The impact of health care on outcomes of suspected testicular torsion: results from the GRAND study.

BACKGROUND: Suspicion of testicular torsion represents a urological emergency, necessitating immediate surgery. Comprehensive data on the current trends and perioperative outcomes regarding surgical exploration are sparse. Therefore, we utilized nationwide data on the prevalence and results of this surgery, aiming to provide evidence on this matter. METHODS: We assessed the GeRmAn Nationwide inpatient Data (GRAND) from 2005 to 2021, provided by the Research Data Center of the Federal Bureau of Statistics. We performed multiple regression analyses to evaluate the perioperative outcomes (length of hospital stay, transfusion, and surgical wound infection) after surgical exploration due to suspected testicular torsion based on both the outcome of surgery (orchiectomy, detorsion with preservation of the testicle, and no testicular torsion) and on the department of operation (urological versus non-urological). RESULTS: A total of 81,899 males underwent surgical exploration due to suspected testicular torsion in Germany from 2005 to 2021. Of them, 11,725 (14%) underwent orchiectomy, 30,765 (38%) detorsion with preservation of the testicle and subsequent orchidopexy, and 39,409 (48%) presented no testicular torsion. Orchiectomy was significantly associated with longer length of hospital stay (day difference of 1.4 days, 95%CI: 1.3-1.4, p < 0.001), higher odds of transfusion (1.8, 95% CI: 1.2-2.6, p = 0.002) and surgical wound infections (1.8, 95%CI: 1.4-2.3, p < 0.001) compared to no testicular torsion. The proportion of patients undergoing orchiectomy was significantly lower in urological departments (14%) versus non-urological departments (16%) and the proportion of patients undergoing preservation of testicle after detorsion was significantly higher in urological departments (38%) versus non-urological departments (37%), p < 0.001. Patients undergoing treatment in a urological department were discharged earlier and presented lower odds of transfusion and surgical wound infection (p < 0.001) compared to patients undergoing treatment in a non-urological department. CONCLUSIONS: Nearly half of patients who underwent surgery for suspected testicular torsion did not have intraoperatively the condition confirmed. Patients treated in urological departments had significantly better perioperative outcomes compared to those treated in non-urological departments. Therefore, we advise to refer patients to urological treatment as early as possible.

The prognostic value of perioperative platelet and leukocyte values in patients undergoing radical cystectomy: a prospective long-term cohort study.

INTRODUCTION: Studies assessing the impact of preoperative and first-day postoperative values of leukocytes, thrombocytes, and platelet/leukocyte ratio (PLR) after radical cystectomy (RC) are sparse. We aimed to assess the impact of these factors on long-term survival after RC. METHODS: An analysis of patients undergoing open RC from 2004 to 2023 at our center was performed. Leukocytosis was defined as ≥8,000 leukocytes/µL and thrombocytosis as ≥400,000 thrombocytes/µL. Similarly, the cutoff for PLR was set at 28. A multivariable Cox regression analysis was performed to assess the role of leukocytosis, thrombocytosis and PLR on long-term survival after RC. For all analyses hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were estimated. RESULTS: A total of 1,817 patients with a median age of 70 years (IQR: 62-77) were included. Overall, 804 (44%), 175 (10%), and 1,296 (71%) patients presented with leukocytosis, thrombocytosis, and PLR ≥28 preoperatively. Accordingly, 1,414 (78%), 37 (2%), and 249 (14%) patients presented with leukocytosis, thrombocytosis, and PLR ≥28 on the first day after RC. At a median follow-up of 26 months (IQR: 8-68) after RC, 896 (49%) patients died. In the multivariate Cox regression analysis after adjusting for major perioperative risk factors, only preoperative leukocytosis (HR: 1.3, 95%CI: 1.1-1.6, p=0.01), as well as both preoperative and first-day thrombocytosis (HR: 2.1, 95%CI: 1.5-2.9 and HR: 2.8, 95%CI: 1.6-5.1, p<0.001, accordingly) were associated with worse overall survival. CONCLUSION: PLR should not be used as a prognostic marker for survival after RC. On the contrary, preoperative leukocytosis, as well as preoperative and first-day thrombocytosis should raise awareness among clinicians performing RC, since they were independently associated with worse survival after RC.

