Periprostatic Adipose Tissue Displays a Chronic Hypoxic State that Limits Its Expandability.

White adipose tissue accumulates at various sites throughout the body, some adipose tissue depots exist near organs whose function they influence in a paracrine manner. Prostate gland is surrounded by a poorly characterized adipose depot called periprostatic adipose tissue (PPAT), which plays emerging roles in prostate-related disorders. Unlike all other adipose depots, PPAT secretes proinflammatory cytokines even in lean individuals and does not increase in volume during obesity. These unique features remain unexplained because of the poor structural and functional characterization of this tissue. This study characterized the structural organization of PPAT in patients compared with abdominopelvic adipose tissue (APAT), an extraperitoneal adipose depot, the accumulation of which is correlated to body mass index. Confocal microscopy followed by three-dimensional reconstructions showed a sparse vascular network in PPAT when compared with that in APAT, suggesting that this tissue is hypoxic. Unbiased comparisons of PPAT and APAT transcriptomes found that most differentially expressed genes were related to the hypoxia response. High levels of the hypoxia-inducible factor 2α confirmed the presence of an adaptive response to hypoxia in PPAT. This chronic hypoxic state was associated with inflammation and fibrosis, which were not further up-regulated by obesity. This fibrosis and inflammation explain the failure of PPAT to expand in obesity and open new mechanistic avenues to explain its role in prostate-related disorders, including cancer.

En bloc resection of bladder tumour: the rebirth of past through reminiscence.

PURPOSE: To learn about the history and development of en bloc resection of bladder tumour (ERBT), and to discuss its future directions in managing bladder cancer. METHODS: In this narrative review, we summarised the history and early development of ERBT, previous attempts in overcoming the tumour size limitation, consolidative effort in standardising the ERBT procedure, emerging evidence in ERBT, evolving concepts in treating large bladder tumours, and the future directions of ERBT. RESULTS: Since the first report on ERBT in 1980, there has been tremendous advancement in terms of its technique, energy modalities and tumour retrieval methods. In 2020, the international consensus statement on ERBT has been developed and it serves as a standard reference for urologists to practise ERBT. Recently, high-quality evidence on ERBT has been emerging. Of note, the EB-StaR study showed that ERBT led to a reduction in 1-year recurrence rate from 38.1 to 28.5%. An individual patient data meta-analysis is currently underway, and it will be instrumental in defining the true value of ERBT in treating non-muscle-invasive bladder cancer. For large bladder tumours, modified approaches of ERBT should be accepted, as the quality of resection is more important than a mere removal of tumour in one piece. The global ERBT registry has been launched to study the value of ERBT in a real-world setting. CONCLUSION: ERBT is a promising surgical technique in treating bladder cancer and it has gained increasing interest globally. It is about time for us to embrace this technique in our clinical practice.

Pathological features of Prostate Imaging Reporting and Data System (PI-RADS) 3 MRI lesions in biopsy and radical prostatectomy specimens.

OBJECTIVE: To assess the whole pathology spectrum of Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified on magnetic resonance imaging, using systematic (SB), targeted biopsy (TB) and radical prostatectomy (RP) specimen analysis. METHODS: From a prospective database of patients undergoing RP after a combination of SB (median 12 cores) and fusion TB (median 3 cores), we included 150 PI-RADS 3 cases. Clinically significant prostate cancer (csPCa) was defined by a Grade Group 2 or more. The primary endpoints were unfavourable features in RP specimens. RESULTS: Targeted biopsy was negative in 20.7% of patients. Final Grade Group 3 or more and a pT3 stage was reported in 36.7% and 38.7% of RP specimens. The upgrading rate was 38.2% between biopsy and RP specimens. The concordance rate between Grade Group on TB and RP was only 38.0%. The two independent predictive factors for unfavourable disease (pT3-4 and/or final Grade Group 3-5) were prostate-specific antigen density (PSAD; P = 0.001) and presence of csPCa on TB (odds ratio 3.7; P = 0.001). The risk of unfavourable disease was increased 2.3-fold and 5.8-fold, respectively, for patients with a PSAD between 0.15 and 0.20, and a PSAD >0.20 ng/mL/g. The 5-year biochemical recurrence-free survival rate was 93.2%. CONCLUSIONS: PI-RADS 3 lesions exhibited aggressive features in almost 40% of cases. PSAD and presence of csPCa on TB are independent predictive factors for high-grade and/or extraprostatic disease. A combination of SB and TB improve grade prediction compared to use of TB alone.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review.

