Comet assay measures of DNA damage are predictive of bladder cancer cell treatment sensitivity in vitro and outcome in vivo.

Bladder cancer patients suffer significant treatment failure, including high rates of recurrence and poor outcomes for advanced disease. If mechanisms to improve tumour cell treatment sensitivity could be identified and/or if tumour response could be predicted, it should be possible to improve local-control and survival. Previously, we have shown that radiation-induced DNA damage, measured by alkaline Comet assay (ACA), correlates bladder cancer cell radiosensitivity in vitro. In this study we first show that modified-ACA measures of cisplatin and mitomycin-C-induced damage also correlate bladder cancer cell chemosensitivity in vitro, with essentially the same rank order for chemosensitivity as for radiosensitivity. Furthermore, ACA studies of radiation-induced damage in different cell-DNA substrates (nuclei, nucleoids and intact parent cells) suggest that it is a feature retained in the prepared nucleoids that is responsible for the relative damage sensitivity of bladder cancer cells, suggestive of differences in the organisation of DNA within resistant vs. sensitive cells. Second, we show that ACA analysis of biopsies from bladder tumours reveal that reduced DNA damage sensitivity associates with poorer treatment outcomes, notably that tumours with a reduced damage response show a significant association with local recurrence of non-invasive disease and that reduced damage response was a better predictor of recurrence than the presence of high-risk histology in this cohort. In conclusion, this study demonstrates that mechanisms governing treatment-induced DNA damage are both central to and predictive of bladder cancer cell treatment sensitivity and exemplifies a link between DNA damage resistance and both treatment response and tumour aggression.

A case report on a rare presentation of adrenal myelolipoma with low-impact traumatic haemorrhage and the challenges of conservative management.

Adrenal myelolipomas are rare, hormonally silent, adipose and myeloid-containing lesions that are mostly asymptomatic. If they do present it is usually with mass-related flank pain or spontaneous haemorrhage. A 55-year-old female presented with right flank pain after a fall from a static pushbike. Computer tomography identified a large adrenal lesion with surrounding acute retroperitoneal haemorrhage. A conservative approach to treatment was decided on as the patient remained haemodynamically stable. The patient developed a pulmonary embolism during the time of conservative management and therefore had to be anticoagulated with close monitoring. Outpatient surveillance imaging was reassuring, hormonal screening was negative and biopsy confirmed myelolipoma. We report a rare presentation of adrenal myelolipoma with the sequelae of haemorrhage from low-impact trauma and the challenges of conservative management.

'No visible lesions?'-an unusual case of Intestinal metaplasia of the bladder.

Intestinal metaplasia (IM) of the bladder is an extremely rare benign condition. The clinical features are similar to other bladder tumours. Its pathogenesis is unclear and its role as a precursor of adenocarcinoma has long been debated. Transurethral resection is the main form of treatment for IM. We report the case of a 49-year-old gentleman who presented with visible haematuria. He was submitted to multiple cystoscopies which showed no macroscopic irregularities. Radiological (CT urogram and multiparametric MRI) imaging revealed abnormalities within the bladder neck, suspicious of a neoplastic lesion. Following transurethral resection of his trigonal area, pathology demonstrated IM occurring on a background of cystitis glandularis. This case highlights the unusual difficulty in macroscopically diagnosing IM of the bladder compared to other neoplasms of the bladder. Therefore, in patients with persistent visible haematuria there should be a low threshold to perform biopsies.

Isolated Red Patches Seen During Endoscopic Surveillance of Bladder Cancer: Incidence of Malignancy and When Should We Biopsy?

OBJECTIVE: To establish whether the regular biopsy of red patches (RPs) seen during endoscopic surveillance for bladder cancer is worthwhile and determine a suitable time frame for repeat biopsy of prior histologically benign persistent RPs in patients on endoscopic surveillance for bladder cancer. PATIENTS AND METHODS: Four thousand eight hundred five flexible cystoscopy (FC) reports over a 12-month period were retrospectively reviewed at a United Kingdom tertiary teaching hospital and those undergoing cystoscopic surveillance for bladder cancer and found to have solitary RPs at FC were included in the study. A proportion of these cases had biopsies taken for histopathologic analysis. RESULTS: Two hundred forty-one FC performed on 183 patients on endoscopic surveillance for bladder cancer had RPs and 120 (49.8%) of them had previous intravesical Bacillus Calmette-Guerin therapy. Eighty-five patients (35.3%) underwent biopsy of the RP. Malignancy was found in 20 biopsies (23.5%), of which, 11 out of 20 (55%) were carcinoma in-situ. Sixteen of these recurrences were biopsied previously, of which 11 (68.8%) were benign at last biopsy, 6 of which were in the last 12 months. The remaining four recurrences had no previous biopsy. No cases of malignancy were identified in patients with low-risk bladder cancer. CONCLUSION: We recommend the biopsy of all RPs found during endoscopic surveillance of patients with intermediate-/high-risk bladder cancer due to the significant incidence of malignant recurrence identified, particularly if no biopsy has been performed within the previous 12 months. This is independent of previous biopsy histology.