Trends and outcomes of hospitalized patients with priapism in Germany: results from the GRAND study.

We aimed to provide evidence on the trends and in-hospital outcomes of patients with low- and high-flow priapism through the largest study in the field. We used the GeRmAn Nationwide inpatient Data (GRAND), provided by the Research Data Center of the Federal Bureau of Statistics (2008-2021), and performed multiple patient-level analyses. We included 6,588 men with low-flow and 729 with high-flow priapism. Among patients with low-flow priapism, 156 (2.4%) suffered from sickle cell disease, and 1,477 (22.4%) patients required shunt surgery. Of them, only 37 (2.5%) received a concomitant penile prosthesis implantation (30 inflatable and 7 semi-rigid prosthesis). In Germany, the total number of patients with low-flow priapism requiring hospital stay has steadily increased, while the number of patients with high-flow priapism requiring hospital stay has decreased in the last years. Among patients with high-flow priapism, 136 (18.7%) required selective artery embolization. In men with low-flow priapism, sickle cell disease was associated with high rates of exchange transfusion (OR: 21, 95% CI: 14-31, p < 0.001). The length of hospital stay (p = 0.06) and the intensive care unit admissions (p = 0.9) did not differ between patients with low-flow priapism due to sickle cell disease versus other causes of low-flow priapism. Accordingly, in men with high-flow priapism, embolization was not associated with worse outcomes in terms of length of hospital stay (p > 0.9), transfusion (p = 0.8), and intensive care unit admission (p = 0.5). Low-flow priapism is an absolute emergency that requires shunt surgery in more than one-fifth of all patients requiring hospital stay. On the contrary, high-flow priapism is still managed, in most cases, conservatively.

The impact of perioperative risk factors on long-term survival after radical cystectomy: a prospective, high-volume cohort study.

INTRODUCTION: Radical cystectomy (RC) is the gold standard for muscle-invasive bladder cancer. Nevertheless, RC is associated with substantial perioperative morbidity and mortality. We aimed to evaluate the role of important perioperative risk factors in predicting long-term survival after RC. METHODS: An analysis of the prospective cohort of patients undergoing open RC from 2004 to 2023 at our center was performed. Patients who died within one month after RC were excluded from the study. A univariate and multivariable Cox regression analysis was performed to assess the role of sex, age, urinary diversion, preoperative values of creatinine and hemoglobin, first-day postoperative values of CRP, leucocytes, and thrombocytes, perioperative Clavien-Dindo complications, perioperative chemotherapy, admission to the intensive or intermediate care unit, as well as type of histology, pathologic T-stage, positive lymph nodes, and positive surgical margins on predicting the long-term overall survival after RC. For all analyses hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were estimated. RESULTS: A total of 1,750 patients with a median age of 70 years (IQR: 62-76) were included. Of them, 1,069 (61%) received ileal conduit and 650 (37%) neobladder. Overall, 1,016 (58%) perioperative complications occurred. At a median follow-up of 31 months (IQR: 12-71), 884 (51%) deaths were recorded. In the multivariable Cox regression analysis, increasing age (HR: 1.03, 95%CI: 1.02-1.04, p < 0.001), higher preoperative creatinine values (HR: 1.27, 95%CI: 1.12-1.44, p < 0.001), lower preoperative hemoglobin values (HR: 0.93, 95%CI: 0.89-0.97, p = 0.002), higher postoperative thrombocyte values (HR: 1.01, 95%CI: 1.01-1.02, p = 0.02), Clavien-Dindo 1-2 complications (HR: 1.26, 95%CI: 1.03-1.53, p = 0.02), Clavien-Dindo 3-4 complications (HR: 1.55, 95%CI: 1.22-1.96, p < 0.001), locally advanced bladder cancer (HR: 1.29, 95%CI: 1.06-1.55, p = 0.009), positive lymph nodes (HR: 1.74, 95%CI: 1.45-2.11, p < 0.001), and positive surgical margins (HR: 1.61, 95%CI: 1.29-2.01, p < 0.001) negatively affected long-term survival. CONCLUSION: Beside increased age and worse oncological status, impaired renal function, lower preoperative hemoglobin values, higher postoperative thrombocyte values, and perioperative complications are independent risk factors for mortality in the long term in patients undergoing open RC.