PURPOSE: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. MATERIAL AND METHODS: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. RESULTS: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. CONCLUSIONS: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

The prognostic value of high-grade prostate cancer pattern on MRI-targeted biopsies: predictors for downgrading and importance of concomitant systematic biopsies.

PURPOSE: To assess the proportion and risk factors for downgrading and reclassification to favorable disease in patients having high-grade (HG) prostate cancer (PCa) pattern on magnetic resonance imaging (MRI)-targeted-biopsy (TB). METHODS: From a radical prostatectomy (RP) cohort, we included patients with pre-biopsy positive MRI and HG [defined by Grade Group (GG) ≥ 3] PCa on MRI-TB. All patients also underwent concomitant systematic biopsy (SB). The main endpoints were the rates of downgrading to GG2, overall downgrading, favorable disease (pT2 and GG2) on RP specimens, and biochemical recurrence-free-survival (RFS). We studied the correlations between HG on concomitant SB, final pathological outcomes and biochemical RFS curves. RESULTS: Overall downgrading, downgrading to GG2 disease and favorable disease were noted in 36.2%, 24.1%, and 15.4% respectively. HG on concomitant SB was correlated with pT3-4 disease (p < 0.001), pN1 disease (p < 0.001), positive surgical margins (p = 0.043), PSA recurrence (p = 0.003). In multivariable analysis, the presence of GG4-5 on TB (p = 0.013; OR 0.263) and the presence of HG on concomitant SB (p = 0.010; OR 0.269) were negatively and independently correlated with the risk of downgrading to GG2. The presence of HG on concomitant SB independently predicted RFS with a hazard ratio of 2.173 (p = 0.049; 95% CI 1.005-4.697). CONCLUSIONS: Our data shows that a limited HG restricted to TB can often be associated with a favorable grade in almost a quarter of the cases and downgraded in almost half of the cases. Detailed SB features, mainly the presence of HG on concomitant SB, was associated with a more accurate pathology and oncologic outcomes prediction, pleading for the maintenance of SB in MRI-positive patients.

Timing and delay of radical prostatectomy do not lead to adverse oncologic outcomes: results from a large European cohort at the times of COVID-19 pandemic.

PURPOSE: The current COVID-19 pandemic is transforming our urologic practice and most urologic societies recommend to defer any surgical treatment for prostate cancer (PCa) patients. It is unclear whether a delay between diagnosis and surgical management (i.e., surgical delay) may have a detrimental effect on oncologic outcomes of PCa patients. The aim of the study was to assess the impact of surgical delay on oncologic outcomes. METHODS: Data of 926 men undergoing radical prostatectomy across Europe for intermediate and high-risk PCa according to EAU classification were identified. Multivariable analysis using binary logistic regression and Cox proportional hazard model tested association between surgical delay and upgrading on final pathology, lymph-node invasion (LNI), pathological locally advanced disease (pT3-4 and/or pN1), need for adjuvant therapy, and biochemical recurrence. Kaplan-Meier analysis was used to estimate BCR-free survival after surgery as a function of surgical delay using a 3 month cut-off. RESULTS: Median follow-up and surgical delay were 26 months (IQR 10-40) and 3 months (IQR 2-5), respectively. We did not find any significant association between surgical delay and oncologic outcomes when adjusted to pre- and post-operative variables. The lack of such association was observed across EAU risk categories. CONCLUSION: Delay of several months did not appear to adversely impact oncologic results for intermediate and high-risk PCa, and support an attitude of deferring surgery in line with the current recommendation of urologic societies.

Urinary diversion after pelvic exenteration for gynecologic malignancies.

