Predictive Ability for Disease-Free Survival of the GRade, Age, Nodes, and Tumor (GRANT) Score in Patients with Resected Renal Cell Carcinoma.

BACKGROUND: Recently, the GRANT (GRade, Age, Nodes, and Tumor) score was validated through an adjuvant trial population. METHODS: This retrospective study evaluated the performance of the GRANT score as a prognostic model for disease-free survival (DFS), compared to the University of California Los Angeles Integrated Staging System (UISS) score, in a "real-life" population of early renal cell carcinoma patients. A uni-/multivariate analysis of DFS was also performed, to weigh the roles of baseline clinical factors. RESULTS: From February 1998 to January 2018, 134 consecutive patients were enrolled, of which 85 patients (63.4%) had a favorable GRANT score, 49 (36.6%) an unfavorable GRANT score, and 21 (15.7%), 84 (62.6%), and 29 (21.6%) patients had a low, intermediate, or high risk of recurrence according to the UISS score, respectively. The median follow-up was 96 months. The median DFS of the overall study population was 53.7 months (95% CI: 38.4-87.8). Only bilateral renal cell carcinoma (p = 0.0041), Fuhrman grade 3/4 (p = 0.0008), pT3b- 4 (p = 0.0324), and pN1-2 (p = 0.0303) pathological status were confirmed as independent predictors of a shorter DFS by the multivariate analysis. The median DFS of patients with favorable and unfavorable GRANT scores were 84.9 (95% CI: 49.8-129) and 38.4 months (95% CI: 24.4-87.8), respectively, with a statistically significant difference (p = 0.0147). The median DFS of patients with low, intermediate, and high risk of recurrence according to the UISS score were 92.3 (95% CI: 18.1-153.9), 51.7 (95% CI: 36.2-87.8), and 49.8 months (95% CI: 31.3-129), respectively, without statistically significant differences (p = 0.4728). DFS c-statistic values were 0.59 (95% CI: 0.51-0.67) and 0.51 (95% CI: 0.42-0.60) for the GRANT and the UISS scores, respectively. CONCLUSION: The GRANT score might be a useful tool that is user-friendly and easy to perform in clinical practice.

Peri-prostatovesicular smooth muscle tumors of undetermined malignant potential: a case report.

INTRODUCTION: Smooth muscle tumors of undetermined malignant potential (STUMPs) are atypical smooth muscle tumors, most of which derived from uterine tissue. STUMPs of male genitourinary system and of the male pelvic organs are uncommon. CASE DESCRIPTION: In this report, we describe the first case of peri-prostatovesicular STUMP that was treated with laparoscopic excision, in a young asymptomatic man. CONCLUSIONS: In most cases, the definitive diagnosis can be made only after surgical resection and accurate histological examination. The usefulness of adjuvant chemotherapy remains unclear, and a standardized follow-up protocol has not been described.

Phenotypic characterization of human prostatic stromal cells in primary cultures derived from human tissue samples.

Emerging evidence has shown that the tumor microenvironment plays a crucial role in prostate cancer (PCa) development and progression. However, the mechanism(s) through which stromal cells regulate epithelial cells and the differences among prostatic stromal cells of different histological/pathological origin in PCa progression remain unclear. Therefore, it is necessary to characterize the stromal cell populations present in benign prostatic hyperplasia (BPH) and PCa. To this end, we used cultures from stromal cells obtained from BPH-derived (15 cases) and PCa-derived (30 cases) primary cultures. In culture, stromal cells are a mixture of fibroblasts, myofibroblasts (MFs) and muscle cells. Fibroblasts are characterized for the expression of vimentin, MFs for the co-expression of α-smooth muscle actin (α-SMA) and vimentin, whereas muscle cells for the expression of α-SMA and desmin. Fibroblasts were present in large amounts in the BPH- compared to the PCa-derived cultures, whereas MFs were more representative of PCa- as opposed to BPH-derived cultures. Some α-SMA-positive cells retained the expression of basal cytokeratin K14. This population was defined as myoepithelial cells and was associated with senescent cultures. The percentage of MFs was higher in high-grade compared to moderate- and low-grade PCa-derived cultures, whereas the number of myoepithelial cells was lower in high-grade compared to moderate- and low-grade PCa-derived cultures. In addition, we analyzed the expression of p75NTR, as well as the expression of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors of MMPs (TIMPs). p75NTR expression was elevated in the stromal cultures derived from PCa compared to those derived from BPH and in cultures derived from cases with Gleason scores ≥7 compared to those derived from cases with Gleason scores <7, as well as in cultures with a high concentration of MFs compared to those with a high concentration of fibroblasts. MMP-2 was secreted by all primary cultures, whereas MMP-9 secretion was observed only in some PCa-derived stromal cells, when the percentage of MFs was significantly higher compared to BPH-derived cultures. TIMP1, TIMP2 and TIMP3 were secreted in elevated amounts in the BPH- compared to the PCa-derived stromal cultures, suggesting the differential regulation of extracellular matrix (ECM) degradation. When we used 22rv1 and PC3 PCa xenograft models for the isolation and characterization of murine cancer-associated fibroblasts (CAFs) we noted that the angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for α-SMA, vimentin, tenascin, calponin, desmin and Masson's trichrome. In conclusion, MF stromal cells from PCa participate in the progression and metastasis of PCa, modualting inflammation, angiogenesis and epithelial cancer cell proliferation.

