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ZusammenfassungWir berichten über einen 64-jährigen Patienten mit einer Penismetastase zehn Jahre nach Erstdiagnose eines polymorphen Adenokarzinoms der kleinen Speicheldrüsen der Zungenbasis. Unserer Kenntnis gibt es bis dato nur zwei in der Literatur beschriebene Fälle.

Propose Using Docetaxel chemotherapy or new hormonal agents (NHT) to intensify upfront systemic therapy resulted in improved survival rates compared to androgen deprivation monotherapy (ADT). Hence, combination therapies have become the new standard of care (SOC) in metastatic hormone-sensitive prostate cancer (mHSPC). However, head-to-head trails comparing different therapies as well as treatment-guiding biomarkers are still lacking. Thus, the aim of the present study was to compare clinical outcomes of Docetaxel versus NHT therapy in the real-world setting as well as to elaborate biomarkers predicting clinical outcome. Methods We retrospectively assessed overall-survival (OS), progression-free survival 1 and 2 (PFS1/2) and time to progression (TTP) in 42 patients treated by either ADT + NHT or ADT + Docetaxel. In addition, we investigated clinical prognostic biomarkers. Results Our survival analysis revealed 3-year OS of 89.4% in the NHT group compared to 82.4% in the Docetaxel group. 3-year PFS1 was 59.6% in the NHT group compared to 32.2% in the Docetaxel group and the TTP was 53.8% vs 32.2% (pOS = 0.189; pPFS1 = 0.082; pTTP = 0.055). In addition, castration-resistance occurred more often in the Docetaxel group (78.6% vs 25%, p = 0.004). Interestingly, a PSA-Nadir ≤ 0.05 ng/ml during therapy was associated with increased survival rates (p 0.001) while PSA levels at primary diagnosis had no influence on therapy outcome. Furthermore, a thyroid-stimulating hormone (TSH) increase during therapy was associated with improved clinical outcome (p = 0.06). Conclusion We observed a trend towards a higher benefit of NHT as first-line treatment compared to Docetaxel in men with mHSPC. Of note, a PSA-Nadir ≤ 0.05 ng/ml or a TSH-increase during therapy were predictors for therapy response.

Prostate cancer (PCa) is one of the most common cancers in developed countries. The results of large trials indicate that the proportion of PCa attributable to hereditary factors is as high as 15%, highlighting the importance of genetic testing. Despite improved understanding of the prevalence of pathogenic variants among men with PCa, it remains unclear which men will most benefit from genetic testing. In this review, we summarize recent evidence on genetic testing in primary PCa and its impact on routine clinical practice. We outline current guideline recommendations on genetic testing, most importantly, for mutations in BRCA1/2, MMR, CHEK2, PALB2, and HOXB13 genes, as well as various single nucleotide polymorphisms associated with an increased risk of developing PCa. The implementation of genetic testing in clinical practice, especially in young patients with aggressive tumors or those with positive family history, represents a new challenge for the coming years and will identify men with pathogenic variants who may benefit from early screening/intervention and specific therapeutic options. Supplementary Information The online version contains supplementary material available at 10.1007/s40291-021-00529-3.

A solely retroperitoneal mass in males in combination with elevated serum Alpha-Fetoprotein (AFP) and beta-human choriogonadotropin (β-HCG) levels is highly indicative of a metastatic testicular cancer. Although testicular cancers are rare, they represent the most common diagnosed cancer in males between 14 and 40 years. However, in cases without evidence of a primary testicular tumor, the rare diagnosis of a retroperitoneal extragonadal germ cell tumor (EGCT) must be assumed. Here, we describe the first published case of a 66-year-old man presenting with this typical clinical picture and the diagnosis of an AFP and β-HCG producing advanced gastric cancer with retroperitoneal lymph node metastases mimicking a primary retroperitoneal EGCT. The final diagnosis was only made by gastroscopy performed after a CT-guided retroperitoneal lymph node biopsy revealed an adenocarcinoma, suggesting an upper gastrointestinal tract primary origin. However, a specific initial anamnesis and also in the primary staging, including a full-body CT-scan there was no hint for another primary tumor. Only the slightly unusual extension of the retroperitoneal mass up to the ligamentum hepatoduodenale and the pylorus, as well as the atypical age made us question our initial diagnosis. This extraordinary case is of special clinical interest to all practising physicians and once again highlights the importance of keeping rare differential diagnosis such as AFP-producing gastrointestinal tumors in mind.

