Mesut Remzi

Safety and morbidity of first and repeat transrectal ultrasound guided prostate needle biopsies: results of a prospective European prostate cancer detection study.

PURPOSE We prospectively evaluate the safety, morbidity and complication rates for first and repeat transrectal ultrasound guided prostate needle biopsies. MATERIALS AND METHODS In this prospective European Prostate Cancer Detection Study 1,051 men, with total prostate specific antigen between 4 and 10 ng./ml., underwent transrectal ultrasound guided sextant biopsy plus 2 additional transition zone biopsies. Biopsy samples were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination. All 820 patients with biopsy samples negative for prostate cancer underwent re-biopsy after 6 weeks. Immediate and delayed (range 1 to 7 days) morbidity, patient satisfaction and complication rates were recorded. RESULTS Of the 1,051 subjects the initial biopsy was positive for prostate cancer in 231 and negative, including benign prostatic hyperplasia or benign tissue, in 820. Of these 820 patients prostate cancer was detected in 10% (83) on re-biopsy. Minor or no discomfort was observed in 92% and 89% of patients at first and re-biopsy, respectively (p = 0.29). Immediate morbidity was minor and included rectal bleeding (2.1% versus 2.4%, p = 0.13), mild hematuria (62% versus 57%, p = 0.06), severe hematuria (0.7% versus 0.5%, p = 0.09) and moderate to severe vasovagal episodes (2.8% versus 1.4%, respectively, p = 0.03). Delayed morbidity of first and re-biopsy was comprised of fever (2.9% versus 2.3%, p = 0.08), hematospermia (9.8% versus 10.2%, p = 0.1), recurrent mild hematuria (15.9% versus 16.6%, p = 0.06), persistent dysuria (7.2% versus 6.8%, p = 0.12) and urinary tract infection (10.9% versus 11.3%, respectively, p = 0.07). Major complications were rare and included urosepsis (0.1% versus 0%) and rectal bleeding that required intervention (0% versus 0.1%, respectively). Furthermore, an age dependent pattern of pain apprehension during biopsy was observed with the highest scores in patients younger than 60 years. CONCLUSIONS Transrectal ultrasound guided biopsy is generally well tolerated with minor morbidity only rarely requiring treatment. Re-biopsy can be performed 6 weeks later with no significant difference in pain or morbidity. Patients younger than 60 years should be counseled in regard to a higher level of discomfort, and local and topical anesthesia if desired.

OPTIMAL PREDICTORS OF PROSTATE CANCER ON REPEAT PROSTATE BIOPSY: A PROSPECTIVE STUDY OF 1,051 MEN

PURPOSE We compare the ability of total prostate specific antigen (PSA), percent free PSA, PSA density and transition zone PSA density to predict the outcome of repeat prostatic biopsy in men with serum total PSA 4 to 10 ng./ml. who were diagnosed with benign prostatic hyperplasia after initial biopsy. MATERIALS AND METHODS In this prospective study 1,051 men with total PSA 4 to 10 ng./ml. underwent transrectal ultrasound guided sextant biopsy with 2 additional transition zone biopsies. In 254 subjects biopsy specimens were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination. All subjects with biopsy specimens negative for prostate cancer underwent repeat biopsy 6 weeks after initial biopsy. The ability of total PSA, percent free PSA, PSA density and transition zone PSA density to improve the diagnostic power of PSA testing was assessed with univariate and multivariate analyses as well as receiver operating characteristics (ROC) curves. RESULTS Initial biopsy was positive (prostate cancer) in 231 and negative (benign prostatic hyperplasia) in 820 of the 1,051 subjects. Prostate cancer was detected on repeat biopsy in 10% of subjects (83 of 820) with negative initial biopsy. Percent free PSA and transition zone PSA density were the most accurate predictors of prostate cancer in these subjects. At a cutoff of 30% percent free PSA would have detected 90% of cancers (sensitivity) and eliminated 50% of unnecessary repeat biopsies (specificity). Sensitivity and specificity of transition zone PSA density at a cutoff of 0.26 ng./ml./cc was 78% and 52%, respectively. ROC curve analysis also showed that percent free PSA was a significantly better predictor of repeat biopsy results than total PSA, PSA density and transition zone PSA density. The area under the ROC curve was 74.5% for percent free PSA, 69.1% for transition zone PSA density, 61.8% for PSA density and 60.3% for total PSA. CONCLUSIONS At least 10% of patients with negative initial prostatic biopsy results will be diagnosed with prostate cancer on repeat biopsy. Percent free PSA and transition zone PSA density enhance the specificity of PSA testing compared to total PSA or PSA density when determining which patients should undergo repeat biopsy. Repeat biopsy should be performed in patients with percent free PSA less than 30% or transition zone PSA density 0.26 ng./ml./cc or greater. In our study percent free PSA was the most accurate predictor of prostate cancer in repeat biopsy specimens.

