MRT/Ultraschall fusionierte Biopsie und multiparametrischer Ultraschall der Prostata bei Verdacht auf ein Prostatakarzinom

EINLEITUNG: Die Kombination aus Sensitivität und Spezifität der mpMRT und der Dynamik des Ultraschalles (US) im Rahmen einer MRT/US fusionierten Biopsie der Prostata hat die die Diagnostik des PCa entscheidend verändert. Hohe Detektionsraten insbesondere von klinisch signifikantem PCa trugen zum Paradigmenwechsel im Wiederholungssetting bei und empfehlen klar den Einsatz einer mpMRT bei Verdacht auf ein PCa und vorangegangener negativer Prostatabiopsie. Die europäische urologische Leitlinie akzeptierte bereits indirekt sogar die mpMRT als Biopsieindikator, indem sie den Verzicht auf eine Prostatabiopsie bei negativer mpMRT und „geringem Verdacht auf ein PCa“ zulässt. Die Empfehlung zum Einsatz einer mpMRT samt gezielter Biopsie im primären Setting gemäß europäischer Leitlinie und weiterhin singulärer systematischer Biopsie ohne mpMRT gemäß deutscher S3-Leitlinie zum PCa, spiegelt die Heterogenität der aktuellen Leitliniensituation wieder. FRAGESTELLUNGEN: (1.) Erhöht die Anwendung der mpMRT/US fusionierten Biopsie die Detektion von PCa und insbesondere klinisch signifikanter PCa im Rahmen einer Wiederholungsbiopsie? (2.) Können mittels unterschiedlicher Ultraschallmethoden währen der MRT/US fusionierten Biopsie klinisch signifikante Prostatakarzinome detektiert werden und mittels eines Summenscores entsprechend PIRADS vorausgesagt werden? (3.) Wie wirkt sich der Einsatz der MRT/US fusionierten Biopsie auf die Detektion von klinisch signifikantem PCa in Patienten ohne Vorbiopsien aus? (4.) Gelingt mittels Einsatz von Kontrastmittel gestütztem Ultraschall und quantitativer Perfusionsanalyse im Rahmen der MRT/Ultraschall fusionierten Biopsie der Prostata eine Detektion und Prädiktion von PCa? (5.) Steigert der Einsatz zusätzlicher ventraler Biopsien in der additiv durchgeführten systematischen Biopsie die Detektion von PCa in Patienten mit multiplen Vorbiopsien? ERGEBNISSE: (1.) Es konnte eine höhere Gesamtdetektionsrate des PCa von 39,8 % im Vergleich zur Pilot-Studie (37,5 %) gezeigt werden. (2.) Der optimale Grenzwert, um ein PCa oder einen PI-RADS score von ≥ 4 vorauszusagen lag bei einem mpUS Summen score von > 8,5 mit einer AUC von 0,86 für PCa- bzw. 0,8 für eine PI-RADS-Vorhersage. (3.) Es zeigte sich eine deutlich erhöhte Gesamtdetektionsrate von 77 % (245/318) und auch seitens der MRT/US-Fusionsbiopsie von 67 % (213/318). In Bezug auf die Detektion klinisch signifikanter PCa wurden 51 % durch MRT/US Fusionsbiopsie detektiert, wobei durch die Kombination von Fusions- und systematischer Biospie 61% detektiert wurden. (4.) In der softwarebasierten Parameteranalyse imponierten „rise time“ (p = 0,026) und „time to peak“ (p = 0,037) als gute Prädiktoren ein PCa von benignem Gewebe abzugrenzen. Die Parameter „peak enhancement“ (p = 0,012), “wash-in rate” (p = 0,011), “wash-out rate” (p = 0,007) und “wash-in perfusion index” (p = 0.014) eigneten sich für eine Differenzierung in klinisch signifikantes und nicht klinisch signifikantes PCa. DISKUSSION: Die hier inkludierten Arbeiten verdeutlichen zum einen die Wertigkeit der mpMRT und den großen Vorteil der simultanen Fusion von Ultraschall und MRT-Bild in der PCa Diagnostik. Ferner konnte auch gezeigt werden, dass die mpMRT jedoch weiterhin auch falsch negative Befunde liefern kann und eine Kombination aus gezielter und systematischer Biopsie aktuell zielführend ist. Die computer-basierte Analyse verdeutlicht aber auch die Tendenz zur Untersucher unabhängigen Analyse nicht nur in der Schichtbildgebung sondern auch in der dynamischen Ultraschallanwendung bei Verdacht auf ein PCa

Evaluation of T1 relaxation time in prostate cancer and benign prostate tissue using a Modified Look-Locker inversion recovery sequence

