Impact of bacillus Calmette-Guerin intravesical therapy on the diagnostic efficacy of The Paris System for Reporting Urinary Cytology in patients with high-grade bladder cancer.

BACKGROUND: In high-grade urothelial carcinoma (UC) of the bladder, bacillus Calmette-Guerin (BCG) therapy is a therapeutic mainstay, and urinary cytology is recommended to detect recurrences. However, intravesical BCG instillations can induce morphologic changes in urothelial cells. The authors investigated the impact of BCG therapy on the efficacy of urinary cytology. METHODS: Matched pathology and cytology samples from patients undergoing transurethral resection of the bladder after BCG therapy were assessed. Cytology samples were graded according to The Paris System for Reporting Urinary Cytology. Diagnostic quality criteria were tested for different cutoff definitions, and the results were compared between those obtained <100 versus ≥100 days after the last BCG instillation. In addition, the oncologic outcome of false-positive results was assessed. RESULTS: In total, 389 matched cases from 197 patients who had a history of high-grade UC (HGUC) were identified. Sixty cases (15.7%) were diagnosed as high-grade urothelial bladder cancer. The cytology diagnoses were as follows: non-HGUC, 191 cases (49.1%); atypical urothelial cells, 80 cases (20.6%); suspicious for HGUC, 56 cases (14.4%); and HGUC, 56 cases (14.4%). Interrater reliability was substantial (κ = 0.660). Sensitivity increased from 45% to 75% when cases diagnosed as suspicious for HGUC were also counted as positive. Notably, sensitivity was reduced within the first 100 days after BCG therapy (61.9%) compared with sensitivity at longer intervals (82.1%). Reactive atypia (odds ratio, 4.155; 95% confidence interval, 2.136-8.085; P < .001) and cellular degeneration (odds ratio, 5.050; 95% CI, 2.094-12.175; P < .001) of urothelial cells were associated with false-positive rates, and 44.7% of patients who had a false-positive cytology classification presented with HGUC during follow-up. CONCLUSIONS: BCG therapy has a short-term adverse impact on the efficacy of urinary cytology. After BCG therapy, cases classified as suspicious for HGUC should be considered positive. Importantly, patients with false-positive cytology findings should be closely monitored.

[Management of urethral stricture]. / Management von Harnröhrenstrikturen.

Urethral strictures most frequently affect the bulbar but are also observed in the penile, glandular, or membranous urethra. They are often iatrogenic. Radiologic diagnosis can be established easily and safely by cystourethrography. Simple Sachse urethrotomy can result in permanent relief in the case of short bulbar strictures in initial findings. Recurrent structures or strictures in other locations should however be treated by open surgery, as cure cannot be achieved by other means. Depending on the diagnosis and comorbidities, end-to-end anastomosis, graft/flap urethroplasty, or perineal urethrostomy can be performed. If open surgery is delayed, aggravation of the diagnosis and worsening of the prognosis can be expected, regardless of the applied treatment.

[Quality medicine initiative in urology]. / Initiative Qualitätsmedizin in der Urologie.

To ensure that high quality, individualized treatment is systematically guaranteed, instruments and mechanisms, which are associated with an increasing number of interwoven processes and interfaces, are increasingly required in complex clinical routine. The main task of internal quality management is to optimize and standardize clinical processes and procedures in order to ensure quality of care. However, external assessment of these processes is also an important part of quality assurance. One of these external assessments can be carried out via the quality medicine initiative (Initiative Qualitätsmedizin). It provides a platform through which participating hospitals can continuously improve quality of care through three mechanisms: assessment of treatment quality using routine data, the transparency of this data, and use of an external peer review process.

Can we define reliable risk factors for anastomotic strictures following radical prostatectomy?