Reporting and Grading of Complications After Urologic Surgical Procedures: An ad hoc EAU Guidelines Panel Assessment and Recommendations

CONTEXT The incidence of postoperative complications is still the most frequently used surrogate marker of quality in surgery, but no standard guidelines or criteria exist for reporting surgical complications in the area of urology. OBJECTIVE To review the available reporting systems used for urologic surgical complications, to establish a possible change in attitude towards reporting of complications using standardised systems, to assess systematically the Clavien-Dindo system when used for the reporting of complications related to urologic surgical procedures, to identify shortcomings in reporting complications, and to propose recommendations for the development and implementation of future reporting systems that are focused on patient-centred outcomes. EVIDENCE ACQUISITION Standardised systems for reporting and classification of surgical complications were identified through a systematic review of the literature. To establish a possible change in attitude towards reporting of complications related to urologic procedures, we performed a systematic literature search of all papers reporting complications after urologic surgery published in European Urology, Journal of Urology, Urology, BJU International, and World Journal of Urology in 1999-2000 and 2009-2010. Data identification for the systematic assessment of the Clavien-Dindo system currently used for the reporting of complications related to urologic surgical interventions involved a Medline/Embase search and the search engines of individual urologic journals and publishers using Clavien, urology, and complications as keywords. All selected papers were full-text retrieved and assessed; analysis was done based on structured forms. EVIDENCE SYNTHESIS The systematic review of the literature for standardised systems used for reporting and classification of surgical complications revealed five such systems. As far as the attitude of urologists towards reporting of complications, a shift could be seen in the number of studies using most of the Martin criteria, as well as in the number of studies using either standardised criteria or the Clavien-Dindo system. The latter system was not properly used in 72 papers (35.3%). CONCLUSIONS Uniformed reporting of complications after urologic procedures will aid all those involved in patient care and scientific publishing (authors, reviewers, and editors). It will also contribute to the improvement of the scientific quality of papers published in the field of urologic surgery. When reporting the outcomes of urologic procedures, the committee proposes a series of quality criteria.

Novel Artificial Neural Network for Early Detection of Prostate Cancer

PURPOSE Two artificial neural networks (ANN) for the early detection of prostate cancer in men with total prostate-specific antigen (PSA) levels from 2.5 to 4 ng/mL and from 4 to 10 ng/mL were prospectively developed. The predictive accuracy of the ANN was compared with that obtained by use of conventional statistical analysis of standard PSA parameters. PATIENTS AND METHODS Consecutive men with a serum total PSA level between 4 and 10 ng/mL (n = 974) and between 2.5 and 4 ng/mL (n = 272) were analyzed. A separate ANN model was developed for each group of patients. Analyses were performed to determine the presence of prostate cancer. RESULTS The area under the receiver operator characteristic (ROC) curve (AUC) was 87.6% and 91.3% for the 2.5 to 4 ng/mL and 4 to 10 ng/mL ANN models, respectively. For the latter model, the AUC generated by the ANN was significantly higher than that produced by the single variables of total PSA, percentage of free PSA, PSA density of the transition zone (TZ), and TZ volume (P <.01), but not significantly higher compared with multivariate analysis. For the 2.5 to 4 ng/mL model, the AUC of the ANN ROC curve was significantly higher than the AUCs for percentage of free PSA (P =.0239), PSA-TZ (P =.0204), and PSA density and total prostate volume (P <.01 for both). CONCLUSION The predictive accuracy of the ANN was superior to that of conventional PSA parameters. ANN models might change the way patients referred for early prostate cancer detection are counseled regarding the need for prostate biopsy.