[Treatment of localized renal cell carcinoma]. / Therapie des lokalisierten Nierenzellkarzinoms.

BACKGROUND: Both partial nephrectomy (pNx) and total nephrectomy (TNx) are the mainstay of the surgical treatment of renal cell carcinoma. In smaller masses, ablative treatment as well as surveillance are possible options. OBJECTIVE: The aim of this article is to provide a closer look at the surgical methods, active surveillance and ablative options as well as the current evidence to support their use. MATERIAL AND METHODS: This study is based on a selective literature review regarding pNx and TNx for renal cell carcinoma using the PubMed database and the review of current European and American guidelines on surgical treatment and conservative options for renal cell carcinoma. RESULTS: The choice of surgical method depends on the intrarenal tumor configuration as well as patient comorbidities. While pNx is used for smaller localized masses TNx is usually performed in larger more complex tumors. Both methods can be performed using a minimally invasive (laparoscopic or robotically assisted) or an open approach. In patients with severe comorbidities or a limited life expectancy, local ablative treatment options as well as surveillance strategies are suitable strategies.

Localised non-metastatic sarcomatoid renal cell carcinoma: a 31-year externally verified study.

OBJECTIVE: To evaluate post-nephrectomy outcomes and predictors of cancer-specific survival (CSS) between patients with localised sarcomatoid renal cell carcinoma (sRCC) and those with Grade 4 RCC (non-sRCC), as most sRCC research focuses on advanced or metastatic disease with limited studies analysing outcomes of patients with localised non-metastatic sRCC. PATIENTS AND METHODS: A total of 564 patients with localised RCC underwent partial or radical nephrectomy between June 1988 to March 2019 for sRCC (n = 204) or World Health Organization/International Society of Urological Pathology Grade 4 non-sRCC (n = 360). The CSS at every stage between groups was assessed. Phase III ASSURE clinical trial data were used to externally validate the CSS findings. The Mann-Whitney U-test and chi-squared test compared outcomes and the Kaplan-Meier method evaluated CSS, overall survival (OS) and recurrence-free survival. Clinicopathological features associated with RCC death were evaluated using Cox proportional hazards regression. RESULTS: The median follow-up was 31.5 months. The median OS and CSS between the sRCC and Grade 4 non-sRCC groups was 45 vs 102 months and 49 vs 152 months, respectively (P < 0.001). At every stage, sRCC had worse CSS compared to Grade 4 non-sRCC. Notably, pT1 sRCC had worse CSS than pT3 Grade 4 non-sRCC. Negative predictors of CSS were sarcomatoid features, non-clear cell histology, positive margins, higher stage (pT3/pT4), and use of minimally invasive surgery (MIS). ASSURE external verification showed worse CSS in patients with sRCC (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.12-2.36; P = 0.01), but not worse outcomes in MIS surgery (HR 1.39, 95% CI 0.75-2.56; P = 0.30). CONCLUSIONS: Localised sRCC had worse CSS compared to Grade 4 non-sRCC at every stage. Negative survival predictors included positive margins, higher pathological stage, use of MIS, and non-clear cell histology. sRCC is an aggressive variant even at low stages requiring vigilant surveillance and possible inclusion in adjuvant therapy trials.

Perioperative Outcomes of Same-Session Bilateral vs Unilateral Ureteroscopy for Stone Removal: Results from the GRAND Study.