BACKGROUND: To identify risk factors for anastomotic strictures in patients after radical prostatectomy. METHODS: In all, 140 prostate cancer patients with one or more postoperative anastomotic strictures after radical prostatectomy were included. All patients underwent transurethral anastomotic resection at the University Hospital of Munich between January 2009 and May 2016. Clinical data and follow-up information were retrieved from patients' records. Statistical analysis was done using Kaplan-Meier curves and log rank-test with time to first transurethral anastomotic resection as endpoint, Chi-square-test, and Mann-Whitney-U test. RESULTS: In all, 140 patients with a median age of 67 years (IQR: 61-71 years) underwent radical prostatectomy. Median age at time of transurethral anastomotic resection was 68 years (IQR: 62-72). Patients needed 2 surgical interventions in median (range: 1-15). Median time from radical prostatectomy to transurethral anastomotic resection was 6 months (IQR: 3.9-17.4). Median duration of catheterization after radical prostatectomy was 10 days (IQR: 8-13). In all, 26% (36/140) received additional radiotherapy. Regarding time to first transurethral anastomotic resection, age and longer duration of catheterization after radical prostatectomy with a cutoff of 7 days showed no statistically significant differences (p = 0.392 and p = 0.141, respectively). Tumor stage was no predictor for development of anastomotic strictures (p = 0.892), and neither was prior adjuvant radiation (p = 0.162). Potential risk factors were compared between patients with up to 2 strictures (low-risk) and patients developing > 2 strictures (high-risk): high-risk patients had more often injection of cortisone during surgery (14% vs 0%, p < 0.001) and more frequently advanced tumor stage pT > 2 (54% vs 38%, p = 0.055), respectively. Other risk factors did not show any significant difference compared to number of prior transurethral anastomotic strictures. CONCLUSIONS: We could not identify a reliable risk factor to predict development of anastomotic strictures following radical prostatectomy.

Open ureteroplasty with buccal mucosa graft for long proximal strictures: A good option for a rare problem.

Purpose: To report a single surgeon experience with one year follow-up after open ureteroplasty with buccal mucosa graft (OUBMG) in the rare situation of long segment proximal ureteral strictures. Materials and Methods: Four patients with long segment proximal ureteral stricture underwent OU-BMG between February and July 2017. Functional outcome was assessed by pre- and postoperative serum creatinine, ultrasound and renal scintigraphy as well as patient reported outcomes. Results: Four patients with an average stricture length of 4 cm underwent OU-BMG between February and July 2017. No major postoperative complications occurred. Retrograde uretero-pyelography 6 weeks postoperatively revealed a watertight anastomosis followed by immediate emptying of the renal pelvis and ureter in all four patients. Ureteroscopy at this time showed a wide lumen with well-vascularized pink mucosa. After a mean follow-up time of 12.5 (12-14) months, postoperative serum creatinine was unimpaired. Renal scintigraphy revealed no signs of renal obstruction. With regard to intraoral surgery, no difficulties with mouth opening or intraoral dryness or numbness were reported. Conclusions: For patients with long segment ureteral strictures OU-BMG is a safe technique with excellent surgical and functional outcomes. Hence, the application of this technique should be encouraged and regarded as one of the standard options in case of this rare problem.

The increase of stage, grading, and metastases in patients undergoing radical prostatectomy during the last decade.

PURPOSE: To investigate changes in clinical data and pathological features of prostatectomy specimens of prostate cancer (PCa) patients in a large tertiary care center over the last 12 years as potential consequence of reduced acceptance of prostate-specific antigen (PSA)-based screening and implementation of active surveillance as a therapeutic option in PCa. METHODS: We retrospectively identified all patients with PCa who underwent radical prostatectomy at our institution between 2004 and 2016 from our clinical database. We reviewed clinical and pathological data including patient age, PSA level, number of positive cores and Gleason score in prostate biopsy, and pathologic N- and T-stage, and Gleason score in radical prostatectomy specimen. RESULTS: Data of 5497 consecutive patients were analyzed. Median PSA increased from 7 (IQR 4.8-10.5) to 9 ng/ml (IQR 5.8-16.1; p < 0.001), and median number of positive biopsy cores increased from 3 (IQR 2-5) to 5 (IQR 3-7; p < 0.001). The proportion of patients with Gleason score ≥ 7 in biopsy and prostatectomy specimens increased from 40 to 78% and 49 to 89% (p < 0.001), respectively. The rate of locally advanced (≥ pT3a) and lymph node-positive tumors increased from 28 to 43% and 5 to 16% (p < 0.001), respectively. CONCLUSIONS: We observed a significant change in clinical and pathological findings in our prostatectomy series with a significantly higher proportion of aggressive and locally advanced PCa in recent years. These findings may be related to a reduced acceptance of PSA-based screening and the use of active surveillance as management strategy and have significant impact on daily patient care.

Skrotales Lymphödem.

