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1.  Staging lymphadenectomy in patients with localized high risk prostate cancer: comparison of the laparoendoscopic single site (LESS) technique with conventional multiport laparoscopy 
BMC Urology  2014;14(1):92.
In patients with localized high-risk prostate cancer awaiting radiation therapy, pelvic lymphadenectomy (PL) is a reliable minimally invasive staging procedure. We compared outcomes after laparoendoscopic single site PL (LESSPL) with those after conventional multiport laparoscopic PL (MLPL).
A retrospective case-control study was carried out at the authors’ center. For LESSPL the reusable X-Cone single port was combined with straight and prebent laparoscopic instruments and an additional 3 mm needlescopic grasper. MLPL was performed via four trocars of different sizes using standard laparoscopic instruments.
Patients who underwent either LESSPL (n = 20) or MLPL (n = 97) between January 2008 and July 2013, were included in the study. Demographic data were comparable between groups. Patients in the LESSPL group tended to be older and had a significantly higher ASA-score. The mean operating time was 172.4 ± 34.1 min for LESSPL and 116.6 ± 40.1 min for MLPL (P < .001). During LESSPL, no conversion to MLPL was necessary. An average of 12 lymph nodes per patient was retrieved, with no significant difference between study groups. Postoperative pain scores were similar between groups. The hospital stay was 2.3 ± 0.7 days after LESSPL and 3.1 ± 1.2 days after MLPL (P = .01). Two days postoperatively, significantly more patients after LESSPL than after MLPL recovered their normal physical activity (P < .001). Six months postoperatively, no complications were registered in the LESSPL group and cosmetic results were excellent.
In the present study, shorter hospitalization and quicker postoperative recovery were major benefits of LESSPL over MLPL. In patients with localized prostate cancer, staging LESS pelvic lymphadenectomy may be a safe alternative to conventional multiport laparoscopy.
PMCID: PMC4247718  PMID: 25412566
Laparoscopy; LESS; Single port; Prostate cancer staging
2.  Risk prediction models for biochemical recurrence after radical prostatectomy using prostate-specific antigen and Gleason score 
Asian Journal of Andrology  2014;16(6):897-901.
Many computer models for predicting the risk of prostate cancer have been developed including for prediction of biochemical recurrence (BCR). However, models for individual BCR free probability at individual time-points after a BCR free period are rare. Follow-up data from 1656 patients who underwent laparoscopic radical prostatectomy (LRP) were used to develop an artificial neural network (ANN) to predict BCR and to compare it with a logistic regression (LR) model using clinical and pathologic parameters, prostate-specific antigen (PSA), margin status (R0/1), pathological stage (pT), and Gleason Score (GS). For individual BCR prediction at any given time after operation, additional ANN, and LR models were calculated every 6 months for up to 7.5 years of follow-up. The areas under the receiver operating characteristic (ROC) curve (AUC) for the ANN (0.754) and LR models (0.755) calculated immediately following LRP, were larger than that for GS (AUC: 0.715; P = 0.0015 and 0.001), pT or PSA (AUC: 0.619; P always <0.0001) alone. The GS predicted the BCR better than PSA (P = 0.0001), but there was no difference between the ANN and LR models (P = 0.39). Our ANN and LR models predicted individual BCR risk from radical prostatectomy for up to 10 years postoperative. ANN and LR models equally and significantly improved the prediction of BCR compared with PSA and GS alone. When the GS and ANN output values are combined, a more accurate BCR prediction is possible, especially in high-risk patients with GS ≥7.
PMCID: PMC4236336  PMID: 25130472
artificial neural network; prostate cancer; recurrence
3.  Comparison of surgical technique (Open vs. Laparoscopic) on pathological and long term functional outcomes following radical prostatectomy 
BMC Urology  2014;14:18.
Few studies to date have directly compared outcomes of retropubic (RRP) and laparoscopic (LRP) radical prostatectomy. We investigated a single institution experience with RRP and LRP with respect to functional and pathological outcomes.
168 patients who underwent RRP were compared to 171 patients who underwent LRP at our institution. Pathological and functional outcomes including postoperative urinary incontinence and erectile dysfunction (ED) of the two cohorts were examined.
