Correction to: The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.

Perioperative assessment of regional ventilation during changing body positions and ventilation conditions by electrical impedance tomography.

BACKGROUND: Lung-protective ventilation is claimed to be beneficial not only in critically ill patients, but also in pulmonary healthy patients undergoing general anaesthesia. We report the use of electrical impedance tomography for assessing regional changes in ventilation, during both spontaneous breathing and mechanical ventilation, in patients undergoing robot-assisted radical prostatectomy. METHODS: We performed electrical impedance tomography measurements in 39 patients before induction of anaesthesia in the sitting (M1) and supine position (M2), after the start of mechanical ventilation (M3), during capnoperitoneum and Trendelenburg positioning (M4), and finally, in the supine position after release of capnoperitoneum (M5). To quantify regional changes in lung ventilation, we calculated the centre of ventilation and 'silent spaces' in the ventral and dorsal lung regions that did not show major impedance changes. RESULTS: Compared with the awake supine position [2.3% (2.3)], anaesthesia and mechanical ventilation induced a significant increase in silent spaces in the dorsal dependent lung [9.2% (6.3); P<0.05]. Capnoperitoneum and the Trendelenburg position led to a significant increase in such spaces [11.5% (8.9)]. Silent space in the ventral lung remained constant throughout anaesthesia. CONCLUSION: Electrical impedance tomography was able to identify and quantify on a breath-by-breath basis circumscribed areas, so-called silent spaces, within healthy lungs that received little or no ventilation during general anaesthesia, capnoperitoneum, and different body positions. As these silent spaces are suggestive of atelectasis on the one hand and overdistension on the other, they might become useful to guide individualized protective ventilation strategies to mitigate the side-effects of anaesthesia and surgery on the lungs.

Adherence of the indication to European Association of Urology guideline recommended pelvic lymph node dissection at a high-volume center: Differences between open and robot-assisted radical prostatectomy.

PURPOSE: Contemporary adherence of the indication to European Association of Urology (EAU) guideline recommendation for pelvic lymph node dissection (PLND) at either open (ORP) or robot-assisted radical prostatectomy (RARP) at a high-volume center is unknown. To assess guideline recommended and observed PLND rates in a high-volume center cohort. METHODS: We relied on the Martini-Clinic database and focused on patients treated with either ORP or RARP, between 2010 and 2013. Actual performed PLND was compared to European Association of Urology (EAU) guideline recommendation defined by nomogram predicted risk of lymph node invasion >5%. Categorical and multivariable logistic regression analyses targeted two endpoints: 1) probability of guideline recommended PLND and 2) probability of no PLND, when not recommended by EAU guideline. RESULTS: Within 7868 PCa patients, adherence to EAU PLND guideline recommendation was 97.1% at ORP and 96.8% at RARP (p = 0.7). When PLND was not recommended, it was more frequently performed at RARP (71.6%) than at ORP (66.2%) (p = 0.002). Gleason score, PSA and number of positive biopsy cores were independent predictors for both either PLND when recommended, or no PLND when not recommended (all p < 0.05). Clinical tumor stage, age and surgical approach were also independent predictors for no PLND when not recommended (all p < 0.05). CONCLUSIONS: Adherence of the indication to EAU guideline recommended PLND is high at this high-volume center. Neither ORP nor RARP represent a barrier for PLND, when recommended. However, a high number of patients underwent PLND despite absence of guideline recommendation. Possible staging advantages and PLND related complications needs to be individually considered, especially, when LNI risk is low.

The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

PURPOSE: To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. METHODS: A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. RESULTS: With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 months and 72 % for GS 3+4, 56 months and 54 % for GS 4 + 3, and 27 months and 32 % for GS 8-10. The retrospective approach is a limitation of our study. CONCLUSIONS: Our study provides data on the BCR in pT2R1-PCa without adjuvant/neoadjuvant therapy and thus a rationale for an individual's risk stratification. The data support patients and physicians in estimating the individual risk and timing of BCR and thus serve to personalize the management in pT2R1-PCa.

[DaVinci robot-assisted laparoscopic prostatectomy: benefit for obese men? - A matched-pair analysis]. / Roboterassistierte radikale Prostatektomie : Vorteil bei adipösen Männern? - Eine Matched-pair-Analyse.

