New EAU/ASCO guideline recommendations on sentinel node biopsy for penile cancer and remaining challenges from a nuclear medicine perspective.

INTRODUCTION: The European Association of Urology (EAU) and the American Society of Clinical Oncology (ASCO) recently issued updated guidelines on penile cancer, emphasising dynamic sentinel node biopsy (DSNB) as the preferred method for surgical staging among patients with invasive penile tumours and no palpable inguinal lymphadenopathy. This paper outlines the rationale behind this new recommendation and describes remaining challenges, as well as strategies for promoting DSNB worldwide. MAIN TEXT: DSNB offers high diagnostic accuracy with the lowest postoperative complications compared to open or minimally invasive inguinal lymph node dissection (ILND), prompting its preference in the new guidelines. Nevertheless, despite its advantages, there are challenges hampering the widespread adoption of DSNB. This includes the false-negative rate associated with DSNB and the potential negative impact on patient outcome. To address this issue, improvements should be made in several areas, including refining the timing and interpretation of the lymphoscintigraphy and the single photon emission computed tomography/computed tomography images. In addition, the quantity of tracer employed and choice of the injection site for the radiopharmaceutical should be optimised. Finally, limiting the removal of nodes without tracer activity during surgery may help minimise complication rates. CONCLUSION: Over the years, DSNB has evolved significantly, related to the dedicated efforts and innovations in nuclear medicine and subsequent clinical studies validating its efficacy. It is now strongly recommended for surgical staging among selected penile cancer patients. To optimise DSNB further, multidisciplinary collaborative research is required to improve SN identification for better diagnostic accuracy and fewer complications.

Penile Sparing Surgery for Penile Cancer: A Multicenter International Retrospective Cohort.

PURPOSE: We evaluated recurrence outcomes of penile sparing surgery in what is to our knowledge the largest multicenter cohort of patients to date. MATERIALS AND METHODS: We retrospectively identified patients treated with penile sparing surgery from May 1990 to July 2016 at 5 tertiary referral institutions. Treatments consisted of circumcision, wide local excision, laser therapy with or without local excision, partial or total glansectomy and glans resurfacing. The study primary end point was local recurrence-free survival, defined from initial treatment to time of local recurrence and estimated with the Kaplan-Meier method. RESULTS: After applying study exclusion criteria 1,188 patients were included in analysis. During the median followup of 43.0 months there were 252 local recurrences (21.2%), of which 99 (39.3%) developed in year 1. Median time to local recurrence was 16.3 months and the 5-year local recurrence-free survival incidence was 73.6%. When stratified by stage, the 5-year local recurrence-free survival rate was 75.0%, 71.4% and 75.9% in Ta/Tis, T1 and T2 cases, respectively (log rank p = 0.748). Of the recurrences 58.3% were treated with repeat organ sparing procedures and the secondary partial (total) penectomy rate was 19.0%. Only margin status was significantly associated with local recurrence on multivariate analysis (p = 0.001). Study limitations included the retrospective design and the heterogeneous clinical approach. CONCLUSIONS: Penile sparing surgery can provide excellent local control for superficial penile tumors as well as for appropriately selected invasive lesions. Strict followup in the early postoperative period is highly recommended.

Peri-operative allogeneic blood transfusion does not adversely affect oncological outcomes after radical cystectomy for urinary bladder cancer: a propensity score-weighted European multicentre study.

