The addition of a sagittal image fusion improves the prostate cancer detection in a sensor-based MRI /ultrasound fusion guided targeted biopsy

Background To explore the diagnostic benefit of an additional image fusion of the sagittal plane in addition to the standard axial image fusion, using a sensor-based MRI/US fusion platform. Methods During July 2013 and September 2015, 251 patients with at least one suspicious lesion on mpMRI (rated by PI- RADS) were included into the analysis. All patients underwent MRI/US targeted biopsy (TB) in combination with a 10 core systematic prostate biopsy (SB). All biopsies were performed on a sensor-based fusion system. Group A included 162 men who received TB by an axial MRI/US image fusion. Group B comprised 89 men in whom the TB was performed with an additional sagittal image fusion. Results The median age in group A was 67 years (IQR 61–72) and in group B 68 years (IQR 60–71). The median PSA level in group A was 8.10 ng/ml (IQR 6.05–14) and in group B 8.59 ng/ml (IQR 5.65–12.32). In group A the proportion of patients with a suspicious digital rectal examination (DRE) (14 vs. 29%, p = 0.007) and the proportion of primary biopsies (33 vs 46%, p = 0.046) were significantly lower. The rate of PI-RADS 3 lesions were overrepresented in group A compared to group B (19 vs. 9%; p = 0.044). Classified according to PI-RADS 3, 4 and 5, the detection rates of TB were 42, 48, 75% in group A and 25, 74, 90% in group B. The rate of PCa with a Gleason score ≥7 missed by TB was 33% (18 cases) in group A and 9% (5 cases) in group B; p-value 0.072. An explorative multivariate binary logistic regression analysis revealed that PI-RADS, a suspicious DRE and performing an additional sagittal image fusion were significant predictors for PCa detection in TB. 9 PCa were only detected by TB with sagittal fusion (sTB) and sTB identified 10 additional clinically significant PCa (Gleason ≥7). Conclusion Performing an additional sagittal image fusion besides the standard axial fusion appears to improve the accuracy of the sensor-based MRI/US fusion platform

A non‐inferiority comparative analysis of micro‐ultrasonography and MRI‐targeted biopsy in men at risk of prostate cancer

Objective: To compare the efficacy of multiparametric magnetic resonance imaging (mpMRI)-directed and micro-ultrasonography (micro-US)-directed biopsy for detecting clinically significant (Grade Group >1) prostate cancer (csPCa). Materials and methods: A total of 203 patients were prospectively enrolled at three institutions across Germany and Austria in the period from January 2019 to December 2019. During each biopsy, the urologist was blinded to the mpMRI report until after the micro-US targets had been assessed. After unblinding, targets were then sampled using software-assisted fusion, followed by systematic samples. The primary outcome measure was non-inferiority of micro-US to detect csPCa, with a detection ratio of at least 80% that of mpMRI. Results: A total of 79 csPCa cases were detected overall (39%). Micro-US-targeted biopsy detected 58/79 cases (73%), while mpMRI-targeted biopsy detected 60/79 (76%) and non-targeted (completion sampling) samples detected 45/79 cases (57%). mpMRI-targeted samples alone detected 7/79 (9%) csPCa cases which were missed by micro-US-targeted and non-targeted samples. Three of these seven were anterior lesions with 2/7 in the transition zone. Micro-US-targeted samples alone detected 5/79 (6%) and completion sampling alone detected 4/79 cases (5%). Micro-US was non-inferior to mpMRI and detected 97% of the csPCa cases detected by mpMRI-targeted biopsy (95% CI 80-116%; P = 0.023). Conclusions: This is the first multicentre prospective study comparing micro-US-targeted biopsy with mpMRI-targeted biopsy. The study provides further evidence that micro-US can reliably detect cancer lesions and suggests that micro-US biopsy might be as effective as mpMRI for detection of csPCA. This result has significant implications for increasing accessibility, reducing costs and expediting diagnosis

Extended Criteria Donors in Living Kidney Transplantation Including Donor Age, Smoking, Hypertension and BMI