Prostate cancer is one of the most common causes of death in males. Even if treatment is often of curative intent in early stages of the disease, up to 50% of patients relapse after primary therapy. Moreover, 10% to 15% of patients present in a primary metastatic stage of disease. In the past years the treatment landscape of metastatic castration-resistant prostate cancer expanded due to the development of second-generation antiandrogens (abiraterone acetate, enzalutamide), chemotherapeutic agents and radium-223. With the availability of several therapeutic lines, we are now confronted with the problem of choosing the most suitable therapy in each state of disease. As often observed in clinical routine, prostate specific antigen is not sufficient for early prediction of a therapy response. Furthermore, biomarkers for prediction of the optimal first-line therapy are badly needed in order to avoid primary resistance. Therefore, the present short review article gives an overview of currently available clinical and preclinical biomarkers for treatment response to metastatic castration-resistant prostate cancer therapeutic agents with the aim of providing support for a personalized decision-making process in everyday use.

Objectives: Upper urinary tract urothelial carcinoma (UTUC) represents about 5–10% of all urothelial malignancies with an increasing incidence. The standard diagnostic tools for the detection of UTUC are cytology, computed tomography (CT) urography, and ureterorenoscopy (URS). No biomarker to be included in the daily clinical practice has yet been identified. The aim of our study was to evaluate the potential role of Xpert® Bladder-Cancer (BC)-Detection in the diagnosis of UTUC. Methods: Eighty-two patients underwent 111 URS with Xpert® BC-Detection, cytology, or Urovysion® analysis of UT for suspicion of UTUC. Twenty-four cases were excluded from the analysis due to a non-diagnostic Xpert® BC-Detection, cytology, or Urovysion®. Samples were analyzed with upper tract (UT) urinary cytology, with Xpert® BC-Detection on UT urines, and with Urovysion® Fluorescence in situ hybridization (FISH) test. After urine collection, the patients underwent retrograde pyelography and/or URS, and if positive a UT biopsy. The Xpert® BC-Detection was reported by the software as negative or positive [cut-off total Linear Discriminant Analysis (LDA) = 0.45]. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of cytology, Xpert® BC-Detection and Urovysion-FISH were calculated using URS and/or histology results as reference. Results: In all, 27 (31%) of 87 URS resulted positive, with 20 low-grade (LG) and 7 high-grade (HG) tumors. Overall sensitivity was 51.9% for cytology, 100% for Xpert® BC-Detection, and 92.6% for Urovysion. The sensitivity of cytology increased from 26% in LG to 100% in HG tumors. For Xpert® BC-Detection, sensitivity was 100% both in LG and in HG, and for Urovysion-FISH, it increased from 90% in LG to 100% in HG tumors. PPV was 82.4% for cytology, 35% for Xpert® BC-Detection, and 73.5% for Urovysion. NPV was 81.4% for cytology, 100% for Xpert® BC-Detection, and 96.2% for Urovysion. Conclusion: The excellent NPV of Xpert® BC-Detection allows to avoid unnecessary endoscopic exploration of the UT, reducing invasiveness and URS complications in the follow-up of UTUC.