OBJECTIVES: To evaluate the effect of peri-operative blood transfusion (PBT) on recurrence-free survival, overall survival, cancer-specific mortality and other-cause mortality in patients undergoing radical cystectomy (RC), using a contemporary European multicentre cohort. PATIENTS AND METHODS: The Prospective Multicentre Radical Cystectomy Series (PROMETRICS) includes data on 679 patients who underwent RC at 18 European tertiary care centres in 2011. The association between PBT and oncological survival outcomes was assessed using Kaplan-Meier, Cox regression and competing-risks analyses. Imbalances in clinicopathological features between patients receiving PBT vs those not receiving PBT were mitigated using conventional multivariable adjusting as well as inverse probability of treatment weighting (IPTW). RESULTS: Overall, 611 patients had complete information on PBT, and 315 (51.6%) received PBT. The two groups (PBT vs no PBT) differed significantly with respect to most clinicopathological features, including peri-operative blood loss: median (interquartile range [IQR]) 1000 (600-1500) mL vs 500 (400-800) mL (P < 0.001). Independent predictors of receipt of PBT in multivariable logistic regression analysis were female gender (odds ratio [OR] 5.05, 95% confidence interval [CI] 2.62-9.71; P < 0.001), body mass index (OR 0.91, 95% CI 0.87-0.95; P < 0.001), type of urinary diversion (OR 0.38, 95% CI 0.18-0.82; P = 0.013), blood loss (OR 1.32, 95% CI 1.23-1.40; P < 0.001), neoadjuvant chemotherapy (OR 2.62, 95% CI 1.37-5.00; P = 0.004), and ≥pT3 tumours (OR 1.59, 95% CI 1.02-2.48; P = 0.041). In 531 patients with complete data on survival outcomes, unweighted and unadjusted survival analyses showed worse overall survival, cancer-specific mortality and other-cause mortality rates for patients receiving PBT(P < 0.001, P = 0.017 and P = 0.001, respectively). After IPTW adjustment, those differences no longer held true. PBT was not associated with recurrence-free survival (hazard ratio [HR] 0.92, 95% CI 0.53-1.58; P = 0.8), overall survival (HR 1.06, 95% CI 0.55-2.05; P = 0.9), cancer-specific mortality (sub-HR 1.09, 95% CI 0.62-1.92; P = 0.8) and other-cause mortality (sub-HR 1.00, 95% CI 0.26-3.85; P > 0.9) in IPTW-adjusted Cox regression and competing-risks analyses. The same held true in conventional multivariable Cox and competing-risks analyses, where PBT could not be confirmed as a predictor of any given endpoint (all P values >0.05). CONCLUSION: The present results did not show an adverse effect of PBT on oncological outcomes after adjusting for baseline differences in patient characteristics.

Surgical management of penile carcinoma in situ: results from an international collaborative study and review of the literature.

OBJECTIVES: To evaluate recurrence after penile-sparing surgery (PSS) in the management of carcinoma in situ (CIS) of the penis in a large multicentre cohort of patients. PATIENTS AND METHODS: We identified consecutive patients from five major academic centres, treated between June 1986 and November 2014, who underwent PSS for pathologically proven penile CIS. The primary outcome was local recurrence-free survival (RFS), which was estimated using the Kaplan-Meier method. RESULTS: A total of 205 patients were identified. Treatment methods included circumcision, glansectomy, wide local excision, laser therapy and total glans resurfacing. Over a median (interquartile range [IQR]) follow-up of 40 (26-65.6) months, there were 48 local recurrences, with 45.8% occurring in the first year and 81.3% occurring by year 5. The majority of recurrences were observed in the laser group (58.3%). The median (IQR) time to local recurrence was 15.9 (5.66-26.14) months. The 1- 2- and 5-year RFS rates were 88.4, 85.6 and 75%, respectively, and the median (IQR) RFS time was 106.5 (80.2-132.2) months. CONCLUSIONS: Among patients with penile CIS selected for surgical management, durable responses at intermediate- to long-term follow-up were noted. For those with glandular CIS, glans resurfacing offered the best outcomes.

A Paratesticular Multicystic Tumor of the Tunica Vaginalis Testis as Rare Paratesticular Cystadenoma.

The cystadenoma of the testis and paratestis arising from an unequivocal oviduct-like structure, which is morphologically almost identical with those of the ovarian surface epithelium. These are very rare benign tumors of young adults. They present as asymptomatic cystic lesions. Bilateral paratesticular cystadenomas are strongly associated with von Hippel-Lindau syndrome and correlate with infertility. It is a neoplasm with low malignant potential. Most cystadenomas are benign but a few cases of malignant transformation of embryonic remnants have been reported in the appendix testis, including cases of adenocarcinoma, cystadenocarcinoma, and a low malignant müllerian-type epithelial tumor. We report the rare case of a 63-year-old man with a paratesticular multicystic cystadenoma of the male adnexa without association to von Hippel-Lindau disease.