Patients had bilateral, unilateral and no nerve sparing technique performed in 83.3%, 1.8% and 14.9% of cases for RRP and 23.4%, 22.8% and 53.8% of cases for LRP, respectively (p < 0.001). Overall positive surgical margin rates were 22.2% among patients who underwent RRP compared to 26.5% of patients who underwent LRP (p = 0.435). Based upon pads/day, urinary continence postoperatively was achieved in 83.2% and 82.8% for RRP and LRP, respectively (p = 0.872). Analysis on postoperative ED was limited due to lack of information on the preoperative erectile status. However, postoperatively there were no differences with respect to ED between the two cohorts (p = 0.151). Based on ICIQ-scores, surgeons with more experience had lower rates of postoperative incontinence irrespective of surgical technique (p = 0.001 and p < 0.001 for continuous and stratified data, respectively).
RRP and LRP represent effective surgical approaches for the treatment of clinically localized prostate cancer. Pathological outcomes are excellent for both surgical techniques. Functional outcomes including postoperative urinary incontinence and ED are comparable between the cohorts. Surgeon experience is more relevant than surgical technique applied.
PMCID: PMC3922887  PMID: 24506815
Prostate cancer; Erectile dysfunction; Incontinence; Radical prostatectomy; Laparoscopic prostatectomy
4.  Impact of surgical technique (open vs laparoscopic vs robotic-assisted) on pathological and biochemical outcomes following radical prostatectomy: an analysis using propensity score matching 
BJU international  2010;107(12):1956-1962.
To investigate a single institution experience with radical retropubic prostatectomy (RRP), laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP) with respect to pathological and biochemical outcomes.
A group of 522 consecutive patients who underwent RARP between 2003 and 2008 were matched by propensity scoring on the basis of patient age, race, preoperative prostate-specific antigen (PSA), biopsy Gleason score and clinical stage with an equal number of patients who underwent LRP and RRP at our institution. Pathological and biochemical outcomes of the three cohorts were examined.
Overall positive surgical margin rates were lower among patients who underwent RRP (14.4%) and LRP (13.0%) compared to patients who underwent RARP (19.5%) (P = 0.010). There were no statistically significant differences in positive margin rates between the three surgical techniques for pT2 disease (P = 0.264). In multivariate logistic regression analysis, surgical technique (P = 0.016), biopsy Gleason score (P < 0.001) and preoperative PSA (P < 0.001) were predictors of positive surgical margins. Kaplan–Meier analysis did not show any statistically significant differences with respect to biochemical recurrence for the three surgical groups.
RRP, LRP and RARP represent effective surgical approaches for the treatment for clinically localized prostate cancer. A higher overall positive SM rate was observed for the RARP group compared to RRP and LRP; however, there was no difference with respect to biochemical recurrence-free survival between groups. Further prospective studies are warranted to determine whether any particular technique is superior with regard to long-term clinical outcomes.
PMCID: PMC3105164  PMID: 21044243
prostate cancer; biochemical recurrence; radical prostatectomy; robotic prostatectomy; laparoscopic prostatectomy
5.  Laparoscopic and open postchemotherapy retroperitoneal lymph node dissection in patients with advanced testicular cancer – a single center analysis 
BMC Urology  2012;12:15.
The open approach represents the gold standard for postchemotherapy retroperitoneal lymph node dissection (O-PCLND) in patients with residual testicular cancer. We analyzed laparoscopic postchemotherapy retroperitoneal lymph node dissection (L-PCLND) and O-PCLND at our institution.
Patients underwent either L-PCLND (n = 43) or O-PCLND (n = 24). Categorical and continuous variables were compared using the Fisher exact test and Mann–Whitney U test respectively. Overall survival was evaluated with the log-rank test.
Primary histology was embryonal cell carcinomas (18 patients), pure seminoma (2 cases) and mixed NSGCTs (47 patients). According to the IGCCCG patients were categorized into “good”, “intermediate” and “poor prognosis” disease in 55.2%, 14.9% and 20.8%, respectively. Median operative time for L-PCLND was 212 min and 232 min for O-PCLND (p = 0.256). Median postoperative duration of drainage and hospital stay was shorter after L-PCLND (0.0 vs. 3.5 days; p < 0.001 and 6.0 vs. 11.5 days; p = 0.002). Intraoperative complications occurred in 21.7% (L-PCLND) and 38.0% (O-PCLND) of cases with 19.5% and 28.5% of Clavien Grade III complications for L-PCLND and O-PCLND, respectively (p = 0.224). Significant blood loss (>500 ml) was almost equally distributed (8.6% vs. 14.2%: p = 0.076). No significant differences were observed for injuries of major vessels and postoperative complications (p = 0.758; p = 0.370). Tumor recurrence occurred in 8.6% following L-PCLND and in 14.2% following O-PCLND with a mean disease-free survival of 76.6 and 89.2 months, respectively. Overall survival was 83.3 and 95.0 months for L-PCNLD and O-PCLND, respectively (p = 0.447).
