Prospective evaluation of the RT-PCR based urinary marker Bladder Epicheck® as a diagnostic tool in upper urinary tract tumor.

BACKGROUND: Upper-tract-urothelial-carcinoma (UTUC) represents 5-10% of all urothelial-neoplasms with increasing incidence in the last decades. Current standard tools for diagnosis of UTUC include cytology, computed tomography (CT) urography and ureterorenoscopy (URS). The aim of this study was to evaluate the impact of Bladder Epicheck® Test as diagnostic tool for UTUC diagnosis and recurrence. METHODS: Overall, 136 urine samples, selective collected from upper-urinary-tract before URS for suspicion of UTUC were analyzed with cytology and Bladder Epicheck® Test. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of both markers were calculated and compared to URS and/or histology as reference. RESULTS: UTUC was detected in 40 cases (33.3%), among them 30 were classified as low-grade (LG) and 10 as high-grade (HG). Overall sensitivity of Bladder Epicheck® for UTUC detection was 65% compared to 42.5% for cytology, increasing to 100% for Bladder Epicheck® and 90% for cytology if considering only HG tumors. Overall specificity of Bladder Epicheck® was 81.2% and of cytology 93.7%. PPV and NPV were 63.4% and 82.2% for Bladder Epicheck® and 77.2% and 76.5% for cytology. Considering an EpiScore cut-off >75, instead of 60, specificity of Bladder Epicheck® improves to 89% and PPV to 74.2%. Limitations include the use of a marker validated only for bladder-cancer and the relatively small number of cases. CONCLUSIONS: Due to its high sensitivity for HG tumors, the Bladder Epicheck® Test can be used in diagnosis and treatment decision-making of UTUC. Furthermore, it could be very useful in follow-up of UTUC, after endoscopic treatment to postpone or avoid unnecessary endoscopic exploration. Even if further studies are needed to validate these findings, Bladder Epicheck® could be a promising clinical tool for detection of UTUC.

[Sigmoid colon conduit volvulus: an extremely rare complication of a sigmoid colon conduit]. / Sigmakonduit Volvulus: eine extrem seltene Komplikation eines Sigmakonduit.

We report the case of an 84-year-old man with the rare diagnosis of a volvulus of an incontinent sigmoid colon urinary conduit after radical cystoprostatectomy due to urinary bladder cancer. To the best of our knowledge, this is the first case in literature of a volvulus of a sigmoid colon conduit.

[From an enterovesical fistula to mammary carcinoma]. / Von einer enterovesikalen Fistel zum Mammakarzinom.

We report a case of a 83-year-old woman with the initial diagnosis of an occult invasive lobular breast carcinoma due to gastrointestinal metastasis with an entervesical fistula.

[Penile metastasis of a carcinoma of the salivary glands at the tongue base: a case report]. / Penismetastase eines Speicheldrüsenkarzinoms der Zungenbasis: Ein Fallbeispiel.

We report the case of a 64-year-old man, initially diagnosed with a polymorphous adenocarcinoma of the small salivary glands at the tongue base, with occurrence of a penile metastasis ten years after diagnosis. To our knowledge, only two such cases have been described in the literature to date.

Transarterial Embolization in the Management of Intractable Haemorrhage.

INTRODUCTION: The purpose of this study was to evaluate the effectiveness and long-term results of selective transarterial iliac embolization (STIE) in patients with intractable bladder haemorrhage (IBH). METHODS: Twenty-five patients with a median age of 84 (range 65-94) years underwent STIE because of IBH between 2002 and 2020. The median follow-up time was 3 (mean 13.9) months. Patients were treated because of bleeding bladder or prostate cancer, radiation-induced haemorrhagic cystitis, and other conditions. Success was defined as technical success (feasibility to embolize bilateral hypogastric arteries or neoplastic arteries) and as clinical success (absence of further or additional therapy). RESULTS: Twenty-five patients with a median age of 84 years with a median hospital stay of 7 days were embolized at our institution. In total, 60% required additional therapy. Only 20% had minor complications, but no complication major was seen; 60% needed an additional therapy because of continuous bleeding. Our 30-day, 90-day, 6-month, and 12-month mortality rates were 28, 44, 64, and 76%, respectively. CONCLUSIONS: STIE in IBH is a safe, well-tolerated, and feasible procedure for palliating haematuria patients in poor general condition. Major complications are very rarely seen. However, patients often need additional therapy after STIE.