BACKGROUND: Open radical retropubic prostatectomy (RRP) in obese patients (BMI ≥30) is associated with increased perioperative morbidity. The aim of the study was to evaluate the possible benefit of DaVinci robotic-assisted laparoscopic prostatectomy (RARP) compared to RRP in obese patients. PATIENTS AND METHODS: We identified 255 patients with a localized prostate cancer (PCa) and BMI ≥30 treated with radical prostatectomy from January 2009 to December 2011. To adjust for risk factors of increased perioperative morbidity (nerve-sparing, pelvic lymph node dissection, prostate volume), a propensity score-based matching was performed between RRP and RARP (n=115 each group). Both groups were compared by taking into consideration histopathological outcomes as well as peri- and postoperative (30 days) morbidity. RESULTS: There were no differences in histopathological characteristics (pT/pN-stage, Gleason score, R-stage; all p>0.05) in both groups. Mean blood loss (276 ml vs. 937 ml), transfusion rate (0.9% vs. 8.7%) and 30-day complications according to the Clavien classification system (Clavien ≥ 2; 9.5% vs. 22.6%) were decreased in RARP (all p<0.05). In a multivariate logistic regression model, RARP vs. RRP was associated with a significantly reduced risk of a Clavien ≥ 2 complication during follow-up (OR 0.3; p= 0.0047). Recovery of continence was significantly better for RARP patients after 3 months (p= 0.02). There was no difference in erectile function 12 months postoperatively. CONCLUSION: Our findings of decreased transfusion and complication rates and a trend of better early recovery of continence in RARP should be considered in obese patients (BMI >30) scheduled for radical prostatectomy.

[Robot-assisted laparoscopic pyeloplasty in adults: Excellent long-term results of primary pyeloplasty]. / Roboterassistierte laparoskopische Pyeloplastik bei Erwachsenen : Exzellente Langzeitergebnisse der primären Pyeloplastik.

PURPOSE: With the development of the robot-assisted surgical technique, robot-assisted pyeloplasty (RAP) has become established as an alternative to open and laparoscopic surgery. Currently there are only a few single-center studies with larger numbers of cases and long-term results. The aim of this study was to investigate perioperative and long-term postoperative success rates of Anderson-Hynes robot-assisted pyeloplasty (RAP) at a single center. MATERIALS AND METHODS: We retrospectively reviewed our RAP experience of 61 patients performed by two surgeons between 2004 and 2013 regarding operating time, length of hospital stay, perioperative complication, and success. Overall success was measured in terms of necessary redo pyeloplasty. We also identified patients with temporary stent placement due to symptomatic hydronephrosis or with further obstruction in diuretic renography. RESULTS: Median age, operating time, and follow-up were 33 years, 195 min, and 64 months, respectively. No conversion to open procedure was necessary. The success rate was 98% (n=60) with 1 patient undergoing open redo pyeloplasty due to a recurrent stenosis. Temporary stent placement was required in 3 patients due to pyelonephritis and dilatation. CONCLUSION: Satisfying long-term success rates including low complication rates of RAP were obtained in this study. RAP presents a safe and standardized procedure for symptomatic ureteropelvic junction obstruction.

No impact of blood transfusion on oncological outcome after radical prostatectomy in patients with prostate cancer.

PURPOSE: To assess the association between blood loss, blood transfusion (BT) and biochemical recurrence (BCR)-free, metastasis-free and overall survival after radical prostatectomy (RP) in a large single-center cohort of patients. Perioperative BT at oncologic surgery has been reported to be a potential risk factor for cancer recurrence and survival in several cancer entities. Current studies addressing the relationship between BT, blood loss and BCR-free survival in prostate cancer patients are controversial and include only series with fairly small patient cohorts. MATERIALS AND METHODS: The data of 11,723 patients who underwent RP between 01/1992 and 08/2011 were analyzed. Cox regression analysis, including preoperative PSA level, pT stage, lymph node status, Gleason score, margin status, blood loss, transfusion rate (allogeneic or autologous), tested the relationship between blood loss, transfusion and BCR-free, metastasis-free and overall survival. Additionally, propensity score-matching analysis was performed to adjust differences in tumor characteristics. RESULTS: There was no statistically significant relationship between blood loss or BT and BCR-free, metastasis-free or overall survival. In multivariate analysis PSA level, pT stage, Gleason score, margin status and lymph node status were independent factors for a BCR (p < 0.0001). These results were identical after propensity score matching analysis, comparing patients with and without BT. CONCLUSIONS: This large-scale analysis revealed no correlation between blood loss, blood transfusion and oncological outcome in prostate cancer patients treated with RP. Therefore, the association between higher blood loss or transfusion rate and cancer recurrence as described in other surgical treated tumor entities seems to be irrelevant in prostate cancer patients.

Principle considerations for the risk assessment of sprayed consumer products.