Since tissue material is often lacking in metastatic prostate cancer (mPCa), there is increasing interest in using liquid biopsies for treatment decision and monitoring therapy responses. The purpose of this study was to validate the usefulness of circulating tumor cells (CTCs) and plasma-derived cell-free (cf) RNA as starting material for gene expression analysis through qPCR. CTCs were identified upon prostate-specific membrane antigen and/or cytokeratin positivity after enrichment with ScreenCell (Westford, Massachusetts, USA) filters or the microfluidic ParsortixTM (Guildford, Surrey, United Kingdom) system. Overall, 50% (28/56) of the patients had ≥5 CTCs/7.5 mL of blood. However, CTC count did not correlate with Gleason score, serum PSA, or gene expression. Notably, we observed high expression of CD45 in CTC samples after enrichment, which could be successfully eliminated through picking of single cells. Gene expression in picked CTCs was, however, rather low. In cfRNA from plasma, on the other hand, gene expression levels were higher compared to those found in CTCs. Moreover, we found that PSA was significantly increased in plasma-derived cfRNA of mPCa patients compared to healthy controls. High PSA expression was also associated with poor overall survival, indicating that using cfRNA from plasma could be used as a valuable tool for molecular expression analysis.

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.

Background The objective of this study was to evaluate the diagnostic accuracy of the Bladder EpiCheck test in the follow-up of patients with non-muscle-invasive bladder cancer (NMIBC) and to compare it with the accuracy of urinary cytology, cystoscopy, and/or histology. Methods In total, 243 patients were enrolled in the current study. Patients were evaluated by voided urine cytology, by the Bladder EpiCheck test, and by white-light cystoscopy. Results Overall sensitivity was 33.3% for cytology, 62.3% for Bladder EpiCheck, and 66.7% for the 2 tests combined. The sensitivity of cytology increased from 7.7% in low-grade (LG) tumors to 66.6% in high-grade (HG) tumors; whereas, for the Bladder EpiCheck test, the sensitivity was 46.1% in LG tumors and 83.3% in HG tumors. Combined cytology and Bladder EpiCheck testing yielded an overall sensitivity of 56.4% for LG tumors and 90% for HG tumors. Overall specificity was 98.6% for cytology, 86.3% for Bladder EpiCheck, and 85.6% for the 2 tests combined. The positive predictive value was 92% for cytology and 68.2% for Bladder EpiCheck. For the 2 tests combined, it was 68.6%. The negative predictive value was similar for the 2 tests: 75.8% for cytology, 82.9% for Bladder EpiCheck, and 84.5% for the 2 tests combined. Conclusions The sensitivity of the Bladder EpiCheck test was significantly higher than that of cytology. The test performed very well in terms of specificity but could not reach the high value of cytology. The positive predictive value was higher for Bladder EpiCheck, whereas the negative predictive value was approximately the same for both tests.

Background Prostate-specific antigen (PSA)-based detection of prostate cancer (PCa) often leads to negative biopsy results or detection of clinically insignificant PCa, more frequently in the PSA range of 2–10 ng/ml, in men with increased prostate volume and normal digital rectal examination (DRE). Objective This study evaluated the accuracy of Proclarix, a novel blood-based diagnostic test, to help in biopsy decision-making in this challenging patient population. Design, setting, and participants Ten clinical sites prospectively enrolled 457 men presenting for prostate biopsy with PSA between 2 and 10 ng/ml, normal DRE, and prostate volume ≥35 cm3. Transrectal ultrasound–guided and multiparametric magnetic resonance imaging (mpMRI)-guided biopsy techniques were allowed. Outcome measurements and statistical analysis Serum samples were tested blindly at the end of the study. Diagnostic performance of Proclarix risk score was established in correlation to systematic biopsy outcome and its performance compared with %free PSA (%fPSA) and the European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculator (RC) as well as Proclarix density compared with PSA density in men undergoing mpMRI. Results and limitations The sensitivity of Proclarix risk score for clinically significant PCa (csPCa) defined as grade group (GG) ≥2 was 91% (n = 362), with higher specificity than both %fPSA (22% vs 14%; difference = 8% [95% confidence interval {CI}, 2.6–14%], p = 0.005) and RC (22% vs 15%; difference = 7% [95% CI, 0.7–12%], p = 0.028). In the subset of men undergoing mpMRI-fusion biopsy (n = 121), the specificity of Proclarix risk score was significantly higher than PSA density (26% vs 8%; difference = 18% [95% CI, 7–28%], p Conclusions In a routine use setting, Proclarix accurately discriminated csPCa from no or insignificant PCa in the most challenging patients. Proclarix represents a valuable rule-out test in the diagnostic algorithm for PCa, alone or in combination with mpMRI. Patient summary Proclarix is a novel blood-based test with the potential to accurately rule out clinically significant prostate cancer, and therefore to reduce the number of unneeded biopsies.

