Outcome of immune checkpoint inhibitors in metastatic renal cell carcinoma across different treatment lines.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have led to a paradigm change in the management of metastatic renal cell carcinoma (mRCC). Prospective trials have focused on ICI treatment in the first or second line. The aim of this analysis is to evaluate the benefit of ICI across different treatment lines. PATIENTS AND METHODS: This is a single-center retrospective study that included mRCC patients who received ICIs in various treatment lines. Objective response rates (ORR), progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Ninety-four patients were eligible for full evaluation. Patients were classified as International mRCC Database Consortium (IMDC) risk group categorization as good, intermediate and poor risk in 26.8%, 61.6% and 14.8% of cases, respectively. They were treated with ICI monotherapy, dual ICI therapy and ICI + tyrosine kinase inhibitor in 59%, 20% and 21% of cases, respectively. ORR, median PFS and OS for the entire cohort was 39.4%, 9.67 months [95% confidence interval (CI) 6.9-12.4 months] and 23.6 months (95% CI 13.3-33.9 months), respectively. The ORR by treatment line was 33% in first, 40.4% in the second, 35% in the third and 43.5% in the fourth line and beyond. Median PFS by treatment line was 8.6, 10.3, 7.9 and 7.23 months, respectively. The median OS was not reached in first-line treatment and was 26.2, 18.1 and 20.7 months in the second, third and fourth line and beyond, respectively. CONCLUSIONS: ICIs or ICI combinations are active in all treatment lines and should also be offered in heavily pretreated patients. Patient selection based on tumor and patient factors allows for maximal benefit from ICI-based therapies.

Androgen receptor expression is associated with adverse pathological features in ureteral but not in pelvicalyceal urothelial carcinomas of the upper urinary tract.

PURPOSE: This study aims to determine the significance of androgen receptor (AR) expression in urothelial carcinoma of the upper urinary tract (UTUC). METHODS: AR expression was assessed on tissue microarrays containing specimens of 737 patients with UTUC who underwent radical nephroureterectomy with curative intent. AR expression was correlated with clinical and pathological tumor features as well as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: Overall, AR was expressed in 11 % of tumors. AR expression was significantly associated with tumor necrosis as well as sessile and multifocal tumor growth but not with RFS, CSS or OS. AR was detected nearly twice as often in tumors of the ureter than of the pelvicalyceal system (p = 0.005). Subgroup analyses showed that the significant associations of AR with unfavorable pathologic features were exclusively attributable to tumors located in the ureter. However, in both ureteral and pelvicalyceal tumors, AR status was independent of RFS, CSS and OS. CONCLUSIONS: In this cohort of patients treated with RNU, AR expression was found in approximately 10 % of UTUCs, twice as often in ureteral than in pelvicalyceal tumors. While AR expression had no impact on postoperative prognosis, it was significantly associated with unfavorable pathologic features in ureteral tumors. Steroid hormone signaling might be relevant for future investigations of differences between ureteral and pelvicalyceal tumors.

Association of perioperative blood transfusion with oncologic outcomes after radical nephroureterectomy for upper tract urothelial carcinoma.

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.

Utility and limitations of 3-Tesla diffusion-weighted magnetic resonance imaging for differentiation of renal tumors.

OBJECTIVE: To investigate utility and limitations of 3-Tesla diffusion-weighted (DW) magnetic resonance imaging (MRI) for differentiation of benign versus malignant renal lesions and renal cell carcinoma (RCC) subtypes. MATERIALS AND METHODS: Sixty patients with 71 renal lesions underwent 3 Tesla DW-MRI of the kidney before diagnostic tissue confirmation. The images were retrospectively evaluated blinded to histology. Single-shot echo-planar imaging was used as the DW imaging technique. Apparent diffusion coefficient (ADC) values were measured and compared with histopathological characteristics. RESULTS: There were 54 malignant and 17 benign lesions, 46 lesions being small renal masses ≤ 4 cm. Papillary RCC lesions had lower ADC values (p=0.029) than other RCC subtypes (clear cell or chromophobe). Diagnostic accuracy of DW-MRI for differentiation of papillary from non-papillary RCC was 70.3% resulting in a sensitivity and specificity of 64.3% (95% CI, 35.1-87.2) and 77.1 (95% CI, 59.9-89.6%). Accuracy increased to 83.7% in small renal masses (≤ 4 cm diameter) and sensitivity and specificity were 75.0% and 88.5%, respectively. The ADC values did not differ significantly between benign and malignant renal lesions (p=0.45). CONCLUSIONS: DW-MRI seems to distinguish between papillary and other subtypes of RCCs especially in small renal masses but could not differentiate between benign and malignant renal lesions. Therefore, the use of DW-MRI for preoperative differentiation of renal lesions is limited.