Pelvic exenteration combines multiple organ resections and functional reconstruction. Many techniques have been described for urinary reconstruction, although only a few are routinely used. The aim of this review is to focus beyond the technical aspects and the advantages and disadvantages of each technique, and to include a critical analysis of continent techniques in the gynecologic and urologic literature. Selecting a technique for urinary reconstruction must take into account the constraints entailed by the natural history of the disease, patient characteristics, healthcare institution, and surgeon experience. In gynecologic oncology, the Bricker ileal conduit is the most commonly employed diversion, followed by the self-catheterizable pouch and orthotopic bladder replacement. Continent and non-continent diversions present similar immediate and long-term complication rates, including lower tract urinary infections and pyelonephritis (5-50%), ureteral stricture (3-27%), urolithiasis (5-25%), urinary fistula (5%), and more rarely, vitamin B12 deficiency and metabolic acidosis. Urinary incontinence for the ileal orthotopic neobladder (50%), stoma-related complications for the Bricker ileal conduit (24%), difficulty with self-catheterization (18%) for the continent pouch, and induction of secondary malignancy for the ureterosigmoidostomy (3%) are the most relevant technique-related complications following urinary diversion. The self-catheterizable pouch and orthotopic bladder require a longer learning curve from the surgical team and demand adaptation from the patient compared with the ileal conduit. Quality of life between different techniques remains controversial, although it would seem that young patients may benefit from continent diversions. We consider that centralization of pelvic exenteration in referral centers is crucial to optimize the oncologic and functional outcomes of complex ablative reconstructive surgery.

The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes.

Bone metastasis remains the most frequent and the deadliest complication of prostate cancer (PCa). Mechanisms leading to the homing of tumor cells to bone remain poorly characterized. Role of chemokines in providing navigational cues to migrating cancer cells bearing specific receptors is well established. Bone is an adipocyte-rich organ since 50 to 70% of the adult bone marrow (BM) volume comprise bone marrow adipocytes (BM-Ads), which are likely to produce chemokines within the bone microenvironment. Using in vitro migration assays, we demonstrated that soluble factors released by human primary BM-Ads are able to support the directed migration of PCa cells in a CCR3-dependent manner. In addition, we showed that CCL7, a chemokine previously involved in the CCR3-dependent migration of PCa cells outside of the prostate gland, is released by human BM-Ads. These effects are amplified by obesity and ageing, two clinical conditions known to promote aggressive and metastatic PCa. In human tumors, we found an enrichment of CCR3 in bone metastasis vs. primary tumors at mRNA levels using Oncomine microarray database. In addition, immunohistochemistry experiments demonstrated overexpression of CCR3 in bone versus visceral metastases. These results underline the potential importance of BM-Ads in the bone metastatic process and imply a CCR3/CCL7 axis whose pharmacological interest needs to be evaluated.

Exclusive B-cell phenotype of primary prostatic lymphomas: a potential role of chronic prostatitis.

AIMS: Primary prostatic lymphomas (PPL) is exceedingly rare. The aim of this study was to investigate the largest series of PPL obtained from a nationwide expert pathologist network, and thus try to understand the pathophysiology of these tumours. METHODS AND RESULTS: Up to 66 000 lymphoma cases have been collected and submitted for central expert review by the French Lymphopath network. We confirm the low frequency of PPL (n = 77; 0.12%), all cases being of B-cell origin. Diffuse large B-cell lymphoma and small lymphocytic lymphoma were the most frequent subtypes, comprising 31% and 26% of cases respectively, followed by mucosa-associated lymphoid tissue (MALT)/lymphoplasmacytic lymphoma (19%), follicular lymphoma (12%), mantle cell lymphoma (6%), Burkitt lymphoma (4%), and unclassified lymphoma (1%). Clinical data obtained in 25 cases suggests that PPLs are rather indolent tumours. Our hypothesis for B-cell recruitment in the prostatic tissue was derived from the observation in chronic inflammation (prostatitis) of frequent heterotopic proliferation of high endothelial venules (HEVs). The latter are dedicated to lymphocyte entry into secondary lymphoid organs, here putatively driving circulating clonal B-lymphocytes from the blood into the inflamed prostate. This may account for the relatively high incidence of small lymphocytic lymphoma consistently reported in series of primary or secondary prostatic lymphoma. As in other organs or glands, chronic inflammation may promote antigen-dependent intraprostatic MALT lymphoma and diffuse large B-cell lymphoma development. CONCLUSIONS: PPLs are exclusively of B-cell origin, and chronic inflammation resulting from the proliferation of high endothelial venules could play some role in their development.

