Value of magnetic resonance imaging/ultrasound fusion prostate biopsy to select patients for focal therapy.

PURPOSE: To investigate the role of transrectal MRI fusion biopsy to select patients for prostate cancer focal therapy. METHODS: Patients with suspected prostate cancer underwent transrectal MRI fusion biopsy with the Koelis trinity device. Two focal therapy eligibility criteria were subsequently defined: Group 1: PSA ≤ 15 ng/ml, unilateral csPCa, ISUP grade ≤ 2, no contralateral PIRADS 3-5 lesion; Group 2: same criteria but ISUP grade 3. These subgroups were correlated with histopathological post-prostatectomy parameters for stage pT2, unilateral csPCa, no ISUP upgrading. In addition, parameters of csPCa detection were analyzed for patients undergoing primary and re-biopsy. RESULTS: Four hundred fourteen consecutive patients were analyzed (314 for primary biopsy, 100 for re-biopsy). Post-prostatectomy whole mount section analysis was available from 155 patients. 39 and 62 of these patients met focal therapy inclusion criteria for group 1 and group 2, respectively. A correlation with final pathology parameters following radical prostatectomy (stage pT2, unilateral csPCa, no ISUP upgrading) revealed a positive predictive value of only 53.8% and 64.5% for Group 1 and 2, respectively. The overall csPCa detection rate was 73.7%. In the re-biopsy group 20% additional patients with csPCa were detected by targeted biopsy. CONCLUSION: Despite high csPCa detection rates following MRI fusion biopsy our study demonstrated that, using final pathology to confirm locally advanced tumor stage, presence of bilateral csPCa and ISUP upgrading, between 35.5 and 46.2% of patients would have been incorrectly selected for focal therapy.

German S3 Evidence-Based Guidelines on Focal Therapy in Localized Prostate Cancer: The First Evidence-Based Guidelines on Focal Therapy.

BACKGROUND: Focal therapy (FT) is an option to treat localized prostate cancer (PCa) and preserve healthy prostate tissue in order to reduce known side effects from primary whole-gland treatment. The available FT modalities are manifold. Until now, national and international PCa guidelines have been cautious to propose recommendations regarding FT treatment since data from prospective controlled trials are lacking for most FT modalities. Moreover, none of the international guidelines provides a separate section on FT. In this purpose, we provide a synopsis of the consensus-based German S3 guidelines for a possible international use. SUMMARY: The recently published update of the German S3 guidelines, an evidence- and consensus-based guideline, provides a section on FT with recommendations for diagnostic work-up, indications, modalities, and follow-up. This section consists of 12 statements and recommendations for FT in the treatment of localized PCa. KEY MESSAGE: The German S3 guidelines on PCa are the first to incorporate recommendations for FT based on evidence and expert consensus including indication criteria for FT, pretreatment, and follow-up diagnostic pathways as well as an extended overview of FT techniques and the current supportive evidence.

Oncological Long-term Outcome After Whole-gland High-intensity Focused Ultrasound for Prostate Cancer-21-yr Follow-up.

BACKGROUND: Owing to the morbidity of established radical treatment options for prostate cancer, alternative whole-gland and focal treatment strategies have emerged. High-intensity focused ultrasound (HIFU) is one of the most studied sources for tissue ablation and has been used since the 1990s. OBJECTIVE: To provide 21-yr oncological long-term follow-up data of an unselected series of patients who underwent whole-gland HIFU for nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: A total of 674 patients were treated between November 1997 and November 2012 in one university center. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The oncological outcome was assessed by biopsy failure-free survival (BFFS), salvage treatment-free survival (STFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Multivariable Cox proportional hazard regression analyses were performed to estimate the prognostic relevance of clinical variables. RESULTS AND LIMITATIONS: In total, 560 patients were included into the evaluation and the median follow-up was 15.1 yr, with a range up to 21.4 yr. At 15 yr, CSS rates for low-, intermediate-, and high-risk patients were 95%, 89%, and 65%, respectively; MFS, STFS-1 (salvage treatment other than HIFU), STFS-2 (salvage treatment including repeat HIFU), and BFFS rates were 91%, 85%, and 58%; 77%, 63%, and 29%; 67%, 52%, and 28%; and 82%, 73%, and 47%, respectively. Preoperative high-risk category was an independent predictor of inferior OS, CSS, MFS, STFS, and BFFS. CONCLUSIONS: Although whole-gland HIFU achieved good long-term cancer control in low- and intermediate-risk patients, high-risk patients should not be treated routinely by HIFU. Intermediate-risk patients achieve high CSS and MFS rates, but a relevant salvage treatment rate has to be reckoned with. Long-term data after whole-gland therapy might help derive implications for focal treatment sources and patient selection. PATIENT SUMMARY: Long-term data after whole-gland high-intensity focused ultrasound (HIFU) therapy are crucial to prove its oncological efficacy, and may help derive implications for focal treatment strategies and patient selection. In this context, whole-gland HIFU achieved good long-term cancer control up to 21 yr in low- and intermediate-risk prostate cancer (PCa) patients. Owing to considerably inferior long-term cancer control, it should not routinely be used in high-risk PCa patients.