Diabetes mellitus without metformin intake is associated with worse oncologic outcomes after radical nephroureterectomy for upper tract urothelial carcinoma.

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.

[Reporting and grading of complications after urologic surgical procedures: an ad hoc EAU guidelines panel assessment and recommendations]. / Notificación y clasificación de complicaciones después de procedimientos quirúrgicos urológicos: una evaluación y recomendaciones del panel de guías clínicas de la EAU.

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.

[Upper tract urothelial carcinoma. An update on clinical and pathological prognostic factors]. / Das Urothelkarzinom des oberen Harntraktes. Ein Update über klinische und pathologische prognostische Faktoren.

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon but potentially lethal disease. Accurate risk stratification remains a challenge owing to the difficulty of clinical staging. Identification of risk factors may lead to individualized treatment and patient counselling and holds the potential to improve outcome. A non-systematic PubMed/Medline literature research was performed to identify and summarize clinical and pathological risk factors and urine-based markers which are associated with clinical outcome. Although knowledge of potential prognostic factors has improved over the last 5 years the overall evidence on UTUC risk factors remains limited and prospective, randomized trials are still missing. Radical nephroureterectomy is currently standard treatment for high-grade and muscle invasive UTUC. Several clinical and pathological factors (e.g. stage, grade, age, hydronephrosis, lymphovascular invasion, tumor necrosis and architecture, delay between diagnosis and surgery) were identified to be associated with outcome. Urinary cytology and fluorescence in-situ hybridization are the most commonly used urinary markers. Prospective randomized controlled trials are urgently needed to identify new risk factors and assess the efficacy. The incorporation of such prognosticators into multivariable prediction models may help to guide decision-making with regard to type of treatment, performance of lymphadenectomy and consideration of neoadjuvant or adjuvant systemic therapy.

[Small incidental renal tumors. Evaluation and biological parameters]. / Der kleine, zufällig entdeckte Nierentumor. Aggressionspotential und Abklärung.

Tumor size is a prognostic marker and correlates to survival after surgical therapy. Of 287 patients with small (or=pT3a in 10.9%, a high Fuhrman grade >or=3, multifocality in 8.5%, and metastases in 2.4%. Tumors with a diameter of 3.1-4 cm showed dramatically more aggressive parameters; 35.7% had stage >or=pT3a, 25.5% Fuhrman grade >or=G3, and 8.4% metastases (M+). However, evaluation of the tumor diameter on CT has an error of about +/-0.3 cm, which will lead to an even more pronounced error in volume determination. Therefore, determination of growth in follow-up imaging is unreliable. With the exception of the typical angiomyolipoma, determination of dignity for small solid kidney lesions is unreliable even with modern imaging. Only 17% of 80 benign lesions in our series were assessed as benign on preoperative CT. Thus, preoperative evaluation not only based on imaging seems to be valuable, especially in patients with higher surgical risk. Percutaneous renal mass biopsy has an accuracy of over 90% for detecting benign lesions and can influence therapeutic decisions, especially in patients with higher surgical risk.

[Artificial neural networks for decision making in urologic oncology]. / Réseaux neuronaux artificiels pour la prise de décision en cancérologie urologique.

This chapter presents a detailed introduction regarding Artificial Neural Networks (ANNs) and their contribution to modern Urologic Oncology. It includes a description of ANNs methodology and points out the differences between Artifical Intelligence and traditional statistic models in terms of usefulness for patients and clinicians, and its advantages over current statistical analysis.

