The effectiveness of mapping-targeted biopsies on the index lesion in transperineal prostate biopsies.

PURPOSE: To evaluate the effectiveness of mapping-targeted biopsies (MTB) on the index lesion for the detection of clinically significant prostate cancer (csPCa) in transperineal fusion-image prostate biopsies. MATERIALS AND METHODS: A retrospective analysis was conducted on 309 men with suspected PCa who underwent prostate biopsies at the Creu Blanca reference center in Barcelona, Spain. The Prostate Imaging-Reporting and Data System (PI-RADS v.2.1) of the magnetic resonance images (MRI) were reclassified by an expert radiologist reading of pre-biopsy biparametric MRI used for segmentation of suspected lesions. Transperineal MTB of suspicious lesions and 12-core systematic biopsies were performed using the Artemis™ platform. CsPCa was defined as International Society of Urological Pathology grade group ≥ 2. RESULTS: CsPCa was detected in 192 men (62.1%), with detection rates of 6.3% for PI-RADS 2, 26.8% for PI-RADS 3, 87.3% for PI-RADS 4, and 93.1% for PI-RADS 5. MTB of the index lesion identified 185 csPCa (96.3%). CsPCa was detected solely in systematic biopsies in three cases (1.6%), while an additional four cases (2.1%) were identified only in the second suspected lesion. A predictive model for csPCa detection in MTB of the index lesion was developed, with an AUC of 0.918 (95% CI 0.887-0.950). CONCLUSIONS: This model had the potential to avoid 23.3% of prostate biopsies without missing additional csPCa cases. MTB of the index lesion was highly effective for identifying csPCa in fusion transperineal prostate biopsies. A developed predictive model successfully reduced the need for almost one quarter of biopsies without missing csPCa cases.

A Systematic Review of the Current Status of Magnetic Resonance-Ultrasound Images Fusion Software Platforms for Transperineal Prostate Biopsies.

Given this new context, our objective is to recognize the suitability of the currently available software for image fusion and the reported series using the transperineal route, as well as to generate new evidence on the complementarity of the directed and systematic biopsies, which has been established through the transrectal approach. EVIDENCE ACQUISITION: This systematic review, registered in Prospero (CRD42022375619), began with a bibliographic search that was carried out in PubMed, Cochrane, and Google Scholar databases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria and the studied eligibility based on the Participants, Intervention, Comparator, and Outcomes (PICO) strategy were followed. Warp analysis of selected studies was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. In addition, a Google search of all currently available fusion platforms was performed. Our Google search found 11 different commercially available robots to perform transperineal image fusion biopsies, of which 10 devices have published articles supporting their diagnostic effectiveness in transperineal prostate biopsies. RESULTS: A total of 30 articles were selected and the characteristics and results of the biopsies of 11,313 patients were analyzed. The pooled mean age was 66.5 years (63-69). The mean pooled PSA level was 7.8 ng/mL (5.7-10.8). The mean pooled prostate volume was 45.4 cc. (34-56). The mean pooled PSA density was 0.17 (0.12-0.27). The overall cancer detection rate for all prostate cancers was 61.4%, while for csPCa it was 47.8%. PCa detection rate was more effective than that demonstrated in the systematic transrectal biopsy. However, the detection of csPCa in the systematic biopsy was only 9.5% in the reported series. To standardize our review, we grouped prostate cancer screening results according to the population studied and the software used. When the same populations were compared between elastic and rigid software, we found that rigid biopsies had a higher csPCa detection rate than biopsies with elastic fusion systems. CONCLUSION: Platforms performing prostate biopsy using transperineal image fusion have better detection rates of csPCa than systematic transrectal biopsies. Rigid fusion systems have a better csPCa detection rate than elastic ones. We found no diagnostic differences between the different types of robotic systems currently available. The complementarity of systematic biopsy has also been demonstrated in transperineal imaging fusion biopsies.

Under-expression of CK2ß subunit in ccRCC represents a complementary biomarker of p-STAT3 Ser727 that correlates with patient survival.