High-intensity focused ultrasound (HIFU) hemiablation of the prostate: Late follow-up MRI findings in non-recurrent patients.

OBJECTIVES: Focal therapy with high-intensity focused ultrasound (HIFU) is an emerging option for the treatment of prostate cancer and often followed up by MRI. Image assessment of treatment failure, however, requires proper knowledge about typical procedure-related changes in prostate MRI, which is sparse, in particular for unilateral HIFU treatment and late follow up (beyond 6 months). The goal of this study was therefore to compile the type and frequency of such MRI findings in selected patients without recurrent cancer 12 months after prostate hemiablation. METHODS: Data from a prospective multicenter trial on HIFU hemiablation were reviewed retrospectively. Trial patients have had a late follow-up by MRI (at around 12 months) and either MRI/transrectal ultrasound (TRUS) fusion or standard TRUS-guided biopsy. This work deliberately included patients with non-recurrent cancer in the treated prostate lobe in per-protocol biopsy leaving 30 men with initial International Society of Urological Pathology (ISUP) Grade Group of 1 or 2. Six categories of potential HIFU-related MRI features were assessed by an expert committee and then evaluated by two readers in consensus: 1. shrinkage of the treated lobe, 2. residual prostate tissue, 3. fluid-filled cavity, 4. fibrosis, 5. hematoma residuals (in the prostate or seminal vesicles) and 6. contrast enhancement of the ablated area. RESULTS: Shrinkage of the ablated lobe was seen in 93% of the cases with an average percent volume change of -37% (range: -70% to +108%). In the contralateral lobe, the volume remained practically the same (-2% on average, p = 0.804). In the ablated lobe, the frequency of fibrosis was 97%. Residual prostate tissue was seen in 93% of the cases. The frequency for fluid-filled cavities was 97%, with the wide majority (90%) contiguous with the urethra. Hematoma residuals in the prostate and in seminal vesicles were found in 47% and 10% of the patients, respectively. Contrast enhancement was both rim-like (50%) as well as diffuse (33%) within the ablated area. CONCLUSION: In our case series of HIFU hemiablation in the prostate, shrinkage, residual prostate tissue, fluid-filled cavities contiguous with the urethra and fibrosis were very common late MRI findings of the ablated lobe in non-recurrent patients. Rim-like contrast enhancement or diffuse one within the ablated area were less frequent.

Potential Candidates for Focal Therapy in Prostate Cancer in the Era of Magnetic Resonance Imaging-targeted Biopsy: A Large Multicenter Cohort Study.

BACKGROUND: Focal therapy (FT) with its favorable side-effect profile represents an option between active surveillance and traditional whole-gland treatment in localized prostate cancer (PCa). Consensus statements recommend eligibility criteria based on magnetic resonance imaging (MRI)-targeted and systematic combination biopsy. OBJECTIVE: To estimate the future potential of FT by analyzing the number of men eligible for FT among all men with biopsy-proven PCa and to judge the potential of different energy sources. DESIGN, SETTING, AND PARTICIPANTS: Consensus criteria on FT were analyzed. Patients with biopsy-proven PCa from six tertiary referral hospitals and one outpatient practice in Germany had received a software-based combination biopsy. Men with Prostate Imaging Reporting and Data System (PI-RADS) ≥3 lesions based on PI-RADS v2 were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were analyzed for potential treatment by FT and hemiablation. MRI lesions were mapped according to prostatic zones. RESULTS AND LIMITATIONS: In total, 2371 patients were analyzed. According to consensus criteria (biopsy-proven unifocal lesion of International Society of Urological Pathology [ISUP] grade group ≤2, prostate-specific antigen [PSA] ≤15ng/mL, and life expectancy >10yr), 303 patients (12.8%; ISUP 1: n=148 [6.2%]; ISUP 2: n=155 [6.5%]) were potential candidates for FT. A maximum PSA level of <10ng/mL would exclude further 60 (2.5%) of these men. The eligibility for hemiablation is slightly higher (16.2%). Unifocal lesions (n=288) were equally distributed within the prostate (anteriorly [31%], apically [29%], and dorsally [36%]). CONCLUSIONS: With adherence to consensus statements, only a minority of PCa patients present as potential candidates for FT. Distribution of tumor localization suggests the need for different energy modalities to warrant an optimal FT treatment. PATIENT SUMMARY: We analyzed how many men who receive a magnetic resonance imaging-targeted and systematic prostate biopsy are candidates for the experimental focal therapy of the prostate. When following expert recommendations, only a small number of men are potential candidates for this alternative treatment.