Background: Same-session bilateral ureteroscopy may reduce the number of surgeries for stone removal but can lead to higher overall complication rates. We aimed to compare same-session bilateral ureteroscopy with unilateral ureteroscopy in terms of perioperative outcomes. Methods: We used the GeRmAn Nationwide inpatient Data (GRAND), provided by the Research Data Center of the Federal Bureau of Statistics (2005-2021). We assessed, through multiple patient-level analyses, severe perioperative complications, mortality, length of hospital stay, hospital revenues, intensive care unit admission, and the evolution of ureteroscopy during the last years in Germany. Results: We included 833,609 patients undergoing either same-session bilateral (n = 6914, 0.8%) or unilateral (n = 826,695, 99.2%) ureteroscopy for stone management. Patients undergoing bilateral ureteroscopy presented worse baseline characteristics. After adjusting for these characteristics, same-session bilateral ureteroscopy, compared to unilateral ureteroscopy, was significantly associated with higher odds of postoperative sepsis (odds ratio [OR]: 2.4, 95% confidence interval [CI]: 2-2.8, p < 0.001), myocardial infarction (OR: 2, 95% CI: 1.03-3.5, p = 0.024), acute kidney disease (OR: 2.8, 95% CI: 2.5-3.2, p < 0.001), transfusion (OR: 4.2, 95% CI: 3.6-4.8, p < 0.001), urinary tract infection (OR: 1.6, 95% CI: 1.5-1.7, p < 0.001), intensive care unit admission (OR: 1.9, 95% CI: 1.6-2.3, p < 0.001), and mortality (OR: 3.1, 95% CI: 2.1-4.5, p < 0.001). Similarly, the length of hospital stay was longer, and the in-hospital costs were higher (p < 0.001) after same-session bilateral ureteroscopy. Interestingly, the annual cases of ureteroscopy have undergone about a threefold increase in the last 17 years. Conclusions: The present real-world data demonstrate that same-session bilateral ureteroscopy leads to higher rates of perioperative myocardial infarction, acute kidney disease, transfusion, urinary tract infections, sepsis, and intensive care unit admission, as well as to increased length of hospital stay, costs, and inpatient mortality compared to unilateral ureteroscopy.

Perioperative outcomes of penile prosthesis implantation in Germany: results from the GRAND study.

We aimed to assess the recommended annual hospital volume for inflatable penile prosthesis implantation (PPI) and to provide evidence on perioperative outcomes of semi-rigid and inflatable PPI in Germany. We used the GeRmAn Nationwide inpatient Data (GRAND) from 2005 to 2021 and report the largest study to date with 7,222 patients. 6,818 (94.4%) patients underwent inflatable and 404 (5.6%) semi-rigid PPI. Inflatable PPI was significantly associated with shorter length of hospital stay (difference of 2.2 days, 95%CI: 1.6-2.7, p < 0.001), lower odds of perioperative urinary tract infections (5.5% versus 9.2%; OR: 0.58, 95%CI: 0.41-0.84, p = 0.003) and surgical wound infections (1% versus 2.5%; OR: 0.42, 95%CI: 0.22-0.88, p = 0.012) compared to semi-rigid PPI. Overall, 4255 (62.4%) inflatable PPIs were undertaken in low- ( < 20 PPI/year) and 2563 (37.6%) in high-volume ( ≥ 20 PPI/year) centers. High-volume centers were significantly associated with shorter length of hospital stay (difference of 1.4 days, 95%CI: 1.2-1.7, p < 0.001) compared to low-volume centers. Our findings suggest that inflatable PPI leads to a shorter length of hospital stay and lower rates of perioperative urinary tract and surgical wound infections compared to semi-rigid PPI. Patients undergoing surgery in high-volume centers for inflatable PPI are discharged earlier from the hospital.

Characterization of Human Papilloma Virus in Prostate Cancer Patients Undergoing Radical Prostatectomy-A Prospective Study of 140 Patients.