Performance of systematic, MRI-targeted biopsies alone or in combination for the prediction of unfavourable disease in MRI-positive low-risk prostate cancer patients eligible for active surveillance.

PURPOSE: To assess the upstaging/upgrading rates of low-risk prostate cancer (PCa) according to the biopsy scheme used (systematic (SB), targeted biopsies (TB), or both) in the setting of positive pre-biopsy MRI. PATIENTS AND METHODS: We included 143 consecutive men fulfilling the Toronto University active surveillance (AS) criteria who underwent a pre-biopsy positive MRI, a combination of SB and software-based fusion TB, and a radical prostatectomy, in two expert centres. The primary endpoints were the pathological upgrading and upstaging rates. Overall unfavourable disease (OUD) was defined by any pT3-4 and/or pN1 and/or ≥ GG 3. RESULTS: Using TB alone would have missed 21.7% of cancers including 16.7% of ≥ GG 3. The use of TB was significantly associated with a lower risk of ≥ Grade Group (GG) 3 disease (p < 0.006) in RP specimens. Combination of SB and TB lowered this risk by 39%, compared with TB alone. The biopsy scheme did not affect the upstaging rates which were substantial even in case of combination scheme (from 37 to 46%). OUD was detected in approximately 50% of cases. The presence of high grade on TB was the only independent predictive factor for both ≥ GG 2 (p = 0.015) and ≥ GG 3 (p = 0.023) in RP specimens. CONCLUSIONS: High grade on TB biopsies represented the major predictor of upgrading. Combination of SB and TB better defined the sub-group of patients having the lowest risk of reclassification, compared with TB or SB alone. The risk of non-organ-confined disease remained high, and could not be accurately predicted by MRI or systematic/targeted biopsy features.

Decreased accuracy of the prostate cancer EAU risk group classification in the era of imaging-guided diagnostic pathway: proposal for a new classification based on MRI-targeted biopsies and early oncologic outcomes after surgery.

PURPOSE: To assess the performance of EAU risk classification in PCa patients according to the biopsy pathway (standard versus MRI guided) and to develop a new, more accurate, targeted biopsy (TB)-based classification. MATERIALS AND METHODS: We included 1345 patients consecutively operated by radical prostatectomy (RP) since 2014, when MRI and TB were introduced in the diagnostic pathway. Patients underwent systematic biopsy (SB) only (n = 819) or SB and TB (n = 526) prior to RP during the same time period. Pathological and biochemical outcomes were compared between PCa men undergoing SB (SB cohort) and a combination of TB and SB (TB cohort). Kaplan-Meier and Cox regression models were used to assess biochemical recurrence-free survival (RFS). RESULTS: Both cohorts were comparable regarding final pathology and RFS (p = 0.538). The EAU risk classification accurately predicted outcomes in SB cohort, but did not significantly separate low from intermediate risk in TB cohort (p = 0.791). In TB cohort, the new proposed three-group risk classification significantly improved the recurrence risk prediction compared with the EAU risk classification: HR 4 (versus HR 1.2, p = 0.009) for intermediate, and HR 15 (versus HR 6.5, p < 0.001) in high-risk groups, respectively. A fourth group defining very high-risk cases (≥ T2c clinical stage or grade group 5) was also proposed. CONCLUSIONS: The new classification integrating TB findings we propose meaningfully improves the recurrence prediction after surgery in patients undergoing a TB-based diagnostic pathway, compared with standard EAU risk classification which is still relevant for patients undergoing only SB. External validation is needed.

Active surveillance eligibility of MRI-positive patients with grade group 2 prostate cancer: a pathological study.