Future of focal therapy for the treatment of prostate cancer- european section of urotechnology (ESUT) position.

INTRODUCTION: Focal therapy (FT) is a treatment option for prostate cancer (PCa), which offers the possibility of an effective therapy in selected patients who have the localized disease, with a significant reduction in treatment related morbidity. Based on the current status of FT, our objective was to determine the most appropriate strategy to improve patient management. MATERIALS AND METHODS: A literature review was done performed through the PubMed database and focused on the following topics: localised prostate cancer,MRI, prostate biopsies, ablative therapy and focal therapy. RESULTS: Indications for FT were mainly patients with a localised PCa, a single lesion at Gleason score 7 (3+4) (Grade group 2) favourable in size. Precise identification of the tumour, currently based on multiparametric MRI data and targeted biopsy, was the cornerstone of FT success. New imaging modalities such as PET/MRI and multiparametric ultrasound have proven to be effectivein detecting and targeting the tumour. Several energy sources were reported for an effective tissue ablation. Non-thermal option should be investigated to further limit the risk of side effects with the same cancer control. CONCLUSION: Focal therapy is a new option in the armamentarium of PCa. Technological improvements and the development of novel energy sources should make it possible to treat lesions with even greater precision, while limiting the risk of side effects. In the future, we should probably be able to effectively expand the indications of this technique to include more aggressive tumours.

INTRODUCCIÓN: La terapia focal (TF) es una opción terapéutica del cáncer de próstata (CaP), que ofrece la posibilidad de un tratamiento efectivo enpacientes seleccionados que tienen enfermedad localizada, con una reducción significativa de la morbilidad relacionada con el tratamiento. Nuestro objetivo es determinar la estrategia más apropiada para mejorar el manejo del paciente en base al estado actual de la terapia focal.MATERIAL Y MÉTODOS: Realizamos una revisión de la literatura por medio de la base de datos PubMed centrada en los siguientes temas: cáncer de próstata localizado, RMN, biopsias de próstata, tratamiento ablativo y terapia focal.RESULTADOS: Las indicaciones de TF eran principalmente pacientes con CaP localizado, lesión única Gleason 7 (3+4) (Grado Grupo 2) con tamaño favorable. La identificación precisa del tumor, actualmente basada en datos de RMN multiparamétrica y biopsia dirigida, es la piedra angular del éxito de la TF. Las nuevas modalidades de técnicas de imagen tales como PET/RMN y ecografía con contraste han demostrado ser eficaces en la detección y abordaje del tumor. Se han comunicado varias fuentes de energía para una ablación eficaz deltumor. La opción no térmica debería investigarse para limitar más aún el riesgo de efectos colaterales con el mismo control del cáncer.CONCLUSIONES: La terapia focal es una nueva opción en el armamentario para el CaP. Las mejoras tecnológicas y el desarrollo de nuevas fuentes de energíadeberían hacer posible el tratamiento de las lesiones con mayor precisión incluso, limitando a la vez el riesgo de efectos colaterales. En el futuro, deberíamos ser capaces probablemente de expandir efectivamente lasindicaciones de esta técnica para incluir tumores más agresivos.

Future of focal therapy for the treatment of prostate cancereuropean section of urotechnology (esut) position / Futuro de la terapia focal para el tratamieto del cáncer de próstata- posición de la sección de urotecnología (ESUT)