INTRODUCTION: The association between human papilloma virus (HPV) and the pathogenesis of prostate cancer (PCa) is still controversial. Existing studies often lack information about clinical risk factors, are limited by their retrospective design or only use a single detection method for HPV. MATERIAL AND METHODS: A total of 140 patients undergoing radical prostatectomy (RP) for PCa at the Department of Urology, Ludwig Maximilian University of Munich, Germany, were prospectively enrolled. Knowledge of HPV and sociodemographic parameters were assessed with questionnaires. The following methods were used for HPV detection: RP specimens were tested for HPV DNA by PCR. If HPV DNA was detected, an LCD-Array hybridization technique was used for HPV subtyping, and immunohistochemical staining for p16 was performed as a surrogate marker for HPV infection. Serological titers of HPV-16 L1 antibodies were measured using an HPV-16-specific immunoassay. RESULTS: HPV DNA was detected in 9.3% (13/140) of RP specimens, with HPV-16 being the most predominantly detected subtype (5/13 = 39%). HPV-16 L1 antibody levels were below the limit of detection in 98% of patients (137/140). We found no significant difference between HPV PCR-positive (HPV+) and -negative (HPV-) patients in terms of HPV-16 antibody levels, history of HPV-associated diseases, level of education or marital status. Seventy-five percent of all PCa patients had never heard of HPV before. An acinar adenocarcinoma of the prostate was the most frequently detected histologic type in both HPV+ (100%) and HPV- (98%) patients (p = 0.86). HPV+ patients had fewer positive biopsy cores (3.5 vs. 5.8; p = 0.01) and a lower maximal tumor infiltration rate per core (37% vs. 57%; p = 0.03) compared to HPV- patients. However, when analyzing the whole prostate and the lymph nodes after RP, there were no significant differences in TNM stage, Gleason score or tumor volume between both groups. In a subgroup analysis of all high-risk HPV patients (n = 6), we found no significant differences in sociodemographic, clinical or histopathological parameters compared to HPV- or low-risk HPV+ patients. CONCLUSION: In our prospective study, we were not able to prove a clinically significant impact of HPV status on tumor characteristics in RP specimens. Most men with PCa had never heard of HPV, despite its proven causal association with other tumor entities.

Radical Prostatectomy without Prior Biopsy in Patients with High Suspicion of Prostate Cancer Based on Multiparametric Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen Positron Emission Tomography: A Prospective Cohort Study.

Modern risk stratification of prostate cancer (PCa) allows for prediction of advanced disease with a high level of certainty. We aimed to evaluate a prospective series of patients undergoing radical prostatectomy without prior biopsy based solely on clinical criteria and imaging results. The patients were divided into three groups. Group 1 included 27 patients with: (i) suspicious digital rectal examination, (ii) PSA ≥ 10 ng/mL, (iii) PI-RADS 4/5 on mpMRI, and (iv) high suspicion of PCa on PSMA-PET. Group 2 included six patients who fulfilled criteria i, ii, and iii but did not undergo PSMA-PET imaging. Group 3 included 17 patients with at least one clinical (i or ii) and one imaging (iii or iv) criterion. All of the patients were diagnosed with PCa. Comparison of Group 1 and 2 versus Group 3 showed a significantly higher ratio of locally advanced PCa for Groups 1 and 2 compared to Group 3 (60.6% versus 11.8%, p = 0.005, respectively). Similarly, these patients displayed a significantly higher ratio of aggressive PCa (ISUP grade > 2: 66.7% versus 23.5%, p = 0.027, respectively) and tumor infiltration (median tumor infiltration: 32.5% vs. 15%, p = 0.001, respectively) in the final specimen compared to Group 3. In conclusion, we have shown that radical prostatectomy without prior biopsy is safe in terms of the diagnosis of clinically significant PCa when proper preoperative risk stratification involving mpMRI and PSMA-PET imaging is applied.

Outcomes and Prognostic Factors of Patients with Urothelial Carcinoma Undergoing Radical Cystectomy and pT0 in the Final Histology Without Neoadjuvant Chemotherapy.

Purpose: Absence of tumor in the final histopathology after radical cystectomy (RC) is a rare but potentially favorable outcome. Therefore, we aimed to analyze outcomes and prognostic factors of patients with urothelial carcinoma (UC) undergoing RC and T0 in the final histology without neoadjuvant chemotherapy at a high-volume academic center. Patients and Methods: We retrospectively analyzed patients undergoing RC for pure UC between 2004 and 2020. Cancer-specific survival (CSS) and overall survival (OS) were calculated using Kaplan-Meier analysis and group comparison by Log rank test. Potential prognostic factors were analyzed using univariate Cox regression models. Results: A total of 1051 patients with UC underwent RC. 72 patients (6.7%) showed pT0 in the final histology. Across all T-stages, 5-year CSS was significantly different with 88% for pT0, 80% for pTa/pTis, 78% for pT1, 76% for pT2, 51% for pT3 and 27% for pT4 in our cohort (p=0.001). Neither instillation therapy (HR 0.31, 95% CI 0.07-1.43), number of TURB prior RC (HR 1.47, 95% CI 0.25-6.18), use of photodynamic diagnostics (PDD) (HR 0.64, 95% CI 0.14-3.02), performing a second resection (HR 0.87, 95% CI 0.27-2.86), muscle-invasive disease prior RC at any TURB (HR 0.7, 95% CI 0.2-2.39) or muscle-invasive disease in the TURB prior RC (HR 1.0, 0.31-3.29) were associated with CSS in univariate analysis. Conclusion: pT0 reveals a survival benefit in patients undergoing RC for UC and therefore presents a distinctive tumor entity. As clinical and cystoscopic characteristics do not improve patient stratification, further research is warranted to define risk groups in this specific tumor entity.

