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OBJECTIVE To compare the efficacy of artificial urinary sphincter (AUS) vs retrourethral transobturator sling (RTS) in men with moderate post-prostatectomy urinary incontinence (PPI) using propensity score-matching analysis to enhance the validity of the comparison (Canadian Task Force classification II-2). PATIENTS AND METHODS Consecutive men with moderate (3-5 pads/day) stress-prevalent PPI were included if implanted with a RTS (TiLOOP® Male; pfm medical, Koln, Germany) or AUS (AMS800® ; Boston Scientific, Boston, MA, USA) since July 2011 to December 2017 and with ≥12 months of follow-up. Preoperative assessment included 24-h pad usage, International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), urethrocystoscopy, and urodynamics if indicated. Propensity score-matching analysis was based on age, body mass index, Charlson Comorbidity Index, pad usage, previous radiotherapy, and urethrotomy. The primary outcome was at least 'much improved' response at 12-months according to the Patient Global Impression of Improvement questionnaire, without additional PPI surgery or prosthesis explantation. RESULTS Of 109 included patients, 70 patients were matched and the study groups were well balanced for the baseline matched variables. The median baseline 24-h pad usage was four in both groups (P = 0.10), and median follow-up was 51.2 months for AUS and 47.2 months (P = 0.5) for RTS patients. In the AUS and RTS cohorts, respectively, 33 (94.3%) and 24 (68.6%) patients achieved the primary outcome (P < 0.001), the 0-1 pad/day rates was 94.3% vs 68.6% (P = 0.012) at 12 months, and 91.4% vs 68.6% (P = 0.034) at last follow-up. At the last follow-up, the median 24-h leakage volumes, median ICIQ-SF scores and satisfaction rates were 0 vs 15 mL (P = 0.017), 4 vs 10 (P = 0.001), and 94.3% vs 68.6% (P = 0.012) in the AUS and RTS cohorts, respectively. There were no significant differences in overall rates of complications and re-interventions, although Clavien-Dindo Grade III complications (n = 3) occurred only in the AUS group. At sensitivity analysis, the study was reasonably robust to hidden bias. CONCLUSION We found that AUS implantation significantly outperformed RTS in patients with moderate PPI for both subjective and objective outcomes.

Primary auricular melanoma is rarely reported. Approximately, it accounts for 1% to 4% of all cutaneous melanoma. Early literature suggested that melanoma of the ear is more aggressive than other melanomas, with a propensity for spreading to both regional lymph nodes and distant sites. Here, we present a case of cytological pleural metastasis from auricular melanoma in a 43-year-old woman. Immunohistochemical staining showed that the tumors cells were positive for S-100 protein and Melan-A. The mutation of the v-raf murine sarcoma viral oncogene homolog B (BRAF)V600E was demonstrated on Sanger sequencing. To our knowledge, this is the first report describing the cytomorphology of metastatic auricular melanoma in pleural effusion.

Background Chemohyperthermia (C-HT) or electromotive drug administration (EMDA) are alternative therapies to radical cystectomy in patients with non-muscle-invasive bladder cancer who do not respond to intravesical therapy with bacille Calmette-Guerin. Methods The authors investigated a group of 87 patients with a diagnosis of high-grade non-muscle-invasive bladder carcinoma or carcinoma in situ. Of these, 45 patients received EMDA of mitomycin (EMDA/MMC) and 42 patients were treated with C-HT and mitomycin therapy (C-HT/MMC). In accordance with the Paris System for Reporting Urinary Cytology, a cytological diagnosis was made and patients with diagnoses of atypical urothelial cells (AUC), suspicious high-grade urothelial carcinoma (SHGUC), or high-grade urothelial carcinoma also underwent histological bladder biopsies. Results In accordance with the Paris System for Reporting Urinary Cytology, the AUC cases may have cytological features of SHGUC present on atypical degenerated cells. In analyzing the AUC group without the SHGUC cases diagnosed on the basis of degenerated urothelial cells, the authors found a significant association between the AUC category and a negative histological biopsy. The SHGUC group, including cases with a SHGUC diagnosis rendered on degenerated urothelial cells, was associated with high-grade urothelial carcinoma or carcinoma in situ (P = .0269 for patients treated with EMDA/MMC and P = .0049 for patients treated with C-HT/MMC). Conclusions In the urine samples from patients treated with EMDA/MMC or C-HT/MMC, a diagnosis of SHGUC could be made even on degenerated urothelial cells when considering cellular degeneration as a "physiological" consequence of the treatment that involves either normal or neoplastic cells. Cancer Cytopathol 2018;126:200-6. © 2018 American Cancer Society.