Purpose of this study was to evaluate the diagnostic performance of T1 relaxation time (T1) for differentiating prostate cancer (PCa) from benign tissue as well as high- from low-grade PCa. Twenty-three patients with suspicion for PCa were included in this prospective study. 3 T MRI including a Modified Look-Locker inversion recovery sequence was acquired. Subsequent targeted and systematic prostate biopsy served as a reference standard. T1 and apparent diffusion coefficient (ADC) value in PCa and reference regions without malignancy as well as high- and low-grade PCa were compared using the Mann-Whitney U test. The performance of T1, ADC value, and a combination of both to differentiate PCa and reference regions was assessed by receiver operating characteristic (ROC) analysis. T1 and ADC value were lower in PCa compared to reference regions in the peripheral and transition zone (p < 0.001). ROC analysis revealed high AUCs for T1 (0.92; 95%-CI, 0.87-0.98) and ADC value (0.97; 95%-CI, 0.94 to 1.0) when differentiating PCa and reference regions. A combination of T1 and ADC value yielded an even higher AUC. The difference was statistically significant comparing it to the AUC for ADC value alone (p = 0.02). No significant differences were found between high- and low-grade PCa for T1 (p = 0.31) and ADC value (p = 0.8). T1 relaxation time differs significantly between PCa and benign prostate tissue with lower T1 in PCa. It could represent an imaging biomarker for PCa

Comparison of PHI and PHI Density for Prostate Cancer Detection in a Large Retrospective Caucasian Cohort

Background: Beyond prostate-specific antigen (PSA), other biomarkers for prostate cancer (PCa) detection are available and need to be evaluated for clinical routine. Objective: The aim of the study was to evaluate the Prostate Health Index (PHI) density (PHID) in comparison with PHI in a large Caucasian group >1,000 men. Methods: PHID values were used from available patient data with PSA, free PSA, and [-2]pro-PSA and prostate volume from 3 former surveys from 2002 to 2014. Those 1,446 patients from a single-center cohort included 701 men with PCa and 745 with no PCa. All patients received initial or repeat biopsies. The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curves comparing area under the ROC curves (AUCs), precision-recall approach, and decision curve analysis (DCA). Results: PHID medians differed almost 2-fold between PCa (1.12) and no PCa (0.62) in comparison to PHI (48.6 vs. 33; p always <0.0001). However, PHID and PHI were equal regarding the AUC (0.737 vs. 0.749; p = 0.226), and the curves of the precision-recall analysis also overlapped in the sensitivity range between 70 and 100%. DCA had a maximum net benefit of only similar to 5% for PHID versus PHI between 45 and 55% threshold probability. Contrary, in the 689 men with a prostate volume <= 40 cm(3), PHI (AUC 0.732) showed a significant larger AUC than PHID (AUC 0.69, p = 0.014). Conclusions: Based on DCA, PHID had only a small advantage in comparison with PHI alone, while ROC analysis and precision-recall analysis showed similar results. In smaller prostates, PHI even outperformed PHID. The increment for PHID in this large Caucasian cohort is too small to justify a routine clinical use

Early Continence and Extravasation After Open Retropubic Radical Prostatectomy – Interrupted vs Continuous Suturing for Vesicourethral Anastomosis

Purpose: To compare running suture (RS) and interrupted suture (IS) of vesicourethral anastomosis (VUA) during open retropubic radical prostatectomy (RRP) on early urinary continence and extravasation. Patients and methods: Single center analysis of 211 patients who underwent RRP performed by a single surgeon during 2008 to 2017 was retrospectively analyzed. For VUA, we used the standard interrupted suture technique (n=100) with a 3-0 PDS suture. The RS (n=111) was performed with 12-bite suture using 3-0 PDS. The primary endpoints were extravasation and early continence. Demographic and peri-operative data were collected and analyzed using Pearson's chi-square, t-Test and Mann-Whitney U-test. A binary logistic regression analysis was carried out to explore predictors that affected early continence after catheter removal. Results: The rates of early urinary incontinence (UI) were 7.7% vs 42.2% (p<0.001). The duration of catheterization and hospitalization was significantly shorter in the interrupted group (4 days vs 5 days, p<0.001 and 5 days vs 6 days, p<0.001). The groups did not differ significantly in body mass index or prostate volume. There were older patients and higher PSA levels in the group with RS technique. No significant difference was found in the postoperative extravasation rates between both groups (13.5% vs 12%, p=0.742). Conclusion: Running vesicourethral anastomosis increased the rate of early urinary incontinence. Both anastomosis techniques provided a similar rate of postoperative urine extravasation. VUA should only be one of the many criteria that must be considered for the preservation of urinary continence of patients after RRP