Influence of Body Mass Index on Clinical Outcome Parameters, Complication Rate and Survival after Radical Cystectomy: Evidence from a Prospective European Multicentre Study.

Background/Aims/Objectives: To evaluate the influence of body mass index (BMI) on complications and oncological outcomes in patients undergoing radical cystectomy (RC). METHODS: Clinical and histopathological parameters of patients have been prospectively collected within the "PROspective MulticEnTer RadIcal Cystectomy Series 2011". BMI was categorized as normal weight (<25 kg/m2), overweight (≥25-29.9 kg/m2) and obesity (≥30 kg/m2). The association between BMI and clinical and histopathological endpoints was examined. Ordinal logistic regression models were applied to assess the influence of BMI on complication rate and survival. RESULTS: Data of 671 patients were eligible for final analysis. Of these patients, 26% (n = 175) showed obesity. No significant association of obesity on tumour stage, grade, lymph node metastasis, blood loss, type of urinary diversion and 90-day mortality rate was found. According to the -American Society of Anesthesiologists score, local lymph node (NT) stage and operative case load patients with higher BMI had significantly higher probabilities of severe complications 30 days after RC (p = 0.037). The overall survival rate of obese patients was superior to normal weight patients (p = 0.019). CONCLUSIONS: There is no evidence of correlation between obesity and worse oncological outcomes after RC. While obesity should not be a parameter to exclude patients from cystectomy, surgical settings need to be aware of higher short-term complication risks and obese patients should be counselled -accordingly.

Integrated Loss of miR-1/miR-101/miR-204 Discriminates Metastatic from Nonmetastatic Penile Carcinomas and Can Predict Patient Outcome.

PURPOSE: Penile squamous cell carcinoma is a rare but aggressive cancer. Little is known about pivotal events in tumor pathogenesis and metastasis. Lymph node metastasis is the prevailing prognostic factor while clinical detection in patients remains difficult. Our aim was to identify distinct miRNAs that are differentially expressed in metastatic vs nonmetastatic penile carcinoma, which may serve as diagnostic biomarkers for disease progression. MATERIALS AND METHODS: TaqMan® arrays and quantitative polymerase chain reaction were applied to analyze miRNA profiles in penile squamous cell carcinoma specimens and glans tissue from 24 patients. The prognostic value of deregulated miRNAs was analyzed using the Kaplan-Meier method. The Spearman test was applied to determine a potential linkage between distinctive miRNAs in individual patients. RESULTS: Loss of miR-1 (p = 0.0048), miR-101 (p = 0.0001) and miR-204 (p = 0.0004) in metastasizing tumors and associated metastases (p = 0.0151, 0.0019 and 0.0003, respectively) distinguished patients with metastatic and nonmetastatic penile squamous cell carcinoma. These 3 miRNAs showed a coherent expression pattern. Consistently, patients with low levels of all 3 miRNAs had worse survival (p = 0.03). We identified a coordinately regulated miRNA target hub that is over expressed in penile squamous cell carcinoma and associated with lymphovascular invasion. CONCLUSIONS: Our results provide evidence of a novel multiple miRNA based signature associated with lymph node metastasis and unfavorable prognosis of penile squamous cell carcinoma. The integrated loss of miR-1, miR-101 and miR-204 may predict the formation of metastases in penile cancer at an early stage.

Evidence from the 'PROspective MulticEnTer RadIcal Cystectomy Series 2011 (PROMETRICS 2011)' study: how are preoperative patient characteristics associated with urinary diversion type after radical cystectomy for bladder cancer?

