Cisplatin eligibility in the neoadjuvant setting of patients with muscle-invasive bladder cancer undergoing radical cystectomy.

BACKGROUND: To examine the agreement of different calculated estimated glomerular filtration rate (eGFR) formulas and measured creatinine clearance (CrCI) at the primary diagnosis of muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We performed a multicenter analysis of patients with MIBC, treated with cisplatin-based neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), or with RC alone, between 2011 and 2021. Baseline eGFR was computed using 4 calculated serum equations including Cockcroft-Gault (CG), MDRD, CKD-EPI 2009, and race-free CKD-EPI 2021. To examine the association between calculated eGFR and measured CrCI, subgroup analyses were performed among patients in whom measured 24-hour urine CrCl was determined. Cisplatin-ineligibility was defined as CrCI and/or eGFR < 60 mL/minute per 1.73 m2. RESULTS: Of 956 patients, 30.0%, 33.3%, 31.9%, and 27.7% were found to be cisplatin-ineligible by the CG, MDRD, CKD-EPI, and race-free CKD-EPI equations (P = .052). The concordance between calculated eGFR formulas was rated substantial (Cohen's kappa (k): 0.66-0.95). Among the subgroup (n = 245) with measured CrCl, 37 (15.1%) patients had a CrCI less than 60 mL/minute. Concordance between measured CrCl and calculated eGFR was poor (ĸ: 0.29-0.40). All calculated eGFR formulas markedly underestimated the measured CrCI. Specifically, 78%-87.5% of patients with a calculated eGFR between 40 and 59 mL/minute exhibited a measured CrCI ≥ 60 mL/minute. CONCLUSIONS: Comparing calculated eGFR formulas, similar percentages of patients with MIBC were deemed cisplatin-ineligible. However, a significant number of patients could be upgraded by being cisplatin-fit based on measured CrCI, particularly when the calculated eGFR was falling within the gray range of 40-59 mL/minute.

Prognostic Value of the De Ritis Ratio for Overall Survival in Patients with Metastatic Castration-Resistant Prostate Cancer Undergoing [177Lu]Lu-PSMA-617 Radioligand Therapy.

The De Ritis ratio (=aspartate transaminase/alanine transaminase) has shown prognostic value in different cancer types. This is the first such analysis in prostate cancer patients undergoing radioligand therapy (RLT) with [177Lu]Lu-PSMA-617. This retrospective monocentric analysis included 91 patients with a median of 3 RLT cycles (range 1-6) and median cumulative activity of 17.3 GBq. Univariable Cox regression regarding overall survival (OS) included age, different types of previous treatment, metastatic patterns and different laboratory parameters before RLT. Based on multivariable Cox regression, a prognostic score was derived. Seventy-two patients (79%) died (median follow-up in survivors: 19.8 months). A higher number of previous chemotherapy lines, the presence of liver metastases, brain metastases, a higher tumor load on PSMA-PET, a higher prostate-specific antigen (PSA) level, lower red blood cell count, lower hemoglobin, higher neutrophil-lymphocyte ratio and higher De Ritis ratio were associated with shorter OS (each p < 0.05). In multivariable Cox, a higher number of chemotherapy lines (range, 0-2; p = 0.036), brain metastases (p < 0.001), higher PSA (p = 0.004) and higher De Ritis ratio before RLT (hazard ratio, 1.27 per unit increase; p = 0.023) remained significant. This prognostic score separated five groups with a significantly different median OS ranging from 4.9 to 28.1 months (log-rank test, p < 0.001). If validated independently, the De Ritis ratio could enhance multifactorial models for OS after RLT.

Explorative analysis of a score predicting the therapy response of patients with metastatic, castration resistant prostate cancer undergoing radioligand therapy with 177Lu-labeled prostate-specific membrane antigen.

