Degenerative Changes in Aging Human Pelvic Lymph Nodes-A Reason to Rethink Staging and Therapy of Regional Malignancies?

Lymph node metastases are common in pelvic urological tumors, and the age-related remodeling process of the pelvic lymph nodes influences metastatic behavior. The aim of this work is to characterize age-related degenerative changes in the pelvic lymph nodes with respect to their occurrence and extent. A total of 5173 pelvic lymph nodes of 390 patients aged 44 to 79 years (median 68 years, IQR 62-71 years) were histologically examined for degenerative structural changes. Lymph node size, lipomatous atrophy, capsular fibrosis, framework fibrosis, and calcifications were recorded semi-quantitatively and evaluated by age group. Significantly more lymph nodes <10 mm were found in older patients (p = 0.001). The incidence of framework fibrosis, capsular fibrosis, and calcifications increased significantly with increasing patient age (p < 0.001). In lipomatous atrophy, an increase in mild to moderate lipomatous atrophy was observed with increasing age (p < 0.001). In this, the largest study to date on this topic, age-related degenerative changes in pelvic lymph nodes were proven. Due to the consecutive decrease in hte filtration function of pelvic lymph nodes with increasing age, staging and therapy of metastatic pelvic urologic carcinomas should be reconsidered.

[Prostate cancer in older men : Special features of the diagnostics and treatment]. / Prostatakarzinom beim älteren Mann : Besonderheiten der Diagnostik und Therapie.

Prostate cancer is the most frequent cancer in men. For localized prostate cancer, surgery and radiotherapy are the standard treatment, with active surveillance also used in low-risk cases. For advanced/metastatic disease, androgen deprivation treatment is carried out. Further options include inhibitors of the androgen receptor axis and taxane-based chemotherapy. The avoidance of side effects should be considered, e.g., by dose adjustment. New options include poly(ADP-ribose) polymerase (PARP) inhibitors, and radioligand treatment. The existing guidelines only provide a few treatment recommendations for older patients; however, the treatment of older patients should primarily consider not only chronological age but also the patient's psychological and physical condition and preferences. In this context, the geriatric assessment represents an important instrument for determining the treatment strategy.

Correction: Luedemann et al. Prostate Cancer-Associated miRNAs in Saliva: First Steps to an Easily Accessible and Reliable Screening Tool. Biomolecules 2022, 12, 1366.

The authors wish to make the following corrections to their paper [...].

Hydrostatic pressure of the renal pelvis as a radiation-free alternative to fluoroscopic nephrostogram following percutaneous nephrolithotomy.

BACKGROUND: We evaluated the hydrostatic pressure of the renal pelvis (RPP) as a radiation-free alternative to fluoroscopic nephrostogram to assess ureteral patency after percutaneous nephrolithotomy (PCNL). METHODS: Retrospective non-inferiority study analyzing 248 PCNL-patients (86 female (35%) and 162 males (65%)) between 2007 and 2015. Postoperatively, RPP was measured using a central venous pressure manometer in cmH2O. The primary endpoint was to assess RPP depending on the patency of the ureter and the nephrostomy tube removal. Secondary, the upper limit of normal RPP of [Formula: see text] 20 cmH2O was assessed as an indicator of an unobstructed patency. RESULTS: The median procedure duration was 141 min (112-171.5) with a stone free rate of 82% (n = 202). RPP was significantly higher in patients with obstructive nephrostogram with 25.0 mmH2O (21.0-32.0) versus 20.0 mmH2O (16.0-24.0; p < 0.001). The pressure was lower in successful nephrostomy removal with 18 cmH2O (15-21) versus 23 cmH2O (20-29) in the leakage group (p < 0.001). The analysis of a cut-off of [Formula: see text] 20 cmH2O showed a sensitivity of 76.9% (95% CI [60.7%; 88.9%]) and a specificity of 61.5% (95% CI [54.6%; 68.2%]). The negative predictive value was 93.4% (95% CI: [87.9%; 97.0%]) and the positive predictive value 27.3% (95% CI [19.2%; 36.6%]). The accuracy of the model showed an AUC = 0.795 (95% CI [0.668; 0.862]). CONCLUSION: The hydrostatic RPP seems to allow a bedside evaluation of ureteral patency after PCNL.