68Ga-EMP-100 PET/CT-a novel ligand for visualizing c-MET expression in metastatic renal cell carcinoma-first in-human biodistribution and imaging results.

BACKGROUND: 68Ga-EMP-100 is a novel positron emission tomography (PET) ligand that directly targets tumoral c-MET expression. Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging of c-MET expression could improve patient management prior to systemic therapy with for instance inhibitors targeting c-MET such as cabozantinib. We present the first in-human data of 68Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC. METHODS: Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent 68Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUVmean) and SUVmax measurements. Additionally, metastatic sites on PET were compared to contrast-enhanced computed tomography (CT) and the respective, quantitative PET parameters were assessed and then compared inter- and intra-individually. RESULTS: Overall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUVmax of 4.35 and SUVmean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUVmax 9.05 (4.86-29.16)), followed by bone metastases (SUVmax 5.56 (0.97-15.85)), and lymph node metastases (SUVmax 3.90 (2.13-6.28)) and visceral metastases (SUVmax 3.82 (0.11-16.18)). The occurrence of visually PET-negative lesions (20.7%) was distributed heterogeneously on an intra- and inter-individual level; the largest proportion of PET-negative metastatic lesions were lung and liver metastases. The highest physiological 68Ga-EMP-100 accumulation besides the urinary bladder content was seen in the kidneys, followed by moderate uptake in the liver and the spleen, whereas significantly lower uptake intensity was observed in the pancreas and the intestines. CONCLUSION: Targeting c-MET expression, 68Ga-EMP-100 shows distinctly elevated uptake in mRCC patients with partially high inter- and intra-individual differences comprising both c-MET-positive and c-MET-negative lesions. Our first clinical results warrant further systemic studies investigating the clinical use of 68Ga-EMP-100 as a biomarker in mRCC patients.

Dynamic contrast-enhanced CT-derived blood flow measurements enable early prediction of long term outcome in metastatic renal cell cancer patients on antiangiogenic treatment.

PURPOSE: To evaluate the role of dynamic contrast-enhanced CT (DCE-CT) as an independent non-invasive biomarker in predicting long term outcome in patients with metastatic renal cell carcinoma (mRCC) on antiangiogenic treatment. MATERIAL AND METHODS: Eighty two mRCC patients were prospectively enrolled from 09/2011 to 04/2015, out of which 71 were included in the final data analysis; the population was observed until 12/2020 to obtain complete overall survival data. DCE-CT imaging was performed at baseline and 10 to 12 weeks after start of treatment with targeted therapy. DCE-CT included a dynamic acquisition after injection of 50 ml of nonionic contrast agent at 6 ml/s using a 4D spiral mode (10 cm z-axis coverage, acquisition time 43 sec, 100 kVp (abdomen), 80 kVp (chest), 80-100 mAs) on a dual source scanner (Definition FLASH, Siemens). Blood flow (BF) was calculated for target tumor volumes using a deconvolution model. Progression free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier statistics (SPSS version 24). RESULTS: Patients were treated with either sunitinib, pazopanib, sorafenib, tivozanib, axitinib, or cabozantinib. A cut-off value of 50% blood flow reduction at follow-up allowed for identification of patients with favorable long-term outcome: Median OS in n = 42 patients with an average blood flow reduction of >50% (mean, 79%) was 34 (range, 14-54) months, while n = 21 patients with an average reduction of less than 50% (mean, 28%) showed a median OS of 12 (range, 6-18) months, and n = 8 patients with an increase in blood flow survived for a median of 7 (range, 3-11) months. CONCLUSION: Blood flow in metastases measured with DCE-CT at first follow-up is a strong predictor of overall survival in mRCC patients on antiangiogenic treatment.

