The Value of Tumour Markers in the Detection of Relapse-Lessons Learned from the Swiss Austrian German Testicular Cancer Cohort Study.

The tumour markers alpha-fetoprotein (AFP), beta human chorionic gonadotropin (ßHCG), and lactate dehydrogenase (LDH) have established roles in the management and follow-up of testicular cancer. While a tumour marker rise can serve as an indicator of relapse, the frequency of false-positive marker events has not been studied systematically in larger cohorts. We assessed the validity of serum tumour markers for the detection of relapse in the Swiss Austrian German Testicular Cancer Cohort Study (SAG TCCS). This registry was set up to answer questions on the diagnostic performance and impact of imaging and laboratory tests in the management of testicular cancer, and has included 948 patients between January 2014 and July 2021.A total of 793 patients with a median follow-up of 29.0 mo were included. In total, 71 patients (8.9%) had a proven relapse, which was marker positive in 31 patients (43.6%). Of all patients, 124 (15.6%) had an event of a false-positive marker elevation. The positive predictive value (PPV) of the markers was limited, highest for ßHCG (33.8%) and lowest for LDH (9.4%). PPV tended to increase with higher levels of elevation. These findings underline the limited accuracy of the conventional tumour markers to indicate or rule out a relapse. Especially, LDH as part of routine follow-up should be questioned. Patient summary: With the diagnosis of testicular cancer, the three tumour markers alpha-fetoprotein, beta human chorionic gonadotropin, and lactate dehydrogenase are routinely measured during follow-up to monitor for relapse. We demonstrate that these markers are often falsely elevated, and, by contrast, many patients do not have marker elevations despite a relapse. The results of this study can lead to improved use of these tumour markers during follow-up of testis cancer patients.

Impact of Statin Use on Localized Prostate Cancer Outcomes after Radiation Therapy: Long-Term Follow-Up.

The impact of statin use on localized prostate cancer (PCa) remains controversial, especially for patients treated with radiation therapy. We assessed the impact of statin use on biochemical recurrence (BCR) in patients treated for PCa with different modalities of radiation therapy. We evaluated 3555 patients undergoing radiation therapy between January 2001 and January 2022. The impact of statin use on BCR was analyzed for three treatment groups: external beam radiotherapy (EBRT), low-dose-rate seed brachytherapy (LDR), and EBRT plus high-dose-rate brachytherapy (EBRT + HDR). Median follow-up was 52 months among 1208 patients treated with EBRT, 1679 patients treated with LDR, and 599 patients treated with EBRT + HDR. A total of 1544 (43%) patients were taking a statin at the time of treatment, and 497 (14%) patients were in the D'Amico high-risk group. Only intermediate-risk patients treated with LDR fared better with statin use in univariate analysis (p = 0.025). This association was not significant in multivariate analysis (HR 0.44, 95% CI 0.18-1.10, p = 0.06). Statin use was not associated with a reduced risk of BCR in patients treated with radiation therapy. In the era of precision medicine, further investigation is needed to assess the benefit of statins in well-defined patients.

Concordance between Preoperative mpMRI and Pathological Stage and Its Influence on Nerve-Sparing Surgery in Patients with High-Risk Prostate Cancer.

BACKGROUND: We aimed to determine the concordance between the radiologic stage (rT), using multiparametric magnetic resonance imaging (mpMRI), and pathologic stage (pT) in patients with high-risk prostate cancer and its influence on nerve-sparing surgery compared to the use of the intraoperative frozen section technique (IFST). METHODS: The concordance between rT and pT and the rates of nerve-sparing surgery and positive surgical margin were assessed for patients with high-risk prostate cancer who underwent radical prostatectomy. RESULTS: The concordance between the rT and pT stages was shown in 66.4% (n = 77) of patients with clinical high-risk prostate cancer. The detection of patients with extraprostatic disease (≥pT3) by preoperative mpMRI showed a sensitivity, negative predictive value and accuracy of 65.1%, 51.7% and 67.5%. In addition to the suspicion of extraprostatic disease in mpMRI (≥rT3), 84.5% (n = 56) of patients with ≥rT3 underwent primary nerve-sparing surgery with IFST, resulting in 94.7% (n = 54) of men with at least unilateral nerve-sparing surgery after secondary resection with a positive surgical margin rate related to an IFST of 1.8% (n = 1). CONCLUSION: Patients with rT3 should not be immediately excluded from nerve-sparing surgery, as by using IFST some of these patients can safely undergo nerve-sparing surgery.