Increased levels of DNA methyltransferases are associated with the tumorigenic capacity of prostate cancer cells.

DNA methylation might be the earliest somatic genome changes in prostate cancer that also play an important role in the process of tumor invasion, growth and metastasis. In recent years, several inhibitors of DNA methyltransferases (DNMTis) have been developed and evaluated in pre-clinical models and in clinical trials. While these compounds are effective in the treatment of hematological conditions, clinical trials in solid tumors and in prostate cancer have shown limited or no efficacy. This may be attributed to inappropriate dose regimens leading to toxicity-related adverse events. As with other anti-target compounds, one of the obstacles encountered with DNMTis in prostate cancer could be the inability to select patients for the clinical studies as well as the inability to monitor the efficacy of the drug if not the conclusion of the study. Primary cultures derived from human prostatic tissues harvested from patients with benign prostatic hyperplasia (BPH) and prostate cancer (PCa) as well as neoplastic and non-neoplastic prostate cell lines were tested for DNMT expression/activity and to monitor azacitidine molecular efficacy. We observed that in primary cultures the levels of DNMT activity as well as the protein levels of DNMT1, DNMT3a and DNMT3b were higher in cultures derived from PCa compared to BPH tissue samples and significantly higher in cultures derived from PCa with Gleason scores ≥7 compared to those observed in cultures derived from Gleason scores <7. In addition, DNMT activity as well as DNMT1, DNMT3a and DNMT3b levels were higher in PCa cell lines compared to their non-neoplastic counterparts. Although DNMT activity was higher in high tumorigenic/aggressive PCa cell lines compared to low tumorigenic/aggressive cell lines, only the levels of DNMT3a and DNMT3b were significantly higher in the first group of cells, suggesting that DNMT1 activity is related to the transition to non-neoplastic versus neoplastic phenotype whereas the de novo methylation enzymes were mainly related to progression. Nevertheless, the comparison in the more aggressive PC3 cell derivatives (PC3-LN4 cells) also possessed higher levels of DNMT1 compared to PC3 and PC3M from which these cells were derived. Collectively, our results confirm previous data on the increased methylation in more aggressive tumors supporting the use of DNMTis in advanced prostate cancer. In addition, since glutathione S-transferase-π (GSTP1) was re-expressed or its protein levels were increased after treatment with non-toxic azacitidine doses and since GSTP1 can easily be measured in patient sera, the monitoring of this protein may aide in the evaluation of therapy in future clinical trials.

Urinary tract reconstruction using the controlateral native ureter and a combined open-retroperitoneoscopic approach after renal transplantation.

An alternative technique for urinary tract (UT) reconstruction is described in a renal transplant recipient who developed a severe stenosis of the graft ureter. This approach entails the retroperitoneoscopic preparation of the native ureter contralateral to the graft, followed by an open reconstruction of the UT. The ureter was dissected along its entire length to the level of the iliac vessels, with its associated mesentery still attached in order to preserve the vascular supply. The corresponding native kidney contralateral to the graft was endoscopically removed. A longitudinal sub-umbilical incision allowed the excision of the stenotic tract and the reconstruction of the UT by means of a manual end-to-end anastomosis between the new ureter and the graft pelvis. No post-operative complications occurred and renal function immediately resumed. The approach described represents an alternative solution for the surgical management of severe ureteric graft stenosis. We believe that the magnification of the anatomy granted by the endoscope during the dissection of the ureter and neighboring structures provides the gentle handling of the tissues and the remote dissection away from the ureter with the highest precision.