Morbidity of laparoscopic extraperitoneal versus transperitoneal radical prostatectomy verus open retropubic radical prostatectomy.

OBJECTIVE: Morbidity and postoperative pain after extraperitoneal (E-LRPE) and transperitoneal (T-LRPE) laparoscopic radical prostatectomy was compared to open extraperitoneal radical prostatectomy (O-RPE). MATERIAL AND METHODS: Between January 2002 and October 2003, we evaluated 41 E-LRPE, 39 T-LRPE and 41 O-RPE prospectively. All operations were performed as standard procedures by the same group of surgeons and perioperative results and complications were evaluated. Pain management was performed with tramadol 50-100 mg on demand, and no other form of anaesthesia was given. Postoperative pain was assessed daily in all patients quantifying analgesic requirement and evaluation of Visual Analogue Scale (VAS). All patients had at least a 12 month follow-up. RESULTS: Mean age, prostate volume, PSA and Gleason score were comparable between all three groups (p>0.05). Mean blood loss was lower with laparoscopy (189+/-140 and 290+/-254 ml), as compared to 385+/-410 ml for O-RPE (p=0.002). However, mean operating times were significantly longer in L-TRPE (279+/-70 min) as compared to E-LRPE (217+/-51 min) and O-RPE (195+/-72 min) (p<0.001), but E-LRPE and O-RPE showed no statistical difference (p=0.1143). Average VAS score on the 1st and 5th postoperative day for E-LRPE versus T-LRPE versus O-RPE was 4.9+/-1.0 versus 7.8+/-1.5 versus 5.8+/-1.9 and 1.6+/-0.9 versus 2.3+/-1.2 versus 2.3+/-0.9 respectively, which was significant lower (p=0.02) between E-LRPE versus T-LRPE (p<0.001) and O-RPE (p=0.008), but equal (p=0.655) between T-LRPE and O-RPE since postoperative day 3. Mean tramadol analgesic consumption within the first postoperative week was 290 versus 490 versus 300 mg respectively, which was statistical different between E-LRPE and T-LRPE (p<0.001), O-RPE and T-LRPE (p<0.001), but not between E-LRPE and O-RPE (p=0.550). Statistical analysis revealed a strong correlation of urinary leakage with increased postoperative pain (p=0.029) in all groups, especially for T-LRPE (p=0.007). Likewise, increased operating times (>240 min) were associated with increased post-operative pain (p=0.049). Full continence defined as no pads at one year was achieved in 36/41 (88%, E-LRPE) versus 33/39 (85%, T-LRPE) versus 33/41 (81%, O-RPE), respectively (p=0.2). CONCLUSION: E-LRPE resulted in a significant subjective (VAS Score, p<0.001) and objective (analgetic consumption, p<0.001) pain reduction compared to T-LRPE, but only in VAS Score compared to O-RPE (p=0.008). Analgetic consumption during first postoperative week was equal in E-LRPE (290 mg) and O-RPE (300 mg) (p=0.550). Shorter operating times, lower urinary leakage rates, lower stricture rates and lower blood loss in E-LRPE compared to T-LRPE are mainly explained due to the long learning curve in LRPE, which we did not overcome yet, and not due to the approach (extraperitoneal versus transperitoneal).

Postradical prostatectomy TRUS-guided anastomotic biopsy. Where do we stand today?

The issue of performing tissue sampling from the vesicourethral anastomotic area postradical prostatectomy (transrectal ultrasound-guided biopsy) after radical surgical treatment of local disease has failed, still remains controversial. We review a selection of articles that evaluate this procedure as well as newer diagnostic modalities and we discuss how this technique may have a position in our treatment dilemmas in cases with biochemical failure of undetermined origin.

Modified laparoscopic nephroureterectomy for treatment of upper urinary tract transitional cell cancer is not associated with an increased risk of tumour recurrence.