This article describes the rare condition of scrotal lymphedema (elephantiasis) in a Caucasian man. To our knowledge, this is the most giant form of scrotal elephantiasis that was ever described in Germany. Aim of this case report is to present an appealing aesthetic possibility of surgical treatment and reconstruction of the genitals while preserving the testes.

Salvage lymph node dissection after 68Ga-PSMA or 18F-FEC PET/CT for nodal recurrence in prostate cancer patients.

The management of patients with biochemical recurrence (BCR) after definitive treatment for prostate cancer remains controversial. Our aim was to determine survival rates and complications of salvage lymph node dissection (sLND) in patients with recurrent prostate cancer after radical prostatectomy, while evaluating biochemical response (BR) with two different positron emission tomography/computed tomography (PET/CT) tracers used for preoperative imaging. sLND was performed in 104 patients diagnosed with isolated nodal recurrence on either 18F-fluoroethylcholine (18F-FEC) or 68Ga-PSMA-HBED-CC (68Ga-PSMA) PET/CT. Surgical complications, BR, clinical recurrence (CR), and cancer-specific survival (CSS) were evaluated. Logistic regression was used to determine predictors of complete BR (cBR) and CR after sLND and survival rates were assessed. Median follow-up was 39.5 months. Median patient age and prostate-specific antigen (PSA) at sLND were 64 years and 4.1 ng/mL. Median number of lymph nodes (LNs) removed was 13; median number of positive LNs was 3 per patient. Rate of Clavien-Dindo Grade III complications was low (4.8%). 29.8% of patients developed cBR (PSA < 0.2 ng/mL), and 56.7% partial BR (PSA postoperative < PSA preoperative) after sLND. Patients with LN metastases diagnosed on 68Ga-PSMA PET/CT showed a higher rate of cBR compared to 18F-FEC PET/CT (45.7 vs. 21.7%, p = 0.040). PSA at sLND (p = 0.031) and choice of PET tracer (p = 0.048) were independent predictors of cBR. The 5-year BCR-free, CR-free and CSS rates were 6.2%, 26.0%, and 82.8%, respectively. While preoperative staging with 68Ga-PSMA seems superior, only a limited number of patients developed cBR after surgery. Most patients experienced BCR and CR during follow-up.

Postoperative upgrading of prostate cancer in men ≥75 years: a propensity score-matched analysis.

PURPOSE: Gleason score upgrading should be considered when indicating surgery in prostate cancer (PCa) patients. In elderly patients, definitive treatment of low-risk PCa must be weighed with the risks of overtreatment. Our aim was to evaluate rates of Gleason score upgrading in patients ≥75 years undergoing radical prostatectomy (RP) for localized PCa and to identify predictors associated with upgrading. METHODS: 3296 patients undergoing RP were retrospectively evaluated and categorized into age groups: <70 years (n = 2971) vs. ≥75 years (n = 325). We analyzed prostate-specific antigen (PSA), biopsy counts, Gleason score, pathologic T- and N-stage, and surgical margin. Propensity score matching was performed to compare rates of up- and downgrading on surgical specimen using the new five-tier pathologic grading system. Logistic regression was used to identify independent predictors of upgrading. RESULTS: Preoperatively, patients ≥75 years had higher PSA (8.8 vs. 7.3 ng/mL) and lower proportion of grade group 1 (Gleason score 6) at biopsy (29.2 vs. 47.9%; both p < 0.001) compared to patients <70 years. At RP, patients ≥75 years were more likely to have extraprostatic disease (50 vs. 30%) and lower rates of grade group 1 (14.1 vs. 34.8%; both p < 0.001). Postoperative downgrading was similar (15.1 vs. 19.5%). However, patients ≥75 years had higher rates of postoperative upgrading (46.6 vs. 27.9%; p < 0.001). Age ≥75 years, higher PSA levels at RP, and an increased number of positive biopsy cores were associated with upgrading. CONCLUSIONS: Patients ≥75 years not only demonstrated higher rates of advanced disease but more frequent upgrading on RP specimen. Age ≥75 years, higher PSA levels at RP, and an increased number of positive biopsy cores were predictive for upgrading. The increased risk of upgrading should be taken into consideration when discussing optimal treatment for this specific cohort.

Comparison of prostate positioning guided by three-dimensional transperineal ultrasound and cone beam CT.