Introduction: Focal therapy (FT) is a treatment option for prostate cancer (PCa), which offers the possibility of an effective therapy in selected patients who have the localized disease, with a significant reduction in treatment related morbidity. Based on the current status of FT, our objective was to determine the most appropriate strategy to improve patient management Materials and methods: A literature review was done performed through the PubMed database and focused on the following topics: localised prostate cancer, MRI, prostate biopsies, ablative therapy and focal therapy. Results: Indications for FT were mainly patients with a localised PCa, a single lesion at Gleason score 7 (3+4) (Grade group 2) favourable in size. Precise identification of the tumour, currently based on multiparametric MRI data and targeted biopsy, was the cornerstone of FT success. New imaging modalities such as PET/MRI and multiparametric ultrasound have proven to be effective in detecting and targeting the tumour. Several energy sources were reported for an effective tissue ablation. Non-thermal option should be investigated to further limit the risk of side effects with the same cancer control. Conclusion: Focal therapy is a new option in the armamentarium of PCa. Technological improvements and the development of novel energy sources should make it possible to treat lesions with even greater precision, while limiting the risk of side effects. In the future, we should probably be able to effectively expand the indications of this technique to include more aggressive tumours

Introducción: La terapia focal (TF) es una opción terapéutica del cáncer de próstata (CaP), que ofrece la posibilidad de un tratamiento efectivo en pacientes seleccionados que tienen enfermedad localizada, con una reducción significativa de la morbilidad relacionada con el tratamiento. Nuestro objetivo es determinar la estrategia más apropiada para mejorar el manejo del paciente en base al estado actual de la terapia focal. Material y métodos: Realizamos una revisión de la literatura por medio de la base de datos PubMed centrada en los siguientes temas: cáncer de próstata localizado, RMN, biopsias de próstata, tratamiento ablativo y terapia focal. Resultados: Las indicaciones de TF eran principalmente pacientes con CaP localizado, lesión única Gleason 7 (3+4) (Grado Grupo 2) con tamaño favorable. La identificación precisa del tumor, actualmente basada en datos de RMN multiparamétrica y biopsia dirigida, es la piedra angular del éxito de la TF. Las nuevas modalidades de técnicas de imagen tales como PET/RMN y ecografía con contraste han demostrado ser eficaces en la detección y abordaje del tumor. Se han comunicado varias fuentes de energía para una ablación eficaz del tumor. La opción no térmica debería investigarse para limitar más aún el riesgo de efectos colaterales con el mismo control del cáncer. Conclusiones: La terapia focal es una nueva opción en el armamentario para el CaP. Las mejoras tecnológicas y el desarrollo de nuevas fuentes de energía deberían hacer posible el tratamiento de las lesiones con mayor precisión incluso, limitando a la vez el riesgo de efectos colaterales. En el futuro, deberíamos ser capaces probablemente de expandir efectivamente las indicaciones de esta técnica para incluir tumores más agresivos

Oncological long-term outcome of whole gland HIFU and open radical prostatectomy: a comparative analysis.

PURPOSE: To compare the oncological long-term efficacy of whole gland high-intensity focused ultrasound (HIFU) therapy and radical prostatectomy (RP) in patients with clinically localized prostate cancer. METHODS: 418 patients after open RP (1997-2004) were compared with 469 patients after whole gland HIFU (1997-2009) without preselection. Oncological follow-up focused on biochemical relapse, salvage treatment, life status and cause-specific mortality. The univariate log rank test was used to compare both treatment options regarding overall survival (OS), cancer-specific survival (CSS), biochemical failure-free survival (BFS) and salvage treatment-free survival (STS). To adjust the treatment effect for further prognostic baseline variables, a multivariable Cox proportional hazards regression model was calculated for each end point. RESULTS: Median follow-up was 13.3 years in the RP group and 6.5 years in the HIFU group. OS/CSS/BFS/STS rates at 10 years were 91/98/80/80% after RP and 76/94/70/71% after HIFU. HIFU therapy (reference RP) was a significant and independent predictor for an inferior OS, CSS and STS. In subgroup analysis, HIFU provided significantly reduced CSS for intermediate- (p = 0.010) and high-risk patients (p = 0.048); whereas no difference was observed in the low-risk group, intermediate-risk HIFU patients showed a significantly inferior STS (p = 0.040). CONCLUSIONS: While whole gland HIFU offers a comparable long-term efficacy for low-risk patients, sufficient cancer control for high-risk patients is more than doubtful. For the subgroup of intermediate-risk patients, CSS rates seem to be comparable up to 10 years suggesting that HIFU may be an alternative for older patients, although a higher risk of salvage treatment should be expected.

Rate of misclassification in patients undergoing radical prostatectomy but fulfilling active surveillance criteria according to the European Association of Urology guidelines on prostate cancer: a high-volume center experience.