Somatic mutations as preoperative predictors of metastases in patients with localized clear cell renal cell carcinoma - An exploratory analysis.

OBJECTIVE: Recurrent genomic alterations in clear cell renal cell carcinoma (ccRCC) have been associated with treatment outcomes; however, current preoperative predictive models do not include known genetic predictors. We aimed to explore the value of common somatic mutations in the preoperative prediction of metastatic disease among patients treated for localized ccRCC. MATERIALS AND METHODS: After obtaining institutional review board approval, data of 254 patients with localized ccRCC treated between 2005 and 2015 who underwent genetic sequencing was collected. The mutation status of VHL, PBRM1, SETD2, BAP1 and KDM5C were evaluated in the nephrectomy tumor specimen, which served as a proxy for biopsy mutation status. The Raj et al. preoperative nomogram was used to predict the 12-year metastatic free probability (MFP). The study outcome was MFP; the relationship between MFP and mutation status was evaluated with Cox-regression models adjusting for the preoperative nomogram variables (age, gender, incidental presentation, lymphadenopathy, necrosis, and size). RESULTS: The study cohort included 188 males (74%) and 66 females (26%) with a median age of 58 years. VHL mutations were present in 152/254 patients (60%), PBRM1 in 91/254 (36%), SETD2 in 32/254 (13%), BAP1 in 19/254 (8%), and KDM5C in 19/254 (8%). Median follow-up for survivors was 8.1 years. Estimated 12-year MFP was 70% (95% CI: 63%-75%). On univariable analysis SETD2 (HR: 3.30), BAP1 (HR: 2.44) and PBRM1 (HR: 1.78) were significantly associated with a higher risk of metastases. After adjusting for known preoperative predictors in the existing nomogram, SETD2 mutations remained associated with a higher rate of metastases after nephrectomy (HR: 2.09, 95% CI: 1.19-3.67, P = 0.011). CONCLUSION: In the current exploratory analysis, SETD2 mutations were significant predictors of MFP among patients treated for localized ccRCC. Our findings support future studies evaluating genetic alterations in preoperative renal biopsy samples as potential predictors of treatment outcome.

Primary Chemotherapy in a 47-Year-Old Patient with Giant Ulcerative and Necrotizing Nonseminomatous Testicular Germ Cell Tumor.

Testicular cancer is a rare disease; however, cure rates are high for all tumor stages. Mostly, the disease is diagnosed in an early (local) stage. We report the case of a 47-year-old male patient with a giant nonseminomatous germ cell tumor. At the time of diagnosis, the patient demonstrated a necrotizing and ulcerating growing mass in the left scrotum with an approximate size of 22 × 18 cm. According to the prognostic classification of the International Germ Cell Cancer Collaborative Group (IGCCCG 1997), the patient exhibited a high-risk profile due to alpha-fetoprotein >10,000 ng/mL and lactate dehydrogenase >10× the upper limit of normal in serum. Primary orchiectomy was infeasible due to the tumor's size, the patient's poor general condition and initial intensive care unit treatment. Primary systemic chemotherapy was applied. After 3 cycles of cisplatin, etoposide and bleomycin, along with 1 cycle of cisplatin, etoposide and ifosfamide, tumor resection with histomorphological examination showed a complete pathological response. Despite the delayed initiation of the therapy, primary chemotherapy was completed timely and showed promising results. Reasons for the late hospitalization were personal responsibilities regarding his family. Better awareness and knowledge of testicular cancer among young men might prevent the here reported delay of medical consultation and avoid testicular tumors of such enormous size. Psychosocial assessment and distress management is important as an integral part of comprehensive care of testicular cancer patients.

A qualitative framework of non-selection factors for cytoreductive nephrectomy.

