULTS: Significant biopsy Gleason sum upgrading was recorded in 1349 (28.2%) patients. In multivariate LRMs, all predictors were highly significant (all P < 0.001). The bootstrap-corrected accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 75.7%. CONCLUSION: Our nomogram might prove highly useful when the possibility of a more aggressive Gleason variant could change the treatment options.

Adult↗

PubMed2006

Circulating tumour-associated plasma DNA represents an independent and informative predictor of prostate cancer.

OBJECTIVE: To investigate whether preoperative plasma levels of free DNA can discriminate between men with localized prostate cancer and benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: In all, 161 referred patients suspicious for prostate cancer either by an elevated prostate-specific antigen (PSA) level and/or abnormal digital rectal examination (DRE) were included in this prospective study. Peripheral plasma was taken before prostate biopsy and genomic DNA was extracted from the plasma using the a commercial kit and a vacuum chamber. After controlling for age, PSA level, the percentage free/total (f/t) PSA and prostate volume, the median prostate cancer plasma DNA concentration served as diagnostic threshold in uni- and multivariate logistic regression models. Multivariate models were subjected to 200 bootstraps for internal validation and to reduce over-fit bias. RESULTS: Subgroups consisted of 142 men with clinically localized prostate cancer and 19 with BPH. The median plasma concentration of cell-free DNA was 267 ng/mL in men with BPH vs 709 ng/mL in men with prostate cancer. In univariate analyses, plasma DNA concentration was a statistically significant and informative predictor (P = 0.032 and predictive accuracy 0.643). In multivariate analyses, it remained statistically significant after controlling for age, tPSA, f/tPSA and prostate volume, increasing the predictive accuracy by 5.6%. CONCLUSIONS: Our data suggest that plasma DNA level is a highly accurate and informative predictor in uni- and multivariate models for the presence of prostate cancer on needle biopsy. The predictive accuracy was substantially increased by adding plasma DNA level. However, larger-scale studies are needed to further confirm its clinical impact on prostate cancer detection.

Adult↗

PubMed2006

A comparative review of apomorphine formulations for erectile dysfunction : recommendations for use in the elderly.

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. First-line oral therapy for ED includes the use of phosphodiesterase type 5 inhibitors (sildenafil, tadalafil and vardenafil) and sublingual apomorphine. Apomorphine is a dopamine D(1) and D(2) receptor agonist that has been approved for marketing in Europe. Different apomorphine formulations have been tested, such as sublingual, subcutaneous and intranasal. However, the sublingual formulation has shown the best results in terms of efficacy, safety and tolerability, especially the 2mg and 3mg doses. Although clinical studies of the efficacy and tolerability of apomorphine sublingual (SL) have included older patients, who are more likely to have ED, no study has specifically assessed the efficacy and tolerability of different doses of apomorphine SL in aging men. Therefore, a MEDLINE search was conducted from January 1987 to November 2005 to identify studies of the efficacy, safety (in particular cardiovascular safety) and tolerability of different apomorphine formulations and doses as treatments for ED in the subcohort of aging men. On the basis of the most recent peer-reviewed publications, the first part of this article critically evaluates data regarding the epidemiology of ED in the aging population. The second part of the article focuses on the mechanism of action and pharmacokinetics of apomorphine both in the general and the elderly population. Finally, a critical analysis of the efficacy and safety of different apomorphine formulations and doses for the treatment of ED is reported. Apomorphine represents a first-line oral treatment for ED. Available formulations include only sublingual administration. Few studies have assessed the efficacy and safety of apomorphine in the elderly population. However, in clinical practice, older patients with multiple vascular risk factors and systematic vascular damage show poor overall response to apomorphine SL for the treatment of ED.

Aged↗

PubMed2006

Prostate cancer nomograms are superior to neural networks.

INTRODUCTION: Several nomograms have been developed to predict PCa related outcomes. Neural networks represent an alternative. METHODS: We provide a descriptive and an analytic comparison of nomograms and neural networks, with focus on PCa detection. RESULTS: Our results indicate that nomograms have several advantages that distinguish them from neural networks. These are both quantitative and qualitative. CONCLUSION: In the field of PCa detection, nomograms appear to outweigh the benefits of neural networks. However, the neural network methodology represents a valid alternative, which should not be underestimated.

Forecasting↗

PubMed2006

Treatment of BCG failures with intravesical BCG/Interferon: the University of Montreal experience.

OBJECTIVE: Bacillus Calmette-Guerin (BCG) has shown promise in large scale studies. We assessed recurrence-free survival in patients treated with intravesical BCG/Interferon (IFN) for non-muscle invasive, BCG refractory, transitional cell carcinoma (TCC) of the urinary bladder at our local institution. METHODS: Cancer control data were gathered for patients enrolled in a BCG/Interferon protocol at the University of Montreal. The main inclusion criteria consisted of pathologically proven evidence of intravesical BCG failure, and of complete transurethral resection of latest post BCG recurrence. Induction consisted of eight intravesical BCG/Interferon instillations. Select patients were treated with BCG/Interferon maintenance therapy. RESULTS: Thirteen patients aged from 45 to 81 years (mean: 65) were included. Stages at TCC diagnosis were distributed as follows: 6 (46%) CIS, 3 (23%) Ta, and 4 (31%) T1. Induction BCG consisted of an average of 11 weekly instillations (range 3-24). Prior to BCG/Interferon stage distribution was as follows: 9 (69%) CIS, and 4 (31%) T1. BCG/Interferon maintenance was administered to 5 (38%) patients. Follow-up ranged from 1.5 to 32 months (mean=15, median=12). Recurrence was diagnosed in 5 patients (38%). Recurrence free survival (RFS) at 24 months was 66%. When stratified according to T stage prior to BCG/IFN, patients with CIS fared worse than T1 patients (50% versus 100%). Maintenance had no effect on RFS (75% versus 69%). CONCLUSIONS: Our results corroborate previous BCG/IFN reports. In selected patients, intravesical BCG/IFN offers a valid alternative to definitive therapy.

Adjuvants, Immunologic↗

PubMed2005

Development and internal validation of a nomogram predicting the probability of prostate cancer Gleason sum upgrading between biopsy and radical prostatectomy pathology.

OBJECTIVE: Previous reports indicate that as many as 43% of men with low grade PCa at biopsy will be diagnosed with high-grade PCa at RP. We explored the rate of upgrading from biopsy to RP specimen in our contemporary cohort, and developed a model capable of predicting the probability of biopsy Gleason sum upgrading. MATERIALS AND METHODS: The study cohort consisted of 2982 men treated with RP, with available clinical stage, serum prostate specific antigen and biopsy Gleason scores. These clinical data were used as predictors in multivariate logistic regression models (LRM) addressing the rate of Gleason sum upgrading between biopsy and RP pathology. LRM regression coefficients were used to develop a nomogram predicting the probability of Gleason sum upgrading and was subjected to 200 bootstrap resamples for internal validation and to reduce overfit bias. RESULTS: Overall, 875 patients were upgraded (29.3%). In multivariate LRMs, all predictors were highly significant (all p values <0.0001). Bootstrap-corrected predictive accuracy of the nomogram predicting the probability of Gleason sum upgrading between biopsy and RP was 0.804. CONCLUSION: We developed a highly accurate clinical aid for treatment decision-making. It may prove useful when the possibility of a more aggressive Gleason variant may change the treatment options.

Biopsy↗