BACKGROUND: The aim of the study was to identify the rate of pathologic upgrading and upstaging in a cohort of patients diagnosed with prostate cancer (PCa) who met inclusion criteria for active surveillance (AS) by the European Association of Urology (EAU) guidelines on prostate cancer but decided to undergo radical prostatectomy (RPE). Our goal was to determine possible predictive parameters that may be associated with unfavorable disease. METHODS: Single center retrospective analysis of patients who underwent RPE despite qualifying for AS according to the EAU AS criteria (defined as PSA≤10 ng/mL, biopsy Gleason Score <7, clinical stage ≤T2a, ≤2 positive biopsy cores and ≤50% cancer involvement of every positive core). Based on the final histopathology report we evaluated the rates of Gleason Score upgrading and upstaging to non-organ confined disease. Multivariate logistic regression analysis was performed to identify preoperative parameters that may correlate with disease upgrading and upstaging. RESULTS: Among 2345 patients, who underwent RPE between March 2007 and October 2013, 372 were included in our study. Final pathology report revealed Gleason Score upgrading in 105 (28.2%) patients and an extraprostatic extension (upstaging ≥pT3a) in 24 (6.4%) patients. There was no preoperative parameter that correlated statistically significantly with unfavorable disease. CONCLUSIONS: Our results indicate that the current criteria for AS cannot reliably differentiate between clinically significant or insignificant PCa and therefore offer limited utility in patient selection. Inclusion of more reliable tools like mpMRI novel biological markers might contribute to refine the current AS criteria.

Which technology to select for primary focal treatment of prostate cancer?-European Section of Urotechnology (ESUT) position statement.

BACKGROUND: With growing interest in focal therapy (FT) of prostate cancer (PCa) there is an increasing armamentarium of treatment modalities including high-intensity focused ultrasound (HIFU), cryotherapy, focal laser ablation (FLA), irreversible electroporation (IRE), vascular targeted photodynamic therapy (VTP), focal brachytherapy (FBT) and stereotactic ablative radiotherapy (SABR). Currently there are no clear recommendations as to which of these technologies are appropriate for individual patient characteristics. Our intention was to review the literature for special aspects of the different technologies that might be of advantage depending on individual patient and tumour characteristics. METHODS: The current literature on FT was screened for the following factors: morbidity, repeatability, tumour risk category, tumour location, tumour size and prostate volume and anatomical issues. The ESUT expert panel arrived at consensus regarding a position statement on a structured pathway for available FT technologies based on a combination of the literature and expert opinion. RESULTS: Side effects were low across different studies and FT modalities with urinary continence rates of 90-100% and erectile dysfunction between 5 and 52%. Short to medium cancer control based on post-treatment biopsies were variable between ablative modalities. Expert consensus suggested that posterior lesions are better amenable to FT using HIFU. Cryotherapy provides best possible outcomes for anterior tumours. Apical lesions, when treated with FBT, may yield the least urethral morbidity. CONCLUSIONS: Further prospective trials are required to assess medium to long term disease control of different ablative modalities for FT. Amongst different available FT modalities our ESUT expert consensus suggests that some may be better for diffe`rent tumour locations. Tumour risk, tumour size, tumour location, and prostate volume are all important factors to consider and might aid in designing future FT trials.

Comparative immunohistochemical characterization of interstitial cells in the urinary bladder of human, guinea pig and pig.

Interstitial cells (ICs) are thought to play a functional role in urinary bladder. Animal models are commonly used to elucidate bladder physiology and pathophysiology. However, inter-species comparative studies on ICs are rare. We therefore analyzed ICs and their distribution in the upper lamina propria (ULP), the deeper lamina propria (DLP) and the detrusor muscular layer (DET) of human, guinea pig (GP) and pig. Paraffin slices were examined by immunohistochemistry and 3D confocal immunofluorescence of the mesenchymal intermediate filament vimentin (VIM), alpha-smooth muscle actin (αSMA), platelet-derived growth factor receptor alpha (PDGFRα) and transient receptor potential cation channel A1 (TRPA1). Image stacks were processed for analysis using Huygens software; quantitative analysis was performed with Fiji macros. ICs were identified by immunoreactivity for VIM (excluding blood vessels). In all species ≥ 75% of ULP ICs were VIM+/PDGFRα+ and ≥ 90% were VIM+/TRPA1+. In human and pig ≥ 74% of ULP ICs were VIM+/αSMA+, while in GP the percentage differed significantly with only 37% VIM+/αSMA+ ICs. Additionally, over 90% of αSMA+ ICs were also TRPA1+ and PDGFRα+ in human, GP and pig. In all three species, TRPA1+ and PDGFRα+ ICs point to an active role for these cells in bladder physiology, regarding afferent signaling processes and signal modification. We hypothesize that decline in αSMA-positivity in GP reflects adaptation of bladder histology to smaller bladder size. In our experiments, pig bladder proved to be highly comparable to human urinary bladder and seems to provide safer interpretation of experimental findings than GP.