OBJECTIVE: Up to 60% of patients with metastatic, castration-resistant prostate cancer (mCRPC) treated with 177Lu prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) achieves a partial biochemical response with a decrease of > 50% in prostate-specific antigen (PSA) levels. The remaining fractions, however, do not respond to RLT. The aim of this explorative analysis was to identify pre-therapeutic factors for the prediction of response. METHODS: 46 patients [age = 68 years (50-87)] with mCRPC who consecutively underwent RLT with 177Lu PSMA [median applied activity = 6 GBq (2.9-6.2)] were included and analysed retrospectively. The association of different clinical and laboratory factors and parameters from pre-therapeutic 68Ga PSMA positron emission tomography (PET) with the outcome of RLT was tested (Fisher's test). Outcome was defined as PSA changes 8 weeks after second RLT [partial response (PR), PSA decrease > 50%; progressive disease (PD), PSA increase ≥ 25%; stable disease (SD), others]. Significant predictive factors were combined in a predictive score. RESULTS: 30% showed a post-treatment PR (median 73% PSA decrease), 35% SD (median 17% PSA decrease) and 35% PD (median 42% PSA increase). Significant predictors for PD were alkaline phosphatase (ALP) > 135 U/l (p = 0.002), PSA > 200 ng/ml (p = 0.036), and maximum standardized uptake value (SUVmax) of the "hottest lesion" in pre-therapeutic PET < 45 (p = 0.005). The predictive score including PSA, ALP and SUVmax could separate 2 distinct groups of patients: ≤ 2 predictive factors (19% PD) and 3 predictive factors (90% PD). CONCLUSION: The presented predictive score allowed a pre-therapeutic estimate of the expected response to 2 cycles of RLT. As our study was retrospective, prospective trials are needed for validation.

Oncological outcomes, quality of life outcomes and complications of partial cystectomy for selected cases of muscle-invasive bladder cancer.

To evaluate the oncological results, associated complications, and postoperative health-related quality of life (HR-QoL) in patients treated with partial cystectomy (PC) for muscle-invasive bladder cancer (MIBC). 27 patients who underwent open PC for cT2 MIBC were included. A simple Cox's proportional hazards regression model was used to assess the association of several potential prognostic factors with survival. Postoperative HR-QoL was assessed with the EORTC (European Organisation for the Research and Treatment of Cancer) QLQ-C30 questionnaire version 3.0. Final pathological tumour stages in PC specimen were: pT0: 18.5%, non-MIBC: 3.7%, MIBC: 74.1%, pCIS: 14.8%. Estimated 5-year overall- and progression-free survival rates were 53.7% and 62.1%. Five (18.5%) patients experienced local recurrence with MIBC. Overall, the salvage cystectomy rate was 18.5%. The 90-day mortality rate was 0%. Significant risk factors for progression-free survival were vascular invasion (HR 5.33) and tumour multilocularity (HR 4.5) in the PC specimen, and a ureteric reimplantation during PC (HR 4.53). The rates of intraoperative complications, 30- and 90-day major complications were 7.4%, respectively and 14.8% for overall long-term complications. Postoperatively, median (IQR) global health status and QoL in our PC cohort was 79.2 (52.1-97.9). Open PC can provide adequate cancer control of MIBC with good HR-QoL in highly selected cases. Open PC can lead to long-term bladder preservation and shows an acceptable rate of severe perioperative complications, even in highly comorbid patients.

Retrospective Analysis of Fifth-Line Targeted Therapy Efficacy in Patients with Metastatic Renal Cell Carcinoma.

OBJECTIVES: Current evidence of sequence-targeted therapy (TT) for patients with metastatic renal cell carcinoma (mRCC) beyond fourth-line is sparse. The aim of this study was to describe the efficacy and toxicity of fifth-line TT in patients with mRCC. METHODS: Out of 406 patients treated in first-line, 25 patients (6.16%) with more than 4 lines of TT were retrospectively reviewed at a German academic high-volume cancer center. Response was assessed by the use of standard Response Evaluation Criteria in Solid Tumors version 1.0, and toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 3.0. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazard models were applied to explore predictors of PFS and OS in univariable and multivariable analyses. RESULTS: Disease control rate for fifth-line treatment was 20%. Median OS from the beginning of first-line therapy was 50.2 months (IQR (interquartile range) 38.9-76.7). Median OS from the time of initiation of fifth-line therapy was 6.2 months (IQR 3.1-23.8). Median PFS for fifth-line TT was 4.1 months (IQR 1.81-9.07) and did not correlate to treatment response in first-line TT. CONCLUSIONS: Highly selected patients might benefit from fifth-line treatment independently from treatment response in first-line TT.

Urolithiasis in Renal Allografts: Complications and Outcomes.