Influence of lymph node degeneration on metastases in prostate cancer: or why we must look for a needle in a haystack.

BACKGROUND: To evaluate the incidence of lymph node degeneration and its association with nodal metastatic pattern in prostate cancer. METHODS: A retrospective analysis of the submitted lymph node specimen of 390 prostatectomies in 2011 was performed. All lymph nodes were histologically re-evaluated and the degree of lymph node degeneration e.g. lipomatous atrophy, capsular and framework fibrosis, and calcifications as well as the lymph node size were recorded. Lymph node degeneration was compared in the anatomic regions of the pelvis as well as in lymph nodes with and without metastases of prostatic cancer. RESULTS: Eighty-one of 6026 lymph nodes demonstrated metastases. Complete histologic examination with analysis of a complete cross-section was possible in 5173 lymph nodes including all lymph nodes with metastases. The incidence of lymph node degeneration was different across the various landing sites. Lymph node metastases were primarily detected in less degenerative and therefore more functional lymph nodes. In metastatic versus non-metastatic lymph nodes low lipomatous atrophy was reported in 84.0% versus 66.7% (p = 0.004), capsular fibrosis in 14.8% versus 35.4% (p < 0.001), calcifications in 35.8% versus 46.1% (p = 0.072) and framework fibrosis in 69.8% versus 75.3% (p = 0.53). Metastases were also identified more frequently in larger than in smaller lymph nodes (63.0% vs. 47.5%; p = 0.007). CONCLUSIONS: Degenerative changes in pelvic lymph nodes are commonly detectable but occur with variable frequency in the various nodal landing sites in the pelvis. The degree of lymph node degeneration of single lymph nodes has a significant influence on whether a lymph node is infiltrated by tumor cells and may harbour metastases.

[Robotic-assisted resection of a symptomatic Müllerian duct cyst]. / Roboter-assistierte Resektion einer symptomatischen Müller-Gang-Zyste.

Cysts in the lesser pelvis are a rare disease and most often an incidental finding from routine diagnostic investigation. Published information is controversial. These cysts are distinguished by localisation, content of the cyst and accompanying anatomical anomalies. In this case, we report a 33 years old man who presented to our clinic due to a large retrovesical cyst. Because of lower abdominal pain and problems with defecation, the cyst was diagnosed by ultrasound. Further radiological diagnostic testing confirmed the presence of a retrovesical cyst of unknown malignancy, which was retrospectively evaluated as a Müllerian duct cyst. Due to symptoms and potential malignancy of the cyst, the decision was made to perform surgery. With the help of the operation robot, this benign cyst was safely and completely removed. In a follow-up, the patient presented free of symptoms and sonographically there was no sign of recurrence. Therefore robotic-assisted resection is a safe procedure to treat large symptomatic Müllerian duct cysts.

Prostate Cancer-Associated miRNAs in Saliva: First Steps to an Easily Accessible and Reliable Screening Tool.

BACKGROUND: Common diagnostic tools for prostate cancer-prostate-specific antigen and transrectal biopsy-show only low predictive value and poor sensitivity. This study examines circulating miRNA in saliva to explore the possibility of a non-invasive and easy-to-execute diagnostic tool for prostate cancer screenings. METHODS: 16 miRNAs were extracted from salivary exosomes and analyzed via the delta-CT method. The presented method enables an application of the test in any health institution and even outpatient sector. Recruited participants were suspected to suffer from prostate cancer due to elevated PSA serum levels. Of these participants, 43 were diagnosed with prostate cancer, while 31 suffered from benign diseases and served as control group. RESULTS: hsa-mir-331-3p and hsa-mir-200b were significantly reduced in prostate cancer patients compared to the control group. ROC curve analysis revealed a reliable differentiation strength (AUC &gt; 0.6) for both miRNAs with positive predictive values of 71% indicating prostate cancer. Differentiation of both groups based on PSA serum measurements was insufficient. The other 14 examined miRNAs showed no significant group differences. CONCLUSIONS: The presented method and miRNA are promising non-invasive tools to augment the current prostate cancer screening, thereby improving screening sensitivity and reducing numbers of false positive cancer suspects admitted to further invasive diagnostic and therapeutic steps.