Prospective Multicenter Phase II Study on Focal Therapy (Hemiablation) of the Prostate with High Intensity Focused Ultrasound.

PURPOSE: We evaluated focal therapy with high intensity focused ultrasound hemiablation in a prospective trial. MATERIALS AND METHODS: We performed a prospective, multicenter, single arm study in patients with unilateral low/intermediate risk prostate cancer who were treated from April 2013 through March 2016 in Germany in AUO (Arbeitsgemeinschaft Urologische Onkologie) Study Protocol AP 68/11. Unilateral prostate cancer was assessed by transrectal ultrasound guided biopsy and multiparametric magnetic resonance imaging. Hemiablation was done using the Ablatherm® or the Focal One® device. The oncologic outcome was assessed by the salvage treatment rate, multiparametric magnetic resonance imaging and rebiopsy at 12 months. Functional outcome, quality of life, anxiety and depression were measured by validated questionnaires at baseline and every 3 months. RESULTS: Of the 54 recruited patients 51 completed 12-month or greater visits. Mean ± SD followup was 17.4 ± 4.5 months. Mean prostate specific antigen decreased from 6.2 ± 2.0 to 2.9 ± 1.9 ng/ml at 12 months (p <0.001). Biopsy at 12 months was positive for any prostate cancer and for clinically significant prostate cancer in 13 (26.5%) and 4 (8.2%) of the 49 patients, respectively. Posttreatment multiparametric magnetic resonance imaging had limited 25% sensitivity for clinically significant prostate cancer. Ten patients (19.6%) underwent salvage treatment. Potency was maintained in 21 of the 30 men who were potent preoperatively. There was no increase in incontinence. Quality of life, anxiety and depression did not change postoperatively. The study was limited by a short followup and the lack of a control arm. CONCLUSIONS: Focal therapy hemiablation is safe with little alteration of functional outcome. The oncologic outcome is acceptable on short-term followup. Followup multiparametric magnetic resonance imaging performed poorly and should not replace repeat biopsy. Focal therapy has no impact on posttreatment anxiety and depression.

Four-point Peritoneal Flap Fixation in Preventing Lymphocele Formation Following Radical Prostatectomy.

BACKGROUND: Symptomatic lymphocele following radical prostatectomy (RP) and concomitant bilateral extended pelvic lymph node dissection (ePLND) has a significant impact on postoperative recovery and may sometimes require surgical intervention. OBJECTIVE: To report on the use of four-point peritoneal flap fixation (4PPFF) during RP to reduce lymphocele occurrence following PLND. DESIGN, SETTING, AND PARTICIPANTS: Between April 2010 and May 2017, 1358 patients underwent RP with concomitant bilateral ePLND. From this cohort, 193 patients who had undergone PNLD with 4PPFF were matched in a 1:1 ratio with respect to age, body mass index, initial PSA, and number of lymph nodes removed to patients who had undergone PLND without 4PPFF. INTERVENTION: 4PPFF was performed by suturing the cut end of the ventral parietal peritoneum at four points (to the anterior and lateral pelvic side wall on both sides) following PLND so that the peritoneal surface was exposed to the iliac vessels and obturator fossa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All patients underwent ultrasound on postoperative days 6, 28, and 90 to test for the presence of lymphocele. For univariate analysis, a χ2 test and analysis of variance were applied, as appropriate. Statistical significance was set at p<0.05, and all p values reported were two-sided. RESULTS AND LIMITATIONS: There were no significant differences between the two groups with respect to intraoperative blood loss, positive surgical margin rate, Gleason score, clinical stage, and number of positive cores. Asymptomatic lymphocele was observed in four patients (2.07%) in the 4PPFF group compared to 16 patients (8.3%) without 4PPFF (p=0.0058). Similarly, a significant difference in the incidence of symptomatic lymphocele was observed: two patients (1.03%) in the 4PPFF group versus nine patients (4.6%) without 4PPFF (p=0.0322). There were no differences in other complication rates between the two groups. The limitations of the study are its retrospective and nonrandomised nature, with postoperative follow-up based on ultrasound imaging rather than computed tomography because of ethical considerations, which could have caused observer bias. CONCLUSIONS: 4PPFF is a safe and effective procedure in preventing lymphocele occurrence in patients undergoing RP with PLND. The increase in exposure of the PLND raw area to the peritoneal surface following this procedure may aid in increased absorption of accumulating lymph fluid. Further prospective randomised multicentre studies are warranted to confirm our observations. PATIENT SUMMARY: We report on the use of a surgical technique to decrease the collection of lymphatic fluid in the abdominal cavity following lymph node removal during radical removal of the prostate gland in patients with prostate cancer. Patients undergoing this procedure had significantly better outcomes when compared to patients operated on in the conventional approach.

