There is a high medical need to develop new strategies for the treatment of patients with acute myeloid leukemia (AML) refractory to conventional therapy. In vitro, the combinations of the blast-modulatory response modifiers GM-CSF + Prostaglandin E1, (summarized as Kit M) have been shown to convert myeloid leukemic blasts into antigen-presenting dendritic cells of leukemic origin (DC_leu) that were able to (re-)activate the innate and adaptive immune system, direct it specifically against leukemic blasts, and induce memory cells. This study aimed to investigate the immune modulatory capacity and antileukemic efficacy of Kit M in vivo. Brown Norway rats suffering from AML were treated with Kit M (twofold application). Blasts and immune cells were monitored in peripheral blood (PB) and spleen. Upon the observation of promising immune modulatory effects in the treated animals, two patients with AML refractory to multiple lines of therapy were offered treatment with Kit M on an individualized basis. Safety, as well as immunological and clinical effects, were monitored. Samples obtained from a third patient in similar clinical conditions not receiving Kit M were used as controls for immune monitoring tests. Animal experiments: Drugs were well tolerated by the treated animals. After 9 days of treatment, DC_leu and memory-like T cells increased in the peripheral blood, whereas regulatory T cells, especially blasts, decreased in treated as compared to untreated control animals. Clinical courses: No severe side effects were observed. In patient 1482, PB blasts remained under the detection threshold during 27 days of treatment, thrombocytes were normalized, and (leukemia specific) immune effector cells of the adaptive and innate immune system increased up to 800-fold compared to the start of treatment. Patient 1601 responded with a 12% reduction in blasts in PB immediately after Kit M treatment. Several subtypes of (leukemia-specific) immune effector cells in PB increased up to four-fold during the 19 days of treatment. In contrast, immune-reactive cells decreased under mild chemotherapy in the PB of control patient 1511 with comparably refractory AML. Within the limitation of low numbers in both animal experiments and clinical applications, our data suggest that Kit M treatment of AML-diseased rats and patients is feasible and may induce leukemia-specific immune reactions and clinical improvement. A larger series and a prospective clinical trial will be required to confirm our observations. Beyond optimized doses and schedules of the applied compounds, the combination with other antileukemic strategies or the application of Kit M in less proliferative stages of the myeloid diseases need to be discussed. If effects are confirmed, the concept may add to the armamentarium of treatments for highly aggressive blood cancer.

Multiparametric magnetic resonance imaging (mpMRI) has emerged as a new cornerstone in the diagnostic pathway of prostate cancer. However, mpMRI is not devoid of factors influencing its detection rate of clinically significant prostate cancer (csPCa). Amongst others, prostate volume has been demonstrated to influence the detection rates of csPCa. Particularly, increasing volume has been linked to a reduced cancer detection rate. However, information about the linkage between PI-RADS, prostate volume and detection rate is relatively sparse. Therefore, the current study aims to assess the association between prostate volume, PI-RADS score and detection rate of csP-Ca, representing daily practice and contemporary mpMRI expertise. Thus, 1039 consecutive patients with 1151 PI-RADS targets, who underwent mpMRI-guided prostate biopsy at our tertiary referral center, were included. Prior mpMRI had been assessed by a plethora of 111 radiology offices, including academic centers and private practices. mpMRI was not secondarily reviewed in house before biopsy. mpMRI-targeted biopsy was performed by a small group of a total of ten urologists, who had performed at least 100 previous biopsies. Using ROC analysis, we defined cut-off values of prostate volume for each PI-RADS score, where the detection rate drops significantly. For PI-RADS 4 lesions, we found a volume > 61.5 ccm significantly reduced the cancer detection rate (OR 0.24; 95% CI 0.16–0.38; p < 0.001). For PI-RADS 5 lesions, we found a volume > 51.5 ccm to significantly reduce the cancer detection rate (OR 0.39; 95% CI 0.25–0.62; p < 0.001). For PI-RADS 3 lesions, none of the evaluated clinical parameters had a significant impact on the detection rate of csPCa. In conclusion, we show that enlarged prostate volume represents a major limitation in the daily practice of mpMRI-targeted biopsy. This study is the first to define exact cut-off values of prostate volume to significantly impair the validity of PI-RADS assessed in a real-world setting. Therefore, the results of mpMRI-targeted biopsy should be interpreted carefully, especially in patients with prostate volumes above our defined thresholds.

Objectives: Holmium laser enucleation of the prostate (HoLEP) can be used regardless of prostate size and offers durable long-term results for patients suffering from lower urinary tract symptoms (LUTS)/benign prostatic obstruction (BPO), with reduced perioperative morbidity. In most western societies almost half of the population are overweight, and obesity itself is often a risk factor for surgical treatment of patients. We therefore analysed the impact of body mass index (BMI) on outcomes and perioperative morbidity in patients undergoing HoLEP for LUTS at our tertiary referral centre. Methods: We retrospectively collected data for 877 patients who underwent HoLEP for LUTS/BPO between 2014 and 2018 and divided patients into group 1 (BMI<25), 2 (BMI 25<30), and 3 (BMI⩾30). We analysed perioperative parameters, safety, and short-term functional outcomes. Results: In preoperative patient characteristics we observed a similar LUTS profile throughout our patient cohorts. The highest proportion of ASA score ⩾III was observed in the obese patient cohort. Enucleation time was significantly prolonged in morbidly obese patients and operative speed was significantly slower, without difference in perioperative complications. Functional outcomes were assessed 30 days post-surgery with significant improvement in IPSS, quality of life (QoL) and Q_max for all groups. Conclusion: Although operating on overweight and obese patients takes significantly longer, HoLEP is efficient and offers acceptable perioperative complication rates even in morbidly obese patients (BMI⩾30). Level of evidence: Not applicable.