In recent years, the official regulation of chemicals and chemical products has been intensified. Explicitly for spray products enhanced requirements to assess the consumers'/professionals' exposure to such product type have been introduced. In this regard the Aerosol-Dispensers-Directive (75/324/EEC) with obligation for marketing aerosol dispensers, and the Cosmetic-Products-Regulation (1223/2009/EC) which obliges the insurance of a safety assessment, have to be mentioned. Both enactments, similar to the REACH regulation (1907/2006/EC), require a robust chemical safety assessment. From such assessment, appropriate risk management measures may be identified to adequately control the risk of these chemicals/products to human health and the environment when used. Currently, the above-mentioned regulations lack the guidance on which data are needed for preparing a proper hazard analysis and safety assessment of spray products. Mandatory in the process of inhalation risk and safety assessment is the determination and quantification of the actual exposure to the spray product and more specifically, its ingredients. In this respect the current article, prepared by the European Aerosol Federation (FEA, Brussels) task force "Inhalation Toxicology", intends to introduce toxicological principles and the state of the art in currently available exposure models adapted for typical application scenarios. This review on current methodologies is intended to guide safety assessors to better estimate inhalation exposure by using the most relevant data.

[F(18)]-fluoroethylcholine combined in-line PET-CT scan for detection of lymph-node metastasis in high risk prostate cancer patients prior to radical prostatectomy: Preliminary results from a prospective histology-based study.

PURPOSE: To evaluate the diagnostic potential of PET/CT using ([F(18)]fluorethylcholine (FEC) for lymph node (LN) staging in high risk prostate cancer (PCa) patients prior to radical prostatectomy (RP). PATIENTS AND METHODS: Twenty patients with localised PCa and > or =20% LN risk according to a published nomogram were prospectively enrolled. FEC PET/CT was done minimum 14 d after prostate biopsy. Afterwards, open RP and extended pelvic LN dissection (ePLND) were performed. Clinical stage, Prostate Specific Antigen (PSA) and biopsy Gleason Grading were assessed and histopathological evaluation of the RP-specimens and dissected LN has been performed. The results from PET/CT were compared with LN metastasis according to their anatomical site. RESULTS: Overall, 285 LN have been removed with a mean number of 15 nodes per patient (7-26). Of the 20 patients, 9 men were LN positive (45%), which corresponds to 31 positive LN with a mean size of 7 mm (0.8-12 mm). Dissection of the obturator fossa, external iliac artery/vein and internal iliac artery/vein revealed 36%, 48% and 16% of positive LN, respectively. FEC PET/CT did not detect one single positive LN, thus was false-negative in 31 metastasis and true negative in 254 LN. CONCLUSION: Based on our results which confirmed experience from the previous studies, FEC PET/CT scan did not prove to be useful for LN staging in localised PCa prior to treatment and should thus not be applied if clinically occult metastatic disease is suspected.

Partin Tables cannot accurately predict the pathological stage at radical prostatectomy.

PURPOSE: The Partin Tables represent the most commonly used staging tool for radical prostatectomy (RP) candidates. The Partin Tables' predictions are used to guide the type (nerve preserving RP) and/or the extent (RP with wide resection) of RP. We examined the ability of the Partin Tables' predictions incorrectly assigning the stage at RP. METHODS: The testing of the Partin Tables (external validation) was based on 3105 patients treated with RP at a single European institution. Standard validation metrics were used (area under the receiver operating characteristics curve, AUC) to test the three endpoints predicted by the Partin Tables, namely the presence of extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node invasion (LNI). RESULTS: Ideal predictions are denoted with 100% accuracy vs. 50% for entirely random predictions. For the 2001 version of the Tables the accuracy defined by the AUC was 79.7, 77.8, and 73.0 for ECE, SVI, and LNI, respectively. For the 2007 version of the Tables the corresponding accuracy estimates were 79.8, 80.5, and 76.2. The relationship between predicted probabilities and observed rates was poor. CONCLUSION: The Partin Tables are meant to guide clinicians about the safety of nerve bundle preservation at RP, about the need for seminal vesicle resection or for lymphadenectomy. Therefore, the use of the Partin Tables predictions may significantly affect the type and/or the extent of RP. In their present format the Partin Tables are not accurate enough to influence the pre-operative decision making regarding the type or extent of RP.

[Technical aspects of nerve sparing during retropubic prostatectomy]. / Aspects techniques de la préservation nerveuse au cours de la prostatectomie rétropubienne.