Does the Identification of a Minimum Number of Cases Correlate With Better Adherence to International Guidelines Regarding the Treatment of Penile Cancer? Survey Results of the European PROspective Penile Cancer Study (E-PROPS).

BACKGROUND: Penile cancer represents a rare malignant disease, whereby a small caseload is associated with the risk of inadequate treatment expertise. Thus, we hypothesized that strict guideline adherence might be considered a potential surrogate for treatment quality. This study investigated the influence of the annual hospital caseload on guideline adherence regarding treatment recommendations for penile cancer. METHODS: In a 2018 survey study, 681 urologists from 45 hospitals in four European countries were queried about six hypothetical case scenarios (CS): local treatment of the primary tumor pTis (CS1) and pT1b (CS2); lymph node surgery inguinal (CS3) and pelvic (CS4); and chemotherapy neoadjuvant (CS5) and adjuvant (CS6). Only the responses from 206 head and senior physicians, as decision makers, were evaluated. The answers were assessed based on the applicable European Association of Urology (EAU) guidelines regarding their correctness. The real hospital caseload was analyzed based on multivariate logistic regression models regarding its effect on guideline adherence. RESULTS: The median annual hospital caseload was 6 (interquartile range (IQR) 3-9). Recommendations for CS1-6 were correct in 79%, 66%, 39%, 27%, 28%, and 28%, respectively. The probability of a guideline-adherent recommendation increased with each patient treated per year in a clinic for CS1, CS2, CS3, and CS6 by 16%, 7.8%, 7.2%, and 9.5%, respectively (each p < 0.05); CS4 and CS5 were not influenced by caseload. A caseload threshold with a higher guideline adherence for all endpoints could not be perceived. The type of hospital care (academic vs. non-academic) did not affect guideline adherence in any scenario. CONCLUSIONS: Guideline adherence for most treatment recommendations increases with growing annual penile cancer caseload. Thus, the results of our study call for a stronger centralization of diagnosis and treatment strategies regarding penile cancer.

Tissue Engineering and Its Potential to Reduce Prostate Cancer Treatment Sequelae-Narrative Review.

Tissue engineering offers the possibility to overcome limitations of current management for postprostatectomy incontinence and ED. Developed in recent years biotechnological feasibility of mesenchymal stem cell isolation, in vitro cultivation and implantation became the basis for new cell-based therapies oriented to induce regeneration of adult tissue. The perspective to offer patients suffering from post-prostatectomy incontinence or erectile dysfunction minimal invasive one-time procedure utilizing autologous stem cell transplantation is desired management.

Current Management of Membranous Urethral Strictures Due to Radiation.

Radiotherapy is a frequently used treatment for prostate cancer. It does not only causes the intended damage to cancer cells, but also affects healthy surrounding tissue. As a result radiation-induced urethral strictures occur in 2.2% of prostate cancer patients. Management of urethral strictures is challenging due to the presence of poor vascularized tissue for reconstruction and the proximity of the sphincter, which can impair the functional outcome. This review provides a literature overview of risk factors, diagnostics and management of radiation-induced urethral strictures.

Application of Graphene in Tissue Engineering of the Nervous System.

Graphene is the thinnest two-dimensional (2D), only one carbon atom thick, but one of the strongest biomaterials. Due to its unique structure, it has many unique properties used in tissue engineering of the nervous system, such as high strength, flexibility, adequate softness, electrical conductivity, antibacterial effect, and the ability to penetrate the blood-brain barrier (BBB). Graphene is also characterized by the possibility of modifications that allow for even wider application and adaptation to cell cultures of specific cells and tissues, both in vitro and in vivo. Moreover, by using the patient's own cells for cell culture, it will be possible to produce tissues and organs that can be re-transplanted without transplant rejection, the negative effects of taking immunosuppressive drugs, and waiting for an appropriate organ donor.

[Diagnostic and therapeutic concepts for vesicovaginal and ureterovaginal fistulas]. / Diagnostik und Therapie vesikovaginaler und ureterovaginaler Fisteln.