PURPOSE: The aim of this study was to examine preoperative patients' characteristics associated with the urinary diversion (UD) type (continent vs. incontinent) after radical cystectomy (RC) and UD-associated postoperative complications. MATERIALS: In 2011, 679 bladder cancer patients underwent RC at 18 European tertiary care centers. Data were prospectively collected within the 'PROspective MulticEnTer RadIcal Cystectomy Series 2011' (PROMETRICS 2011). Logistic regression models assessed the impact of preoperative characteristics on UD type and evaluated diversion-related complication rates. RESULTS: Of 570 eligible patients, 28.8, 2.6, 59.3, and 9.3% received orthotopic neobladders, continent cutaneous pouches, ileal conduits, and ureterocutaneostomies, respectively. In multivariable analyses, female sex (odds ratio [OR] 3.9; p = 0.002), American Society of Anesthesiologists score ≥3 (OR 2.3; p = 0.02), an age-adjusted Charlson Comorbidity Index ≥3 (OR 4.1; p < 0.001), and a positive biopsy of the prostatic urethra in the last transurethral resection of the bladder prior to RC (OR 4.9; p = 0.03) were independently associated with incontinent UD. There were no significant differences in 30- and/or 90-day complication rates between the UD types. Perioperative transfusion rates and 90-day mortality were significantly associated with incontinent UD (p < 0.001, respectively). Limitations included the small sample size and a certain level of heterogeneity in the application of clinical pathways between the different participating centers. CONCLUSIONS: Within this prospective contemporary cohort of European RC patients treated at tertiary care centers, the majority of patients received an incontinent UD. Female sex and pre-existing comorbidities were associated with receiving an incontinent UD. The risk of overall complications did not vary according to UD type.

Predicting postoperative complications of inguinal lymph node dissection for penile cancer in an international multicentre cohort.

OBJECTIVES: To assess the potential complications associated with inguinal lymph node dissection (ILND) across international tertiary care referral centres, and to determine the prognostic factors that best predict the development of these complications. MATERIALS AND METHODS: A retrospective chart review was conducted across four international cancer centres. The study population of 327 patients underwent diagnostic/therapeutic ILND. The endpoint was the overall incidence of complications and their respective severity (major/minor). The Clavien-Dindo classification system was used to standardize the reporting of complications. RESULTS: A total of 181 patients (55.4%) had a postoperative complication, with minor complications in 119 cases (65.7%) and major in 62 (34.3%). The total number of lymph nodes removed was an independent predictor of experiencing any complication, while the median number of lymph nodes removed was an independent predictor of major complications. The American Joint Committee on Cancer stage was an independent predictor of all wound infections, while the patient's age, ILND with Sartorius flap transposition, and surgery performed before the year 2008 were independent predictors of major wound infections. CONCLUSIONS: This is the largest report of complication rates after ILND for squamous cell carcinoma of the penis and it shows that the majority of complications associated with ILND are minor and resolve without prolonged morbidity. Variables pertaining to the extent of disease burden have been found to be prognostic of increased postoperative morbidity.

Risk stratification for locoregional recurrence after radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: To externally validate the Christodouleas risk model incorporating pathological tumor stage, lymph node (LN) count and soft tissue surgical margin (STSM) and stratifying patients who develop locoregional recurrence (LR) after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). In addition, we aimed to generate a new model including established clinicopathological features that were absent in the Christodouleas risk model. METHODS: Prospectively assessed multicenter data from 565 patients undergoing RC for UCB in 2011 qualified for final analysis. For the purpose of external validation, risk group stratification according to Christodouleas was performed. Competing-risk models were calculated to compare the cumulative incidences of LR after RC. RESULTS: After a median follow-up of 25 months (interquartile range 19-29), the LR-rate was 11.5 %. The Christodouleas model showed a predictive accuracy of 83.2 % in our cohort. In multivariable competing-risk analysis, tumor stage ≥pT3 (HR 4.32, p < 0.001), positive STSM (HR 2.93, p = 0.005), lymphovascular invasion (HR 3.41, p < 0.001), the number of removed LNs <10 (HR 2.62, p < 0.001) and the administration of adjuvant chemotherapy (HR 0.40, p = 0.008) independently predicted the LR-rate. The resulting risk groups revealed significant differences in LR-rates after 24 months with 4.8 % for low-risk patients, 14.7 % for intermediate-risk patients and 38.9 % for high-risk patients (p < 0.001 for all), with a predictive accuracy of 85.6 %, respectively. CONCLUSIONS: The Christodouleas risk model has been successfully externally validated in the present prospective series. However, this analysis finds that overall model performance may be improved by incorporating lymphovascular invasion. After external validation of the newly proposed risk model, it may be used to identify patients who benefit from an adjuvant therapy and suit for inclusion in clinical trials.