OBJECTIVE: The accuracy of a transperineal three-dimensional ultrasound system (3DUS) was assessed for prostate positioning and compared to fiducial- and bone-based positioning in kV cone beam computed tomography (CBCT) during definitive radiotherapy of prostate cancer. METHODS: Each of the 7 patients had three fiducial markers implanted into the prostate before treatment. Prostate positioning was simultaneously measured by 3DUS and CBCT before each fraction. In total, 177 pairs of 3DUS and CBCT scans were collected. Bone-match and seed-match were performed for each CBCT. Using seed-match as a reference, the accuracy of 3DUS and bone-match was evaluated. Systematic and random errors as well as optimal setup margins were calculated for 3DUS and bone-match. RESULTS: The discrepancy between 3DUS and seed-match in CBCT (average ± standard deviation) was 0.0 ± 1.7 mm laterally, 0.2 ± 2.0 mm longitudinally, and 0.3 ± 1.7 mm vertically. Using seed-match as a reference, systematic errors for 3DUS were 1.2 mm, 1.1 mm, and 0.9 mm; and random errors were 1.4 mm, 1.8 mm, and 1.6 mm, on lateral, longitudinal, and vertical axes, respectively. By analogy, the difference of bone-match to seed-match was 0.1 ± 1.1 mm laterally, 1.3 ± 3.8 mm longitudinally, and 1.3 ± 4.5 mm vertically. Systematic errors were 0.5 mm, 2.2 mm, and 2.6 mm; and random errors were 1.0 mm, 3.1 mm, and 3.9 mm on lateral, longitudinal, and vertical axes, respectively. The accuracy of 3DUS was significantly higher than that of bone-match on longitudinal and vertical axes, but not on the lateral axis. CONCLUSION: Image-guided radiotherapy of prostate cancer based on transperineal 3DUS was feasible, with overall small discrepancy to seed-match in CBCT in this retrospective study. Compared to bone-match, transperineal 3DUS achieved higher accuracy on longitudinal and vertical axes.

Dosimetry for (177)Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer.

PURPOSE: Dosimetry is critical to achieve the optimal therapeutic effect of radioligand therapy (RLT) with limited side effects. Our aim was to perform image-based absorbed dose calculation for the new PSMA ligand (177)Lu-DKFZ-PSMA-617 in support of its use for the treatment of metastatic prostate cancer. METHODS: Whole-body planar images and SPECT/CT images of the abdomen were acquired in five patients (mean age 68 years) for during two treatment cycles at approximately 1, 24, 48 and 72 h after administration of 3.6 GBq (range 3.4 to 3.9 GBq) (177)Lu-DKFZ-PSMA-617. Quantitative 3D SPECT OSEM reconstruction was performed with corrections for photon scatter, photon attenuation and detector blurring. A camera-specific calibration factor derived from phantom measurements was used for quantitation. Absorbed doses were calculated for various organs from the images using a combination of linear approximation, exponential fit, and target-specific S values, in accordance with the MIRD scheme. Absorbed doses to bone marrow were estimated from planar and SPECT images and with consideration of the blood sampling method according to the EANM guidelines. RESULTS: The average (± SD) absorbed doses per cycle were 2.2 ± 0.6 Gy for the kidneys (0.6 Gy/GBq), 5.1 ± 1.8 Gy for the salivary glands (1.4 Gy/GBq), 0.4 ± 0.2 Gy for the liver (0.1 Gy/GBq), 0.4 ± 0.1 Gy for the spleen (0.1 Gy/GBq), and 44 ± 19 mGy for the bone marrow (0.012 Gy/GBq). The organ absorbed doses did not differ significantly between cycles. The critical absorbed dose reported for the kidneys (23 Gy) was not reached in any patient. At 24 h there was increased uptake in the colon with 50 - 70 % overlap to the kidneys on planar images. Absorbed doses for tumour lesions ranged between 1.2 and 47.5 Gy (13.1 Gy/GBq) per cycle. CONCLUSION: The salivary glands and kidneys showed high, but not critical, absorbed doses after RLT with (177)Lu-DKFZ-PSMA-617. We suggest that (177)Lu-DKFZ-PSMA-617 is suitable for radiotherapy, offering tumour-to-kidney ratios comparable to those with RLT agents currently available for the treatment of neuroendocrine tumours. Our dosimetry results suggest that (177)Lu-DKFZ-PSMA-617 treatment with higher activities and more cycles is possible without the risk of damaging the kidneys.