Heterogenous NECTIN4 expression in urothelial high-risk non-muscle-invasive bladder cancer.

High-grade non-muscle-invasive bladder cancer (HG NMIBC) patients are at high risk (HR) of progression to muscle-invasion. Bladder-preserving therapies for this patient subgroup are limited, and additional treatments are desirable. Recently, enfortumab vedotin, targeting cancer-associated NECTIN4, has been approved for the treatment of advanced urothelial carcinoma. However, data on the expression of NECTIN4 and its therapeutic potential for HR NMIBC are scarce. Here, NECTIN4 was immunohistochemically analyzed in urothelial HG NMIBC by studying cohorts of carcinoma in situ (CIS)/T1HG (N = 182 samples), HG papillary tumors from mixed-grade lesions (mixed TaHG) (N = 87) and papillary HG tumors without a history of low-grade disease (pure TaHG/T1HG) (N = 98) from overall 225 patients. Moreover, inter-lesional NECTIN4 heterogeneity in multifocal HG NMIBC tumors was determined. A high prevalence of NECTIN4 positivity was noted across HG NMIBC subgroups (91%, N = 367 samples), with 77% of samples showing moderate/strong expression. Heterogenous NECTIN4 levels were observed between HG NMIBC subgroups: non-invasive areas of CIS/T1HG and pure TaHG/T1HG samples showed NECTIN4 positivity in 96% and 99%, with 88% and 83% moderate/strong expressing specimens, respectively, whereas significantly lower NECTIN4 levels were detected in mixed TaHG lesions (72% positivity, 48% of samples with moderate/strong NECTIN4 expression). Moreover, higher NECTIN4 heterogeneity was observed in patients with multifocal mixed TaHG tumors (22% of patients) compared to patients with multifocal CIS/T1HG and pure TaHG/T1HG tumors (9% and 5%). Taken together, NECTIN4-directed antibody-drug conjugates might be promising for the treatment of HR NMIBC patients, especially for those exhibiting CIS/T1HG and pure TaHG/T1HG tumors without a history of low-grade disease.

Are Parents Informed Well Enough About Their Child's Long-term Risks Related to Undescended Testis?

Worldwide, recommendations for timely surgical repair of undescended testis (UDT) are not well translated into clinical practice, potentially due to suboptimal patient/parent education. We evaluated the frequency and content of information provided to affected parents of 310 consecutive cases of UDT undergoing orchidopexy. Parents were enquired regarding details of education provided by the attending clinician. 18% of parents were not provided with detailed information regarding any long-term consequences of untreated UDT. In the 79% who were educated, information about impaired fertility was frequent, while malignant degeneration, hypogonadism and testicular atrophy were poorly communicated. 49% of all parents searched for further information on the internet or through a second medical opinion. The frequency and level of detail of information regarding long-term complications provided to parents of children with UDT is suboptimal and needs to be improved.

Effectiveness and Safety of a Modified Technique of Transvesical Obturator Nerve Block to Avoid Adductor Contractions during Transurethral Resection of Bladder Tumors.