MRI-guided core needle biopsy of the prostate: acceptance and side effects

PURPOSEWe aimed to study side effects, complications, and patient acceptance of magnetic resonance imaging-guided real-time biopsy (MRI-GB) of the prostate.METHODSFifty-four men (49–78 years) with elevated prostate-specific antigen after at least one negative systematic transrectal ultrasound-guided biopsy (TRUS-GB) were included in a prospective clinical study. Suspicious areas on images were selectively sampled by obtaining a median of four specimens (range, 1–9 specimens) using MRI-GB. In TRUS-GB, a median of 10 specimens (range, 6–14 specimens) were obtained. Telephone interviews were conducted one week after outpatient MRI-GB, asking patients about pain and side effects (hematuria, hemospermia, rectal bleeding, fever, and chills) of the two biopsy procedures and which of the two procedures they preferred. Multinomial regression analysis and Fisher’s exact test was used to test for differences.RESULTSMRI-GB was preferred by 65% (35/54), and 82% (44/54) would undergo MRI-GB again. Pain intensity (P = 0.005) and bleeding duration (P = 0.004) were significantly lower for MRI-GB compared with TRUS-GB. Hematuria was less common after MRI-GB compared with TRUS-GB (P = 0.006). A high correlation was given between bleeding intensity and bleeding duration for TRUS-GB (r=0.77) and pain intensity and pain duration for MRI-GB (r=0.65). Although hemospermia, rectal hemorrhage, fever, and chills were less common in MRI, they showed no statistically significant difference.Z CONCLUSIONMRI-GB of the prostate seems to have fewer side effects and less pain intensity than TRUS-GB and was preferred by the majority of patients

Cost‐effectiveness analysis of multiple imaging modalities in diagnosis and follow‐up of intermediate complex cystic renal lesions

Objectives: To compare health-economic aspects of multiple imaging modalities used to monitor renal cysts, the present study evaluates costs and outcomes of patients with Bosniak IIF and III renal cysts detected and followed-up by either contrast-enhanced computed tomography (ceCT), contrast-enhanced magnetic resonance imaging (ceMRI), or contrast-enhanced ultrasonography (CEUS). Patients and methods: A simulation using Markov models was implemented and performed with 10 cycles of 1 year each. Proportionate cohorts were allocated to Markov models by a decision tree processing specific incidences of malignancy and levels of diagnostic performance. Costs of imaging and surgical treatment were investigated using internal data of a European university hospital. Multivariate probabilistic sensitivity analysis was performed to confirm results considering input value uncertainties. Patient outcomes were measured in quality-adjusted life years (QALY), and costs as averages per patient including costs of imaging and surgical treatment. Results: Compared to the 'gold standard' of ceCT, ceMRI was more effective but also more expensive, with a resulting incremental cost-effectiveness ratio (ICER) >€70 000 (Euro) per QALY gained. CEUS was dominant compared to ceCT in both Bosniak IIF and III renal cysts in terms of QALYs and costs. Probabilistic sensitivity analysis confirmed these results in the majority of iterations. Conclusion: Both ceMRI and CEUS can be used as alternatives to ceCT in the diagnosis and follow-up of intermediately complex cystic renal lesions without compromising effectiveness, while CEUS is clearly cost-effective. The economic results apply to a large university hospital and must be adapted for smaller hospitals

MRI-TRUS fusion for electrode positioning during irreversible electroporation for treatment of prostate cancer

We aimed to introduce an approach for image-guided positioning of electrodes for irreversible electroporation (IRE) in patients with prostate cancer using a magnetic resonance imaging-transrectal ultrasonography (MRI-TRUS) fusion technique. In 10 consecutive patients with biopsy-proven Gleason score ≤3+4 prostate cancer, 19 G electrodes were inserted into the prostate using a transperineal access. Magnetic resonance images of the prostate acquired before IRE were fused with transrectal ultrasound images acquired during IRE. The position of the ultrasound probe was tracked via a sensor and corresponding magnetic resonance images were calculated in real-time. While MRI allowed delineation of the target volume, the position of the electrodes could be visualized on ultrasound images; the distance between individual electrode pairs was measured. Based on these measurements the software installed on the IRE unit was able to calculate the voltage necessary to generate the electric field for ablation. Using contrast-enhanced ultrasound, changes in perfusion within the ablation zone after IRE were documented. This technique allowed positioning of the electrodes around the target volume under image guidance in all patients treated with IRE. The target lesion and a safety margin were covered within the estimated ablation zone. MRI-TRUS guidance for IRE combines the advantages of good visualization of the target lesion on MRI with the ability of ultrasound to acquire imaging in real-time with a mobile device

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years