[Juvenile granulosa cell tumor-Testicular tumor of the very young : Report of three cases and contemporary recommendations]. / Der juvenile Granulosazelltumor ­ der Hodentumor der Kleinsten : Aktuelle Handlungsempfehlungen anhand von drei Kasuistiken.

Juvenile granulosa cell tumor of the testis is a relevant differential diagnosis regarding testicular neoplasia of the very young. This benign lesion requires surgical treatment. Metastases or recurrences have not been described in literature. We present three different cases and give recommendations for diagnosis and treatment.

The association of cigarette smoking and pathological response to neoadjuvant platinum-based chemotherapy in patients undergoing treatment for urinary bladder cancer - A prospective European multicenter observational study of the EAU Young Academic Urologists (YAU) urothelial carcinoma working group.

OBJECTIVE: To prospectively study the impact of smoking on pathological response to neoadjuvant chemotherapy (NAC) in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). MATERIALS & METHODS: We collected standard clinicopathological variables, including smoking status (never, former, current) in patients undergoing NAC and RC for UCB at 12 European tertiary care centers between 12/2013-12/2015. Clinicopathological variables were compared according to smoking status. Multivariable logistic regression models were built to assess the association of smoking status and a) complete (no residual disease), b) partial (residual, non-muscle invasive disease), c) no pathological response (residual muscle invasive or lymph node positive disease). Kaplan-Meier and Cox regression analyses were employed to study the impact of response to NAC on survival. RESULTS AND LIMITATIONS: Our final cohort consisted of 167 NAC patients with a median follow-up of 15 months (interquartile range (IQR) 9-26 months) of whom 48 (29%), 69 (41%), and 50 (30%) where never, former, and current smokers, respectively. Smoking was significantly associated with advanced age (p = 0.013), worse ECOG performance status (p = 0.049), and decreased pathological response to NAC (p = 0.045). On multivariable logistic regression analyses, former and current smoking status was significantly associated with lower odds of complete pathological response (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.16-0.87, p = 0.023, and OR 0.34, 95% CI 0.13-0.85, p = 0.021), while current smoking status was significantly associated with a greater likelihood of no pathological response (OR 2.49, 95% CI 1.02-6.06, p = 0.045). Response to NAC was confirmed as powerful predictor of survival. CONCLUSIONS: Smoking status is adversely associated with pathological response to NAC. Smokers should be informed about these adverse effects, counseled regarding smoking cessation, and possibly be considered for immunotherpeutics as they may be more effective in smokers.

Discovery of Molecular DNA Methylation-Based Biomarkers through Genome-Wide Analysis of Response Patterns to BCG for Bladder Cancer.

BACKGROUND: Bacillus Calmette-Guérin (BCG) immunotherapy, the standard adjuvant intravesical therapy for some intermediate and most high-risk non-muscle invasive bladder cancers (NMIBCs), suffers from a heterogenous response rate. Molecular markers to help guide responses are scarce and currently not used in the clinical setting. METHODS: To identify novel biomarkers and pathways involved in response to BCG immunotherapy, we performed a genome-wide DNA methylation analysis of NMIBCs before BCG therapy. Genome-wide DNA methylation profiles of DNA isolated from tumors of 26 BCG responders and 27 failures were obtained using the Infinium MethylationEPIC BeadChip. RESULTS: Distinct DNA methylation patterns were found by genome-wide analysis in the two groups. Differentially methylated CpG sites were predominantly located in gene promoters and gene bodies associated with bacterial invasion of epithelial cells, chemokine signaling, endocytosis, and focal adhesion. In total, 40 genomic regions with a significant difference in methylation between responders and failures were detected. The differential methylation state of six of these regions, localized in the promoters of the genes GPR158, KLF8, C12orf42, WDR44, FLT1, and CHST11, were internally validated by bisulfite-sequencing. GPR158 promoter hypermethylation was the best predictor of BCG failure with an AUC of 0.809 (p-value < 0.001). CONCLUSIONS: Tumors from BCG responders and BCG failures harbor distinct DNA methylation profiles. Differentially methylated DNA regions were detected in genes related to pathways involved in bacterial invasion of cells or focal adhesion. We identified candidate DNA methylation biomarkers that may help to predict patient prognosis after external validation in larger, well-designed cohorts.