PURPOSE: To assess the final pathology risk in MRI-positive grade group (GG) 2 prostate cancer (PCa) patients undergoing targeted (TB) and systematic (SB) biopsies, and thereby, the possibility of active surveillance (AS) in this population. PATIENTS AND METHODS: We included 242 consecutive men diagnosed with GG2 PCa by a combination of SB and software-based fusion TB undergoing a radical prostatectomy (RP). The primary endpoints were the pathological findings in RP specimens, including favourable disease which was defined by a pT2 and GG1-2 disease. RESULTS: The rate of upgrading was 33% including 3% of GG 4-5 disease. MRI lesion size (p = 0.038) and tumor length per core (p < 0.001) were significantly lower in case of favourable pathology. Only 34.2% of not organ-confined disease was reported when only SB were positive, compared with 45.7% and 57.1% when GG2 was detected on TB only and on TB plus SB, respectively (p = 0.035). The number of positive cores on SB was significantly higher in not organ-confined disease (4.3 versus 2.9; p = 0.005). The risk of not organ-confined disease was only 20.8% in men who had a PSAD ≤ 0.20 ng/ml/gr, 1-2 positive biopsies and a maximal tumor length ≤ 6 mm per core, compared with 52.3% in men who did not fulfil all these criteria (p = 0.003). CONCLUSIONS: This study identified clinical, imaging, and pathological factors that were significantly associated with the final pathology risk. In case of positive MRI followed by TB showing GG2, AS could be offered in patients having a PSAD ≤ 0.20, a tumor length ≤ 6 mm and 1-2 positive cores.

Added Value of Concomitant Systematic and Fusion Targeted Biopsies for Grade Group Prediction Based on Radical Prostatectomy Final Pathology on Positive Magnetic Resonance Imaging.

PURPOSE: We assessed the added value of concomitant systematic biopsy for final grade group prediction in patients with positive magnetic resonance imaging who were undergoing targeted biopsy. MATERIALS AND METHODS: Included in study were 478 consecutive patients with prebiopsy positive multiparametric magnetic resonance imaging and a greater than 10-core systematic biopsy combined with fusion targeted biopsy who underwent radical prostatectomy. The primary end point was the grade group concordance between biopsy and radical prostatectomy pathology according to the biopsy technique. Clinical and biological factors associated with the performance of systematic biopsy were analyzed. RESULTS: Adding systematic biopsy to targeted biopsy modified the d'Amico risk classification toward more intermediate and high risk in 7.8% of cases, mainly from low to intermediate risk with low risk prostate cancer on targeted biopsy in 44.3%. This reclassification was significantly higher in patients with lower prostate specific antigen and with prostate specific antigen density less than 0.20 ng/ml/gm (11.7% vs 2.4%, p <0.001). The concordance rate between biopsy pathology and radical prostatectomy pathology significantly differed between targeted biopsy and targeted biopsy plus systematic biopsy (45.2% and 51.7%, respectively). The upgrading rate in radical prostatectomy specimens decreased by 22% when systematic biopsy was added to targeted biopsy. Patients in whom systematic biopsy did not modify grading were more likely to have pT3-4 and/or pN1 disease on final pathology (56.9% vs 38.3%, p=0.007). CONCLUSIONS: Grading concordance between biopsy pathology and radical prostatectomy pathology was improved by adding systematic biopsy in all patient subgroups. Patients with prostate specific antigen density less than 0.20 ng/ml/gm benefited the most from this combined biopsy strategy. Systematic biopsy reclassified a nonnegligible number of cases toward a higher risk category, mainly the low risk cases. Thus, systematic biopsy could modify treatment decision making.

Refining the risk-stratification of transrectal biopsy-detected prostate cancer by elastic fusion registration transperineal biopsies.

PURPOSE: To evaluate image-guided Transperineal Elastic-Registration biopsy (TPER-B) in the risk-stratification of low-intermediate risk prostate cancer detected by Transrectal-ultrasound biopsy (TRUS-B) when estimates of cancer grade and volume discorded with multiparametric Magnetic Resonance Imaging (MRI). METHODS: All patients referred for active surveillance or organ-conservative management were collegially reviewed for consistency between TRUS-B results and MRI. Image-guided TPER-B of the index target (IT) defined as the largest Prostate Imaging-Reporting Data System-v2 ≥ 3 abnormality was organized for discordant cases. Pathology reported Gleason grade, maximum cancer core length (MCCL) and total CCL (TCCL). RESULTS: Of 237 prostate cancer patients (1-4/2018), 30 were required TPER-B for risk-stratification. Eight cores were obtained [Median and IQR: 8 (6-9)] including six (IQR: 4-6) in the IT. TPER-B of the IT yielded longer MCCL [Mean and (95%CI): 6.9 (5.0-8.8) vs. 2.6 mm (1.9-3.3), p < 0.0001] and TCCL [19.7 (11.6-27.8) vs. 3.6 mm (2.6-4.5), p = 0.0002] than TRUS-B of the gland. On TPER-B cores, longer MCCL [Mean and (95%CI): 8.7 mm (6.7-10.7) vs. 4.1 mm (0.6-7.6), p = 0.002] were measured in Gleason score-7 cancers. TPER-B cores upgraded 13/30 (43.3%) patients. 14/30 (46.7%) met University College London-definition 1 and 18/30 (60.0%) definition 2, which correlate with clinically significant cancers > 0.5 mL and > 0.2 mL, respectively. 7/16 (43.8%) patients under active surveillance were re-allocated toward prostatectomy (n = 5) or radiation therapy (n = 2). In 14 patients not yet assigned, TPER-B risk-stratification spurred the selection (13/14, 92.9%) of treatments with curative intent. CONCLUSION: Image-guided TPER-B of the index target provided more cancer material for pathology. Subsequent re-evaluation of cancer volume and grade switched a majority of patients towards higher-risk groups and treatments with curative intent.