OBJECTIVES: Urinary calculi rarely occur in renal transplant. However, because of peculiarities shown with renal allografts, a prudent approach is necessary to prevent further complications or even graft failure. There are no well-established guidelines for uro?ithiasis in renal grafts regarding adequate therapy selection. In the present article, different therapeutic interventions are discussed, including in 1 case a pyelovesicostomy as an uncommon intervention. MATERIALS AND METHODS: We retrospectively reviewed data of 1115 patients who underwent renal transplant between January 2002 and December 2014 for urolithiasis in different databases. RESULTS: Eight patients in our study group formed urinary calculi after renal transplant. Only 5 patients were included, with incidence rate of 0.45%, since 3 patients received transplants elsewhere. Time between transplant and diagnosis ranged from 2 to 98 months. Extracorporeal shock wave lithotripsy (50%) was the most common intervention, followed by ureterorenoscopy (29%) and percutaneous nephrolithotomy (16%). One patient required 20 interventions due to recurrent urinary stones, necessitating an alternative procedure. In this case, a pyelovesicostomy was performed (an uncommon and previously not performed procedure for urolithiasis after renal graft). All patients were stone free at last follow-up. CONCLUSIONS: In contrast to other studies, renal stones from donors were not observed. Treatment took into account stone size, number, and localization, similar to the approach in the general population. However, alternative procedures, especially pyelovesicostomy, could be considered in patients with recurrent urolithiasis and who require multiple interventions.

Prevalence of Late-Onset Hypogonadism in Men with Localized and Metastatic Renal Cell Carcinoma.

BACKGROUND: Cancer-related fatigue is a common symptom in patients with renal cell carcinoma (RCC) and can be similar to the fatigue found in late-onset hypogonadism (LOH). The aim of this study was to investigate the prevalence of LOH in patients with localized RCC (loRCC) and metastatic RCC (mRCC) disease under targeted therapy (TT) and compare the results to findings of epidemiologic studies. METHODS: A total of 51 mRCC patients under TT and 33 patients with loRCC undergoing nephrectomy were included. Total testosterone (tT) levels and clinical signs of LOH were recorded (testicular volume, body-mass index (BMI), hip-to-waist ratio, International Index of Erectile Function, IIEF-5, Androgen Deficiency in the Aging Male, ADAM, and quality of life questionnaire-C30). LOH was defined according to current guidelines. RESULTS: Morning tT and calculated free testosterone levels showed no significant difference in patients with mRCC and loRCC (p = 0.551 and p = 0.430). A significant difference was found for clinical signs and symptoms including the ADAM score (p = 0.003), hip-to-waist ratio (p = 0.017) and testicular volume (p < 0.001). IIEF-5 score and BMI were not significantly different. The prevalence of LOH according to the current EAU definition was 13.7 and 15.2% for the mRCC and loRCC cohort, respectively (p = 0.302). CONCLUSIONS: LOH was present in a significant proportion of RCC patients. Prevalence rates of LOH were higher in patients with RCC compared to patients without cancer.

Efficacy of fourth-line targeted therapy in patients with metastatic renal cell carcinoma: a retrospective analysis.

INTRODUCTION: Evidence for sequencing targeted therapy (TT) in patients with metastatic renal cell carcinoma (mRCC) beyond third line is limited. Treatment decisions for these sequence options are largely based on individual preferences and experience. The aim of this study was to describe the efficacy and toxicity of fourth-line TT. MATERIALS AND METHODS: We retrospectively reviewed patients treated with fourth-line TT for mRCC after failure of previous treatment lines at a German academic high-volume center. Out of 406 patients treated in first line, 56 patients (14.8 %) were identified with more than three lines of TT. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazards models were applied to explore predictors of PFS and OS in uni- and multivariable analysis. RESULTS: For the fourth-line treatment, disease control rate was 35.7 %. Median OS from beginning of first-line therapy was 47.4 months (IQR 31.0-76.5). Primary resistance at first-line TT, metastatic disease at initial diagnosis and an intermediate MSKCC score were independent predictors of shorter OS from start of first-line TT. Median OS from the time of initiation of fourth-line therapy was 10.5 months (IQR 5.6-22.6). The corresponding median PFS for fourth-line TT was 3.2 months (IQR 1.6-8.0) and was not correlated with treatment response in first-line TT. The rate of toxicity-induced treatment termination was 16.1 %. Limitations are the retrospective and unicentric design with a limited number of patients. CONCLUSIONS: Patients might benefit from subsequent treatment lines independently from treatment response in first line.