INTRODUCTION: The aim of the study was to evaluate the effectiveness of a modified transvesical obturator nerve block (ONB) in the prevention of obturator nerve reflex and consecutive bladder perforations (BPs) during transurethral resection of bladder tumors (TURBTs). MATERIALS AND METHODS: A retrospective analysis of all patients resected in 2014-2015 due to a bladder tumor of the lateral walls, including a follow-up period until December 2018, was performed. Two groups were defined: in the first group, all patients underwent TURBT with a modified transvesical ONB. The second group underwent conventional TURBT with intermittent resection. Primary endpoints were the rates of adductor contractions and BPs. RESULTS: Ninety-four out of 1,145 resected patients presented with tumors on the lateral wall of the bladder and a complete dataset including a long-term follow-up. Thirty-six patients were treated in the ONB group, and 58 patients comprised the control group. The median age in the 2 groups was 70.8 and 71.8 years in the first and second groups, respectively. Adductor spasms were reported in 8.33 versus 25.86% (p = 0.057) and perforation in 2.78 versus 17.24% (p = 0.047) in groups 1 and 2, respectively. After a median follow-up of 32.5 months, there was no significant difference in recurrence rates (52.78 vs. 51.72%, p = 0.672). In a subgroup analysis, lower perforation rates were recorded for the ONB group in patients with tumors <3 cm (0/30 vs. 8/46, p = 0.076) and in patients with unifocal tumors (0/12 vs. 5/23, p = 0.141). DISCUSSION/CONCLUSION: The simplified approach of transvesical ONB demonstrated in this study appears to be an inexpensive, safe, effective, and simple-to-use technique.

Intratumoral heterogeneity of surrogate molecular subtypes in urothelial carcinoma in situ of the urinary bladder: implications for prognostic stratification of high-risk non-muscle-invasive bladder cancer.

Reliable factors predicting the disease course of non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) are unavailable. Molecular subtypes have potential for prognostic stratification of muscle-invasive bladder cancer, while their value for CIS patients is unknown. Here, the prognostic impact of both clinico-pathological parameters, including CIS focality, and immunohistochemistry-based surrogate subtypes was analyzed in a cohort of high-risk NMIBC patients with CIS. In 128 high-risk NMIBC patients with CIS, luminal (KRT20, GATA3, ERBB2) and basal (KRT5/6, KRT14) surrogate markers as well as p53 were analyzed in 213-231 biopsies. To study inter-lesional heterogeneity of CIS, marker expression in independent CIS biopsies from different bladder localizations was analyzed. Clinico-pathological parameters and surrogate subtypes were correlated with recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Forty-six and 30% of CIS patients exhibited a luminal-like (KRT20-positive, KRT5/6-negative) and a null phenotype (KRT20-negative, KRT5/6-negative), respectively. A basal-like subtype (KRT20-negative, KRT5/6-positive) was not observed. A significant degree of inter-lesional CIS heterogeneity was noted, reflected by 23% of patients showing a mixed subtype. Neither CIS surrogate subtype nor CIS focality was associated with patient outcome. Patient age and smoking status were the only potentially independent prognostic factors predicting RFS, PFS, OS, and PFS, respectively. In conclusion, further clarification of heterogeneity of surrogate subtypes in HR NMIBC and their prognostic value is of importance with regard to potential implementation of molecular subtyping into clinical routine. The potential prognostic usefulness of patient age and smoking status for high-risk NMIBC patients with CIS needs further validation.

Diagnostic value of Xpert® Bladder Cancer Monitor in the follow-up of patients affected by non-muscle invasive bladder cancer: an update.

AIMS: Xpert® Bladder Cancer Monitor is a urinary marker based on the evaluation of five target mRNAs overexpressed in patients with bladder cancer (BC). The aim of our study is to update our results regarding the diagnostic accuracy of the Xpert® Bladder Cancer Monitor test in the follow-up of patients with non-muscle invasive bladder cancer (NMIBC). METHODS: We conducted a prospective study on 1015 samples of 416 patients (mean age 72.2 ± 10.3 years) under follow-up for NMIBC. Patients underwent voided urinary cytology, the Xpert® Bladder Cancer Monitor test and cystoscopy and, if positive, a transurethral resection of the bladder. Xpert® Bladder Cancer Monitor was reported as negative or positive: cut-off total Linear Discriminant Analysis (LDA) = 0.5. RESULTS: We identified 168 recurrent tumours: 126 (75%) were low-grade (LG) and 42 (25%) high-grade (HG). Overall sensitivity was 17.9% for cytology, 52.4% for Xpert® Bladder Cancer Monitor and 54.2% for the two tests combined. The sensitivity of cytology increased from 6.3% in LG to 52.4% in HG tumours whereas Xpert® Bladder Cancer Monitor showed a sensitivity ranging from 42.9% in LG to 80.9% in HG tumours. Combined cytology and Xpert® Bladder Cancer Monitor yielded an overall sensitivity of 45.2% for LG and 80.9% for HG tumours. Overall specificity was 98.5% for cytology and 78.4% for Xpert® Bladder Cancer Monitor and 78.2% for the two tests combined. The area under the curve (AUC) for Xpert® Bladder Cancer Monitor was 0.71; stratifying the patients according to the European Association of Urology risk groups, the AUC was 0.69, 0.67 and 0.85 for low, intermediate and high risk, respectively (p = 0.0003). CONCLUSION: Our data confirm a significantly higher sensitivity of Xpert® Bladder Cancer Monitor than for cytology in a larger patient cohort. The test performed very well in terms of specificity but could not reach the high value of cytology. Along with voided urinary cytology the test could allow to reduce cystoscopies in follow-up patients, reducing discomfort to the patients and costs.