Elderly patients undergoing cystectomy, comparing preoperative American Society of Anesthesiology and Eastern Cooperative Oncology Group scores and operative approaches.

OBJECTIVE: To evaluate preoperative scoring systems and operative management and their relation to complications in patients older than 75 years undergoing cystectomy at two academic institutions. METHODS: In total, 212 patients aged 75-95 years with muscle invasive bladder cancer underwent cystectomy at the University of Utah and Central Hospital of Bolzano, Italy. The rates of Grade 3 Clavien-Dindo complications and above in radical cystectomy patients (n = 199) were compared using Eastern Cooperative Oncology Group Scores and American Society of Anesthesiologists Physical Status Classification. The rates of Grade 3 Clavien-Dindo complications and above were also compared by urinary diversion type. Logistic regression was used to control for source institution. RESULTS: In total, 199 cases were included in the primary analysis. Neither of the preoperative scoring systems were predictive for identification of radical cystectomy patients with ⩾Grade 3 Clavien-Dindo complications. In secondary analysis (n = 212, including partial cystectomy), none of the urinary diversion types associated with radical cystectomy had a significantly different rate of complications. However, partial cystectomy (n = 13) had a significantly lower rate of complications. CONCLUSION: Complication rates among elderly patients undergoing cystectomy for muscle invasive bladder cancer were very high. For patients who are approved for surgery after the history and physical exam, none of our objective metrics adequately predicted operative risk. A unique diversion procedure described by the Bolzano group, uretero-ureterocutaneostomy, had equivalent complication rates to the more common diversion procedures. It also appears based on outcomes in this cohort that partial cystectomy is a particularly favorable option within the elderly population in terms of perioperative morbidity.

[Urethral sarcoma 14 years after brachytherapy of the prostate gland]. / Urethrasarkom 14 Jahre nach Prostata-Brachytherapie.

We report a case of an 83-year-old male patient with the rare diagnosis of a urethral sarcoma.

Use and duration of antibiotic prophylaxis and the rate of urinary tract infection after radical cystectomy for bladder cancer: Results of a multicentric series.

OBJECTIVES: To assess the rate of urinary tract infection (UTI), the characteristics of the bacterial aetiological agents involved, the type and duration of antibiotics used, and the clinical risk factors of UTI in a multi-institutional cohort of patients who had undergone radical cystectomy (RC). PATIENTS AND METHODS: The pre- and postoperative characteristics of patients who had undergone open RC at 1 of 3 institutions between 2009 and 2015 were analyzed by means of the patient charts. Patients were classified according to the presence or absence of UTI. Analysis of the severity of UTI was based on the EAU/EAU Section of Infections in Urology (ESIU) classification system. The bacterial aetiological agents and their antibiotic susceptibility were also assessed. Factors predicting postoperative UTI were identified using univariable and multivariable logistic regression analysis. RESULTS: Of 217 patients, 42 (19.4%) had developed postoperative UTI, of whom 50% had urosepsis or uroseptic shock. Multivariable analysis showed continent urinary derivation as the only significant predictor of UTI with an odds ratio of 5.03 (95% confidence interval 2.12-11.9, P < 0.001). The duration of perioperative antibiotic prophylaxis was not associated with an increased risk of UTI. Enterococcus was the most commonly isolated bacteria (25.7%), but this species is not covered by the recommended antibiotic prophylaxis. CONCLUSION: Patients with continent urinary diversion after RC have a significantly higher risk of developing UTI. Prolonged perioperative administration of antibiotics does not seem to reduce the risk of UTI. Enterococcus as the most commonly isolated bacteria is not covered by most recommended antibiotic prophylaxis regimens. Therefore different antibiotic regimens should be considered for high-risk patients.