Purpose: An expansion of selection criteria for deceased organ transplantation already exists to manage the current donor shortage. Comparable evaluation of risk factors for living donors should be investigated to improve this issue. Patients and methods: Our retrospective single-centre study analysed 158 patients with living kidney transplants performed between February 2006 and June 2012. We investigated the influence of donor risk factors (RF) including body mass index over 30 kg/m2, age >60 years, active nicotine abuse and arterial hypertension on postoperative kidney function with focus on the recipients. This was measured for long-term survival and glomerular filtration rate (GFR) in a 5-year follow-up. Results: Overall, out of 158 living donors, 84 donors were identified to have no risk factors, whereas 74 donors had at least one risk factor. We noted a significant higher delayed graft function (p=0.042) in the first 7 days after transplantation, as well as lower GFR of recipients of allografts with risk factors in the first-year after transplantation. In our long-term results, there was no significant difference in the functional outcome (graft function, recipient and graft survival) between recipients receiving kidneys from donors with no and at least one risk factors. In the adjusted analysis of subgroups of different risk factors, recipients of donors with "age over 60 years" at time of transplantation had a decreased transplant survival (p=0.014). Conclusion: Thus, a careful expansion for selection criteria for living donors with critical evaluation could be possible, but especially the age of the donors could be a limited risk factor

Active surveillance inclusion criteria under scrutiny in magnetic resonance imaging-guided prostate biopsy : a multicenter cohort study

Background Although multiparametric magnetic resonance imaging (mpMRI) is recommended for primary risk stratification and follow-up in Active Surveillance (AS), it is not part of common AS inclusion criteria. The objective was to compare AS eligibility by systematic biopsy (SB) and combined MRI-targeted (MRI-TB) and SB within real-world data using current AS guidelines. Methods A retrospective multicenter study was conducted by a German prostate cancer (PCa) working group representing six tertiary referral centers and one outpatient practice. Men with PCa and at least one MRI-visible lesion according to Prostate Imaging Reporting and Data System (PI-RADS) v2 were included. Twenty different AS inclusion criteria of international guidelines were applied to calculate AS eligibility using either a SB or a combined MRI-TB and SB. Reasons for AS exclusion were assessed. Results Of 1941 patients with PCa, per guideline, 583–1112 patients with PCa in both MRI-TB and SB were available for analysis. Using SB, a median of 22.1% (range 6.4–72.4%) were eligible for AS. Using the combined approach, a median of 15% (range 1.7–68.3%) were eligible for AS. Addition of MRI-TB led to a 32.1% reduction of suitable patients. Besides Gleason Score upgrading, the maximum number of positive cores were the most frequent exclusion criterion. Variability in MRI and biopsy protocols potentially limit the results. Conclusions Only a moderate number of patients with PCa can be monitored by AS to defer active treatment using current guidelines for inclusion in a real-world setting. By an additional MRI-TB, this number is markedly reduced. These results underline the need for a contemporary adjustment of AS inclusion criteria

New perspectives on the renal slit diaphragm protein podocin

Podocin is a critical component of the glomerular filtration barrier, its mutations causing recessive steroid-resistant nephrotic syndrome. A GenBank analysis of the human podocin (NPHS2) gene resulted in the possible existence of a new splice variant of podocin in the kidney, missing the in-frame of exon 5, encoding the prohibitin homology domain. Using RT–polymerase chain reaction and immunoblotting followed by sequence analysis, we are for the first time able to prove the expression of a novel podocin isoform (isoform 2), exclusively and constitutively expressed in human podocytes. Furthermore, we reveal singular extrarenal podocin expression in human and murine testis. Our data show the Sertoli cells of the seminiferous tubules to be the origin of testicular podocin. Confocal laser microscopy illustrates the co-localization of podocin with filamentous actin within Sertoli cells, suggesting a role of podocin in the blood/testis barrier. These results led to the rationale to examine podocin expression in testes of men with Sertoli cell-only syndrome, a disorder characterized by azoospermia. Interestingly, we observed a complete down-regulation of podocin mRNA in Sertoli cell-only syndrome, indicating a possible role of podocin in the pathogenesis of this germinal aplasia. Men with Sertoli cell-only syndrome show normal renal podocin expression, suggesting an alternate regulation of the testicular promoter. Our findings may change the perception of podocin and give new insights into the ultrastructure of glomerular slit diaphragm and the blood/testis barrier