Background: This study was conducted in order to analyze factors predicting malignancy in patients undergoing organ-sparing surgery (OSS) for small testicular lesions. Methods: Patients with small (&le, 20 mm) marker-negative clinical stage I testicular tumors were managed by OSS with tumor enucleation and frozen section examination (FSE) for the past 15 years at our institution. Benign and malignant cases were compared, focusing on preoperative and postoperative lesion sizes. Results: Eighty-nine patients were enrolled in this retrospective study. Ten (11.2%) of them were treated for synchronous bilateral tumors. Sixty-seven (67.7%) of ninety-nine lesions were benign, confirming a high concordance rate (98%) between FSE and final histology. Patients with benign tumors were significantly older than patients with malignant tumors (p = 0.026), and benign tumors were detected more frequently during urologic work-up of hormone disorders (p = 0.001). Preoperative tumor size was a strong predictor of malignancy (area under the curve (AUC) = 0.726, p &lt, 0.001). According to the Youden index, the best cutoff to predict tumor dignity was 13.5 mm, resulting in a sensitivity and specificity of 53% and 85%, respectively. No cases of local recurrence or distant metastasis were confirmed after a median follow-up of 42 months. Conclusion: Our findings are consistent with previous reports, supporting an OSS approach in small testicular tumors whenever possible. Most tumors &le, 20 mm were benign, and in the case of malignancy, OSS with FSE and consecutive orchiectomy is oncologically safe due to the high concordance rate of FSE and final histology, thus preventing a two-stage procedure.

Purpose: Prostate biopsy is the gold standard for prostate cancer diagnosis; unfortunately, this procedure is not free from complications. Recent studies have shown an increase in antibiotic resistance. The aim of our prospective randomized study was to evaluate the efficacy and safety of a prostate biopsy prophylaxis protocol using 2 vs. 3 fosfomycin doses. Methods: Two hundred and ninety-seven patients undergoing transrectal systematic ultrasound (US)-guided (n = 277) or transrectal fusion prostate biopsy (n = 20) were prospectively evaluated and randomized by date of birth, to receive 2 (even years, group A) versus 3 doses of fosfomycin (odd years, group B), and prospectively evaluated. Results:Two hundred and ninety-seven patients were randomized to group A (n = 162) or group B (n = 135). The 2 groups were comparable with respect to age, comorbidity, PSA value, prostate volume, operative time and urine culture results. Out of 297 patients, 44 (14.8%) developed complications after the procedure; 2.7% (8/297) of patients developed fever >38° requiring hospitalization (6 [3.7%] in group A and 2 [1.5%] in group B, p = 0.29). Patients who underwent fusion biopsy were more frequently readmitted in comparison with patients undergoing US-guided prostate biopsy (p = 0.000). Conclusion: The low fever and prostatitis rate suggest that fosfomycin prophylaxis is safe and efficient. There is no significant difference in clinical outcome between the 2 dosage regimens.

