(1) Background: Secondary lymphedema is a chronic, progressive, and debilitating condition with an important impact on quality of life. Lymphedema is a frequently reported complication in oncological surgery but has not been systematically studied in the setting of prostate cancer. (2) Methods: Pubmed/MEDLINE and Embase were systematically searched to identify articles reporting on lower limb or genital lymphedema after primary treatment (surgery of radiation therapy) of the prostate and the pelvic lymph nodes in men with prostate cancer. Primary outcome was the prevalence of lower limb and genital lymphedema. (3) Results: Eighteen articles were eligible for qualitative synthesis. Risk of bias was high in all included studies, with only one study providing a prespecified definition of secondary lymphedema. Eleven studies report the prevalence of lower limb (0–14%) and genital (0–1%) lymphedema after radical prostatectomy with pelvic lymph node dissection (PLND) Seven studies report a low prevalence of lower limb (0–9%) and genital (0–8%) lymphedema after irradiation of the pelvic lymph nodes. However, in the patient subgroups that underwent pelvic irradiation after staging pelvic lymph node dissections, the prevalence of lower limb (18–29%) and genital (2–22%) lymphedema is substantially elevated. (4) Conclusion: Prostate cancer patients undergoing surgery or irradiation of the pelvic lymph nodes are at risk of developing secondary lymphedema in the lower limbs and the genital region. Patients receiving pelvic radiation after pelvic lymph node dissection have the highest prevalence of lymphedema. The lack of a uniform definition and standardized diagnostic criteria for lower limb and genital lymphedema hampers the accurate estimation of their true prevalence. Future clinicals trials are needed to specifically evaluate secondary lymphedema in patients undergoing prostate cancer treatments, to identify potential risk factors and to determine the impact on quality of life.

Improvement of bladder emptying by modulating afferent nerve activity is an attractive therapeutic strategy for detrusor underactivity. Transient receptor potential vanilloid 4 (TRPV4) is a sensory ion channel in urothelial cells that contribute to the detection of bladder filling. To investigate the potential benefit of intravesical TRPV4 agonists in a pelvic nerve injury rat model for detrusor underactivity. Female wild-type and Trpv4 knockout rats underwent sham surgery or bilateral pelvic nerve injury (bPNI). Four weeks later, rats underwent cystometry with infusion of the TRPV4 agonist GSK1016790A. Bladders were harvested for in vitro pharmacological studies, quantitative reverse polymerase chain reaction and immunohistochemistry. Data are expressed as median ± interquartile range. Statistical comparisons were made using the Mann-Witney U test and Wilcoxon signed rank test as appropriate. Rats with bPNI showed a phenotype characteristic of detrusor underactivity with lower-amplitude voiding contractions, decreased voiding frequency, and increased postvoid residual. Intravesical application of GSK1016790A increased voiding frequency and reduced postvoid residual in wild-type, but not Trpv4-/-, rats. In isolated bladder strips, GSK1016790A did not induce relevant contractions, indicating that the observed improvements in bladder function are the result of increased afferent signalling through TRPV4 activation, rather than a local effect on the detrusor. The altered urinary phenotype of Trpv4-/- mice was not apparent in the Trpv4-/- rat model, suggesting species-related functional variations. Our results are limited to the preclinical setting in rodents. Intravesical activation of TRPV4 improves bladder dysfunction after bPNI by increasing afferent signalling. We demonstrate that the sensory protein transient receptor potential vanilloid 4 (TRPV4) can be targeted to improve bladder function in animals that have iatrogenic injury to the nerves innervating the bladder. Further research is required to determine whether these results can be translated to patients with an underactive bladder.

Germline pathogenic alterations in the breast cancer susceptibility genes 1 (BRCA1) and 2 (BRCA2) are the most prevalent causes of hereditary breast and ovarian cancer. The increasing trend in proportion of cancer patients undergoing genetic testing, followed by predictive testing in families of new index patients, results in a significant increase of healthy germline BRCA1/2 mutation carriers who are at increased risk for breast, ovarian, and other BRCA-related cancers. This review aims to give an overview of available screening guidelines for female and male carriers of pathogenic or likely pathogenic germline BRCA1/2 variants per cancer type, incorporating malignancies that are more or less recently well correlated with BRCA1/2. We selected guidelines from national/international organizations and/or professional associations that were published or updated between January 1, 2015, and February 1, 2020. In total, 12 guidelines were included. This review reveals several significant discordances between the different guidelines. Optimal surveillance strategies depend on accurate age-specific cancer risk estimates, which are not reliably available for all BRCA-related cancers. Up-to-date national or international consensus guidelines are of utmost importance to harmonize counseling and proposed surveillance strategies for BRCA1/2 carriers.

The cation channel TRPM3 is activated by heat and the neurosteroid pregnenolone sulfate. TRPM3 is expressed on sensory neurons innervating the skin, where together with TRPV1 and TRPA1, it functions as one of three redundant sensors of acute heat. Moreover, functional upregulation of TRPM3 during inflammation contributes to heat hyperalgesia. The role of TRPM3 in sensory neurons innervating internal organs such as the bladder is currently unclear. Here, using retrograde labeling and single-molecule fluorescent RNA in situ hybridization, we demonstrate expression of mRNA encoding TRPM3 in a large subset of dorsal root ganglion (DRG) neurons innervating the mouse bladder, and confirm TRPM3 channel functionality in these neurons using Fura-2-based calcium imaging. After induction of cystitis by injection of cyclophosphamide, we observed a robust increase of the functional responses to agonists of TRPM3, TRPV1, and TRPA1 in bladder-innervating DRG neurons. Cystometry and voided spot analysis in control and cyclophosphamide-treated animals did not reveal differences between wild type and TRPM3-deficient mice, indicating that TRPM3 is not critical for normal voiding. We conclude that TRPM3 is functionally expressed in a large proportion of sensory bladder afferent, but its role in bladder sensation remains to be established.