Comparison of Open Versus Laparoscopic Pyeloplasty Techniques in Treatment of Uretero- Pelvic Junction Obstruction

PURPOSE Open dismembering pyeloplasty has high success rates but is associated with significant morbidity and moderate cosmetic results. Aim of this study was to evaluate laparoscopic dismembering pyeloplasty compared with other laparoscopic techniques and open surgery in this respect. MATERIAL AND METHODS Between September 1999 and September 2002 we performed 25 laparoscopic dismembering (LDP), 15 laparoscopic non-dismembering (LNDP) and 15 open pyeloplasties (ODP) in 55 patients. For laparoscopy two 12 mm and two 5mm ports were used, a ureteric stent remained in place for 4 weeks. ODP was performed via a flank incision, a percutaneous ureteric stent and a nephrostomy remained for 10 days. Postoperative morbidity was assessed by visual analogue scale (VAS). Mean follow-up was 23.4+/-9.1 months (range 7-42) for laparoscopy vs. 21.9+/-8.8 (range 9-41) months for open surgery. Success was evaluated with postoperative i.v. pyelogram or diuretic nephrography. RESULTS A crossing vessel could be identified in 82.5% (33/40) with laparoscopy vs. 47.0% (7/15) in ODP. Postoperative VAS score was lower in the laparoscopic group (day 1 3.5+/-1.6 vs. 5.4+/-3.1, day 5 0.9+/-1.2 vs. 3.1+/-1.8, p=0.001). Length of skin incision was 4.1+/-0.7 vs. 23.8+/-9.1 cm and hospital stay was 5.9+/-2.1 vs. 13.4+/-3.8 days for laparoscopy and ODP respectively. Success rate was 96.0% (24/25) for LDP, 73.3% (11/15) for LNDP and 93.4% (14/15) for ODP. Two patients with LNDP and one with ODP required re-operation. Clot retention was observed in two with LDP and one with ODP. Two abdominal wall herniations and one thromboembolism occurred with ODP. CONCLUSION Short-term results demonstrate that dismembering laparoscopic pyeloplasty has the same success rates as open surgery but morbidity and complications are significantly decreased. Non-dismembering techniques have the least favourable results. This finding may suggest that LDP has the potential to replace open surgery as the gold standard for treatment of uretero-pelvic junction obstruction.

PSA, PSA DENSITY, PSA DENSITY OF TRANSITION ZONE, FREE/TOTAL PSA RATIO, AND PSA VELOCITY FOR EARLY DETECTION OF PROSTATE CANCER IN MEN WITH SERUM PSA 2.5 TO 4.0 ng/mL

OBJECTIVES To enhance the specificity of prostate cancer (PCa) detection and reduce unnecessary biopsies in men with prostate-specific antigen (PSA) levels of 2.5 to 4.0 ng/mL, we prospectively evaluated various PSA-based diagnostic parameters. METHODS This study included 273 consecutive men with serum PSA of 2.5 to 4.0 ng/mL referred for early PCa detection or lower urinary tract symptoms. All men underwent prostate ultrasound and sextant biopsy with two additional transition zone (TZ) biopsies. If the first biopsies were negative, repeated biopsies were performed at 6 weeks. Total PSA, PSA density (PSAD), PSA density of the transition zone (PSA-TZ), free/total PSA ratio (f/t PSA), and PSA velocity (PSAV) were determined, and the sensitivity, specificity, and predictive values of these various parameters were calculated. RESULTS Of 273 patients, 207 had histologically confirmed benign prostatic hyperplasia (BPH) and 66 had PCa. f/t PSA and PSA-TZ were the most powerful predictors of PCa, followed by PSA, PSAD, and PSAV. Areas under the receiver operating characteristic curves for f/t PSA and PSA-TZ were 74.9% and 70.1%, respectively. With a 95% sensitivity for PCa detection, an f/t PSA cutoff of 41% and a PSA-TZ cutoff of 0.095 would result in the lowest number of unnecessary biopsies (29.3% and 17.2% specificity for f/t PSA and PSA-TZ, respectively) compared with all other PSA-related parameters evaluated. CONCLUSIONS Compared with standard total PSA assays, f/t PSA and PSA-TZ significantly enhance the sensitivity and specificity of PCa detection in a referral patient population with a total PSA of 2.5 to 4.0 ng/mL.