BACKGROUND/AIM Hydrocele testis is a common disease with a prevalence of 1% in adults. Although it can be diagnosed by physical examination, scrotal ultrasound represents a standard diagnostic tool, to exclude underlying pathologies among them testicular or scrotal malignancies. PATIENTS AND METHODS We conducted a retrospective analysis of 156 patients aged between 20 and 60 years who underwent surgical hydrocelectomy between 2003 and 2018. Pre-surgical ultrasound, histological results, complications and patients' characteristics were analysed. RESULTS Malignancies were found in 0% of patients in the pre-surgical ultrasound. Interestingly, we found a higher incidence of hydrocele testis in patients with increasing age and 27% presented with symptoms other than painless enlargement of the scrotum. Among them recurrent pain was the most common. Surgical complications occurred in only 3.2%. CONCLUSION Testicular cancer is an important differential diagnosis of hydrocele testis. However, in our study no case of incidental testicular cancer or scrotal malignancy was found in the pre-surgical ultrasound.

The expanded use of second-generation antiandrogens revolutionized the treatment landscape of progressed prostate cancer. However, resistances to these novel drugs are already the next obstacle to be solved. Various previous studies depicted an involvement of the enzyme AKR1C3 in the process of castration resistance as well as in the resistance to 2nd generation antiandrogens like enzalutamide. In our study, we examined the potential of natural AKR1C3 inhibitors in various prostate cancer cell lines and a three-dimensional co-culture spheroid model consisting of cancer cells and cancer-associated fibroblasts (CAFs) mimicking enzalutamide resistant prostate cancer. One of our compounds, named MF-15, expressed strong antineoplastic effects especially in cell culture models with significant enzalutamide resistance. Furthermore, MF-15 exhibited a strong effect on androgen receptor (AR) signaling, including significant inhibition of AR activity, downregulation of androgen-regulated genes, lower prostate specific antigen (PSA) production, and decreased AR and AKR1C3 expression, indicating a bi-functional effect. Even more important, we demonstrated a persisting inhibition of AR activity in the presence of AR-V7 and further showed that MF-15 non-competitively binds within the DNA binding domain of the AR. The data suggest MF-15 as useful drug to overcome enzalutamide resistance.

Aggressive angiomyxoma is a rare mesenchymal neoplasm, occurring mainly in females. It is located in the pelvis and perineum, with known metastasis and hormone sensitivity only in females. Local recurrence is relatively common. We describe the case of a 62-year-old man who presented with symptoms and signs of a spermatocele. Scrotal exploration with surgical excision of the lesion was done. Because a benign setting was assumed, no radical inguinal orchiectomy was performed. The specimen sent to pathology confirmed an aggressive angiomyxoma with positive resection margins. Despite the plurality of benign scrotal masses such as spermatoceles or hydroceles, rare neoplasms should always be kept in mind. Hence, complete excision should be performed whenever possible. We selected an active surveillance strategy despite positive margins, since there is no described case of metastasis in men to date. Therefore, regular scrotal ultrasound examinations every 3 months were arranged as follow-up.

Background: Upper tract urothelial carcinomas (UTUCs) are infrequent neoplasms occurring in the pelvis renalis or the ureter with an incidence between 5% and 10% of all urothelial carcinomas. In addition, a synchronous bilateral appearance is extremely rare with a quantity of only 1.6% of all UTUCs. Since an oncologically-safe treatment would be a radical nephroureterectomy, consequently leading to dialysis, a satisfying therapy is challenging. Case Presentation: We present the case of a 64-year-old woman with bilateral UTUCs at primary diagnosis and the sincere wish of a kidney-preserving treatment option. Therefore, multiple endoscopic ablations with a laser were performed, until a tumor-free status could be achieved. Owing to her medical history with a gynecologic tumor, a genetic examination was initiated, revealing the diagnosis of a Lynch syndrome. Based on promising results in the first 3-month follow-up we decided on a short-term endoscopic follow-up to keep control of tumor progression by endoscopic ablations when needed. In this way we are trying to spare our patient the dialysis. Conclusions: An oncologically satisfying treatment for bilateral UTUCs stays a challenging problem in urology. Despite little available data and expected high recurrence rates, we decided on an endoscopic kidney-preserving therapy approach to eventually spare our patient the dialysis. Up to now we are pleasantly surprised about the result and since a short-term follow-up is possible in our department, we hope to attain endoscopic control of the tumor. In addition, we want to point out that genetic background might be underestimated and should be keep it in mind for special cases. In this way, an early detection of other related tumors or tumor detection in relatives could be possible through preventive checkups.

