DaBlaCa-11: Photodynamic Diagnosis in Flexible Cystoscopy-A Randomized Study With Focus on Recurrence.

OBJECTIVE: To examine whether photodynamic diagnosis (PDD) in addition to flexible cystoscopy in the outpatient clinic can reduce risk of tumor recurrence in patients with previous nonmuscle invasive bladder cancer. PDD is an optical technique that enhances the visibility of pathologic tissue and helps guidance tumor resection. METHODS: From February 2016 to December 2017, 699 patients from 3 urologic departments in Denmark were enrolled in a randomized controlled trial. Four months after transurethral resection of bladder tumor patients were randomized 1:1 to either an intervention group (hexaminolevulinate was instilled in the bladder before flexible cystoscopy with PDD video cystoscope) or a control group (white light flexible cystoscope), only. Primary endpoint was tumor recurrence within 8 months from the randomization. Secondary outcomes were numbers of procedures in general anesthesia, time to the first recurrence, differences in tumor size, risk of tumor progression, and identification of carcinoma in situ. RESULTS: A total of 351 patients were allocated to the intervention group (flexible PDD), and 348 to the control group (flexible white light). Throughout the following 8 months after randomization, only 117 patients in the intervention group had at least 1 tumor recurrence compared to 143 patients in the control group (P = .049). Odds ratio of 0.67 (P = .02, 95% CI: 0.48-0.95) correlates with a tumor reduction of 33% in favor of the intervention group. CONCLUSION: Use of PDD in a routine surveillance cystoscopy first time after transurethral resection of bladder tumor for nonmuscle invasive bladder cancer reduces subsequent risk of tumor recurrence compared to WL cystoscopy alone.

Comparison of White Light, Photodynamic Diagnosis, and Narrow-band Imaging in Detection of Carcinoma In Situ or Flat Dysplasia at Transurethral Resection of the Bladder: the DaBlaCa-8 Study.

OBJECTIVE: To compare findings in NBI to findings in WL and PDD in a high-risk patient population. MATERIALS AND METHODS: A total of 171 patients were included in the study from 4 different urology departments in Denmark and Norway. Patients were scheduled for a PDD-guided transurethral tumor resection or cystoscopy-guided biopsy in accordance with Danish guidelines, on the suspicion of primary or concomitant CIS. All patients were examined with WL cystoscopy followed by both NBI and PDD before biopsy. RESULTS: A total of 136 patients were biopsied due to findings with suspicion of CIS in at least 1 modality (482 biopsies with a mean of 3.5 biopsies per patient). Analysis at patient level showed that NBI and PDD had a significantly higher sensitivity regarding identification of CIS and dysplasia compared with WL (NBI: 95.7%, PDD: 95.7% vs WL: 65.2%, P < .05). Specificity was not significantly different between the 3 methods (NBI: 52.0%, PDD: 48.0%, and WL: 56.8%). When analyzed per biopsy, NBI and PDD had a significantly higher sensitivity than WL (NBI: 72.7% and PDD: 78.2% vs WL: 52.7%, P < .05), whereas the positive predictive values were not significantly different (NBI: 23.7%, PDD: 22.2%, and WL: 19.0%). CONCLUSION: NBI was found to be a valid alternative to PDD regarding diagnosis of CIS and flat dysplasia.

Integrated genetic and epigenetic analysis of bladder cancer reveals an additive diagnostic value of FGFR3 mutations and hypermethylation events.

The bladder cancer genome harbors numerous oncogenic mutations and aberrantly methylated gene promoters. The aim of our study was to generate a profile of these alterations and investigate their use as biomarkers in urine sediments for noninvasive detection of bladder cancer. We systematically screened FGFR3, PIK3CA, TP53, HRAS, NRAS and KRAS for mutations and quantitatively assessed the methylation status of APC, ARF, DBC1, INK4A, RARB, RASSF1A, SFRP1, SFRP2, SFRP4, SFRP5 and WIF1 in a prospective series of tumor biopsies (N = 105) and urine samples (N = 113) from 118 bladder tumor patients. We also analyzed urine samples from 33 patients with noncancerous urinary lesions. A total of 95 oncogenic mutations and 189 hypermethylation events were detected in the 105 tumor biopsies. The total panel of markers provided a sensitivity of 93%, whereas mutation and methylation markers alone provided sensitivities of 72% and 70%, respectively. In urine samples, the sensitivity was 70% for all markers, 50% for mutation markers and 52% for methylation markers. FGFR3 mutations occurred more frequently in tumors with no methylation events than in tumors with one or more methylation events (78% vs. 33%; p < 0.0001). FGFR3 mutation in combination with three methylation markers (APC, RASSF1A and SFRP2) provided a sensitivity of 90% in tumors and 62% in urine with 100% specificity. These results suggest an inverse correlation between FGFR3 mutations and hypermethylation events, which may be used to improve noninvasive, DNA-based detection of bladder cancer.

Custom-designed MLPA using multiple short synthetic probes: application to methylation analysis of five promoter CpG islands in tumor and urine specimens from patients with bladder cancer.

Ligation of two oligonucleotide probes hybridized adjacently to a DNA template has been widely used for detection of genome alterations. The multiplex ligation-dependent probe amplification (MLPA) technique allows simultaneous screening of multiple target sequences in a single reaction by using pairs of probes that carry tails for binding of common amplification primers. Resolution of the various targets is achieved by electrophoresis on the basis of predefined differences in amplicon length. In the conventional MLPA approach, one of the two target probes is generated by cloning in a single-stranded bacteriophage vector to introduce a sequence of defined length between the primer binding site and the specific target sequence. Here we demonstrate that differences in amplicon length can be achieved by using multiple short synthetic probes for each target sequence. When joined by a DNA ligase, these probes will form a single amplifiable template whose length is defined by the number and lengths of the individual probes. We have used this principle to establish a methylation-specific MLPA (MS-MLPA) assay that simultaneously determines the methylation status of five promoter CpG islands, and we have used this assay to analyze DNA from tumor tissue and corresponding urine samples from patients with bladder cancer. Our data show that the use of multiple short synthetic probes provides a simple means for custom-designed MS-MLPA analysis.

[Urological training in the county of Roskilde]. / Den urologiske uddannelse i Roskilde Amt.

INTRODUCTION: Training in surgical skills and the importance of function-bearing units are the subject of much debate at the moment. An exposition is given of the quality of the urological training in the County of Roskilde, which corresponds to a function-bearing unit as to size. MATERIAL AND METHODS: The exposition is based on charts of specific oncological diagnoses during one year and the list of operations performed by phase III interns during a period of six months. RESULTS: The number of operations performed by phase III interns during the two periods in compared with the informal claims of The Danish Urological Society. DISCUSSION: As regards open surgery, the number of operations performed by phase III interns fully lives up to the informal requirements of the Danish Urological Society and the number of operations per intern exceeds what has previously been calculated at branch-specialized departments. The number of endoscopic operations was a little lower than expected and did not quite live up to the requirements. It is concluded that the urological training at a county urological department meets the requirements of the Danish Urological Society.

[Angiosarcoma of the adrenal gland]. / Angiosarkom i binyren.

We describe a case of angiosarcoma of the adrenal gland in a 71-year-old man. Angiosarcomas are collectively one of the rarest forms of soft tissue neoplasms. They comprise less than 1% of all sarcomas. The primary treatment of choice is radical surgery.