Inverse relationship of Rho kinase and myosin-light chain kinase expression in the aging human detrusor smooth muscle.

BACKGROUND: Rho kinase (ROCK) and myosin-light chain kinase (MLCK) are key enzymes in smooth muscle contraction. Previous data have suggested that ROCK contribution to human detrusor contraction is increasing with age. Here, we have analyzed the transcriptional expression of Rho kinase isoforms (ROCK1 and ROCK2) as well as MLCK in the aging human detrusor smooth muscle obtained from resected tissue. METHODS: Small pieces of macroscopically healthy human detrusor smooth muscle (urothelium-free) were prepared for quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). Transcript expression (mRNA level) of the target genes ROCK1, ROCK2 and MLCK was normalized to three common reference genes (glyceraldehyde-3-phosphate dehydrogenase, ß-actin, phosphoglycerate kinase 1). RESULTS: We found that across all ages the expression level of ROCK (i.e. ROCK1 and ROCK2 together) was almost equal to that of MLCK in the human bladder. Further, ROCK2 showed a significantly higher expression level than ROCK1. Among all subjects, there was no significant correlation of any single target gene to age, but expression levels of ROCK and MLCK were inversely correlated. Moreover, the within-subject analysis revealed that the ROCK-to-MLCK ratio showed a significantly negative correlation to age. Thus, within a given subject, there is a relative ROCK down-regulation and concomitant MLCK up-regulation. CONCLUSIONS: Together with previous data in human detrusor specimens showing increased ROCK contribution to detrusor contraction, we speculate that the drop of the ROCK-to-MLCK ratio may occur as an attempt to compensate for the increased Rho kinase activity.

Ultraviolet matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for phosphopeptide analysis with a solidified ionic liquid matrix.

A solidified ionic liquid matrix (SILM) consisting of 3-aminoquinoline, α-cyano-4- hydroxycinnamic acid and ammonium dihydrogen phosphate combines the benefits of liquid and solid MALDI matrices and proves to be well suitable for phosphopeptide analysis using MALDI-MS in the low femtomole range. Desalting and buffer exchange that typically follow after phosphopeptide elution from metal oxide affinity chromatography (MOAC) materials can be omitted. Shifting the pH from acidic to basic during target preparation causes slow matrix crystallization and homogeneous embedding of the analyte molecules, forming a uniform preparation from which (phospho)peptides can be ionized in high yields over long periods of time. The novel combination of MOAC-based phosphopeptide enrichment with SILM preparation has been developed with commercially available standard phosphopeptides and with α-casein as phosphorylated standard protein. The applicability of the streamlined phosphopeptide analysis procedure to cell biological and clinical samples has been tested (i) using affinity-enriched endogenous TRIM28 from cell cultures and (ii) by analysis of a two-dimensional gel-separated protein spot from a bladder cancer sample.

Age-related decrease of adenosine-mediated relaxation in rat detrusor is a result of A2B receptor downregulation.