Retropubic radical prostatectomy is the most commonly used therapeutic option for the treatment of clinically localized prostate cancer. An ongoing stage migration towards organ-confined cancers allows performing a nerve-sparing procedure in a growing number of patients. Key elements for achieving convincing functional results are a sphincter preserving Ligation of the distal part of Santorini's plexus and the subtle preparation of the neurovascular bundle. This article gives a detailed description of the operative technique. Furthermore, a strategy for patient selection and tumour selection for the indication of nerve-sparing radical prostatectomy (NSRP) is suggested.

Transition zone cancers undermine the predictive accuracy of Partin table stage predictions.

PURPOSE: The Partin tables represent the most widely used predictor of pathological stage in men with localized prostate cancer (PCa). The accuracy and performance of the tables have been tested across different populations. However, to our knowledge the potential limitations that may stem from differences between transition zone (TZ) and peripheral zone (PZ) prostate cancers has not been explored. We tested the predictive accuracy and performance of the Partin tables according to TZ vs PZ tumor predominance. MATERIALS AND METHODS: Preoperative serum prostate specific antigen, clinical stage and biopsy Gleason sum data on 1,990 patients treated with radical retropubic prostatectomy were used to define the 2001 Partin probabilities of organ confinement and seminal vesicle invasion (SVI). Data on 1,320 patients who underwent staging pelvic lymphadenectomy and radical retropubic prostatectomy were used to define the probabilities of lymph node invasion (LNI) and organ confined disease (OC). ROC area under the curve was used to assess the predictive accuracy of the 2001 Partin tables relative to observed extracapsular extension (ECE), SVI, LNI and OC. Performance characteristics for each prediction were explored graphically with local regression, nonparametric smoothing plots. Results were compared between 222 TZ cancers and 1,768 PZ cancers. RESULTS: The 1,990 radical retropubic prostatectomy specimens demonstrated ECE in 689 cases (34.6%) (TZ in 58 or 27.1% and PZ in 631 or 35.8%) and SVI in 224 (TZ in 13 or 6.1% and PZ in 211 or 11.9%). The 1,320 lymphadenectomy specimens demonstrated LNI in 56 cases (TZ in 2 or 0.9% and PZ in 54 or 4.6%). OC was found in 784 cases (59.4%) (TZ in 95 or 69.9% and PZ in 689 or 58.2%). Predictive accuracy was for ECE 76.4% (TZ 69.0% and PZ 77.2%), 78.0% for SVI (TZ 73.5% and PZ 78.3%), 78.6% for LNI (TZ 44.5% and PZ 79.9%) and 79.4% for OC (TZ 73.8% and PZ 80.0%). CONCLUSIONS: The biological tumor characteristics of TZ PCa differ from those of PZ PCa. These differences appear to undermine the accuracy of pathological stage predictions.

[Isoforms of free prostate-specific antigen]. / Isoformen des freien prostataspezifischen Antigens.

Detection of prostate-specific antigen remains the mainstay in the early detection of prostate cancer. A problem yet unsolved is the lack of specificity of this organ- but not cancer-specific marker, which generates subsequent, invasive procedures in a high number of patients without detecting prostate cancer. While the separate detection of free PSA and the ratio of free to total PSA has significantly improved specificity while maintaining high sensitivity, the number of patients undergoing unnecessary further diagnostics is still of concern. In this context, the evolving knowledge on isoforms of free PSA is a major focus of current research. Isoforms of free PSA are variants of free PSA that circulate, e.g., as precursor forms, internally cleaved variants of intact molecules, and are suggested to be either more associated with cancer or more with benign diseases. This article describes biochemical and clinical properties of the isoforms of free PSA.

[Serum markers for early detection and staging of prostate cancer. Status report on current and future markers]. / Serummarker in der Früherkennung und dem Staging des Prostatakarzinoms. Eine Bestandsaufnahme aktueller und zukünftiger Marker.

Prostate-specific antigen (PSA) is by far the most important tumor marker in urology and has revolutionized early detection, staging, treatment, and aftercare of prostate cancer [77]. Despite these merits, inadequacies have surfaced which prohibit characterizing PSA as a perfect tumor marker. First, PSA is not a marker for prostate cancer as such:benign prostate hyperplasia, prostatitis [40,69], or prostatic manipulation [66] influence serum concentrations of PSA and lead to biopsies that are costly and potentially harmful. In the entire PSA range between 4 and 10 ng/ml, the specificity at a sensitivity of 95% continues to remain unsatisfactory. Furthermore, 30-40% of all men develop prostate cancer, but only 9-11% a clinically significant tumor burden, and 2.5-4.3% of all men die from prostate cancer. The vast majority of all carcinomas are thus in significant in terms of the patient's life expectancy. PSA is incapable of differentiating these clinically insignificant carcinomas from significant ones. Finally, prevalence of prostate cancer is increasing due to higher life expectancy. On the other hand, particularly patients aged 50-70 years are the ones who develop an aggressive form of carcinoma and profit from early detection and treatment. The global term "total PSA"encompasses a heterogeneous blend of bound and free molecular forms of PSA. Complexed PSA represents the major form of total PSA. The smaller portion, free PSA, is enzymatically inactive. In addition, different isoforms of free PSA exist Recent studies provide support for clinical application of these isoforms for early detection of prostate cancer. Clinical measurement of human glandular kallikrein 2 (hK2) serves as a complementary marker to PSA for early detection of prostate cancer and constitutes a considerable improvement over PSA as a staging marker for clinically localized prostate cancer. This overview summarizes established and potentially new forms of PSA and hK2 for early detection and staging of prostate cancer.