INTRODUCTION: Laparoscopic nephroureterectomy reduces the morbidity of surgical management of urinary tract transitional cell carcinoma (TCC), but a potentially increased risk for local tumour spreading was reported. We evaluated results obtained from patients undergoing a modified laparoscopic approach and open procedures in this respect. PATIENTS AND METHODS: Between January 2000 and March 2002 we performed 19 modified laparoscopic nephroureterectomies (LNU) with open intact specimen retrieval in conjunction with open distal ureter and bladder cuff removal and 15 open standard nephroureterectomies (ONU). Staging lymphadenectomy was performed in 14/19 (73.7%) patients with LNU and in 6/15 (40.0%) with ONU. In all patients operating time, blood loss, complications, pain score (VAS) and data in respect to tumour recurrence were analysed. Mean follow-up was 22.1+/-9.2 (range 14-34) months for LNU and 23.1+/-8.8 (14-36) for ONU respectively. RESULTS: In LNU and ONU pathological features were 12 pT1 vs. 10 pT1, 2 pT2 vs. 2 pT2 and 5 pT3 vs. 3 pT3, respectively. All patients had TCC and were R0 at final histology. Four patients with LNU had lymph node involvement, one in ONU. LNU had decreased operating times (p=0.057), blood loss (p=0.018), complications (p=0.001) and VAS scores (p=0.001). One tumour recurrence occurred in LNU, associated with a pT3b pN2 G3 TCC at final histology. One patient with ONU had local tumour recurrence at the site of the bladder cuff. No port-site metastasis occurred during follow-up with LNU. CONCLUSION: Improved peri-operative results and same cancer control as compared to open surgery by this modified LNU was not associated with an increased risk for tumour recurrence, since strict "non-touch" preparation, avoiding of urine spillage and intact specimen retrieval prevents tumour seeding. However, results from long term studies are still warranted to clarify this issue.

Benefits of laparoscopic renal surgery are more pronounced in patients with a high body mass index.

PURPOSE: Aim of this prospective study was to determine whether patients with a higher body mass index (BMI) will benefit more from laparoscopic procedures in respect to postoperative morbidity and pain as compared to regular patients. PATIENTS AND METHODS: Between September 1999 and October 2001, we performed 36 laparoscopic radical nephrectomies and 18 nephron sparing partial nephrectomies for renal cell carcinoma and 6 nephrectomies for benign disease (group 1, n=60). In addition, we performed 24 open radical nephrectomies and 18 nephron spearing interventions for renal cell carcinoma (group 2, n=42). Mean age was 59+/-17.9 years and average BMI was 27.1+/-3.3 kg/m(2) in the entire group. All techniques were evaluated for intraoperative results and complications. Postoperative morbidity was assessed in all patients by quantifying pain medication and by daily evaluation of Visual Analogue Scale (VAS). RESULTS: Mean hospitalisation time in group 1 as compared to group 2 was 10.1 days versus 5.4 days, average operating time was 273 minutes versus 187 minutes, mean length of skin incision was 7.2 cm versus 30.8 cm. Overall analgesic consumption was lower in the laparoscopic group (190 mg versus 590 mg, p<0.001), in patients with a BMI >28 kg/m(2) the difference was even more pronounced (160 mg versus 210 mg, p=0.032). In group 1, patients with a BMI >28 kg/m(2) had significantly less pain on the first and fourth postoperative day in a linear regression analysis (VAS1=10.714-0.218 BMI; r=0.688 (p<0.001) and VAS4=3.98-0.09 BMI, r=0.519 (p<0.001), respectively). In group 1, 3/60 (5.0%) and in group 2, 5/42 (11.9%) complications occurred, no difference was found in respect to a high BMI (p=0.411). CONCLUSION: Patients with a higher BMI (cut-off >28 kg/m(2)) benefit more from laparoscopy than slim patients in respect to postoperative pain and morbidity but do not experience more complications. Consequently, reluctance to perform laparoscopic procedures in patients with a higher BMI is no longer justified.

Can total and transition zone volume of the prostate determine whether to perform a repeat biopsy?