Urinary calprotectin: a new diagnostic marker in urothelial carcinoma of the bladder.

PURPOSE: Recently, a proteomic study of sera from patients with bladder cancer identified S100A8 and S100A9 as tumor-associated proteins. The present cross-sectional study investigates whether calprotectin, the heterodimer of S100A8/S100A9 may serve as a urinary biomarker for the detection of urothelial bladder cancer. METHODS: Urinary calprotectin concentrations were assessed in a population of 181 subjects including 46 cases of bladder cancer. 41 cases of renal cell cancer, 54 cases of prostate cancer, and 40 healthy subjects served as control. Acute kidney injury, urinary tract infection, previous BCG-treatment and secondary transurethral resection of the bladder tumor were defined as exclusion criteria. Assessment was performed by enzyme-linked immunosorbent assay and immunohistochemistry detecting calprotectin. RESULTS: Median calprotectin concentrations (ng/ml) were significantly higher in patients with bladder cancer than in healthy controls (522.3 vs. 51.0, p < 0.001), renal cell cancer (90.4, p < 0.001), and prostate cancer (71.8, p < 0.001). In urothelial carcinoma prominent immunostaining occurred in a subset of tumor cells and in infiltrating myeloid cells. Receiver operating characteristic analysis provided an area under the curve of 0.88 for the differentiation of bladder cancer and healthy control. A cut-off value of 140 ng/ml (determined by Youden's index) resulted in sensitivity and specificity values of 80.4 and 92.5 %. Low grade tumors were associated with significantly lower calprotectin concentrations than high grade tumors (351.9 vs. 1635.2 ng/ml, p = 0.004). CONCLUSIONS: Urothelial malignancies are associated with highly increased concentrations of calprotecin in the urine. In absence of renal failure and pyuria, calprotectin constitutes a promising biomarker for the detection of bladder cancer.

Categories of response to first line vascular endothelial growth factor receptor targeted therapy and overall survival in patients with metastatic renal cell carcinoma.

INTRODUCTION: Sequential use of targeted therapy (TT) has improved overall survival (OS) of patients with metastatic renal cell carcinoma (mRCC). The value of objective response (OR) as compared to stable disease (SD) is unclear. We aimed to investigate OR of first-line TT and its impact on OS. MATERIAL AND METHODS: Retrospective analysis of OS among 331 mRCC patients with a first-line assessment according to RECIST 1.0. Characteristics between objective responders (complete response [CR] or partial remission [PR]), patients with SD and non-responders (progressive disease [PD] and toxicity [Tox]) were compared with the Chi-square test and the Kruskal-Wallis test. Kaplan-Meier analysis of OS and progression-free survival (PFS). Cox model analysis of Predictors of OS . RESULTS: Best response was CR, PR, SD, PD and Tox in 9 (2.7%), 61 (18.4%), 167 (50.5%), 80 (24.2%) and 14 (4.2%) patients respectively resulting in an OR rate of 21%. Median OS in months: CR 63.2; PR 37.6; SD 35.9; PD 14.6; TOX 22.5 (p<0.0001). Median PFS for responders was 14.8, 11.5 for patients with SD and 2.5 for non-responders (p<0.0001). Similarly median OS was 38.7, 35.9 and 15.5 (p<0.00001). Primary resistance and a first-line PFS <6months were the strongest independent predictors of OS. The achievement of OR as compared to SD did not impact OS. CONCLUSIONS: In our cohort of unselected patients OR was not associated with superior OS as compared to SD.

Retrospective comparison of triple-sequence therapies in metastatic renal cell carcinoma.

