Routine urethroscopic surveillance is of limited value after radical cystectomy: a single centre retrospective cohort analysis.

PURPOSE: The incidence of urethral recurrence (UR) following radical cystectomy (RC) for transitional cell carcinoma (TCC) of the bladder varies between 1.5 and 6%. There is debate over the timing of urethrectomy for patients undergoing RC. We evaluated the requirement for a formal surveillance programme for UR in patients after RC. METHODS: We retrospectively reviewed the outcomes of patients who underwent RC between 2006 and 2019. Females, non-TCC cases and patients with neo-bladder diversions were excluded. Histological prostatic urethral involvement at the time of RC was deemed high risk for UR. Carcinoma in-situ, multifocal tumours and bladder neck involvement were deemed intermediate risk and the absence of the above features was considered low risk. RESULTS: 417 patients underwent RC, 300 cases remained after exclusion criteria were applied. 42 patients were high-risk for UR, 102 patients were intermediate risk and 156 were low risk. Of the 300, 24 urethrectomy cases were recorded. Six cases of UR occurred. Of these, 5 presented with symptoms and only 1 case was detected by surveillance. Only 1 low-risk patient developed UR, 7 years post RC. Using our risk stratification, UR rates for high, intermediate and low-risk cohorts were 25%, 10.5% and 0.8%, respectively. CONCLUSIONS: In our cohort, routine surveillance for all patients with annual urethroscopy was of limited value in detecting UR post RC. Staged Urethrectomy for high and intermediate-risk patients, and patient counselling in self-identification of recurrence symptoms for low-risk patients will improve the early detection of UR.

Androgen receptor (AR) antagonism triggers acute succinate-mediated adaptive responses to reactivate AR signaling.

Treatment-induced adaptive pathways converge to support androgen receptor (AR) reactivation and emergence of castration-resistant prostate cancer (PCa) after AR pathway inhibition (ARPI). We set out to explore poorly defined acute adaptive responses that orchestrate shifts in energy metabolism after ARPI and identified rapid changes in succinate dehydrogenase (SDH), a TCA cycle enzyme with well-known tumor suppressor activity. We show that AR directly regulates transcription of its catalytic subunits (SDHA, SDHB) via androgen response elements (AREs). ARPI acutely suppresses SDH activity, leading to accumulation of the oncometabolite, succinate. Succinate triggers calcium ions release from intracellular stores, which in turn phospho-activates the AR-cochaperone, Hsp27 via p-CaMKK2/p-AMPK/p-p38 axis to enhance AR protein stabilization and activity. Activation of this pathway was seen in tissue microarray analysis on prostatectomy tissues and patient-derived xenografts. This adaptive response is blocked by co-targeting AR with Hsp27 under both in vitro and in vivo studies, sensitizing PCa cells to ARPI treatments.

Cold weather increases the risk of scrotal torsion events: results of an ecological study of acute scrotal pain in Scotland over 25 years.

The role of ambient temperature in the aetiology of acute scrotal pain (ASP) remains uncertain. The most common causes of ASP are torsion of the testis (TT) or its appendages (TA) and epidymo-orchitis (EO). We undertook an ecological study of ASP in Scotland to determine whether a seasonal variation could be observed. Episode reports for TT, TA and EO in Scotland over 25 years were collated monthly. Statistical analyses were performed to determine whether changes in ambient temperature during the year could explain variations in monthly frequency. 7882 episodes of TT and TA (Group A), and 25,973 episodes of EO (Group B) were reported. There was significant variance in the frequency of Group A (p < 0.0001) and B (p = 0.0031) episodes by month, higher frequency of Group A episodes in the colder half of the year (p < 0.0001), and an inverse correlation between the frequency of Group A episodes and ambient temperature (Spearman r = - 0.8757, 95% CI - 0.9661 to - 0.5941, p = 0.0004). Ambient temperature is likely to be playing a role in the aetiology of TT and TA in Scotland but not EO. Further study is warranted to explain underlying mechanisms.

Outcomes of scrotal exploration for acute scrotal pain suspicious of testicular torsion: a consecutive case series of 173 patients.

OBJECTIVE: • To determine the surgical outcome of all scrotal explorations performed on patients presenting with acute scrotal pain suspicious of testicular torsion. PATIENTS AND METHODS: • Data was collected prospectively from a consecutive case series of patients of all ages who had scrotal exploration for acute testicular pain from 1998 to 2008. • The main outcome measures were pathology found during scrotal exploration, relationship between patient age and cause of scrotal pain, orchidectomy rate and the association between testicular torsion and cold weather. RESULTS: • Data for 173 patients out of 179 was available for analysis. • The median age of the patients was 14 (0-92) years. 51% (n = 89) had testicular torsion, 24% (n = 42) had torsion of testicular appendages, 9% (n = 16) had epididymo-orchitis, and other pathology made up 5%. • No obvious pathology was seen in 10% (n = 17). • Patients with Torsion of Appendages were significantly younger than other patients with scrotal pain (P < 0.0001). • Age was not useful in discriminating between patients with Testicular Torsion from other patients with scrotal pain. 9% (n = 16) of all patients required an orchidectomy. • Frequency of Testicular Torsion was higher during the colder half of the year (n = 0.02). CONCLUSIONS: • Testicular torsion was the most common finding at surgical exploration, followed by torsion of testicular appendages. • Age had limited value in diagnosing the cause of acute scrotal pain. • Testicular torsion was associated with cold weather. • Our findings support the practice of surgical exploration for acute scrotal pain suspicious of testicular torsion in patients of any age.

A novel technique for repair of testicular rupture after blunt trauma.

OBJECTIVE: To present a simple technique for the repair of a ruptured testis after blunt trauma when extruded but viable testicular tissue prevents closure of the testicular capsule during surgical exploration. Preservation of viable testicular tissue is important because the risk of impaired fertility and hormone function is minimized. METHODS: A 25-year-old male sustained a ruptured right testis confirmed by ultrasound. Testicular exploration was performed and hematoma evacuated. Extruded but viable testicular tissue was identified and preserved. The free edges of parietal tunica vaginalis was used to create a "neocapsule" around the testis and extruded tissue. RESULTS: There were no postoperative complications. Follow-up Doppler ultrasound scan at 3 months showed a viable testis with no atrophic changes. CONCLUSIONS: This technique avoids the loss of extruded but viable testicular tissue and may reduce the risk of impaired fertility and hormone function, without compromising the goals of scrotal exploration.

Androgen regulates ADAMTS15 gene expression in prostate cancer cells.

Prostate cancer is a major cause of mortality, largely as a consequence of metastases and transformation to androgen-independent growth. Metalloproteinases are implicated in cancer progression. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) are expressed in prostate cancer cells, with ADAMTS-1 and ADAMTS-15 being the most abundant. ADAMTS-15 but not ADAMTS-1 expression was downregulated by androgen in LNCaP prostate cancer cells, possibly through androgen response elements associated with the gene. ADAMTS-15 expression is predictive for survival in breast cancer, and the situation may be similar in prostate cancer, as androgen independence is usually due to aberrant signaling through its receptor.