OBJECTIVES: To analyze the effect of adenosine on detrusor smooth muscle contraction and to assess age-related changes of adenosine function. METHODS: Sustained contractions were induced in young (10-30 days) and old (>60 days) rat detrusor muscle strips by application of 30 mmol/L K(+) and adenosine (0.1-400 µmol/L), which was either applied before raising the K(+) concentration or added to the precontracted muscle strip. Quantitative polymerase chain reaction analyses were used to study adenosine receptor expression in rat and human detrusor specimens. RESULTS: Pretreatment with adenosine dose-dependently reduced subsequent K(+) -induced contraction in detrusor muscle strips from young rats (half-maximal effect = 40 µmol/L). The residual depolarization-induced contraction strength in young tissue was significantly smaller than in tissue from old animals, showing a greater potency of adenosine in young detrusor samples. Likewise, the relaxing effect of adenosine on precontracted detrusor muscle was also significantly more pronounced in young compared with older detrusor. Quantitative polymerase chain reaction showed an age-related downregulation of the adenosine A2B receptor in rat detrusor tissues, which could be confirmed in human detrusor samples. Furthermore, relaxation of both K(+) -induced as well as carbachol-induced contraction by the specific A2B receptor agonist BAY 60-6583 was significantly more pronounced in young than in old rats. CONCLUSIONS: Adenosine powerfully counteracts contraction of detrusor smooth muscle, which is lost in the aging bladder. This is paralleled by an age-dependent transcriptional downregulation of the low-affinity A2B receptor. Hence, this might be pathophysiologically relevant in conditions of raised adenosine concentrations, such as hyperactive bladder contractility.

Salvage surgical resection for isolated locally recurrent inguinal lymph node metastasis of penile cancer: international study collaboration.

PURPOSE: We assessed the merit of performing salvage inguinal lymph node dissection in those infrequent cases of penile cancer with locally recurrent inguinal lymph node metastases in the absence of other suspected sites of disease. MATERIALS AND METHODS: A total of 20 patients were retrospectively identified as having undergone salvage inguinal lymph node dissection for locally recurrent penile cancer. Patients were previously treated with primary inguinal lymph node dissection with curative intent. At the time of salvage inguinal lymph node dissection, superficial and deep inguinal lymph node dissection was performed with resection outside of the standardized surgical template if there was inguinal recurrence outside of this region. RESULTS: All cases were primary penile squamous cell carcinomas. Median time to recurrence from initial inguinal lymph node dissection was 7.7 months (range 3.1 to 35.0). At salvage inguinal lymph node dissection a median of 3 lymph nodes (range 1 to 17) was resected with a median of 2 (range 1 to 7) nodes positive for malignancy. Median overall survival after salvage inguinal lymph node dissection was 10.1 months (95% CI 1.9-18.3) and median disease specific survival after salvage inguinal lymph node dissection was 16.4 months (95% CI 5.1-27.8). Of the initial 20 patients 9 have no evidence of disease (median followup 12.0 months, range 7.1 to 70.1). Postoperative complications developed in 11 patients, including wound infections in 6, postoperative severe (debilitating) lymphedema in 4 and seroma in 1. CONCLUSIONS: Salvage inguinal lymph node dissection is a potentially curative treatment in patients with penile cancer with locally recurrent inguinal lymph node metastases in the absence of occult disease. Patients undergoing such salvage surgery should be informed of the high likelihood of postoperative complications.

Age-dependent contribution of Rho kinase in carbachol-induced contraction of human detrusor smooth muscle in vitro.