Objective: Over the last decade, active surveillance (AS) of low-risk prostate cancer has been increasing. The mpMRI fusion-guided biopsy of the prostate (FBx) is considered to be the gold standard in preoperative risk stratification. However, the role of FBx remains unclear in terms of risk stratification of low-risk prostate cancer outside high-volume centers. The aim of this study was to evaluate adverse pathology after radical prostatectomy (RP) in a real-world setting, focusing on patients diagnosed with Gleason score (GS) 6 prostate cancer (PCa) and eligible for AS by FBx. Subjects and Methods: Between March 2015 and March 2022, 1297 patients underwent FBx at the Department of Urology, Ludwig-Maximilians-University of Munich, Germany. MpMRI for FBx was performed by 111 different radiology centers. FBx was performed by 14 urologists from our department with different levels of experience. In total, 997/1297 (77%) patients were diagnosed with prostate cancer; 492/997 (49%) of these patients decided to undergo RP in our clinic and were retrospectively included. Univariate and multivariable logistic regression analyses were performed to evaluate clinical and histopathological parameters associated with adverse pathology comparing FBx and RP specimens. To compare FBx and systematic randomized biopsies performed in our clinic before introducing FBx (SBx, n = 2309), we performed a propensity score matching on a 1:1 ratio, adjusting for age, number of positive biopsy cores, and initial PSA (iPSA). Results: A total of 492 patients undergoing FBx or SBx was matched. In total, 55% of patients diagnosed with GS 6 by FBx were upgraded to clinically significant PCa (defined as GS ≥ 7a) after RP, compared to 52% of patients diagnosed by SBx (p = 0.76). A time delay between FBx and RP was identified as the only correlate associated with upgrading. A total of 5.9% of all FBx patients and 6.1% of all SBx patients would have been eligible for AS (p > 0.99) but decided to undergo RP. The positive predictive value of AS eligibility (diagnosis of low-risk PCa after biopsy and after RP) was 17% for FBx and 6.7% for SBx (p = 0.39). Conclusions: In this study, we show, in a real-world setting, that introducing FBx did not lead to significant change in ratio of adverse pathology for low-risk PCa patients after RP compared to SBx.

Introduction: Testicular cancer is the most common cancer in young men. Studies show that general awareness among the risk group is low, and anticipatory guidance is of paramount importance for early detection. We queried pediatricians and pediatric surgeons on their perceived role and their interaction with patients regarding education on this issue. Materials and Methods: A survey was sent to pediatricians and pediatric surgeons in Germany to assess the extent of genitourinary examinations, health education about testicular cancer, and instructions for testicular self-examination during well-child visits and clinic contacts. Statistics were processed using R software (Version 4.5.1). Results: Data from 150 participating pediatricians and 21 pediatric surgeons were analyzed. Genitourinary examinations were performed routinely by the majority of participants, especially those in solo or group practices (p < 0.05). In particular, physicians who provide health education about testicular cancer perform testicular examinations significantly more often than those who do not provide such education (p < 0.05). Four percent of the participants offered a special consultation for male adolescents to provide information about male sexual diseases. There was a significant correlation between the length of experience of physicians and the level of health education (p < 0.01). Discussion: Although the majority of participants perform regular genitourinary examinations, only a minority provide special health education about testicular cancer or provide instructions for testicular self-examination. Most participating pediatricians and pediatric surgeons asked for more support regarding testicular cancer screening and health education.

Zusammenfassung: Der Einsatz moderner molekularer Technologien gab uns im letzten Jahrzehnt neue Einblicke in die komplexen Interaktionen des menschlichen Mikrobioms in Bezug auf Gesundheit und Krankheitsentstehung. Hierbei wurde unter anderem das Sterilitätskonzept des Harntrakts verworfen, sodass man sich nun als Ziel gesetzt hat, die verschiedenen mikrobiellen Signaturen zu identifizieren, die mit diversen Erkrankungen assoziiert sind. So stehen Dysbalancen des Mikrobioms zunehmend im Verdacht, negative Auswirkungen auf diverse maligne und benigne Krankheitsbilder zu verursachen. Kürzlich konnten solche Zusammenhänge auch für das Prostatakarzinom, Nierenzellkarzinom und Harnblasenkarzinom gezeigt werden. Das Ergebnis hiervon ist die Entdeckung potenziell neuer Biomarker zur Diagnostik und als Therapieziel der genannten Erkrankungen. Für die Diagnostik einiger benigner Krankheitsbilder wie der interstitiellen Zystitis, der Dranginkontinenz und der chronischen Prostatitis bzw. dem chronischen Beckenschmerzsyndrom galt eine mikrobielle Beteiligung bislang als Ausschlusskriterium. Jedoch zeigen auch hier die aktuellen Studien, dass das patientenindividuelle Mikrobiom durchaus Einfluss auf Entstehung und Ausprägung der jeweiligen Erkrankung haben kann.