BACKGROUND In the 2014, The International Society of Urological Pathology (ISUP) consensus conference update the grading of prostate, last revised in 2005. In this study we evaluate the SOCS3 immunohistochemical protein expression in different Gleason prostatic adenocarcinoma: classical Gleason grade 3, classical Gleason grade 3 upgraded to Gleason grade 4 according to the ISUP modifications and classical and modified Gleason grade 4. The major conclusions were: (i) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (ii) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (iii) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than all as pattern 4; and (iv) Intraductal carcinoma of the prostate without invasive carcinoma should not assigned Gleason grade and a comment about aggressive carcinoma probably associated should be made. In a recent report we analyzed the methylathion status of cytokine signaling (SOCS) proteins 3 (SOCS3) gene and the consequences of promoter hypermethylation on mRNA and protein expression in a collection of prostate cancer and benign prostate hyperplasia (BPH) and for the first time we demonstrated that a hypermethylation of SOCS3 with a significant reduction of its mRNA and protein expression identifies a subgroup of prostate cancer with a more aggressive behavior. Moreover we demonstrated that the immunohystochemical analysis of SOCS3 protein expression in prostatic cancer biopsies may provide a useful and easier method than SOCS3 methylation analysis to individuate in cancer with intermediate-high grade Gleason score a subgroup of prostate cancer with a more aggressive behavior. METHODS A total of 148 radical prostatectomy with diagnosis of prostatic acinar adenocarcinoma were stratified into three different categories on the basis of Gleason grade: (i) Twenty-six prostatic adenocarcinoma with classical and modified Gleason grade 3; (ii) Fifty seven prostatic adenocarcinoma with classical Gleason grade 3 upgraded to Gleason grade 4 by 2005 and 2014 ISUP Consensus Conference; and (iii) Sixty five prostatic adenocarcinoma with classical and modified Gleason grade 4. Immunohistochemical analysis for SOCS3 was performed and SOCS3 staining intensity were evaluated by two pathologists in three different ways on the basis of the intensity of cytoplasmatic staining: positive (intense cytoplasmatic staining in more than 50% of neoplastic cells) (+), negative (absence of cytoplasmatic staining in more than 50% of neoplastic cells) (−), weakly positive (weak cytoplasmatic staining in more than 50% of neoplastic cells (+/−). RESULTS In the group of prostatic adenocarcinoma Gleason grade 3 we found that SOCS3 positivity (+) were observed in 19 out of 26 cases (73.1%); in 5 out of 26 prostatic adenocarcinoma the neoplastic glands showed weak intensity SOCS3 staining (+/−) (19.2%), while in only two cases we found SOCS-3 negativity (−) (7.7%); in the group of cases with prostatic adenocarcinoma with Gleason grade 4, 16 out 65 cases (24.6%) showed SOCS3 positivity (+); 18 out 65 cases (27.7%) SOCS3 weakly positive (+/−), and in 31 cases (47.7%) SOCS3 negative staining (−) were observed. Interestingly, the group of prostatic adenocarcinoma with histological Gleason 3 pattern upgraded to Gleason 4 pattern according to the 2005 and 2014 ISUP modified grading system, showed SOCS3 positivity (+) in 16 out of 57 cases (28%), in 16 out 57 cases (28%) a weakly positive for SOCS3 (+/−) were observed, while 25 cases (44%) showed negative SOCS3 staining (−). CONCLUSIONS In this study we demonstrated a significant association of SOCS3 positivity (+) with prostatic carcinoma classical Gleason pattern 3 (P