AIM: Activation of muscarinic receptors on the detrusor smooth muscle is followed by contraction, which involves both myosin light chain kinase (MLCK) and Rho kinase (ROCK). The aim of this study was to determine the relative contributions of MLCK and ROCK to carbachol-induced contraction of human detrusor smooth muscle in vitro. METHODS: Detrusor smooth muscle strips were prepared from the macroscopically unaffected bladder wall of patients underwent cystectomy. The strips were fixed in an organ bath, and carbachol or KCl-induced isometric contractions were measured by force transducers. RESULTS: Addition of carbachol (0.4-4 µmol/L) into the bath induced concentration-dependent contractions of detrusor specimens, which was completely abolished by atropine (1 µmol/L). Pre-incubation of detrusor specimens with either the MLCK inhibitor ML-9 or the ROCK inhibitors HA1100 and Y-27632 (each at 10 µmol/L) significantly blocked carbachol-induced contractions as compared to the time-control experiments. Moreover, MLCK and ROCK inhibition were equally effective in reducing carbachol-induced contractions. The residual carbachol-induced contractions in the presence of both MLCK and ROCK inhibitors were significantly smaller than the contractions obtained when only one enzyme (either MLCK or ROCK) was inhibited, suggesting an additive effect of the two kinases. Interestingly, ROCK-mediated carbachol-induced contractions were positively correlated to the age of patients (r=o.52, P<0.05). CONCLUSION: Both MLCK and ROCK contribute to carbachol-induced contractions of human detrusor smooth muscle. ROCK inhibitors may be a new pharmacological approach to modulate human bladder hyperactivity.

AB0 incompatible kidney transplantation using unspecific immunoadsorption.

BACKGROUND: A protocol for ABO-incompatible kidney transplantation with antigen specific immunoadsorption, rituximab and conventional immunosuppression has been successfully implemented in many European centers. We report an alternative method for the elimination of isoagglutinins with a number of advantages - large amount of treatable plasma, parallel removal of other rejection-inducing antibodies, long operating life, favorable cost-benefit ratio. METHOD: We report our first successfully treated case of an ABO-incompatible living donor kidney transplantation using Immunoadsorption with Ig-TheraSorb. We performed 5 sessions preoperatively and one after transplantation. Per treatment session twice the calculated plasma volume (4400 ml in this patient) was treated. RESULTS: Per treatment session the IgM- isoagglutinin-titers were reduced from 1:16 to 1:1 and the IgG- isoagglutinin-titers from 1:32 to 1:2. There were no side effects and the procedure was well tolerated with good renal function 500 days post transplantation. CONCLUSION: Ig-TheraSorb-Immunoadsorption is an alternative method of elimination of harmful antibodies and it enables successful integration of ABO-incompatible transplantation into regular transplantation programs.

[Pain therapy in urology-overview of current S3 guideline recommendations]. / Schmerztherapie in der Urologie ­ Überblick zu aktuellen Empfehlungen der S3-Leitlinen.

Dealing efficiently with patients suffering from pain is a central medical task. Pain, as an important function in developmental physiology, warns against damage to the body caused by external noxious agents as well as internal malfunctions and requires special attention in modern medicine. Peri- and postoperative pain is known to have a negative influence on postoperative convalescence. Treatment of tumor-related pain represents another relevant challenge in uro-oncology and palliative medicine. The updated guideline on perioperative pain therapy and palliative medicine for patients with incurable diseases or cancer is dedicated to these two topics.

International case series of metastasis to penis.

Objectives: To evaluate clinical characteristics associated with survival in patients with metastases to the penis. Methods: After approval by the IRB, records of collaborating centres in Leuven, London, Rostock, Amsterdam and Tampa were screened for men presenting with metastatic disease to penis. Multivariate logistic regression analyses were used to identify covariables associated with survival. We analysed clinical data on 34 patients. Results: Primary sites were most frequently prostate (n = 14, 41%) and bladder (n = 9, 26%). Twenty-eight of 34 (82%) presented with metachronous penile metastases, and 11 (32%) patients had penile metastases as the sole metastatic site. Penile metastatic locations were most frequently in the corpora (n = 18; 53%). Seven (21%) patients with penile metastases had priapism on presentation. Systemic therapy was frequent and variable (chemotherapy n = 12; immunotherapy n = 5; hormones n = 3). Local management included either surgery (n = 10) or RT (n = 8). Twelve- and 24-month overall survival rate were 67% and 35%, respectively. No clinical parameter including primary histology, synchronous or metachronous metastases or priapism showed statistical survival benefit or detriment. Conclusion: Metastasis to penis arises most frequently from pelvic primaries. Priapism does not appear to correlate with survival in this large, well-defined series.