PURPOSE: Cytoreductive nephrectomy (CN) benefits a subset of patients with metastatic renal cell carcinoma (mRCC), however proper patient selection remains complex and controversial. We aim to characterize urologists' reasons for not undertaking a CN at a quaternary cancer center. METHODS: Consecutive patients with mRCC referred to MSKCC urologists for consideration of CN between 2009 and 2019 were included. Baseline clinicopathologic characteristics were used to compare patients selected or rejected for CN. The reasons cited for not operating and the alternative management strategies recommended were extrapolated. Using an iterative thematic analysis, a framework of reasons for rejecting CN was designed. Kaplan-Meier estimates tested for associations between the reasons for not undertaking a CN and overall survival (OS). RESULTS: Of 297 patients with biopsy-proven mRCC, 217 (73%) underwent CN and 80 (27%) did not. Median follow-up of patients alive at data cut-off was 27.3 months. Non-operative patients were older (p = 0.014), had more sites of metastases (p = 0.008), harbored non-clear cell histology (p = 0.014) and reduced performance status (p < 0.001). The framework comprised seven distinct themes for recommending non-operative management: two patient-fitness considerations and five oncological considerations. These considerations were associated with OS; four of the oncological factors conferred a median OS of less than 12 months (p < 0.001). CONCLUSION: We developed a framework of criteria by which patients were deemed unsuitable candidates for CN. These new insights provide a novel perspective on surgical selection, could potentially be applicable to other malignancies and possibly have prognostic implications.

Safety and Efficacy of Robotic Radiosurgery for Visceral and Lymph Node Metastases of Renal Cell Carcinoma: A Retrospective, Single Center Analysis.

Despite rapid advances of systemic therapy options in renal cell carcinoma (RCC), local tumor or metastases treatment remains important in selected patients. Here, we assess the safety and efficacy of robotic radiosurgery (RRS) as an ablative therapy for visceral and lymph node metastases of RCC. Patients with histologically confirmed RCC and radiologically confirmed progression of visceral or lymph node metastases underwent RRS and were retrospectively analyzed. Overall survival and progression free survival were calculated by the Kaplan-Meier method and log-rank test. Sixty patients underwent RRS and were included in the analysis. Patients presented for RRS treatment with a median age at RRS treatment of 64 years (range 42-83), clear cell histology (88.3%) and favorable international metastatic renal cell carcinoma database (IMDC) risk score (58.3%). Treatment parameters differed for the number of fractions (median visceral metastases: 1, range 1-5; median lymph node metastases: 1, range 0-5; p = 0.003) and prescription dose (median visceral metastases 24 Gy, range 8-26; median lymph node metastases 18 Gy, range 7-26, p < 0.001). The median overall survival was 65.7 months (range: 2.9-108.6), the median progression free survival was 17.4 months (range: 2.7-70.0) and local tumor control was achieved in 96.7% of patients. Adverse events were limited to 8.3% of patients, with one grade 4 toxicity within 6 weeks after RRS therapy. RRS is a safe and effective treatment option in selected patients with metastatic RCC in a multimodal approach. Further research is warranted to confirm our findings prospectively.

The natural course of urinalysis after urinary diversion.

OBJECTIVE: To evaluate the impact of urinary diversion on regular features of urinalysis and to screen for risk factors of infection-related complications. METHODS: We conducted a retrospective, single-centre study of 429 patients who underwent open radical cystectomy. Patients were followed for 12 months and data of the complete urinalyses were analysed at three pre-defined time points. RESULTS: Two weeks after surgery, dipstick testing with positive reactions for leukocyte esterase and haemoglobin were confirmed in 80.7% and 80% after ileal conduit (IC) and orthotopic ileal neobladder (NB), respectively. Every patient was positive for these parameters 12 months after surgery. Correspondingly, the microscopic examination detected leukocytes (84% vs. 85.4%), erythrocytes (82.8% vs. 83.8%) and bacteria (94.3% vs. 96.8%) following IC and NB reconstruction. After 12 months, all parameters were positive irrespective of the type of urinary diversion. Two weeks after surgery positive urine cultures were obtained in more than 50% of cases after IC (52.5%) and NB (60.5%) (p > 0.05). All urine cultures were positive after 12 months with significantly more poly-microbial results found after NB (81.3%) compared with IC (67.2%) (p = 0.018). In univariate and multivariate logistic regression analysis the presence of hydronephrosis was independently associated with the occurrence of infectious complications (OR 4.2; CI 95% 1.525-11.569; p = 0.006). CONCLUSION: A positive urinalysis is a common finding after urinary diversion. Hydronephrosis is a serious risk factor with respect to infection-related complications. The simple fact of a positive urinalysis does not warrant antimicrobial treatment.