[Transrectal ultrasound-guided punch biopsies of the prostate. Indication, technique, results, and complications]. / Ultraschallgesteuerte transrektale Prostatastanzbiopsien. Indikation, Technik, Ergebnisse und Komplikationen.

The golden standard for diagnosis of prostate cancer is transrectal ultrasound-guided systematic biopsy (TRUS-Bx). The optimal number of cylinders, sampling design, and indications for repeat biopsy are still in a state of flux. At the beginning of the 1980s, considerable doubts persisted regarding the benefit of ultrasound-guided punch biopsy for the diagnosis of prostate cancer. The examination on a chair with a fixed ultrasound head caused the patient substantial discomfort. Besides, in the pre-PSA era, most prostate carcinomas were detected by palpation and digitally guided biopsies were easily obtained. Indeed, the DRU procedure alone exhibited low sensitivity. Keetch et al. found that in only 25% of patients with abnormal palpatory findings and PSA between 4 and 20 ng/ml was a carcinoma revealed upon biopsy. On the other hand, patients with suspicious palpatory findings and proven malignancy suffered more frequently from locally advanced and systemic metastasizing tumors. As a result of restaging based on PSA, in most series more than half of the detected carcinomas presented normal palpatory findings. Ultrasound examination made precise imaging of zonal structures possible and thus offered the advantage of precision guidance for tissue biopsy despite lower sensitivity and specificity for diagnosis of suspicious lesions. Furthermore, calculation of prostate volume was possible. At the end of the 1980s, Hodge defined the systematic sextant biopsy as the first golden standard for early detection of prostate cancer. This meant the systematic removal of three punch cylinders from both lateral lobes of the prostate in the parasagittal midline at various levels (apex, middle, and base).

[Indications for and results of radical prostatectomy]. / Indikationstellung und Ergebnisse der radikalen Prostatektomie.

Radical prostatectomy represents the mainstay of therapy for clinically localized prostate cancer. The combination of diagnostic parameters such as PSA or biopsy Gleason grade in nomograms allows a safe prediction of pathologic stage and prognosis of the disease. Imaging techniques are useful in a subset of patients. International studies have proven a high cancer control rate of radical prostatectomy. A nerve-sparing modification of the operative technique does not compromise radicality of the procedure if patients are carefully selected. For this purpose simple and reliable algorithms are available.

[Can nomograms derived in the U.S. applied to German patients? A study about the validation of preoperative nomograms predicting the risk of recurrence after radical prostatectomy]. / Sind statistische Vorhersagemodelle aus den USA auf deutsche Patienten übertragbar? Eine Validierungstudie präoperativer Nomogramme zur Vorhersage des Rezidivrisikos nach radikaler Prostatektomie.

In patients suffering from prostate cancer, preoperative nomograms, which predict the risk of recurrence may provide a helpful tool in regard to the counselling and planning of an appropriate therapy. The best known nomograms were published by the Baylor College of Medicine, Houston and the Harvard Medical School, Boston. We investigated these nomograms derived in the U.S. when applied to German patients. Data from 1003 patients who underwent radical prostatectomy at the University-Hospital Hamburg were used for validation. Nomogram predictions of the probability for 2-years (Harvard nomogram) and 5-years (Kattan nomogram) freedom from PSA recurrence were compared with actual follow-up recurrence data using areas under the receiver-operating-characteristic curves (AUC). The recurrence free survival after 2 and 5 years was 78% and 58%, respectively. The AUC of the Harvard nomogram predicting 2-years probability of freedom from PSA recurrence was 0.80 vs. Kattan-Nomogram 5-years prediction of 0.83. Thereby, the Kattan nomogram showed a significant higher predictive accuracy (p=0.0274). For that reason preoperative nomograms derived in the U.S. can be applied to german patients. However, we would recommend the utilization of the Kattan nomogram due to its higher predictive accuracy.