Critical appraisal of literature comparing minimally invasive extraperitoneal and transperitoneal radical prostatectomy: A systematic review and meta-analysis.

OBJECTIVES: To systematically review studies comparing extraperitoneal (E-RP) and transperitoneal minimally invasive radical prostatectomy (T-RP). METHODS: The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in September 2015. Several databases were searched including Medline and Scopus. Only studies comparing E-RP and T-RP (either laparoscopic or robot-assisted approach) were evaluated. The follow-up of the included patients had to be ≥6 months. RESULTS: In all, 1256 records were identified after the initial database search. Of these 20 studies (2580 patients) met the inclusion criteria. The hospital stay was significantly lower in the E-RP cohort, with a mean difference of -0.30 days (95% confidence interval [CI] -0.35, -0.24) for the laparoscopic group and 1.09 days (95% CI -1.47, -0.70) for the robotic group (P < 0.001). Early continence rates favoured the E-RP group, although this was statistically significant only in the laparoscopic group (odds ratio [OR] 2.52, 95% CI 1.72, 3.70; P < 0.001). There was no statistically significant difference between the E-RP and T-RP cohorts for 12-month continence rates for both the laparoscopic (OR 1.55, 95% CI 0.89, 2.69; P = 0.12) and robotic groups (OR 3.03, 95% CI 0.54, 16.85; P = 0.21). The overall complication and ileus rates were significantly lower in the E-RP cohort for both the laparoscopic and robotic groups. The symptomatic lymphocele rate favoured the T-RP cohort, although this was statistically significant only in the laparoscopic group (OR 8.69, 95% CI 1.60, 47.17; P = 0.01). CONCLUSION: This review suggests that the extraperitoneal approach is associated with a shorter hospital stay, lower overall complication rate, and earlier return to continence when compared to the transperitoneal approach. The transperitoneal approach has a lower lymphocele rate.

Nuclear magnetic resonance spectroscopy as a new approach for improvement of early diagnosis and risk stratification of prostate cancer.

Prostate cancer (PCa) is the second most common male cancer worldwide and the fifth leading cause of death from cancer in men. Early detection and risk stratification is the most effective way to improve the survival of PCa patients. Current PCa biomarkers lack sufficient sensitivity and specificity to cancer. Metabolite biomarkers are evolving as a new diagnostic tool. This review is aimed to evaluate the potential of metabolite biomarkers for early detection, risk assessment, and monitoring of PCa. Of the 154 identified publications, 27 and 38 were original papers on urine and serum metabolomics, respectively. Nuclear magnetic resonance (NMR) is a promising method for measuring concentrations of metabolites in complex samples with good reproducibility, high sensitivity, and simple sample processing. Especially urine-based NMR metabolomics has the potential to be a cost-efficient method for the early detection of PCa, risk stratification, and monitoring treatment efficacy.

Protease Expression Levels in Prostate Cancer Tissue Can Explain Prostate Cancer-Associated Seminal Biomarkers-An Explorative Concept Study.

Previously, we described prostate cancer (PCa) detection (83% sensitivity; 67% specificity) in seminal plasma by CE-MS/MS. Moreover, advanced disease was distinguished from organ-confined tumors with 80% sensitivity and 82% specificity. The discovered biomarkers were naturally occurring fragments of larger seminal proteins, predominantly semenogelin 1 and 2, representing endpoints of the ejaculate liquefaction. Here we identified proteases putatively involved in PCa specific protein cleavage, and examined gene expression and tissue protein levels, jointly with cell localization in normal prostate (nP), benign prostate hyperplasia (BPH), seminal vesicles and PCa using qPCR, Western blotting and confocal laser scanning microscopy. We found differential gene expression of chymase (CMA1), matrix metalloproteinases (MMP3, MMP7), and upregulation of MMP14 and tissue inhibitors (TIMP1 and TIMP2) in BPH. In contrast tissue protein levels of MMP14 were downregulated in PCa. MMP3/TIMP1 and MMP7/TIMP1 ratios were decreased in BPH. In seminal vesicles, we found low-level expression of most proteases and, interestingly, we also detected TIMP1 and low levels of TIMP2. We conclude that MMP3 and MMP7 activity is different in PCa compared to BPH due to fine regulation by their inhibitor TIMP1. Our findings support the concept of seminal plasma biomarkers as non-invasive tool for PCa detection and risk stratification.