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Einfluss der MRT/Ultraschall-fusionierten Zielbiopsie auf die Diagnose des Prostatakarzinoms

PCa presents the most common cancer in men of the western world. In the past two decades, the diagnostics of PCa was defined by the PSA test and the TRUS guided systematic prostate biopsy. The primary TRUS guided biopsy reveals PCa in only about half the men. Men with a negative biopsy and further elevated PSA levels often undergo subsequent TRUS guided biopsies with further declining PCa detection rates. Historically, imaging of the prostate with MRI played no role in the diagnostics of PCa, but recently the paradigm has started to shift. Visualizing the cancer suspicious lesions within the prostate on the mpMRI allowed for MRI/US fusion guided targeted biopsies rather than systematic sampling. The mpMRI and targeted biopsy therefore presented an option to improve on the standard of care. The first study therefore analyzed the cancer detection rates for men undergoing a MRI/US fusion guided targeted biopsy in combination with a 10-core systematic biopsy. The analysis included 310 men with a suspicious lesion according to PI-RADS. The detection rate of the whole cohort was 51% and 62% of cancers were GS ≥ 7. In patients undergoing a primary biopsy cancer was detected in 75% and a GS ≥ 7 was diagnosed in 75% of the cases. In the repeat biopsy setting, the detection of PCa ranged from 44% for men with ≥ 3 negative to 54% for men with one negative systematic biopsy. The PI-RADS score of the target lesion was a significant predictor for GS ≥ 7 detection. We concluded that the combination of targeted biopsies with a systematic biopsy seem to advance the performance of the standard biopsy regimen. Furthermore, we established a need to evaluate the impact of the PI-RADS score on targeted biopsies. The second publication focused on correlating each single PI-RADS score with the cancers detected by of MRI/US fusion biopsy. The PI-RADS classification for the standardized reporting of mpMRI was published in 2012. Data on the actual value of the PI- RADS score at the time our study was scarce and with 408 included men, our study presented the largest PI-RADS based analysis. In 56% of men PCa was found and the detection rates regarding the number of previous prostate biopsy were further improved compared to the first analysis. Further, the analysis showed again that the detection of significant PCa stayed constant independent of the number of prior biopsies (76-79%). Whereas men with PI-RADS 3 lesions had cancer in 26% of cases, men with PI-RADS 5 lesions were diagnosed with PCa in 89%. The study showed the strong correlation of the PI-RADS score to the detection of clinically relevant PCa. Nonetheless, we also recommend combining targeted biopsies with systematic biopsies for increased diagnostic accuracy. The data of the cancers missed by targeted biopsy and detected by the systematic biopsy raised the question of the underlying reasons. The retrospective analysis included 61 men in which a blinded re-evaluation of each PI-RADS score was performed. This was followed by an unblinded correlation of the mpMRI targets and the biopsy outcome and documentation of the reasons targeted biopsy failure. In 50% of the 90 evaluated lesions the re-reading lead to a downgrading of the initial PI-RADS score, which would have not indicated a targeted biopsy. In 40% of the lesions, the site of the cancer detected by systematic biopsy could clearly be linked to the suspicious mpMRI lesion, indicating a miss of the targeted biopsy. Interestingly, these lesions were mostly PI-RADS 4 or 5 and had a GS ≥ 7. The implications of the analysis was that adding the systematic biopsy will compensate for targeting errors and that “false high” mpMRI readings will affect the targeted biopsy outcome. The analysis of the targeted biopsy failures lead to the question if an additional image fusion in the sagittal plane would yield a diagnostic benefit. Of the 251 men included into the analysis, 89 men had an additional biopsy taken in sagittal image registration without increasing the total number of targeted biopsies. The analysis showed a significant correlation of the sagittal image fusion with