Prospective evaluation of the performances of narrow-band imaging flexible videoscopy relative to white-light imaging flexible videoscopy, in patients scheduled for transurethral resection of a primary NMIBC.

PURPOSE: To evaluate on a lesion-by-lesion basis Narrow-Band Imaging flexible videoscopy (NBI-FV) in the detection of cancer compared to White-Light Imaging flexible videoscopy (WLI-FV). METHODS: WLI-FV and NBI-FV were sequentially performed in patients scheduled for TURBT for primary bladder cancer. Suspicious findings were individually harvested and characterized under WLI-FV (suspicious/non-suspicious) and NBI-FV (5-point Likert scale) and pathology. The primary objective was to determine if NBI-FV informed at least 20% more cancer lesions than WLI-FV (Relative true-positive rate > 1.19). A minimum of 120 specimens was to be analyzed to reach 90% power. RESULTS: Of 147 specimens taken in 68 patients, 101 were found suspicious under WLI-FV and 64 (64/101, 63.4%) confirmed as cancer. Of the 46 lesions undetected by WLI-VF, 16 were found positive for cancer (16/46, 34.8%). For NBI-FV, a significant increase in positive samples was observed with increments in Likert scale (p < 0.0002). Relative true-positive rate was 1.22 (95% CI 1.12-1.39)-NBI-FV detected 22% more cancer lesions compared to WLI-FV. Relative false-positive rate was 1.35 (95% CI 1.19-1.59). CONCLUSION: Researching alterations in mucosa and microvasculature by narrow-band imaging flexible videoscopy augmented by 22% the detection of cancer foci and contributed to the objective of complete resection of all visible lesions. Conversely, it entailed a 35% increase in false-positive results compared to white-light imaging, although the structured analysis of narrow-band imaging findings might be used to grade suspicion according to the Likert scale and balance the risk of a false-positive result to the benefit of demonstrating cancer.

SIU-ICUD on bladder cancer: pathology.

Many changes have been made during these last years and concepts for understanding bladder cancer have evolved. We make an update with the latest findings of the WHO (World Health Organistaion) 2016, ICCR (International Collaboration on Cancer Reporting) and other official organisms and try to show the latest developments. In this document we provide new consensus guidelines and insights. We kept this document short and concise providing consensus guidelines to clinicians for the best patient care, it should be easy to understand for a non pathologists. We focussed on several burning issues, such as the anatomical and histological understanding of the bladder wall, the prognostic significance of grading and the most challenging problems in staging, we underline our needs from the clinicians such as clinical information, we further discuss the histological subtypes of bladder cancer, which is an extremely important issue in the light of molecular classifications and give prognostic insights. Furthermore, we discuss the ICCR worldwide consensus reporting, urinary cytology with the Paris system and several issues such as frozen section specimen.

Epidemiology, prevention, screening, diagnosis, and evaluation: update of the ICUD-SIU joint consultation on bladder cancer.