BACKGROUND The current study compared ThinPrep urinary cytology and conventional cytospin urinary cytology in the diagnosis of bladder cancer, applying the Paris System for Reporting Urinary Cytology. METHODS Between January 2010 and December 2011, a total of 3659 urine samples were processed using conventional cytospin methods. Between January 2012 and December 2013, a total of 4186 urine cytological cases were analyzed using ThinPrep methods. In 131 cases (65 processed by conventional cytospin and 66 processed by ThinPrep), a subsequent biopsy was performed. The authors reclassified these cases according to the Paris System and an analysis between the 2 methods with regard to bladder biopsies was performed. RESULTS No significant differences were observed in terms of sensitivity and specificity between the 2 methods in cases with positive cytology for high-grade carcinoma. According to the Paris System, cases of atypical urothelial cells (AUC) and atypical urothelial cells suspicious for high-grade carcinoma (AUC-H) that were processed using cytospin did not correlate with urothelial carcinoma or with negative biopsies; conversely, the AUC cases processed using ThinPrep appeared to correlate with negative histological biopsies or low-grade urothelial carcinoma. CONCLUSIONS The results of the current study demonstrated that according to the Paris System, there were no significant differences in sensitivity or specificity for the diagnosis of high-grade urothelial carcinoma or AUC-H between the 2 methods. Cases of AUC should be easy to recognize using Thin Prep rather than cytospin and only AUCs diagnosed with ThinPrep were found to be statistically linked to negative cases for carcinoma or with low-grade urothelial carcinoma. Cancer Cytopathol 2016;124:519–23. © 2016 American Cancer Society.

BACKGROUND Chronic inflammation and subsequent tissutal alterations may play a key role in prostate carcinogenesis. In this way, molecular alterations of the suppressor of cytokine signaling 3 (SOCS3), one of the most important inhibitory molecule of inflammatory signal transduction circuitries, could contribute to explain the pleiotropic role of interleukin-6 (IL-6) in this type of cancer. METHODS We analyzed the methylation status and mRNA expression of SOCS3 in 20 benign prostate hyperplasias (BPH) and in 51 prostate cancer specimens. We analyzed the SOCS3 methylation status using methylation-specific PCR. Hypermethylation was confirmed by sequencing after subcloning. Epigenetic silencing of this gene was also demonstrated by real-time PCR and by immunohistochemestry. Results and correlation with clinical data were statistically analyzed. RESULTS We found that the promoter of SOCS3 was methylated in 39.2% of prostate cancer. On the contrary, all BPH and normal controls had an unmethylated pattern. Real-time analysis showed that in methylated cases SOCS3 mRNA expression was reduced by three and four folds as compared to BPH and unmethylated cases, respectively. Interestingly, SOCS3 mRNA level was higher in unmethylated prostate cancer than in BPH. The immunohistochemical staining analysis for SOCS 3 confirmed mRNA results. Moreover, methylation of SOCS3 promoter significantly associated with intermediate–high grade Gleason score (P = 0.0007) and with an unfavorable clinical outcome (P = 0.0019). CONCLUSIONS Our data suggest that SOCS3 hypermethylation may be involved in the pathogenesis of prostate cancer and could identify a tumor subset with an aggressive behavior. Prostate 71:318–325, 2011. © 2010 Wiley-Liss, Inc.

Tumor angiogenesis is a complex process that involves a series of interactions between tumor cells and endothelial cells (ECs). In vitro, glioblastoma multiforme (GBM) cells are known to induce an increase in proliferation, migration and tube formation by the ECs. We have previously shown that in human GBM specimens the proliferating ECs of the tumor vasculature express the catalytic component of telomerase, hTERT, and that telomerase can be upregulated in human ECs by exposing these cells to GBM in vitro. Here, we developed a controlled in vivo assay of tumor angiogenesis in which primary human umbilical vascular endothelial cells (HUVECs) were subcutaneously grafted with or without human GBM cells in immunocompromised mice as Matrigel implants. We found that primary HUVECs did not survive in Matrigel implants, and that telomerase upregulation had little effect on HUVEC survival. In the presence of GBM cells, however, the grafted HUVECs not only survived in Matrigel implants but developed tubule structures that integrated with murine microvessels. Telomerase upregulation in HUVECs enhanced such effect. More importantly, inhibition of telomerase in HUVECs completely abolished tubule formation and greatly reduced survival of these cells in the tumor xenografts. Our data demonstrate that telomerase upregulation by the ECs is a key requisite for GBM tumor angiogenesis.