Neoadjuvant platinum-based chemotherapy and lymphadenectomy for penile cancer: an international, multi-institutional, real-world study.

INTRODUCTION: This study investigated the efficacy and safety of neoadjuvant chemotherapy for locally advance penile squamous cell carcinoma for which current evidence is lacking. METHODS: Included patients had locally advanced penile squamous cell carcinoma with clinical lymph node metastasis treated with at least 1 dose of neoadjuvant chemotherapy prior to planned consolidative lymphadenectomy. Objective response rates were assessed using Response Evaluation Criteria in Solid Tumors v1.1. The primary and secondary outcomes were overall survival and progression-free survival, estimated by the Kaplan-Meier method. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events v5.0. RESULTS: A total of 209 patients received neoadjuvant chemotherapy for locally advanced and clinically node-positive penile squamous cell carcinoma. The study population consisted of 7% of patients with stage II disease, 48% with stage III, and 45% with stage IV. Grade 2 treatment-related adverse events occurred in 35 (17%) patients, and no treatment-related mortality was observed. Of the patients, 201 (97%) completed planned consolidative lymphadenectomy. During follow-up, 106 (52.7%) patients expired, with a median overall survival of 37.0 months (95% confidence interval [CI] = 23.8 to 50.1 months) and median progression-free survival of 26.0 months (95% CI = 11.7 to 40.2 months). Objective response rate was 57.2%, with 87 (43.2%) having partial response and 28 (13.9%) having a complete response. Patients with objective response to neoadjuvant chemotherapy had a longer median overall survival (73.0 vs 17.0 months, P < .01) compared with those who did not. The lymph node pathologic complete response rate was 24.8% in the cohort. CONCLUSION: Neoadjuvant chemotherapy with lymphadenectomy for locally advanced penile squamous cell carcinoma is well tolerated and active to reduce the disease burden and improve long-term survival outcomes.

Management of Lymph Node-positive Penile Cancer: A Systematic Review.

CONTEXT: Lymph node (LN) involvement in penile cancer is associated with poor survival. Early diagnosis and management significantly impact survival, with multimodal treatment approaches often considered in advanced disease. OBJECTIVE: To assess the clinical effectiveness of treatment options available for the management of inguinal and pelvic lymphadenopathy in men with penile cancer. EVIDENCE ACQUISITION: EMBASE, MEDLINE, the Cochrane Database of Systematic Reviews, and other databases were searched from 1990 to July 2022. Randomised controlled trials (RCTs), nonrandomised comparative studies (NRCSs), and case series (CSs) were included. EVIDENCE SYNTHESIS: We identified 107 studies, involving 9582 patients from two RCTs, 28 NRCSs, and 77 CSs. The quality of evidence is considered poor. Surgery is the mainstay of LN disease management, with early inguinal LN dissection (ILND) associated with better outcomes. Videoendoscopic ILND may offer comparable survival outcomes to open ILND with lower wound-related morbidity. Ipsilateral pelvic LN dissection (PLND) in N2-3 cases improves overall survival in comparison to no pelvic surgery. Neoadjuvant chemotherapy in N2-3 disease showed a pathological complete response rate of 13% and an objective response rate of 51%. Adjuvant radiotherapy may benefit pN2-3 but not pN1 disease. Adjuvant chemoradiotherapy may provide a small survival benefit in N3 disease. Adjuvant radiotherapy and chemotherapy improve outcomes after PLND for pelvic LN metastases. CONCLUSIONS: Early LND improves survival in nodal disease in penile cancer. Multimodal treatments may provide additional benefit in pN2-3 cases; however, data are limited. Therefore, individualised management of patients with nodal disease should be discussed in a multidisciplinary team setting. PATIENT SUMMARY: Spread of penile cancer to the lymph nodes is best managed with surgery, which improves survival and has curative potential. Supplementary treatment, including the use of chemotherapy and/or radiotherapy, may further improve survival in advanced disease. Patients with penile cancer with lymph node involvement should be treated by a multidisciplinary team.