The natural history of muscle-invasive bladder cancer in geriatric patients undergoing transurethral resection only: Outcome and cost.

PURPOSE: Bladder cancer is predominant in the elderly. Up to 70% of geriatric patients with muscle-invasive bladder cancer do not receive curative treatment. We analyzed the outcome of patients managed only by transurethral resection of bladder tumor (TURBT) without chemo- or radio-therapy, and performed a cost analysis of the cumulative inpatient interventions throughout the course of the disease. METHODS: From 2010 to 2016 81 patients ≥75 years with de novo muscle-invasive bladder cancer who were not eligible for curative treatment options were analyzed retrospectively. All patients were treated only with TURBT. Overall survival (OS) was measured by Kaplan-Meier plots (log-rank test) and clinical parameters predicting OS by a multivariate analysis. The cost analysis was based on actual billing from the hospital provider and referenced standardized pricing in Germany for bladder cancer treatment. RESULTS: The median age was 83 years. The OS was 11 months, the 1-year OS was 42%. In the multivariate model Charlson Comorbidity Index <8 (P = 0.016), tumor size ≤3 cm (P = 0.011), complete (T0) tumor resection (P = 0.003), normal C-reactive protein level (P = 0.010), and initial elective surgery (P = 0.035) were shown to be independent predictors of longer OS in palliative TURBT regimes. Median treatment cost for the TURBT regimen was $16,175 vs. $16,467 for a salvage radical cystectomy in this cohort. CONCLUSIONS: In a TURBT-only concept elective surgery, tumor size, Charlson Comorbidity Index, C-reactive protein level and complete TURBT are independent predictors of OS. The treatment-related cumulative cost appears to be higher in patients not managed by cystectomy.

Multicenter Analysis of Acquired Undescended Testis and Its Impact on the Timing of Orchidopexy.

OBJECTIVE: To assess whether late orchidopexy for undescended testis represents delayed treatment of primary undescended testis or later-occurring acquired undescended testis. STUDY DESIGN: We examined boys undergoing orchidopexy for cryptorchidism regarding age at surgery and entity of undescended testis. We characterized differences between primary undescended testis and acquired undescended testis and evaluated the knowledge regarding the diagnosis and management of acquired undescended testis among practicing physicians. We conducted an observational study using a mixed-method multicenter cross-sectional design. A total of 310 consecutive boys undergoing orchidopexy for undescended testis at 6 pediatric medical centers in Germany between April 2016 and June 2018 were investigated regarding testicular position at birth and age at surgery. In addition, a survey on acquired undescended testis management was carried out in 1017 multidisciplinary physicians and final-year medical students. RESULTS: Only 13% of all patients were operated on in their first year of life. Among patients with known previous testicular position (67%), primary undescended testis (n = 103) and acquired undescended testis (n = 104) were equally frequent. More than one-half (56%) of orchidopexies performed after the first year of life were due to acquired undescended testis. Remarkably, only 15% of physicians considered acquired undescended testis as an indication for late surgery. CONCLUSIONS: Acquired undescended testis is more common than previously perceived and accounts for a significant proportion of "late" orchidopexies in patients with undescended testis. Acquired undescended testis needs to be better recognized in clinical practice and screening should continue in older children with previously descended testes. TRIAL REGISTRATION: German Clinical Trials Registry: DRKS00015903.