Impact of Lymph Node Dissection on Cancer Specific Survival in Patients With Upper Tract Urothelial Carcinoma Treated With Radical Nephroureterectomy

PURPOSE We examined the impact of lymphadenectomy on the clinical outcomes of patients with upper tract urothelial cancer treated with radical nephroureterectomy. MATERIALS AND METHODS Data were collected on 1,130 consecutive patients with pT1-4 upper tract urothelial cancer treated with radical nephroureterectomy at 13 centers worldwide. Patients were grouped according to nodal status (pN0 vs pNx vs pN+). The choice to perform lymphadenectomy was determined by the treating surgeon. All pathology slides were reevaluated by dedicated genitourinary pathologists. Univariable and multivariable Cox regression models measured the association of nodal status (pN0 vs pNx vs pN+) with cancer specific survival. RESULTS Overall 412 patients (36.5%) had pN0 disease, 578 had pNx disease (51.1%) and 140 had pN+ disease (12.4%). The 5-year cancer specific survival estimate was lower in patients with pN+ compared to those with pNx disease (35% vs 69%, p <0.001), which in turn was lower than that in those with pN0 disease (69% vs 77%, p = 0.024). In the subgroup of patients with pT1 disease (345) cancer specific survival rates were not different in those with pN0 and pNx. In pT2-4 cases (813) cancer specific survival estimates were lowest in pN+, intermediate in pNx and highest in pN0 (33% vs 58% vs 70%, p = 0.017). When adjusted for the effects of standard clinicopathological features pN+ was an independent predictor of cancer specific survival (p <0.001). pNx was significantly associated with worse prognosis than pN0 in pT2-4 upper tract urothelial cancer only. CONCLUSIONS Nodal status is a significant predictor of cancer specific survival in upper tract urothelial cancer. pNx is significantly associated with a worse prognosis than pN0 in pT2-4 tumors. Patients expected to have pT2-4 disease should undergo lymphadenectomy to improve staging and thereby help guide decision making regarding adjuvant chemotherapy.

Rationale for Percutaneous Biopsy and Histologic Characterisation of Renal Tumours

CONTEXT The use of percutaneous biopsy of renal tumours has been traditionally reserved for selected cases because of uncertainties regarding its safety, accuracy, and clinical utility. With the adoption of modern biopsy techniques and increasing expertise in interpreting biopsy specimens, renal tumour biopsy today has limited morbidity and allows histologic diagnosis in the majority of cases in centres with expertise. OBJECTIVE To review the current rationale, indications, and outcomes of percutaneous biopsies and histologic characterisation of renal tumours. EVIDENCE ACQUISITION We conducted a systematic review of English-language articles on percutaneous biopsies of renal tumours published between January 1999 and December 2011 using the Medline, Embase, and Web of Science databases. One hundred twelve articles were selected with the consensus of all authors and analysed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria. EVIDENCE SYNTHESIS In recent years, the increasing incidence of incidental small renal masses (SRMs), the development of conservative and minimally invasive treatments for low-risk renal cell carcinoma (RCC), and the discovery of novel targeted treatments for metastatic disease have provided the rationale for expanding the indications for renal tumour biopsy. Percutaneous biopsy for diagnostic assessment of SRMs can avoid unnecessary surgeries and support treatment decisions, especially in patients at high surgical risk. Biopsies can confirm histologic success after thermal ablation of SRMs and support the selection of the appropriate systemic therapy for metastatic RCC. There is increasing evidence that further diagnostic and prognostic information can be obtained from renal tumour biopsies with the use of immunohistochemistry, cytogenetic and molecular analysis, and high-throughput gene expression profiling. CONCLUSIONS Percutaneous biopsies have increasing indications and can significantly contribute to clinical management of renal tumours but are still underutilised in clinical practice. Further research is needed to define optimal and standardised patterns of biopsy and improve the accuracy of biopsies to determine tumour histology. Molecular and genetic analysis of biopsy specimens can provide additional information to support patient counselling and treatment decision making.