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of renal cancer. STAT3 pathway is altered in these tumors and p-STAT3 Ser727 is an independent prognostic factor for ccRCC. Protein kinase CK2 is altered in different types of tumors and overexpression of CK2α is considered predictive of bad prognosis and metastatic risk. CK2 subunits analyses in ccRCC samples showed increased CK2α/α' nuclear content in all cases, but decreased cytosolic CK2ß (CK2ßcyt) levels in the more advanced tumors. Stable downregulation of CK2ß in renal proximal tubular (HK-2) and clear cell adenocarcinoma (786-O) cells triggered changes in E-cadherin, vimentin and Snail1 protein levels indicative of epithelial-to-mesenchymal transition (EMT), and increased HIF-α. Moreover, CK2ß was required in order to observe STAT3 Ser727 phosphorylation in HK-2 but not in 786-O cells. We also observed that CK2ß improved the prognostic value of p-STAT3 Ser727, as CK2ßcyt>41 (median value) discriminates patients free of disease for a period of 10 years upon surgery, from those with CK2ßcyt<41, when p-STAT3 Ser727levels are low. We conclude that CK2ß down-regulation might represent a mechanism to support EMT and angiogenesis and that CK2ßcyt levels are instrumental to refine prognosis of ccRCC patients with low p-STAT3 Ser727 levels.

HAVCR/KIM-1 activates the IL-6/STAT-3 pathway in clear cell renal cell carcinoma and determines tumor progression and patient outcome.

Renal cell carcinoma (RCC), the third most prevalent urological cancer, claims more than 100,000 lives/year worldwide. The clear cell variant (ccRCC) is the most common and aggressive subtype of this disease. While commonly asymptomatic, more than 30% of ccRCC are diagnosed when already metastatic, resulting in a 95% mortality rate. Notably, nearly one-third of organ-confined cancers treated by nephrectomy develop metastasis during follow-up care. At present, diagnostic and prognostic biomarkers to screen, diagnose, and monitor renal cancers are clearly needed. The gene encoding the cell surface molecule HAVCR1/KIM-1 is a suggested susceptibility gene for ccRCC and ectodomain shedding of this molecule may be a predictive biomarker of tumor progression. Microarray analysis of 769-P ccRCC-derived cells where HAVCR/KIM-1 levels have been upregulated or silenced revealed relevant HAVCR/KIM-1-related targets, some of which were further analyzed in a cohort of 98 ccRCC patients with 100 month follow-up. We found that HAVCR/KIM-1 activates the IL-6/STAT-3/HIF-1A axis in ccRCC-derived cell lines, which depends on HAVCR/KIM-1 shedding. Moreover, we found that pSTAT-3 S727 levels represented an independent prognostic factor for ccRCC patients. Our results suggest that HAVCR/KIM-1 upregulation in tumors might represent a novel mechanism to activate tumor growth and angiogenesis and that pSTAT-3 S727 is an independent prognostic factor for ccRCC.

The reproducibility and predictive value on outcome of renal biopsies from expanded criteria donors.

Reproducibility and predictive value on outcome are the main criteria to evaluate the utility of histological scores. Here we analyze the reproducibility of donor biopsy assessment by different on-call pathologists and the retrospective evaluation by a single renal pathologist blinded to clinical outcomes. We also evaluate the predictive value on graft outcome of both evaluations. A biopsy was performed in donors with any of the following: age≥55 years, hypertension, diabetes, creatinine>1.5 mg/dl, or stroke. Glomerulosclerosis, interstitial fibrosis, tubular atrophy, intimal thickening, and arteriolar hyalinosis evaluated according to the Banff criteria were added to obtain a chronic score. Biopsies were classified as mild (≥3), intermediate (4-5), or advanced (6-7) damage, and unacceptable (≥8) for transplantation of 127 kidneys biopsied. Weighted κ value between both readings was 0.41 (95% CI: 0.28-0.54). Evaluation of biopsies by the renal pathologist was significantly and independently associated with estimated 12-month glomerular filtration rate and a significant composite outcome variable, including death-censored graft survival and time to reach an estimated glomerular filtration rate<30 ml/min per 1.73 m2. Thus, there was no association between readings of on-call pathologists and outcome. The lack of association between histological scores obtained by the on-call pathologists and graft outcome suggests that a specific training on renal pathology is recommended to optimize the use of kidneys retrieved from expanded criteria donors.

Hepatitis A virus cellular receptor 1/kidney injury molecule-1 is a susceptibility gene for clear cell renal cell carcinoma and hepatitis A virus cellular receptor/kidney injury molecule-1 ectodomain shedding a predictive biomarker of tumour progression.