Comparison of 2 new real-time polymerase chain reaction-based urinary markers in the follow-up of patients with non-muscle-invasive bladder cancer.

BACKGROUND: The objective of the current study was to compare the diagnostic accuracy of 2 new real-time polymerase chain reaction-based urinary markers with each other and with urinary cytology, cystoscopy, and/or histology in patients being followed for non-muscle-invasive bladder cancer. METHODS: A total of 487 patients were enrolled in the study. Patients were evaluated using voided urine cytology, the Xpert Bladder Cancer Monitor, the Bladder EpiCheck test, and white light cystoscopy. RESULTS: The overall sensitivity was 27.17% for cytology, 64.13% for the Bladder EpiCheck test, and 66.3% for the Xpert Bladder Cancer Monitor. The overall specificity was 98.82% for cytology, 82.06% for the Bladder EpiCheck test, and 76.47% for the Xpert Bladder Cancer Monitor. The negative predictive value was very similar for the 3 tests at 83.56% for cytology, 89.42% for the Bladder EpiCheck test, and 89.35% for the Xpert Bladder Cancer Monitor. When combined, the Bladder EpiCheck test and Xpert Bladder Cancer Monitor detected overall 79.35% of the tumors: 70.37% in low-grade and 92.11% in high-grade tumors. CONCLUSIONS: The Xpert Bladder Cancer Monitor and Bladder EpiCheck test were found to perform very well in terms of sensitivity. Together, the 2 tests detected approximately 92.11% of high-grade tumors. Their specificity was high but could not reach the excellent value of cytology. The negative predictive value was the same for both tests and was higher than that for cytology, especially when the tests were used together (92.24%). These 2 new tests hold promise as urinary biomarkers. They may be used in combination to maximize sensitivity in a less invasive way, thereby reducing invasiveness in the follow-up of patients with non-muscle-invasive bladder cancer and decreasing discomfort for the patients as well as complications and costs.

Impact of CYP2D6 Polymorphisms on Tamoxifen Treatment in Patients With Retroperitoneal Fibrosis: A First Step Towards Tailored Therapy?

OBJECTIVE: To investigate the influence of CYP2D6 polymorphisms on outcomes and health-related quality of life of patients with retroperitoneal fibrosis (RPF) receiving tamoxifen (TMX). TMX is an effective alternative to corticosteroids for patients with RPF. Conversion of TMX to more potent endoxifen is dependent on enzyme activity of CYP2D6. MATERIALS AND METHODS: CYP2D6 genotyping and phenotype prediction of all patients treated with TMX between 02/2007 and 01/2018 was assessed using multiplex polymerase chain reaction (PCR). Groups were classified by phenotype: extensive (EM) vs poor and intermediate (PM + IM) vs ultrarapid metabolizer (UM). Retrospective evaluation of outcome (including magnetic resonance imaging and positron emission tomography-computed tomography) and health-related quality of life using the SF-36 was performed. RESULTS: A total of 63/194 patients received TMX, 40/63 with complete follow-up were sequenced: Twenty-nine patients with EM phenotype, 8 PM + IM and 3 UM. The median therapy duration was 364.5 days with a mean follow-up of 62.9 months. Seven therapy terminations occurred due to lack of response (17.5%), including all UM patients (P <.001). Magnetic resonance imagings showed a regression of fibrosis for EM and PM + IM in 69% and 62.5% of cases and a progression for UM in 100% (P = .004). In positron emission tomography-computed tomography, glucose utilization of RPF decreased significantly for EM and PM + IM. The physical sum-score of SF-36 improved for EM and PM + IM and decreased for UM (P <.05). The removal of DJ-stents was successful for EM, PM + IM, and UM in 48.3%, 75%, and 0% of cases (P = .0581). CONCLUSION: Contrary to expectations, UM showed the lowest success rate, which concludes that genotyping of RPF-patients may be useful in the sense of a tailored-therapy.