OBJECTIVES: To compare the ability of total prostate (TP) and transition zone (TZ) volume to predict the outcome of a repeat prostate biopsy in patients with serum prostate-specific antigen (PSA) levels of 4 to 10 ng/mL. METHODS: A total of 1137 patients were included and underwent transrectal ultrasound-guided needle sextant and two transition zone biopsies of the prostate. All patients with a prior negative biopsy (benign prostatic tissue) underwent a repeat biopsy after 6 weeks. The TP and TZ volumes of the prostate were measured by transrectal ultrasonography. RESULTS: Of the 1137 patients, prostate cancer was diagnosed in 364 (32%), in 276 (24.2%) after the first biopsy and in 88 (7.7%) after the repeated biopsy. The TP and TZ volumes were larger in the patients with prostate cancer detected on the repeated biopsy (P <0.0001). Using a cutoff for TP volume of less than 20 cm3 and greater than 80 cm3 and for TZ volume of less than 9 cm3 and greater than 41 cm3 would have spared 7.1% and 10% of repeated biopsies, respectively. CONCLUSIONS: The probability for a positive repeat prostate biopsy increases in a logarithmic function for larger prostates, as well as for larger TP and, especially, for larger TZ volumes. The probability of finding prostate cancer on a repeat biopsy in prostates with small (less than 20 cm3) and large (greater than 79 cm3) TP, as well as in small (less than 9.3 cm3) and large (greater than 41 cm3) TZ volumes, was very low. Therefore, a repeat prostate biopsy within 6 weeks is unnecessary. These patients should be followed up by serial PSA determination.

Morbidity of transrectal ultrasound-guided prostate needle biopsy in patients receiving immunosuppression.

OBJECTIVES: To prospectively evaluate the safety and early and delayed morbidity of transrectal ultrasound-guided needle biopsies in patients receiving immunosuppressive therapy. METHODS: A total of 59 men receiving immunosuppressive agents after kidney transplantation, with a total prostate-specific antigen level between 4 and 10 ng/mL, were prospectively studied. All patients underwent transrectal ultrasound (TRUS)-guided sextant biopsy plus two additional transition zone biopsies. Biopsy samples were also obtained from suspicious areas identified during TRUS and digital rectal examination. The immediate and delayed morbidity, patient satisfaction, and complication rates were recorded and compared with the morbidity data recorded in the same period from 1051 men in the European Prostate Cancer Detection study. RESULTS: Of the 59 subjects, prostate cancer was detected in 17; 231 men were found to have cancer in the European Prostate Cancer Detection Study. Minor or no discomfort was observed in 88% and 92% of the transplant recipients and controls, respectively (P = 0.31). Twelve percent versus 8% experienced pain. Early morbidity included rectal bleeding (2.6% versus 2.1%, P = 0.19), severe hematuria (0.8% versus 0.7%, P = 0.08), and moderate to severe vasovagal episodes (1.9% versus 2.8%, P = 0.04). Late morbidity included fever (3.5% versus 2.9%, P = 0.1), hematospermia (11.0% versus 9.8%, P = 0.1), recurrent mild hematuria (17.4% versus 16.8%, P = 0.08), persistent dysuria (6.4% versus 7.2%, P = 0.2), and urinary tract infections (12.0% versus 10.9%, P = 0.08). Major complications were rare: urosepsis (0% versus 0.1%). CONCLUSIONS: The results of our study demonstrate that TRUS-guided biopsy of the prostate is generally well tolerated, with minor morbidity, in patients receiving immunosuppression. No differences were noted in pain apprehension or early and delayed morbidity, suggesting that TRUS-guided biopsies can be performed safely in these patients.

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.

Pathological features of prostate cancer detected on initial and repeat prostate biopsy: results of the prospective European Prostate Cancer Detection study.