BACKGROUND: Vesico- and ureterovaginal fistulas are defined as abnormal connections between the urinary tract, on the one side, and the female genital system, on the other. Despite being highly prevalent as an acquired pathology of the urogenital system, there has as yet been no standardized protocol in place for diagnosing and treating these fistulas. This review analyses the current literature concerning vesico- and ureterovaginal fistulas in order to profile common diagnostic and therapeutic concepts. METHODS: Literature research was carried out using the data bases of Medline and PubMed. A general internet research was added as well as the subsequent analysis of textbooks. Subsequently 40 scientific publications, four textbooks and one internet source were consulted. RESULTS: In the diagnostic process of not only vesicovaginal, but also ureterovaginal fistulas a timely vaginal examination followed by a cystoscopy and further imaging by retrograde vaginal methylene blue instillation should be carried out. In order to further the differential diagnosis of ureterovaginal fistulas in particular, additional imaging techniques may be required. However, the therapies of both fistulas manifest essential differences. Ureterovaginal fistulas are closed in a two-stage procedure. At first, a percutaneous nephrostomy is placed to decompress the renal collecting system and further drain the urine, followed by a second intervention, which closes the fistula. The management of vesicovaginal fistulas includes both conservative and surgical concepts, the latter of which may in turn be divided into a transabdominal and/or a transvaginal approach. Essentially, transabdominal fistula surgery should, at first, include the identification of the orifices of both ureters to subsequently splint them as indicated. This should be followed by the excision of the fistula. In the case of large fistulas a flap reconstruction of the area may be considered after the mobilisation of the surrounding tissue. Despite almost all surgical techniques leading to successful outcomes, patients with radiogenic damage to the area might require an alternative form of urinary drainage. CONCLUSIONS: Industrial and developing countries continue to display significant differences in the etiology of fistulas as well as the operative treatment. The therapeutic concepts in place exhibit high success rates irrespecitve of the surgical approach and should be individually developed in accordance with the etiology, location and size of the fistula as well as the condition of the surrounding tissue.

Comparison of complications from radical cystectomy between old-old versus oldest-old patients.

INTRODUCTION: The purpose of this study was to evaluate and compare complications after radical cystectomy in patients aged ≥75 years. MATERIALS AND METHODS: 251 patients aged 75-95 years (median 79) underwent radical cystectomy between 2000 and 2012 at four institutions. The patients were divided into two groups: ≥75-84 years of age (group 1) versus ≥85 years of age (group 2). Comorbidities, body mass index, and complications were obtained retrospectively, except at the Central Hospital of Bolzano and Weill Cornell Medical Center, which collected data prospectively. Cancer-specific survival, overall mortality, hospital stay, clinical outcome and complications were assessed. Complications were categorized using the Clavien-Dindo classification reporting system. The mean follow-up was 21 months. RESULTS: The median hospital stay was 17 (2-91) days. Perioperative Clavien-Dindo grade ≥III complications were seen in 24.1% (48/199) of group 1 patients and 19.2% (10/52) of group 2 patients (p = 0.045). 30- and 90-day mortality was 4.5 and 13.5% in group 1 and 6.5 and 32.3% in group 2, respectively. Only the 90-day mortality rate was statistically significant (p < 0.05) between the two groups. The 3-year overall survival was 40% in group 1 and 34% in group 2. The 3-year cancer-specific survival was 52% in group 1 and 50% in group 2. CONCLUSIONS: We evaluated a large series of elderly (≥75 years) patients undergoing radical cystectomy at four institutions. Comparing patients aged ≥75-84 and ≥85 years revealed no significant difference in complications, 30-day mortality, overall and cancer-specific survival rates. Only 90-day mortality rates were significantly higher in the ≥85-year-old patients.

A comparative assessment of active surveillance for localized prostate cancer in the community versus tertiary care referral center.