a positive targeted biopsy result. The rate of significant PCa overlooked by the targeted biopsy was reduced by 8% by the supplemental sagittal image fusion and in nine men (10%), PCa was solely diagnosed on the sagittal targeted biopsy. Extending the standard MRI/US fusion protocol by a sagittal image fusion and sagittal targeted biopsy may improve the accuracy of a sensor-based MRI/US fusion guided targeted biopsy. Most published studies are based on the combination of targeted and systematic biopsies. The limitations of the targeted biopsy alone may be overcome by identifying the suitable patient rather than choosing a “one fits all” approach. We therefore retrospectively analyzed possible predictors for an equivalent or even superior outcome of a sole targeted biopsy compared to the systematic biopsy in regard to the PCa risk group. The analysis revealed that the lesion size >12mm, suspicious digital rectal examination and free/total PSA ratio were possible predictors for a sole targeted biopsy approach. Choosing the lesion size (137 men) as an entry test for a targeted only biopsy would have saved 1370 systematic biopsy cores, missing 11 low risk and two high risk PCa. Combining the lesion size with the total/free PSA ratio (70 men) would have reduced the biopsy burden by 700 cores, overlooking two high- risk PCa and underestimating the risk group in three men. Our data may be helpful in guiding patients inquiring the option of a targeted-only biopsy. The mpMRI of the prostate and targeted biopsies have heavily changed the current approach of PCa diagnostics, but there is remaining room for improvement. Combining the mpMRI with biological markers, implementing positron emission tomography (PET)/MRI or developing MRI radionomics for increased data extraction, may further enhance the diagnostic accuracy and improve patient care.Das Prostatakarzinom stellt das häufigste Karzinom des Mannes in der westlichen Welt dar. In den letzten zwei Dekaden, wurde die Diagnose des PCa durch den PSA-Test und eine TRUS gestützte systematische Biopsie definiert. Die primäre TRUS Biopsie ergab lediglich bei der Hälfte der Männer ein PCa. Männer mit negativer Biopsie und weiterhin erhöhten PSA-Werten, werden häufig weiteren TRUS Biopsie unterzogen, mit einer weiteren Abnahme der Karzinomdetektion. Bisher spielte die Bildgebung mittels MRT in der Diagnose des PCa keine wesentliche Rolle, jedoch begann dieses Paradigma sich in letzter Zeit zu wandeln. Die Visualisierung der karzinomsuspekten Läsion innerhalb der Prostata ermöglichte eine gezielte MRT/US fusionierte Biopsie anstatt einer systematischen Biopsie. Das MRT und die Zielbiopsie stellte so eine Option für eine Verbesserung der Behandlungsqualität dar. Die erste Studie untersuchte folgend die Karzinomdetektion bei Männern, die eine MRT/US Fusionsbiopsie in Kombination mit einer 10-fach systematischen Biopsie erhielten. Die Analyse umfasste 301 Männer mit nach PI-RADS klassifizierten suspekten Läsionen. Die Detektionsrate der Gesamtgruppe lag bei 51% und 62% der Tumore hatten einen GS ≥ 7. Patienten mit einer Primärbiopsie hatten ein Karzinom in 75% der Fälle und einen GS ≥ 7 in 75%. Bei der Wiederholungsbiopsie lag die Detektion zwischen 44% bei Männern mit ≥ 3 negativen bis zu 54% bei Männern mit nur einer vorherigen negativen Biopsie. Der PI-RADS Score der Zielläsion war ein signifikanter Prädiktor für die Detektion eines GS ≥ 7 Karzinoms. Wir schlussfolgerten, dass eine Kombination einer Zielbiopsie mit einer systematischen Biopsie einen Vorteil gegenüber des Standardvorgehens darzustellen scheint. Zudem stellten wir die Notwendigkeit her, den Einfluss des PI-RADS Score auf die Zielbiopsie weiter zu untersuchen. Die zweite Publikation fokussierte auf die Korrelation des einzelnen PI-RADS Score mit der Tumordetektion in der MRT/US Fusionsbiopsie. Die PI-RADS Klassifikation für den Befundungsstandard für das mpMRT wurde 2012 erstmalig publiziert. Daten zum Stellenwert des PI-RADS Score waren zum Zeitpunkt unserer Studie rar, so dass unsere Studie mit 408 Männern, die größte PI-RADS basierte Analyse darstellte. In 56% der Männer wurde ein PCa diagnostiziert und die Karzinomrate konnte in Bezug auf die Anzahl der vorherigen negativen Biopsie im Vergleich