BACKGROUND: The optimal sequence of targeted therapy in patients with metastatic renal cell carcinoma (mRCC) has not been defined. OBJECTIVE: To describe the efficacy and toxicity of the most common sequences of targeted therapy, namely, receptor tyrosine kinase inhibitor (rTKI) and mammalian target of rapamycin inhibitor (mTORi), in different sequences after failure of vascular endothelial growth factor signaling inhibition (VEGFi) in first-line therapy. DESIGN, SETTING AND PARTICIPANTS: Retrospective study of 103 patients receiving VEGFi-rTKI-mTORi (n=62) or VEGFi-mTORi-rTKI (n=41) at two German academic centers. INTERVENTION: Sequence of systemic targeted treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Response was assessed using Response Evaluation Criteria in Solid Tumors 1.0 and toxicity was measured using the Common Terminology Criteria for Adverse Events 3.0. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Predictors of survival were analyzed using Cox regression. RESULTS AND LIMITATIONS: Sequence groups did not significantly differ by patient characteristics and response rate following first VEGFi failure. Median PFS for second-line therapy was 4.6 mo (95% confidence interval [CI], 3.8-5.4), 4.1 mo (95% CI, 3.4-4.9) for rTKI treatment, and 5.4 mo (95% CI, 2.7-8.1) for mTORi treatment (p=0.400). No differences in PFS were observed among third-line therapy groups (3.6 mo for mTORi; 3.7 mo for rTKI). Treatment duration following first VEGFi failure (combined second- and third-line PFS) was 10.0 mo for VEGFi-rTKI-mTORi and 12.2 mo for VEGFi-mTORi-rTKI (p=0.103). No significant differences in OS were observed among sequence groups (33.7 mo [95% CI, 30.4-37.1] for VEGFi-rTKI-mTORi; 38.7 mo [95% CI, 24.4-52.9] for VEGFi-mTORi-rTKI). Primary resistance on first-line therapy was an independent predictor of OS, but type of sequence was not. Limitations are the retrospective design and limited numbers of cases. CONCLUSIONS: The sequence therapies VEGFi-mTORi-rTKI and VEGFi-rTKI-mTORi with the currently available agents appear to be equally efficacious in terms of PFS, OS, and response rate, with no apparent beneficial effect with an early use of mTORi.

Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Over the past decade, minimally invasive laparoscopic radical prostatectomy and more recently robot-assisted laparoscopic prostatectomy have been introduced and have proven equally effective compared with open surgery in terms of mid-term cancer control and complication rates. Because long-term data is lacking, open prostatectomy is still considered the 'gold standard' by some authors, who argue that minimally invasive approaches have to measure up to the excellent long-term results of open surgery. This study represents one of the largest series (1845 patients) of minimally invasive radical prostatectomy with extended follow-up (11.3 years) and detailed data on oncological outcome and postoperative incontinence. It therefore supplies previously lacking information on these details for minimally invasive prostate surgery and provides important information for patient counselling. OBJECTIVE: • To investigate biochemical recurrence (BCR) rates and data on postoperative incontinence in a large laparoscopic radical prostatectomy (LRP) cohort with extended follow-up. MATERIALS AND METHODS: • BCR and independent predictors of BCR were identified using Kaplan-Meier and Cox regression analysis of 1845 patients who underwent LRP from 1999 to 2007. • Urinary incontinence was evaluated by pads per day and stratified as follows: 0-1 pad: no incontinence; 2-3 pads: mild incontinence; and ≥ 3 pads: severe incontinence. RESULTS: • Organ-confined disease, extraprostatic extension, seminal vesicle invasion and lymph node metastasis were present in 71.3%, 20.5%, 6.7% and 3.2% of patients, respectively. The positive surgical margin rate was 29.2%. • Postoperatively, 74.9% of the patients were continent, while 9.2% had mild and 15.9% severe incontinence. • The mean follow-up was 5 years with a maximum follow-up of 11.3 years. • There were 51 overall deaths and six deaths from prostate cancer. The 5-year, 8-year and 10-year BCR-free survival rates were 83.9%, 78.6% and 75.6%, respectively. • On univariate analyses preoperative D'Amico risk classification, pathological tumour stage, postoperative Gleason sum and surgical margin status were predictors of BCR (P < 0.001). • On multivariable analysis, D'Amico classification, Gleason sum (P < 0.001), postoperative tumour stage (P < 0.001), nodal status (P < 0.001) and surgical margin status (P = 0.002) were independent predictors of BCR. CONCLUSIONS: • LRP offers excellent long-term functional and oncological results with a low incidence of BCR for patients with localized disease. • These results could be used for patient counselling before robot-assisted laparascopic prostatectomy (RALP) until long-term follow-up data for RALP is available.

Laparoscopic and open postchemotherapy retroperitoneal lymph node dissection in patients with advanced testicular cancer--a single center analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: L-PCLND represents a safe surgical option for well selected patients at an experienced center.

