Urinary estrogen metabolites and prostate cancer : a case-control study and meta-analysis

Objective: To investigate prostate cancer (Pca) risk in relation to estrogen metabolism, expressed as urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1) and 2-OHE1 to 16α-OHE1 ratio. Methods: We conducted a case-control study within the Western New York Health Cohort Study (WNYHCS) from 1996 to 2001. From January 2003 through September 2004, we completed the re-call and follow-up of 1092 cohort participants. Cases (n = 26) and controls (n = 110) were matched on age, race and recruitment period according to a 1:4 ratio. We used the unconditional logistic regression to compute crude and adjusted odds ratios (OR) and 95% confident interval (CI) of Pca in relation to 2-OHE1, 16αOHE1 and 2-OHE1 to 16α-OHE1 by tertiles of urine concentrations (stored in a biorepository for an average of 4 years). We identified age, race, education and body mass index as covariates. We also conducted a systematic review of the literature which revealed no additional studies, but we pooled the results from this study with those from a previously conducted case-control study using the DerSimonian-Laird random effects method. Results: We observed a non-significant risk reduction in the highest tertile of 2-OHE1 (OR 0.72, 95% CI 0.25-2.10). Conversely, the odds in the highest tertile of 16α-OHE1 showed a non-significant risk increase (OR 1.76 95% CI 0.62-4.98). There was a suggestion of reduced Pca risk for men in the highest tertile of 2-OHE1 to 16α-OHE1 ratio (OR 0.56, 95% CI 0.19-1.68). The pooled estimates confirmed the association between an increased Pca risk and higher urinary levels of 16α-OHE1 (third vs. first tertile: OR 1.82, 95% CI 1.09-3.05) and the protective effect of a higher 2-OHE 1 to 16α-OHE1 ratio (third vs. first tertile: OR 0.53, 95% CI 0.31-0.90). Conclusion: Our study and the pooled results provide evidence for a differential role of the estrogen hydroxylation pathway in Pca development and encourage further study

Characterizing the tumor microenvironment in rare renal cancer histological types

The tumor microenvironment (TME), including immune cells, cancer-associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high-grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial-to-mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry. Marker expression was compared by Mann-Whitney and Kruskal-Wallis tests and correlations across markers using Spearman's rank correlation coefficient. Multivariable Poisson regression analysis was used to compare marker expression between histological types, while accounting for variation in tissue size. Several immune markers showed different rates of expression across histological types of renal carcinoma. Using pRCC1 as reference, the incidence rate ratio (IRR) of CD3+ T cells (IRR [95% confidence interval, CI] = 2.48 [1.53-4.01]) and CD20+ B cells (IRR [95% CI] = 4.38 [1.22-5.58]) was statistically significantly higher in CDC. In contrast, CD68+ macrophages predominated in pRCC1 (IRR [95% CI] = 2.35 [1.42-3.9]). Spatial analysis revealed CD3+ T-cell and CD20+ B-cell expressions in CDC to be higher at the proximal (p < 0.0001) and distal (p < 0.0001) tumor periphery than within the central tumor core. In contrast, expression of CD68+ macrophages in pRCC2 was higher in the tumor center compared to the proximal (p = 0.0451) tumor periphery and pRCC1 showed a distance-dependent reduction, from the central tumor, in CD68+ macrophages with the lowest expression of CD68 marker at the distal tumor periphery (p = 0.004). This study provides novel insights into the TME of rare kidney cancer types, which are often understudied. Our findings of differences in marker expression and localization by histological subtype could have implications for tumor progression and response to immunotherapies or other targeted therapies

Impact of uni- or multifocal perineural invasion in prostate cancer at radical prostatectomy

Background: Aim of this study was to correlate perineural invasion (PNI) with other clinical-pathological parameters in terms of prognostic indicators in prostate cancer (PC) cases at the time of radical prostatectomy (RP). Methods: Prospective study of 288 consecutive PC cases undergoing RP. PNI determination was performed either in biopsy or in RP specimens classifying as uni- and multifocal PNI. The median follow-up time was 22 (range, 6-36) months. Results: At biopsy PNI was found in 34 (11.8%) cases and in 202 (70.1%) cases at the time of surgery. Among those identified at RP 133 (46.1%) and 69 (23.9%) cases had uni- and multi-PNI, respectively. Presence of PNI was significantly (P<0.05) correlated with unfavorable pathological parameters such higher stage and grade. The percentage of extracapsular extension in PNI negative RP specimens was 18.6% vs. 60.4% of PNI positive specimens. However, the distribution of pathological staging and International Society of Urological Pathology (ISUP) grading did not vary according to whether PNI was uni- or multifocal. The risk of biochemical progression increased 2.3 times in PNI positive cases was significantly associated with the risk of biochemical progression (r=0.136; P=0.04). However, at multivariate analysis PNI was not significantly associated with biochemical progression [hazard ratio (HR): 1.87, 95% confidence interval (CI): 0.68-3.12; P=0.089]. Within patients with intermediate risk disease, multifocal PNI was able to predict cases with lower mean time to biochemical and progression free survival (chi-square 5.95; P=0.04). Conclusions: PNI at biopsy is not a good predictor of the PNI incidence at the time of RP. PNI detection in surgical specimens may help stratify intermediate risk cases for the risk of biochemical progression

The genomic and epigenomic evolutionary history of papillary renal cell carcinomas