zur ersten Analyse weiter verbessert werden. Zudem zeigte die Analyse erneut, dass die Rate an signifikanten Karzinomen unabhängig von den vorhergegangen Biopsien konstant blieb Further (76-79%). Wohingegen Männer mit einer PI-RADS 3 Läsion in 26% der Fälle ein Karzinom aufwiesen wurden Männer mit PI-RADS 5 Läsion in 89% der Fälle mit einem Karzinom diagnostiziert. Die Studie zeigte eine deutliche Korrelation zwischen dem PI- RADS und der Detektion eines klinisch signifikanten PCa. Nichtsdestotrotz befürworteten wir für eine verbesserte Genauigkeit, die Zielbiopsie mit einer systematischen Biopsie zu kombinieren. Die Daten bezüglich der durch die Zielbiopsien übersehenen Karzinome brachte die Frage der möglichen Ursachen auf. Die retrospektive Analyse beinhaltete 61 Fälle, bei denen eine verblindete Re-Evaluation des PI-RADS Score erfolgte. Gefolgt wurde dies von einer ungeblindeten Korrelation der Läsionen im mpMRT und des Biopsie Ergebnisses sowie die Dokumentation der zugrundeliegenden Ursache. In 50% der 90 analysierten Läsionen zeigte sich in der Re-Evaluation ein Downgrading des PI-RADS Score, welche initial keine Biopsie veranlasst hätte. In 40% der Läsionen konnte die Lokalisation des Karzinoms in der systematischen Biopsie eindeutig mit der Lokalisation im mpMRT korreliert werden und zeigte somit ein Verfehlen der Zielbiopsie auf. Interessanterweise, handelte es hierbei vor allem um PI-RADS 4 oder 5 Läsionen mit einem GS ≥ 7. Die Folgerung der Analyse war, dass eine zusätzliche systematische Biopsie im Rahmen der Zielbiopsie ein Versagen diese zu kompensieren vermag und dass initiale „falsch hohe“ PI-RADS Bewertung das Ergebnis der Zielbiopsie beeinflussen. Die Analyse des Versagens der Zielbiopsie führte zu der Frage ob eine zusätzliche Bildfusion in der Sagittalebene eine diagnostische Verbesserung ermögliche könnte. Von den 251 eingeschlossenen Männern, erhielten 89 Männer eine zusätzliche Zielbiopsien nach einer Bildregistrierung in der Sagittaleben ohne die Anzahl der Zielbiopsie zu erhöhen. Die Analyse ergab eine signifikante Korrelation zwischen der sagittalen Bildfusion und den positiven Biopsie Ergebnis. Die Rate an signifikanten Karzinomen, welche von der Zielbiopsie übersehen worden wären, konnte durch die zusätzliche sagittale Zielbiopsie um 8% gesenkt werden. In neun Fällen (10%) wurde die Diagnose alleinig durch die sagittale Fusionsbiopsie gestellt. Eine Erweiterung der Standard MRT/US Fusionsbiopsie durch eine sagittale Bildfusion und sagittale Zielbiopsie könnte die Genauigkeit der sensor-basierten MRT/US fusionierten Zielbiopsie weiter verbessern. Die meisten publizierten Arbeiten basieren auf der Kombination einer Zielbiopsie mit einer systematischen Biopsie. Die Limitation einer alleinigen Zielbiopsie könnte durch eine geeignete Selektion der Patienten überwunden werden. Deshalb analysierten wir retrospektiv mögliche Prädiktoren für eine Äquivalenz oder Überlegenheit einer alleinigen Zielbiopsie im Vergleich zu einer systematischen Biopsie in Bezug auf die Karzinom Risiko- Einteilung. Die Analyse ergab, dass Läsionsgröße von >12mm, eine auffällige digital rektale Untersuchung sowie die PSA Ratio mögliche Prädiktoren für einen alleinigen Zielbiopsie-Ansatz darstellten. Im Falle der Läsionsgröße (137 Männer) als Entscheidung für eine alleinige Zielbiopsie, hätten 1370 systematische Biopsie Zylinder gespart werden können. Insgesamt wären 11 low risk und zwei high risk PCa übersehen worden. Die Kombination der Läsionsgröße und der PSA Ratio (70 Männer) hätte die Biopsielast der Patienten um 700 Zylinder gesenkt und wären lediglich zwei high-risk PCa übersehen und die Risikogruppe bei drei Männern unterschätzt worden. Unsere Daten könnten in der Beratung der Patienten in Bezug auf eine alleinige Zielbiopsie nützlich sein. Das mpMRT der Prostata und die Zielbiopsie haben die aktuelle diagnostische Herangehensweise an das Prostatakarzinom deutlich verändert. Trotzdem besteht die Notwendigkeit weiterer Verbesserungen. Die Kombination der mpMRT mit Biomarkern, der Einsatz der Positron Emission Tomographie (PET)/MRT oder die Entwicklung von MRT Radionomics für eine optimierte Datenextraktion könnten die diagnostische Genauigkeit und damit auch die Patientenversorgung verbessern