L-PCLND represents a safe surgical option for well selected patients at an experienced center.
PMCID: PMC3431976  PMID: 22651395
Advanced testicular cancer; Postchemotherapy; Retroperitoneal lymph node dissection; Laparoscopy; Metastasis
6.  Impact of Body Mass Index on Biochemical Recurrence Rates After Radical Prostatectomy: An Analysis Utilizing Propensity Score Matching 
Urology  2008;72(6):1246-1251.
To investigate the significance of body mass index (BMI) as an independent predictor of biochemical recurrence in men treated with surgery for clinically localized adenocarcinoma of the prostate.
A total of 1877 obese patients who underwent radical prostatectomy were matched to overweight and normal-weight patients in a 1:1 ratio on the basis of propensity scores. This resulted in an overall study population of 5631 men. Clinicopathologic characteristics and biochemical recurrence outcomes after surgery were compared between the three BMI cohorts.
Normal-weight patients exhibited lower-grade disease compared with overweight and obese patients (P = 0.021). Lower BMI was also significantly associated with lower rates of positive surgical margins (P <0.001) and extraprostatic extension (P <0.001). Body mass index was not associated with lymph node involvement (P = 0.226) or seminal vesicle invasion (P = 0.142). Body mass index, age, biopsy Gleason score, preoperative prostate-specific antigen level, and clinical tumor stage were independent predictors of biochemical recurrence (P <0.001).
Propensity score– based matched analyses indicate that higher BMI is associated with adverse pathologic findings and is a strong independent predictor of biochemical recurrence after radical prostatectomy. These results support the hypothesis that inherent differences may exist in the biological properties of prostate cancer in obese men compared with normal-weight men. Therefore, BMI is an important criterion to consider during subsequent decision making and counseling of patients with prostate cancer.
PMCID: PMC3354532  PMID: 18387658
7.  Significance of preoperative PSA velocity in men with low serum PSA and normal DRE 
World journal of urology  2010;29(1):11-14.
A PSA velocity (PSAV) >0.35 ng/ml/year approximately 10–15 years prior to diagnosis is associated with a greater risk of lethal prostate cancer. Some have recommended that a PSAV >0.35 ng/ml/year should prompt a prostate biopsy in men with a low serum PSA (<4 ng/ml) and benign DRE. However, less is known about the utility of this PSAV cutpoint for the prediction of treatment outcomes among men undergoing radical prostatectomy (RP).
Between 1992 and 2007, 339 men underwent RP at our institution with a preoperative PSA <4 ng/ml, benign DRE, and multiple preoperative PSA measurements. PSAV was calculated by linear regression analysis using all PSA values within 18 months prior to diagnosis. Kaplan–Meier survival analysis was performed, and biochemical progression rates were compared between PSAV strata using the log-rank test.
The preoperative PSAV was >0.35 ng/ml/year in 124 (36.6%) of 339 men. Although there were no significant differences in clinicopathological characteristics based upon PSAV, men with a PSAV >0.35 ng/ml/year were significantly more likely to experience biochemical progression after RP at a median follow-up of 4 years (P = 0.022).
In this low-risk population with a preoperative PSA <4 ng/ml and benign DRE, approximately 1/3 had a preoperative PSAV >0.35 ng/ml/year. Physicians should carefully monitor men with a preoperative PSA >0.35 ng/ml/year as they are at increased risk of biochemical progression following RP.
PMCID: PMC3034139  PMID: 21153643
Prostate cancer; Radical prostatectomy; Pathologic stage; PSA; PSAV; Gleason score
8.  Analysis of a Serum Test for Prostate Cancer That Detects a Second Epitope of EPCA-2 
The Prostate  2009;69(11):1188-1194.
We have previously shown that EPCA-2 can serve as a highly specific and sensitive serum marker for prostate cancer. As a component of our validation of this marker, we have performed an initial evaluation of an assay that detects a distinct epitope of the same protein: EPCA-2.19. The goals of this study are to characterize the sensitivity and specificity of the EPCA-2.19 assay, in a non-screening population, and to demonstrate that such test based has similar characteristics as the initial assay produced.