OBJECTIVES: To date, evidence on active surveillance (AS) is restricted to protocol-based studies. Conversely, practice patterns outside of such protocols are unknown. The aim of this study was to capture the current AS treatment patterns for localized prostate cancer in patients managed by office-based urologists compared to patients treated at a tertiary care center. METHODS AND MATERIALS: Two prospective cohorts were investigated: 361 AS arm patients of the German Hormonal treatment, Active surveillance, Radiation therapy, OP, Watchful waiting (HAROW) study, an observational health service study and 387 protocol-based AS patients treated at the Department of Urology of the Kantonsspital Aarau, Switzerland were included. Observational non-protocol HAROW versus on-protocol Kantonsspital Aarau (KSA) was compared, and active-treatment-free survival represented the primary outcome. RESULTS: Study population of the observational HAROW versus tertiary care protocol-based KSA cohorts differed statistically significantly regarding age (p < 0.001) and proportion of patients meeting the Chism criteria (p < 0.001). In stratified analyses, AFTS at 1 and 2 years was, respectively, 87.7 % (95 % CI 84.0-91.7) and 75.0 % (95 % CI 69.7-80.8) in HAROW patients compared to 90.8 % (95 % CI 87.8-93.9) and 75.3 % (95 % CI 70.7-80.1) for patients in the KSA cohort (p = 0.97). CONCLUSION: We demonstrate significant differences in terms of AS inclusion, surveillance and discontinuation criteria between patients managed by office-based urologists compared to their tertiary care counterparts. Interestingly, the risk of deferred active therapy was equally moderate for both groups in the short-term follow-up.

Transperineal reanastomosis for the treatment for highly recurrent anastomotic strictures as a last option before urinary diversion.

PURPOSE: To evaluate safety and efficacy of open transperineal reanastomosis (TPRA) for highly recurrent anastomotic strictures (AS) after radical prostatectomy. While the majority of AS can be managed successfully by endoscopic treatment, in highly recurrent AS, open reanastomosis represents a viable therapeutic option. METHODS: Retrospective analysis by standardized questionnaire, inquiring for recurrence, incontinence, sexual function, satisfaction and changes in quality of life (QoL) in 15 patients undergoing TPRA 08/2007-03/2010. RESULTS: Mean patient age was 65 years (51-75) and mean follow-up 20.5 months (5.8-37.0). Success rate was 93.3 % (14/15). The single recurrence was successfully treated by cold knife incision. Incontinence was found in 93.3 % (14/15) preoperatively and aggravated in 60 % (9/15) after surgery; no de novo incontinence occurred. Implantation of an artificial urinary sphincter (AUS) has been performed successfully in 10 patients, 2 refused implantation and 2 are scheduled for surgery. Erectile dysfunction was present in 86.7 % (13/15); 13.3 % (2/15) reported a severely declined rigidity. Compared to preoperative status, 33.3 % (5/15) complained about impaired erectile function after TPRA. A good or very good subjective overall health status and an improvement in QoL were noted in 86.7 % (13/15). Patient satisfaction with the outcome of TPRA was high or very high in 13; two were undecided. CONCLUSIONS: After repeated endoscopic treatment, TPRA is a valuable therapeutic option in selected patients with an overall success rate of 93.3 % (14/15) for anastomotic patency, which can even be raised to 100 % by further transurethral surgery. Incontinence can be easily treated by implantation of an AUS.

Local tumor destruction in renal cell carcinoma--an inpatient population-based study.

OBJECTIVES: Local tumor destruction (LTD) is a recommended therapy alternative for localized T1 renal cell carcinoma for patients who are unfit for surgery. We examined patterns of use and complication rates of LTD in a large population-based cohort. MATERIALS AND METHODS: Overall, data for 5,285 patients undergoing LTD for renal cell carcinoma were extracted from the Nationwide Inpatient Sample database from 2006 to 2010. We assessed patient and hospital characteristics, as well as postoperative complications, using International Classification of Diseases, Ninth Revision codes. The effect of patient and hospital characteristics on peri-interventional complications (overall or specific) was tested using univariable or multivariable logistic regression models. RESULTS: Most patients were male (61.2%), aged 71 to 80 years (34.9%), and had 3 or more comorbidities (30.6%). Most LTDs were performed at urban (93.5%), teaching (57.7%), and low-volume (75.7%) hospitals. Overall complications were recorded in 15.4% of patients. In multivariable analyses adjusted for clustering, overall complications occurred more frequently in older, sicker patients who were treated at low-volume hospitals (all P<0.05). Similar results were recorded when each complication category was addressed individually. CONCLUSIONS: In the current population-based cohort, complications of LTD occurred in 1 of 6 patients and were more frequent in individuals with advanced age or multiple comorbidities, or both, especially if LTDs were performed at lower-volume hospitals.