Preoperative multivariable prognostic model for prediction of nonorgan confined urothelial carcinoma of the upper urinary tract

PURPOSE We created a prognostic tool for the accurate preoperative prediction of nonorgan confined upper tract urothelial carcinoma. MATERIALS AND METHODS A computerized data bank containing comprehensive information on 1,453 patients who underwent radical nephroureterectomy at 13 academic institutions was generated and continuously updated. This study comprised a subset of 659 patients in whom all appropriate preoperative prognostic variables (age, gender, race, symptoms, Eastern Cooperative Oncology Group performance status, primary tumor location, tumor architecture, tumor grade and history of previous bladder cancer) were available for statistical analysis. A multivariable logistic regression model containing relevant clinicopathological variables addressed the prediction of nonorgan confined stage disease (T3-4 and/or N+) at radical nephroureterectomy. A backward step-down selection process was applied to achieve the most informative and parsimonious model. Internal validation was performed using 200 bootstrap resamples. RESULTS Pathological nonorgan confined urothelial carcinoma was found in 40% of patients. Grade, architecture and location of the tumor were independently associated with nonorgan confined disease. A nomogram including these 3 variables achieved 76.6% accuracy in predicting nonorgan confined upper tract urothelial cancer. CONCLUSIONS We developed a simple and accurate prognostic tool for the prediction of locally advanced upper tract urothelial cancer. This preoperative prediction model can be used for designing clinical trials, selecting patients for preoperative systemic therapy and guiding the extent of concomitant lymph node dissection at nephroureterectomy.

The extent of lymphadenectomy seems to be associated with better survival in patients with nonmetastatic upper-tract urothelial carcinoma: how many lymph nodes should be removed?

BACKGROUND The role and extent of lymphadenectomy in patients with upper-tract urothelial carcinoma (UTUC) is debated. OBJECTIVE To establish whether the number of lymph nodes (LNs) removed might be associated with better cause-specific survival in patients with UTUC. DESIGN, SETTING, AND PARTICIPANTS The study included 552 consecutive patients who underwent radical nephroureterectomy (RNU) and lymphadenectomy between 1992 and 2006. INTERVENTION Patients were treated with RNU and lymphadenectomy. MEASUREMENTS Univariable and multivariable Cox proportional hazards regression models addressed the association between the number of LNs removed and cause-specific mortality (CSM). The number of LNs removed was coded as a cubic spline to allow for nonlinear effects. Finally, the most informative cut-off for the number of removed LNs was identified. RESULTS AND LIMITATIONS In the entire population, the number of LNs removed was not associated with CSM in univariable (hazard ratio [HR]: 0.99; p=0.16) or in multivariable (HR: 0.97; p=0.12) analyses. In contrast, in the subgroup of pN0 patients (n=412), the number of LNs removed achieved the independent predictor status of CSM (HR: 0.93; p=0.02). Eight LNs removed was the most informative cut-off in predicting CSM (HR: 0.42; p=0.004). The inclusion of the variable defining dichotomously the number of removed LNs (< 8 vs > or = 8) in the base model (age, Eastern Cooperative Oncology Group performance status, pathologic stage, grade, architecture, and lymphovascular invasion) significantly increased the accuracy in predicting CSM (+1.7%; p<0.001). CONCLUSIONS The extension of the lymphadenectomy in pN0 UTUC patients seems to be associated with CSM. Longer survival was observed in patients in whom at least eight LNs had been removed.