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.Wir berichten über einen 64-jährigen Patienten mit einer Penismetastase zehn Jahre nach Erstdiagnose eines polymorphen Adenokarzinoms der kleinen Speicheldrüsen der Zungenbasis. Unserer Kenntnis gibt es bis dato nur zwei in der Literatur beschriebene Fälle.

Currently, there are various therapeutic approaches to reduce hypertrophic scarring; however, there is no standard evidence-based treatment protocol. Hence, a systematic review was performed to obtain a summary of the latest clinical trials to evaluate evidence for the treatment of hypertrophic scars. The review protocol was registered and approved by PROSPERO (CRD42015027040). PubMed and Web of Science were searched using predefined MeSH-Terms to identify studies published within the last 10 years regarding treatment for hypertrophic scars. Exclusion criteria included a level of evidence (LoE) lower than I, nonhuman in vivo studies, in vitro studies, studies on keloids, literature reviews, and non-English articles. The literature search identified 1,029 unique articles, whereas 6 articles were prospective, randomized, blinded, controlled clinical trials with a LoE I, and were thus included in the systematic analysis. Three clinical trials evaluated silicone products and pressure garments, and the other three studies investigated the efficacy of intralesional injections of triamcinolone (TAC), 5-Fluorouracil (5-FU) combined with TAC as well as the additional irradiation with a 585 nm pulsed-dye laser (PDL). Intralesional injections revealed significant improvements of the scar quality in terms of height, thickness, erythema, and pigmentation. Pressure garments showed favorable results but there was no evidence that silicone products were able to improve the scar quality. The systematic review demonstrated that there are just a few clinical trials with a LoE of I. Consequently, evidence is still lacking especially for noninvasive treatment regimens for hypertrophic scars. Intralesional injections of 5-FU mixed with a low dose of TAC can be seen as most appropriate treatment modality. Prospective clinical trials to determine the efficiency of silicone products are warranted.

Currently, there are various therapeutic approaches to reduce hypertrophic scarring; however, there is no standard evidence-based treatment protocol. Hence, a systematic review was performed to obtain a summary of the latest clinical trials to evaluate evidence for the treatment of hypertrophic scars. The review protocol was registered and approved by PROSPERO (CRD42015027040). PubMed and Web of Science were searched using predefined MeSH-Terms to identify studies published within the last 10 years regarding treatment for hypertrophic scars. Exclusion criteria included a level of evidence (LoE) lower than I, nonhuman in vivo studies, in vitro studies, studies on keloids, literature reviews, and non-English articles. The literature search identified 1,029 unique articles, whereas 6 articles were prospective, randomized, blinded, controlled clinical trials with a LoE I, and were thus included in the systematic analysis. Three clinical trials evaluated silicone products and pressure garments, and the other three studies investigated the efficacy of intralesional injections of triamcinolone (TAC), 5-Fluorouracil (5-FU) combined with TAC as well as the additional irradiation with a 585 nm pulsed-dye laser (PDL). Intralesional injections revealed significant improvements of the scar quality in terms of height, thickness, erythema, and pigmentation. Pressure garments showed favorable results but there was no evidence that silicone products were able to improve the scar quality. The systematic review demonstrated that there are just a few clinical trials with a LoE of I. Consequently, evidence is still lacking especially for noninvasive treatment regimens for hypertrophic scars. Intralesional injections of 5-FU mixed with a low dose of TAC can be seen as most appropriate treatment modality. Prospective clinical trials to determine the efficiency of silicone products are warranted.