Pediatric cystic diseases of the kidney.

Pediatric renal cystic diseases include a variety of hereditary or non-hereditary conditions. Numerous classifications exist and new data are continuously published. Ultrasound is the primary technique for evaluating kidneys in children: conventional and high-resolution US allows a detailed visualization of renal parenchyma and of number, size and location of the cysts, hence representing the most important diagnostic imaging technique for the first diagnosis and follow-up of these young patients. The purpose of this pictorial essay is to review the spectrum of renal cystic lesions in children from simple, complex or malignant single cysts to the several poly/multicystic kidney diseases.

Malignant mesothelioma of tunica vaginalis testis: Report of a very rare case with review of the literature.

INTRODUCTION: Mesothelioma of the tunica vaginalis testis is a extremely rare tumor and represents 0.3 to 0.5% of all malignant mesotheliomas. Exposure to asbestos often precedes illness. Because of its low incidence and nonspecific clinical presentation, it is mostly diagnosed accidentally during surgery for other reasons and the prognosis is usually poor. We present a case of a patient with a mesothelioma of tunica vaginalis testis, diagnosed secondarily during hydrocele surgery, with long-term survival after radical surgery. MATERIALS AND METHODS: a 40 years old patient was admitted to our department for routine surgery of a left hydrocele. During the operation a frozen section analysis was requested because of the unusual nodular thickening of the tunica vaginalis: the examination revealed a diffuse malignant mesothelioma with epithelioid structure and tubular-papillary proliferation. Therefore a left hemi-scrotectomy with left inguinal lymph node dissection was performed. RESULTS: The definitive histology confirmed the previous report of diffuse malignant mesothelioma with angio-invasion but normal testicle findings and negative lymph nodes. No metastases were found on the CT-scan. For the first 2 years a CT was repeated every 4 months, for other 3 years every 6 months and then yearly. Six years after surgery the patient is classified as no evidence of disease. CONCLUSIONS: malignant mesothelioma of the tunica vaginalis testis is a rare entity, often initially thought to be a hydrocele or an epididymal cyst. An aggressive approach with hemiscrotectomy with or without inguinal and retroperitoneal lymphadenectomy can reduce the risk of recurrence.

Bladder cancer in nonagenarians: a multicentre study of 123 patients.

OBJECTIVE: To investigate the oncological outcome of nonagenarians with bladder cancer, as a substantial rise in bladder cancer in the old-old age group in the upcoming decades is expected, due to demographic changes and the peak incidence around the age of 85 years. The paucity of data of nonagenarians prompted us to investigate the outcomes of such patients. PATIENTS AND METHODS: A retrospective, multicentre study was designed to assess patient demographics, tumour patterns, treatment strategies and outcome in patients aged ≥90 years treated at participating centres. Patients entered either as de novo or as recurrent cancer. The study period ranged from 01.01.2006 to 31.12.2016. RESULTS: A total of 123 patients with a mean (range) age of 91 (90-99) years were recruited. The American Society of Anesthesiologists Physical Status Classification (ASA-score) distribution was as follows: II, 38%; III, 50%; IV, 12%; and the male to female ratio 2.4:1. The median (range) follow-up was 8 (1-132) months. In all, 60% of patients had a de novo cancer diagnosis. Histological findings revealed: pTa 39% (n = 48), pT1 28.5% (n = 35), and ≥pT2 33% (n = 40). Overall, 67.5% patients had no recurrence, 25.2% one and 7.5% two or more. pTa tumours (n = 48) recurred in 20 patients (42%), pT1 tumours (n = 35) in 12 (34%), and ≥pT2 tumours (n = 40) in six (15%). The median overall survival (OS) was 30.0 months for patients with pTa tumours, 14.0 months for pT1 tumours, and 6.0 months for ≥pT2 tumours. The overall mortality rate of patients with pTa tumours was 40%, with pT1 tumours at 60%, and ≥pT2 tumours 75%. The ASA-score also had a strong influence on median OS after stratification by ASA-score (II, 30 months; III, 12 months; IV, 4 months). CONCLUSIONS: In nonagenarians with bladder tumours, pTa/pT1/≥pT2 stages are almost evenly distributed and two-thirds of patients had no recurrence after transurethral resection of the bladder. The mean OS was 1.3 years, and 6 months for ≥pT2 tumours. Further case-series of patients in this specific age-group are required to identify the best management of this increasing proportion of patients with bladder tumours.