Extended mesometrial resection (EMMR): Surgical approach to the treatment of locally advanced cervical cancer based on the theory of ontogenetic cancer fields.

BACKGROUND: Based on ontogenetic-anatomic considerations, we have introduced total mesometrial resection (TMMR) and laterally extended endopelvic resection (LEER) as surgical treatments for patients with cancer of the uterine cervix FIGO stages I B1 - IV A. For a subset of patients with locally advanced disease we have sought to develop an operative strategy characterized by the resection of additional tissue at risk for tumor infiltration as compared to TMMR, but less than in LEER, preserving the urinary bladder function. METHODS: We conducted a prospective single center study to evaluate the feasibility of extended mesometrial resection (EMMR) and therapeutic lymph node dissection as a surgical treatment approach for patients with cervical cancer fixed to the urinary bladder and/or its mesenteries as determined by intraoperative evaluation. None of the patients received postoperative adjuvant radiotherapy. RESULTS: 48 consecutive patients were accrued into the trial. Median tumor size was 5cm, and 85% of all patients were found to have lymph node metastases. Complete tumor resection (R0) was achieved in all cases. Recurrence free survival at 5years was 54.1% (95% CI 38.3-69.9). The overall survival rate was 62.6% (95% CI 45.6-79.6) at 5years. Perioperative morbidity represented by grade II and III complications (determined by the Franco-Italian glossary) occurred in 25% and 15% of patients, respectively. CONCLUSION: We demonstrate in this study the feasibility of EMMR as a surgical treatment approach for patients with locally advanced cervical cancer and regional lymph node invasion without the necessity for postoperative adjuvant radiation.

Acute focal bacterial nephritis is associated with invasive diagnostic procedures - a cohort of 138 cases extracted through a systematic review.

BACKGROUND: Acute focal bacterial nephritis (AFBN) is a rare disease currently described only in case reports and small case series. In this study we summarize the clinical features of AFBN as has been documented in the literature and draw recommendations on the proper diagnosis and therapy. METHODS: A systematic literature review was undertaken in PUBMED, Web of Science and The Cochrane Library online databases for relevant literature on AFBN in adults. RESULTS: Literature review revealed a total of 38 articles according to our inclusion criteria, of which we could extract data from 138 cases of AFBN. Fever (98%) and flank pain (80%) were most commonly reported symptoms. E. coli was the most frequent pathogen. Diagnosis was set by CT and/or MRI (52%) with or without sonography or by sonography alone (20%) as well as by sonography combined with IVU. In total, sonography was applied in 83% of cases. All but one patient received antibiotic treatment. Kidney lesions were occasionally mistaken for neoplasms or renal abscesses and as a result, cases were subjected to percutaneous puncture (12.3%), surgical exploration (5.1%) and partial or radical nephrectomy (4.4%). Four cases (2.9%) developed a renal abscess. CONCLUSIONS: The diagnosis of AFBN is set by characteristic clinico-radiological findings. Differential diagnoses of this interstitial bacterial infection include renal abscess and tumor. Correct diagnosis is occasionally impeded by atypical symptoms. Invasive diagnostic and therapeutic procedures should be limited as the majority of cases respond well to conservative treatment.

Impact of the use of an endorectal coil for 3 T prostate MRI on image quality and cancer detection rate.

This work aims to assess the impact of an additional endorectal coil on image quality and cancer detection rate within the same patients. At a single academic medical center, this transversal study included 41 men who underwent T2- and diffusion-weighted imaging at 3 T using surface coils only or in combination with an endorectal coil in the same session. Two blinded readers (A and B) randomly evaluated all image data in separate sessions. Image quality with respect to localization and staging was rated on a five-point scale. Lesions were classified according to their prostate imaging reporting and data system (PIRADS) score version 1. Standard of reference was provided by whole-mount step-section analysis. Mean image quality scores averaged over all localization-related items were significantly higher with additional endorectal coil for both readers (p < 0.001), corresponding staging-related items were only higher for reader B (p < 0.001). With an endorectal coil, the rate of correctly detecting cancer per patient was significantly higher for reader B (p < 0.001) but not for reader A (p = 0.219). The numbers of histologically confirmed tumor lesions were rather similar for both settings. The subjectively rated 3-T image quality was improved with an endorectal coil. In terms of diagnostic performance, the use of an additional endorectal coil was not superior.