PURPOSE: We evaluated pathological features of prostate cancer detected on repeat prostate biopsy in men with a serum total prostate-specific antigen (PSA) level between 4 and 10 ng/ml who were diagnosed with benign prostatic tissue after an initial biopsy and compared them to those cancers detected on initial prostate biopsy. MATERIALS AND METHODS: In this prospective European prostate cancer detection study, 1,051 men with a total PSA level between 4 and 10 ng/ml underwent transrectal ultrasound (TRUS)-guided sextant biopsy and two additional transition zone biopsies. All subjects whose biopsy samples were negative for prostate cancer (CaP) underwent a repeat biopsy after 6 weeks. Those with clinically localized cancers underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either initial or repeat biopsy and clinically organ confined disease who agreed to undergo radical prostatectomy were compared. RESULTS: Initial biopsy was positive (CaP) in 231 of 1,051 enrolled subjects and negative (benign histology) in 820 subjects. Of these 820 subjects, CaP was detected in 10% (83/820) upon repeat biopsy. Of cancers detected on initial and repeat biopsy, 148/231 (64%) and 56/83 (67.5%) had clinically localized disease, respectively, and were offered radical prostatectomy. 10/148 (6.7%) and 3/56 (5.3%), respectively, opted for radiation therapy and thus, 138/148 (93.3%) and 53/56 (94.7%), respectively, underwent radical retropubic prostatectomy. There were statistically significant differences with respect to multifocality (P = 0.009) and cancer location (P < 0.001) with cancers on repeat biopsy showing a lower rate of multifocality and a more apico-dorsal location. In contrast, there were no differences with respect to stage (P = 0.2), Gleason score (P = 0.36), percentage Gleason grade 4/5 (P = 0.1), serum PSA (P = 0.62), and patient age (P = 0.517). CONCLUSIONS: At least 10% of patients with negative prostatic biopsy results will be diagnosed with CaP on repeat biopsy. Despite differences in location and multifocality, pathological and biochemical features of cancers detected on initial and repeat biopsy are similar, suggesting similar biological behavior and thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy. Cancers missed on initial biopsy and subsequently detected on repeat biopsy are located in a more apico-dorsal location. Repeat biopsies should thus be directed to this rather spared area in order to improve cancer detection rates.

[Effect of the learning phase on safety and efficiency of laparoscopic fundoplication]. / Einfluss der Lernphase auf Sicherheit und Effizienz der laparoskopischen Fundoplicatio.

The introduction of laparoscopic techniques into surgical practice has required a learning process on the part of the surgeons involved. The duration, morbidity, and functional outcome of laparoscopic fundoplication were evaluated in our institution's first 146 cases. During a 34-month period the patients underwent laparoscopic Nissen (n = 102) or Toupet (n = 44) fundoplication. Conversion to open access was necessary in 7 cases, re-operation for complications in 2, all among the first 40 cases of the series. The median operating time was 165 min (range 75-375) in the first 40 cases, and 105 min (range 50-235) thereafter (P < 0.001). Body mass index, grade of esophagitis, and the surgeon's experience were independent predictors of the operating time. One hundred and thirty-four patients (92%) could be evaluated for recurrence of reflux, which was encountered in 2 (5%) of the first 40 cases and 8 (8%) of 94 patients in the later group.

Targeted transurethral microwave thermotherapy versus alpha-blockade in benign prostatic hyperplasia: outcomes at 18 months.

OBJECTIVES: To compare directly the efficacy, safety, and durability of targeted transurethral microwave thermotherapy with that of alpha-blocker treatment for lower urinary tract symptoms of benign prostatic hyperplasia. METHODS: In a randomized, controlled clinical trial, 52 patients with lower urinary tract symptoms due to benign prostatic hyperplasia received terazosin treatment and 51 underwent microwave treatment under topical anesthesia. The patient evaluation included the International Prostate Symptom Score, peak flow rate, and quality-of-life score before microwave treatment or initiation of terazosin treatment and at periodic intervals thereafter up to 18 months. RESULTS: The mean International Prostate Symptom Score, peak flow rate, and quality-of-life score all improved significantly in both groups by 6 months. However, the magnitude of improvement was significantly greater in the microwave group than in the terazosin group. The significant between-group differences observed at 6 months in the mean International Prostate Symptom Score, peak flow rate, and quality-of-life score were fully maintained at 18 months, at which time the improvements in these three outcome measures were significantly greater (P <0.0005), by 35%, 22%, and 43%, respectively, in the microwave group than in the terazosin group. The actuarial rate of treatment failure at 18 months was significantly greater by sevenfold in the terazosin group. Adverse events were generally infrequent and readily manageable in both groups. CONCLUSIONS: Although the initial onset of terazosin action was more rapid, the longer term clinical outcomes of targeted microwave treatment were markedly superior. The more favorable results in patients who underwent microwave treatment were maintained for at least 18 months.