AIM OF THE STUDY: To correlate hepatitis A virus cellular receptor (HAVCR)/kidney injury molecule-1 (KIM-1) expression in clear cell renal cell carcinoma (ccRCC) tumours with patient outcome and study the consequences of HAVCR/KIM-1 ectodomain shedding. METHODS: HAVCR/KIM-1 expression in ccRCC, oncocytomes, papillary carcinomas and unaffected tissue counterparts was evaluated. Minimal change disease and pre-clamping normal and ccRCC tissue biopsies were included. Tissue microarrays from 98 ccRCC tumours were analysed. Tumour registry data and patient outcome were retrospectivelly collected. Deletions in HAVCR/KIM-1 ectodomain and lentiviral infection of 786-O cells with HAVCR/KIM-1 mutated constructs to determine their subcellular distribution and invasive capacity were performed. RESULTS: HAVCR/KIM-1 was expressed in ccRCC, papillary tumours and in tubule cells of adjacent and distal unaffected counterparts of ccRCC tumours. The latest was not related to ischemic or tumour-related paracrine effects since pre-clamping normal biopsies were positive for HAVCR/KIM-1 and unaffected counterparts of papillary tumours were negative. HAVCR/KIM-1 analyses in patients and the invasive capacity of HAVCR/KIM-1 shedding mutants in cell lines demonstrated that: (i) relative low HAVCR/KIM-1 membrane levels correlate with activated shedding in ccRCC patients and mutant cell lines; (ii) augmented shedding directly correlates with higher invasiveness and tumour malignancy. CONCLUDING STATEMENTS: Constitutive expression of HAVCR/KIM-1 in kidney might constitute a susceptibility trait for ccRCC tumour development. Enhanced HAVCR/KIM-1 ectodomain shedding promotes invasive phenotype in vitro and more aggressive tumours in vivo.

Risk factors for positive findings in patients with high-grade T1 bladder cancer treated with transurethral resection of bladder tumour (TUR) and bacille Calmette-Guérin therapy and the decision for a repeat TUR.

OBJECTIVE: To determine factors predictive of positive findings at the 3-month follow-up evaluation (after transurethral resection of bladder tumour [TUR] and bacille Calmette-Guérin [BCG] therapy) in patients with initial high-grade (HG)T1 bladder cancer, and to assess the depth of lamina propria (LP) invasion and effectiveness of BCG therapy. PATIENTS AND METHODS: In all, 138 patients with initial HGT1-transitional cell carcinoma (TCC) were prospectively assigned, after TUR + BCG and according to depth of LP invasion, to a postBCG-TUR (T1b) or cystoscopy/cytology (T1a) at 3 months. Any finding at 3 months was considered positive. The predictive value of 11 clinical and pathological variables was assessed by chi-squared, Mann-Whitney U and multivariate logistic regression. RESULTS: Of the 138 patients (14 women, mean age 69 years), 42% had T1a and 58% T1b TCC. Tumour size and carcinoma in situ (CIS) were significantly associated with positive findings and present in 26% (36/138) of the patients. The postBCG-TUR (T1b cases), was positive in 31% (25/80), including seven infiltrating tumours. On multivariate analysis, again a tumour size of >3 cm (odds ratio, OR, 7.02) and associated CIS (OR 5.4) were significantly related to a positive postBCG-TUR. A secondary finding was that at 20.3 months; patients with T1a TCC, who did not undergo a repeat TUR, did not have increased progression; only 3% (two of 58) had progressed compared with 21% (17/80) of those with T1b/c TCC (P < 0.002). CONCLUSIONS: In initial HGT1-TCC, tumour size and CIS were predictive factors of positive findings at 3 months after the initial TUR + BCG therapy. Patients with HGT1-TCC invading the LP (T1b TCC) had a seven times higher risk of a positive repeat TUR if the initial tumour was >3 cm and a five-fold increased risk if associated with CIS. The repeat TUR after BCG therapy allowed confirmation of complete resection and pathological evaluation of the BCG response. Although data are still preliminary, the strategy of performing a repeat TUR only in cases with LP involvement, i.e. T1b TCC, did not increase the risk of progression in cases with T1a TCC.