Sarcopenia as a comorbidity-independent predictor of survival following radical cystectomy for bladder cancer.

BACKGROUND: A multicentre study was conducted to investigate the impact of sarcopenia as an independent predictor of oncological outcome after radical cystectomy for bladder cancer. METHODS: In total, 500 patients with available digital computed tomography scans of the abdomen obtained within 90 days before surgery were identified. The lumbar skeletal muscle index was measured using pre-operative computed tomography. Cancer-specific survival (CSS) and overall survival (OS) were estimated using Kaplan-Meier curves. Predictors of CSS and OS were analysed by univariable and multivariable Cox regression models. RESULTS: Based on skeletal muscle index, 189 patients (37.8%) were classified as sarcopenic. Patients with sarcopenia were older compared with their counterparts (P = 0.002), but both groups were comparable regarding to gender, comorbidity, tumor, node, metastasis (TNM) stage, and type of urinary diversion (all P > 0.05). In total, 234 (46.8%) patients died, and of these, 145 (29.0%) died because of urothelial carcinoma of the bladder. Sarcopenic patients had significantly worse 5 year OS (38.3% vs. 50.5%; P = 0.002) and 5 year CSS (49.5% vs. 62.3%; P = 0.016) rates compared with patients without sarcopenia. Moreover, sarcopenia was associated independently with both increased all-cause mortality (hazard ratio, 1.43; 95% confidence interval 1.09-1.87; P = 0.01) and increased cancer-specific mortality (hazard ratio, 1.42; 95% confidence interval, 1.00-2.02; P = 0.048). Our results are limited by the lack of prospective frailty assessment. CONCLUSIONS: Sarcopenia has been shown to be an independent predictor for OS and CSS in a large multicentre study with patients undergoing radical cystectomy for bladder cancer.

Impact of age on outcomes of patients with non-muscle-invasive bladder cancer treated with immediate postoperative instillation of mitomycin C.

OBJECTIVES: To evaluate whether age affects the clinical benefit afforded by immediate postoperative intravesical instillation of mitomycin C in a contemporary cohort of patients with NMIBC. PATIENTS AND METHODS: A total of 4,258 patients with NMIBC treated with transurethral resection of the bladder with (n = 2,605, 61%) or without (n = 1,652, 39%) one immediate instillation of mitomycin C from 5 institutions (study period: 2000-2007) were included. No patients received adjuvant instillations. A multivariable Cox proportional hazards regression model adjusting for standard clinical and pathological features tested the potential interaction term between age and administration of mitomycin C with regard to disease recurrence. RESULTS: A total of 2,063 patients experienced disease recurrence with a median follow-up of 48 months for those who did not recur. In multivariable Cox regression analysis, immediate postoperative instillation of mitomycin C (HR: 0.62; 95% CI: 0.56-0.68; P<0.0001) and age (HR: 1.04; 95% CI: 1.00-1.09; P = 0.036) were associated with disease recurrence. We observed only slight decreases in recurrence-free survival with age irrespective of treatment administration of mitomycin C or not. CONCLUSION: We confirmed reduced disease recurrence rates associated with 1 immediate postoperative intravesical instillation of mitomycin C in NMIBC patients. The benefit on recurrence-free survival of a postoperative intravesical instillation was preserved across all ages and therefore age by itself should not be taken into consideration when deciding to use it.

Radical cystectomy: do we need standardization?