PURPOSE: To update current recommendations on prevention, screening, diagnosis, and evaluation of bladder cancer (BC) based on a thorough assessment of the most recent literature on these topics. METHODS: A non-systematic review was performed, including articles until June 2017. A variety of original articles, reviews, and editorials were selected according to their epidemiologic, demographic, and clinical relevance. Assessment of the level of evidence and grade of recommendations was performed according to the International Consultation on Urological Diseases grading system. RESULTS: BC is the ninth most common cancer worldwide with 430,000 new cases in 2012. Currently, approximately 165,000 people die from the disease annually. Absolute incidence and prevalence of BC are expected to rise significantly during the next decades because of population ageing. Tobacco smoking is still the main risk factor, accounting for about 50% of cases. Smoking cessation is, therefore, the most relevant recommendation in terms of prevention, as the risk of developing BC drops almost 40% within 5 years of cessation. BC screening is not recommended for the general population. BC diagnosis remains mainly based on cystoscopy, but development of new endoscopic and imaging technologies may rapidly change the diagnosis algorithm. The same applies for local, regional, and distant staging modalities. CONCLUSIONS: A thorough understanding of epidemiology, risk factors, early detection strategies, diagnosis, and evaluation is essential for correct, evidence-based management of BC patients. Recent developments in endoscopic techniques and imaging raise the hope for providing better risk-adopted approaches and thereby improving clinical outcomes.

Neurotensin Receptor-1 Expression in Human Prostate Cancer: A Pilot Study on Primary Tumors and Lymph Node Metastases.

Neurotensin and its high-affinity receptor, NTR1, are involved in the growth of various tumors. Few data are available regarding NTR1 expression in normal and tumoral human prostate tissue samples. NTR1 expression was assessed using immunohistochemistry in 12 normal prostate tissues, 11 benign prostatic hyperplasia (BPH), 44 prostate cancers, and 15 related metastatic lymph nodes (one per patient, when available). NTR1-staining was negative in normal prostate and BPH samples. NTR1 was overexpressed in four out of 44 (9.1%) primary tumors. There was no clear association between NTR1 overexpression and age, PSA-values, Gleason score, pT-status, nodal-status, or margin. NTR1 was expressed at a high level of five out of 15 (33.3%) metastatic lymph nodes. NTR1 overexpression was thus more frequent in metastatic lymph nodes than in primary tumors (p = 0.038). In this limited series of samples, NTR1 overexpression was observed in few primary prostate cancers. Upregulation was more frequent in related lymph nodes. The presence of this target in metastatic lymph nodes may open new perspectives for imaging and radionuclide therapy of prostate cancer. Factors driving NTR1 expression in primary prostate cancer and in nodal and distant metastases still need to be characterized.

Precision Matters in MR Imaging-targeted Prostate Biopsies: Evidence from a Prospective Study of Cognitive and Elastic Fusion Registration Transrectal Biopsies.

Purpose To measure the precision in placement of a biopsy needle in a magnetic resonance (MR) imaging-detected target with transrectal ultrasonography (US), to document the clinical relevance of precision, and to report on the precision of cognitive and software-based registrations. Materials and Methods This prospective study was approved by the institutional review board and performed between June 2013 and September 2013. Patients provided informed verbal consent. Two cores each were obtained with cognitive and fusion techniques in 88 patients with a Prostate Imaging Reporting and Data System version 1 score of at least 3. Precision was measured with Euclidian geometry by using the Digital Imaging and Communications in Medicine archives of the biopsy as the distance from the core to the center (dCC) and the distance from the core to the surface of the target modeled as a sphere. To address clustering of data from multiple cores in the same patients, analyses of precision focused on the best shot for a patient or a technique. The Welch unequal variance t test and Yates corrected χ2 test were used as appropriate. Results Mean precision was 2.5 mm (95% confidence interval: 1.8 mm, 3.3 mm). Positive cores were closer to the center than were negative cores (dCC: 1.7 mm vs 3.1 mm, respectively; P = .025). More cancers were detected with on-target than off-target cores (33 of 71 cores [46.5%] vs three of 17 cores [17.6%]; P = .03). Cores obtained with the fusion technique achieved a higher precision than did cores obtained with the cognitive technique (dCC: 2.8 mm vs 7.1 mm, respectively; P < .0001). Targeted cores demonstrated cancer in 44 patients. Fewer cancers were detected with the cognitive technique than with the fusion technique (31 of 44 patients [70.5%] vs 40 of 44 patients [90.9%]; P = .03). Conclusion A deformable MR imaging/transrectal US image registration system achieved a higher precision and depicted cancer in more patients than did the cognitive freehand technique. © RSNA, 2018.