The Ureter in the Kidney Transplant Setting: Ureteroneocystostomy Surgical Options, Double-J Stent Considerations and Management of Related Complications

Purpose of Review: In the setting of kidney transplantation, the ureter is a common source for complications. As a result, prevention of ureteral complications and their management is of crucial importance. In this context, the purpose of this review is to summarize recent literature on the ureter in the kidney transplant setting with a special focus on new findings. We conducted a PubMed and Medline search over the last 10 years to identify all new publications related to ureteroneoimplantations, stents and management of complications in the kidney transplant setting. Recent Findings: Performance of the “Lich-Gregoir” technique for ureteroneocystostomy seems to be favourable in regard to postoperative complications when compared with other methods described in the literature. Moreover, major urologic complications can be further reduced by ureteral stenting. Summary: A new approach for management of ureteral strictures in renal transplants is presented. We discussed the usage of a ureteral stent covered with a biostable polymer aiming to prevent tissue ingrowth into the lumen as a new option for management of ureteral stricture in the kidney transplant setting

Validation of the PI-RADS language: predictive values of PI-RADS lexicon descriptors for detection of prostate cancer

Objectives: To assess the discriminatory power of lexicon terms used in PI-RADS version 2 to describe MRI features of prostate lesions. Methods: Four hundred fifty-four patients were included in this retrospective, institutional review board-approved study. Patients received multiparametric (mp) MRI and subsequent prostate biopsy including MRI/transrectal ultrasound fusion biopsy and 10-core systematic biopsy. PI-RADS lexicon terms describing lesion characteristics on mpMRI were assigned to lesions by experienced readers. Positive and negative predictive values (PPV, NPV) of each lexicon term were assessed using biopsy results as a reference standard. Results: From a total of 501 lesions, clinically significant prostate cancer (csPCa) was present in 175 lesions (34.9%). Terms related to findings of restricted diffusion showed PPVs of up to 52.0%/43.9% and NPV of up to 91.8%/89.7% (peripheral zone or PZ/transition zone or TZ). T2-weighted imaging (T2W)-related terms showed a wide range of predictive values. For PZ lesions, high PPVs were found for "markedly hypointense," "lenticular," "lobulated," and "spiculated" (PPVs between 67.2 and 56.7%). For TZ lesions, high PPVs were found for "water-drop-shaped" and "erased charcoal sign" (78.6% and 61.0%). The terms "encapsulated," "organized chaos," and "linear" showed to be good predictors for benignity with distinctively low PPVs between 5.4 and 6.9%. Most T2WI-related terms showed improved predictive values for TZ lesions when combined with DWI-related findings. Conclusions: Lexicon terms with high discriminatory power were identified (e.g., "markedly hypointense," "water-drop-shaped," "organized chaos"). DWI-related terms can be useful for excluding TZ cancer. Combining T2WI- with DWI findings in TZ lesions markedly improved predictive values