INTRODUCTION: The first series of radical cystectomy with a definition of surgical landmarks was published in 1949 and was characterized by a high perioperative mortality and a 5-year survival rate around 50%. Decades later, nevertheless many surgical progresses were made and the perioperative mortality dropped to 2,5%, this had not lead to an improvement of long term survival rates, also because a standardization of the procedure is still missing. Areas covered: Radical cystectomy is performed with different surgical techniques obmitting a standardization. The comparability of many studies is therefore difficult or havely compromised. A paragon with other diciplines was made emphazing that there high surgical quality is defined, measured and controlled. A systematic literature search was made selecting finally 76 article adressing this issue. Expert commentary: Surgical guidelines in uro-oncology are vague and a definition of surgical quality is missing. A view outside of the box could be very helpful. This is a plea for a change.

90-Day Mortality after Radical Cystectomy for Bladder Cancer: Prognostic Factors in a Multicenter Case Series.

OBJECTIVES: To identify preoperative risk factors for 90-day mortality and to validate existing nomograms in a multicenter series of patients undergoing radical cystectomy (RC). MATERIALS AND METHODS: We evaluated 90-day mortality in 475 patients following RC and urinary diversion at 2 Italian institutions and validated Aziz and Isbarn nomogram. Univariable logistic models assessed the predictive ability of operative volume, age at intervention, gender, body mass index, carcinoma in situ at transurethral resection of the bladder, American Society of Anesthesiologist (ASA) score, Charlson Comorbidity Index, clinical stage and pathological stage (TNM). RESULTS: Of the total number of patients, 387 of them (81%) were male. The median age at RC was 71.8. The most frequent ASA score was 2 (53%). Twenty-five deaths occurred within 90 days (5.3%), all among patients who had undergone RC and incontinent urinary diversion. Risk was higher in patients with advanced disease (OR 2.4); moreover, 90-day mortality odd in 70-79-year-old patients was 13 times higher than those of younger patients (<70). Predictive accuracy using Isbarn's and Aziz's nomogram were 67 and 71%, respectively. CONCLUSIONS: Our multicenter study confirmed the moderate predictive value of the Aziz nomogram. Larger studies are needed to improve on existing nomograms with the aim of enhancing preoperative counseling.

Risk and timing of biochemical recurrence in pT3aN0/Nx prostate cancer with positive surgical margin - A multicenter study.

BACKGROUND AND PURPOSE: Positive surgical margins (PSM) after radical prostatectomy have been shown to be associated with impaired outcome. In pT3pN0 patients with PSM either immediate radiotherapy or clinical and biological monitoring followed by salvage radiotherapy is recommended by the latest guidelines of the European Association of Urology. MATERIALS AND METHODS: A retrospective, multicenter study of eight urological centers was conducted on 536 prostatectomy patients with pT3aN0/NxR1 tumors and no neoadjuvant/adjuvant therapy. A pathological re-review of all prostate specimens was performed. Association of clinical and pathological features with biochemical recurrence (BCR) was analyzed using univariate and multivariate analysis. RESULTS: With 48months median follow-up, BCR occurred in 39.7%. Preoperative PSA value, performance of pelvic lymph node dissection and Gleason score were significantly associated with BCR. In multivariate analysis, Gleason score was the only independent prognostic factor (p<0.001) for BCR. Five-year BCR-free survival rates were 74%, 70%, 38%, and 51% with Gleason score 6, 3+4=7a, 4+3=7b, and 8-10, respectively. CONCLUSIONS: In pT3aN0/NxR1 patients with no adjuvant/neoadjuvant treatment, Gleason Score permits independent prediction of the risk for BCR. These findings could help to estimate and discuss the individual risk for BCR with our patients on an individual basis.

Urinary cytology in bladder cancer: why is it still relevant?

Bladder carcinoma is the most common malignancy of the urinary tract and cystoscopy with cytology is currently considered the gold standard for the detection and surveillance of primary tumors and for the follow-up of patients after transurethral resection. Even if cytology has a low sensitivity especially in low-grade bladder carcinomas, the high specificity and the inexpensive nature of the equipment required, justify performing it. The greatest value of cytology for patients with low-grade, nonmuscle-invasive bladder cancer (NMIBC) is the detection of those lesions that may progress to high-grade urothelial carcinoma.