From Springer Nature via Jisc Publications RouterHistory: received 2019-09-11, accepted 2020-05-10, registration 2020-05-12, pub-electronic 2020-06-18, online 2020-06-18, collection 2020-12Publication status: PublishedFunder: This work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHSAbstract: Intratumor heterogeneity (ITH) and tumor evolution have been well described for clear cell renal cell carcinomas (ccRCC), but they are less studied for other kidney cancer subtypes. Here we investigate ITH and clonal evolution of papillary renal cell carcinoma (pRCC) and rarer kidney cancer subtypes, integrating whole-genome sequencing and DNA methylation data. In 29 tumors, up to 10 samples from the center to the periphery of each tumor, and metastatic samples in 2 cases, enable phylogenetic analysis of spatial features of clonal expansion, which shows congruent patterns of genomic and epigenomic evolution. In contrast to previous studies of ccRCC, in pRCC, driver gene mutations and most arm-level somatic copy number alterations (SCNAs) are clonal. These findings suggest that a single biopsy would be sufficient to identify the important genetic drivers and that targeting large-scale SCNAs may improve pRCC treatment, which is currently poor. While type 1 pRCC displays near absence of structural variants (SVs), the more aggressive type 2 pRCC and the rarer subtypes have numerous SVs, which should be pursued for prognostic significance

ANALISI EPIDEMIOLOGICA DEL RENE POLICISTICO NEL LAZIO: RISULTATI SU 50 FAMIGLIE

RESULTS OF A CLINICAL STUDY ON 50 FAMILIES AFFECTED BY AUTOSOMAL POLYCITIC KIDNEY DISEASE IN LAZIO ( A CENTRAL REGION OF ITALY) ARE REPORTED. THIS IS THE FIRST PART OF A STUDY AIMED AT IDENTIFYING THE EPIDEMIOLOGIC,GENETICS AND CLINICAL FEATURES OF THIS DISEASE. iT ALSO PERMITS A FIRST COMPARISON WITH DATA FROM OTHER STUDIES

Robot-assisted radical cystectomy with intracorporeal neobladder: impact of learning curve and long-term assessment of functional outcomes

BACKGROUND: There is paucity of data about functional outcomes of Robot-assisted Radical Cystectomy (RARC) with intracorporeal orhotopic neobladder (ICON), and the impact of learning curve (LC) on those outcomes remains to be addressed. We aimed to report long-term functional outcomes of our single center series of RARC with ICON, assessing the role of LC in their achievement.METHODS: Patients treated with Robot assisted radical cystectomy with intracorporeal orthotopic neobladder in our center between January 2012 an August 2019 were retrospectively analysed. Preoperative, clinical, perioperative, pathologic and functional data were reported. The first cases were divided in tertiles, for assessing the impact of learning curve on the outcomes evaluated. Long-term functional outcomes of the whole cohort were evaluated.RESULTS: Overall, 167 patients were included. Concerning tertiles analysis, operative time (p<0.001), incidence of low (p=0.002) and high grade (p=0.001) complications and hospital stay (p=0.04) decreased significantly over time. Day-time continence recovery probability was significantly lower in the initial case series (1-yr rate 68.4%, 87% and 89.8 for I, II and III tertile, respectively; p=0.04;). Accordingly, Trifecta achievement was significantly higher in II and III tertiles (p=0.01). At a median follow- up of 34 months, the incidence of significant renal function deterioration of the whole cohort was 16.7%. Overall, 12, 24 and 60-mo day-time continence rates were 74.8 %, 82.7 % and 82.7 %.CONCLUSIONS: Patients treated at the beginning of the learning curve show worse perioperative and functional results. Once standardized the procedure, complications rates, hospital stay and daytime continence recovery experienced a significant improvement. At a long-term analysis of functional outcomes of our patients, renal function preservation and continence recovery results are encouraging

Impact of learning curve on perioperative outcomes of off-clamp minimally invasive partial nephrectomy: propensity score matched comparison of outcomes between training versus expert series

Background: Off-Clamp Robotic partial nephrectomy (Off C-RPN) is a challenging technique, hard to teach since bleeding control is not easily reproducible in training settings. We compared preoperative outcomes of two propensity score matched (PSM) cohorts of patients undergone Off C-RPN by either a training or an expert surgeon in the same Institution. Methods: The prospectively maintained "renal cancer" database was queried for "off-clamp", "robotic", "partial nephrectomy" performed between January 2017 and June 2018. Achievement of main outcomes along the learning curve of training surgeon was assessed with logistic regression and Lowess analysis. A 1:1 PSM analysis generated two populations homogeneous for demographics, ASA score, tumor size, nephrometry score, baseline hemoglobin and estimated glomerular filtration rate (eGFR). Multiple tumors, and imperative indications were excluded. Categorical and continuous variables were compared by Chi square and t test. Results: Overall, 111 were treated by the expert, 51 by the training surgeon, respectively. Training surgeon experienced a significant decrease of console time (p=0.01). Patients treated by the expert surgeon had significantly larger tumors, higher PADUA and ASA scores (all p≤0.04). After applying the PSM, two cohorts of 29 patients, homogeneous for all baseline demographic and clinical variables (all p≥0.34) were selected. Hilar clamping was never necessary. Hospital stay, hemoglobin and eGFR at discharge, complication and positive surgical margins rates were comparable between the two cohorts (all p≥0.15). Conclusions: Our results proved that the impact of learning curve on outcomes of Off C-RPN is negligible after completion of a proper training in minimally invasive surgery