Morbidity and Quality of Life in Bladder Cancer Patients following Cystectomy and Urinary Diversion: A Single-Institution Comparison of Ileal Conduit versus Orthotopic Neobladder.

Objective. To evaluate and compare noncontinent and continent urinary diversion after radical cystectomy in patients with bladder cancer. Methods. A total of 301 patients submitted to radical cystectomy at the Charité-University Hospital Berlin from 1993 to 2007 including 146 with an ileal conduit and 115 with an ileal neobladder. Clinical and pathological data as well as oncological outcome were retrospectively analyzed and compared. Quality of life was analyzed using the EORTC QLQ-C30 and BLM30 questionnaires. Results. 69.1% and 69.6% of all patients who received an ileal conduit and ileal neobladder, respectively, developed early complications. The two groups differed significantly concerning the occurrence of postoperative ileus (P = 0.02) favoring patients who received an ileal conduit but not with regard to any other early-onset complication evaluated. Patients with ileal neobladder had a significantly better global health status and quality of life (P = 0.02), better physical functioning (P = 0.02), but also a higher rate of diarrhoea (P = 0.004). Conclusion. Cystectomy with any type of diversion remains a complication-prone surgery. Even if the patient groups are not homogeneous in all respects, there are many arguments in favor of the ileal neobladder as the urinary diversion of choice.

Selective lymph node dissection for castration-resistant prostate cancer.

BACKGROUND: No relevant data have been published on the impact of retroperitoneal lymph node dissection (LND) on clinical outcome in patients with castration-resistant prostate cancer. METHODS: We retrospectively studied the records of 6 patients with lymph node metastases from castration-resistant prostate cancer who underwent a retroperitoneal LND between 2005 and 2010. Complication rate and clinical outcome were examined. RESULTS: Mean patient age was 69.2 (63-81) years. Primary therapy was radical prostatectomy, radiation therapy, or pelvic LND and androgen deprivation in 3, 2 and 1 cases, respectively. Mean prostate-specific antigen (PSA) at LND was 37.6 (20.3-139) ng/dl. LND was performed as a modified unilateral (n = 3), bilateral (n = 1) and bilateral extended (n = 2) approach with a median lymph node density of 0.739 (0.111-1). Preoperative Charlson index was 0 (n = 3) or 1 (n = 3). No intra- or postoperative complications occurred. The average postoperative decline of PSA was 39.3% (-99.4 to +31.3). Differences between mean pre- and postoperative PSA velocities and densities were 23.9 ng/ml/year and 11.2 months, respectively (p = 0.24 and p = 0.40). Four patients (67%) developed bone metastases after a mean period of 23.5 (5-58) months. Median bone metastases-free survival was 15.5 months and median overall survival after LND was 31.7 months on Kaplan-Meier analysis. CONCLUSIONS: A selective LND in castration-resistant prostate cancer patients could be safely performed. A positive effect on the PSA and PSA kinetics was accomplished for the majority of patients. This new surgical approach represents an alternative treatment option in the palliative setting of prostate cancer patients and could delay toxic systemic therapy up to 12 months.

Sucrose acceptance and different forms of associative learning of the honey bee (apis mellifera L.) in the field and laboratory.

The experiments analyze different forms of learning and 24-h retention in the field and in the laboratory in bees that accept sucrose with either low (/=30% or >/=50%) concentrations. In the field we studied color learning at a food site and at the hive entrance. In the laboratory olfactory conditioning of the proboscis extension response (PER) was examined. In the color learning protocol at a feeder, bees with low sucrose acceptance thresholds (/=50%). Retention after 24 h is significantly different between the two groups of bees and the choice reactions converge. Bees with low and high acceptance thresholds in the field show no differences in the sucrose sensitivity PER tests in the laboratory. Acceptance thresholds in the field are thus a more sensitive behavioral measure than PER responsiveness in the laboratory. Bees with low acceptance thresholds show significantly better acquisition and 24-h retention in olfactory learning in the laboratory compared to bees with high thresholds. In the learning protocol at the hive entrance bees learn without sucrose reward that a color cue signals an open entrance. In this experiment, bees with high sucrose acceptance thresholds showed significantly better learning and reversal learning than bees with low thresholds. These results demonstrate that sucrose acceptance thresholds affect only those forms of learning in which sucrose serves as the reward. The results also show that foraging behavior in the field is a good predictor for learning behavior in the field and in the laboratory.