Three hundred twenty-eight serum samples from men with PSA values < and >2.5 ng/ml who had negative biopsies, men with BPH, men with organ-confined and non-organ-confined prostate cancer, as well as control populations were evaluated using the EPCA-2.19 assay.
At a cut-off of 0.5 ng/ml and above, EPCA-2.19 has a specificity of 94% and a sensitivity of 91% in separating normal men with PSA < and >2.5 ng/ml, and men with BPH from those with prostate cancer. Receiver Operator Curve analyses of the EPCA-2.19 assay demonstrate an area under the curve of 0.982 (95% CI 0.952–0.996, P < 0.0001).
This study confirms our earlier findings that the assay that detects against a second epitope of EPCA-2 yields almost identical results to those obtained for the first published assay (EPCA-2.22). While this provides some validation of our earlier studies, larger multi-institutional studies still need to be performed.
PMCID: PMC3178806  PMID: 19418497
prostate cancer; proteomics; biomarkers; nuclear matrix; immunoassay
9.  Intrinsic resistance to tyrosine kinase inhibitors is associated with poor clinical outcome in metastatic renal cell carcinoma 
BMC Cancer  2011;11:295.
Data on sequential therapy in patients with metastatic renal cell carcinoma (mRCC) and intrinsic resistance to receptor tyrosine kinase inhibitor (rTKI) treatment remains vague.
We retrospectively studied treatment characteristics and outcome of mRCC patients refractory to first rTKI therapy.
Thirty-five mRCC patients (male, 18; female, 11) with primary resistance to first rTKI therapy (sunitinib, n = 28; sorafenib, n = 7) and a median treatment interval of 2.4 months (1 - 4.6) were identified. In 22 patients, progressive disease (PD) was determined by a new metastatic lesion. Of these, 16 patients received subsequent therapy with 12 patients remaining refractory and 4 patients achieving disease stabilization. In 13 patients continuous growth of existing metastatic lesions determined PD. Of these, 9 received sequential therapy with 6 achieving disease stabilization. Altogether, 25 patients were treated sequentially (rTKI: n = 15; mTOR-inhibitor: n = 10) and achieved a median PFS of 3.2 months (range, 1-16.6). Fifteen patients failed to respond to either line of therapy. Disease control was not associated with type of subsequent therapy. Median OS was 14.9 months (CI: 5.5-24.4).
Intrinsic resistance to rTKI is associated with a low chance of response to sequential therapy and a poor prognosis in mRCC patients.
PMCID: PMC3154177  PMID: 21756335
10.  Prostate Specific Antigen versus Prostate Specific Antigen Density as a Prognosticator of Pathological Characteristics and Biochemical Recurrence following Radical Prostatectomy 
The Journal of urology  2008;179(5):1780-1784.
The utility of PSAD for predicting pathological stage and biochemical recurrence after radical prostatectomy (RP) has not been well defined. The goal of this study was to investigate whether PSAD yielded an advantage over total PSA in predicting adverse pathologic characteristics and disease recurrence following RP.
Materials and methods
A total of 13,434 men who underwent radical prostatectomy for clinically localized prostate cancer between 1984 and 2006 were included in this study. The study population was stratified by Gleason score (≤ 6, 7, and ≥ 8) and clinical and pathological characteristics of each group were compared. We constructed receiver operating characteristic (ROC) curves and determined the areas under the receiver operating curves (AUC) and c-index to specifically investigate the accuracy of PSA and PSAD for the prediction of pathological stage and biochemical recurrence.
PSAD was better than PSA in predicting EPE (p<0.001) and BCR (p<0.001) in patients with a biopsy Gleason score ≤ 6. In patients with biopsy Gleason scores of 7, PSA was more predictive than PSAD for SV involvement (p<0.001), LN involvement (p=0.017), and BCR (p<0.001). For men with biopsy Gleason scores ≥ 8, there was no statistical difference between PSA and PSAD in prognostic value for pathological or clinical outcomes.
PSAD is highly associated with pathological stage and biochemical free survival following RP. In lower grade prostate cancers, PSAD is significantly more accurate in predicting EPE and BCR compared to total PSA and should be considered when counseling patients on outcomes following RP.
PMCID: PMC2675005  PMID: 18343439
Prostate cancer; PSA; PSA density; biochemical recurrence; radical prostatectomy

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