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EpiCheck is a new urinary test that analyses DNA methylation biomarkers in order to identify high-risk urothelial cancer MATERIALS AND METHODS: A prospective single centre study was performed. We analysed Epicheck results in a population of 231 patients in follow-up for non-muscle invasive bladder cancer. The primary endpoint was to evaluate sensitivity and specificity of Epicheck in detecting any type of bladder cancer recurrence. The secondary endpoint was to evaluate specificity and sensitivity of Epicheck in patients with high-risk recurrence and in patients recently treated with endovesical therapy (3 months).Negative predictive value (NPV) for cytology was 83 % while for bladder Epicheck it was 89 %, while positive predictive value (PPV) was 67 % and 73 % for cytology and Epicheck respectively. Considering only high grade non muscle invasive bladder cancer the sensitivity of Epicheck was 91 % and for cytology was 81 %, specificity was 85 % and 83 % and negative predictive value of Epicheck outreached 96 % compared to 92 % of cytology. Among patients with an ongoing or recent endovesical treatment it appears that sensitivity of Epicheck was 88% % compared to 73 % of cytology, specificity was 97 % and 85 % and NPV was 92 % compared to 82 % for cytology.The EpiCheck (test showed very high diagnostic values, higher than the currently, gold standard. The test might clinically improve the BCa management in terms of, reduced number of inconclusive/suspicious reports of cytology and endoscopy, reduced number of further examinations, reduced associated patient and economic.

We designed a retrospective study to assess the surgical and economic outcomes of robot-assisted laparoscopic pyeloplasty (RALP) compared with open pyeloplasty (OP), including consecutive patients suffering from ureteropelvic junction obstruction and operated on from January 2012 to January 2022 at a single center. Preoperative, intraoperative, and postoperative outcomes, including costs, were comparatively analyzed. The primary outcome was 3-month success, defined as symptom resolution and no obstruction upon diuretic renal scintigraphy. Overall, 91 patients were included (48 OP and 43 RALP). The success rate at 3 months was 93.0% and 83.3% in the RALP and OP group, respectively (p = 0.178), and the results remained stable at the last follow-up (35.4 ± 22.8 months and 56.0 ± 28.1 months, respectively). Intraoperative blood loss (p < 0.001), need for postoperative analgesics (p = 0.019) and antibiotics (p = 0.004), and early postoperative complication rate (p = 0.009) were significantly lower in the RALP group. None of the assessed variables were a predictor for failure. The mean total direct cost per surgical procedure and related hospital stay was 2373 € higher in the RALP group. RALP is an effective and safe treatment for ureteropelvic junction obstruction; however, further studies are needed to evaluate the cost-effectiveness of RALP, accounting for indirect costs and cost-saving with new surgical platforms.

Robot-assisted radical prostatectomy (RARP) is the most adopted treatment for localized prostate cancer. The aim of this study was to explore the learning curves (LC) for overall and site-specific positive surgical margins (PSM) occurrence after RARP of multiple surgeons within a step-structured mentor-initiated training program. The study included consecutive patients undergoing RARP between January 2013 and March 2020, by three surgeons: a mentor and his two trainees. Prospectively collected patients’ data were retrospectively analyzed. The cumulative summation (CUSUM) method was used to generate the LCs, with turning points indicating the number of cases to reach proficiency levels. Furthermore, the association between PSM and surgical experience was evaluated, adjusting for case mix. A total of 761 consecutive patients were included, 370 treated by the Mentor surgeon, 247 and 144 treated, respectively, by the two Trainees. Mentor and Trainees had similar PSM rates (31.6% vs 28.0% vs 31.3%, p = 0.6). CUSUM charts showed different LC shapes for different PSM locations (postero-lateral, bladder neck, apex, and multifocal/> 3 mm). Surgical experience was significantly associated with overall, postero-lateral, and multifocal/> 3 mm PSMs, in the Mentor series only. Trainees reached their turning points after far fewer cases then the Mentor, both for overall (12 and 31 vs 153), postero-lateral (24 and 30 vs 120), and multifocal/> 3 mm PSMs (9 and 31 vs 153). The achievement of stable SM proficiency takes involved different LCs depending on the prostatic location being considered. Monitoring site-specific LC can indicate the surgical steps for which there may be still room for further technical refinements, even when an apparent proficiency status seems achieved.

Purposes: Little research exists on potential learning curve for male sling procedures. We aimed to perform a learning curve analysis of a single surgeon’s experience of sling placement evaluating multiple outcomes and using the cumulative sum failure methodology. Methods: The study included 65 consecutive patients that underwent implantation of a fixed transobturator sling (TiLOOP Male) for post-radical prostatectomy stress incontinence at our institution from January 2013 to December 2018. Dichotomous outcomes evaluated with cumulative sum failure analysis included 12-months continence defined based on Patient Global Impression of Improvement (PGI-I) questionnaire (primary outcome), 24 h pad test and, 24 h pad use, operative time (⩽/>60 min), and complications (yes/no). Univariate and multivariate logistic regression analyses were performed to evaluate the association of the procedures’ chronological sequence number with the outcomes. Results: Cumulative sum failure curves revealed a clear and lengthy learning curve effect for most of subjective and quantitative continence outcomes and for operative time. For the primary outcome (at least much improved at PGI-I), 62 procedures were required to overcome the learning curve. Accordingly, multivariate analyses showed that the sequence number was statistically significant for predicting failures based on PGI-I (adjusted OR 0.95; 95% CI: 0.91–0.99; p = 0.02), objective outcomes, and operative time. Conclusions: An evident and lengthy learning curve was observed in our series of male sling placement to achieve the end level of proficiency, independently from case-mix. Individualized structured training on male sling surgery will benefit patients treated in the initial surgeon’s experience. Surgical experience should be considered when reporting studies on male slings.

Background Primary Central Nervous System (CNS) extranodal marginal zone B-cell lymphoma (MZBL) is a rare low-grade non-Hodgkin lymphoma, characterized predominantly by small B cells, plasma cells, monocytoid cells, and scattered large immunoblasts. Primary CNS MZBL is a slow-growing tumour that remains localized and is characterized by an excellent clinical prognosis. Case presentation: A 48-year-old HIV-negative female with a history of a head trauma a year earlier, presented with worsening neurological symptoms and an MRI finding of an extra-axial mass of about 3 cm within the left lateral ventricle. From histopathology and immunohistochemistry, the lesion was diagnosed as a CNS MZBL: since no other primary lesions were found, the base of the chorioid plexuses of the left lateral ventricle was considered the primary site. Conclusions The current case is the first literature reported primary CNS MZBL arising in this anatomical site and paves the way for further studies on the role of chronic inflammation (in our case resulting from a trauma) in the pathogenesis not only of primary CNS MZBLs, but also of lymphomas in general. Additionally, it could be a starting point for studies analyzing the role of meningothelial cells in the pathogenesis of primary CNS MZBL.

The goal of precision medicine in prostate cancer (PCa) is to individualize the treatment according to the patient's germline mutation status. PCa has a very high rate of genetic predisposition compared with other cancers in men, with an estimated rate of cancers ascribable to hereditary factors of 5-15%.A systematic search (PubMed, Web of Science, and ClinicalTrials.gov) of English literature from 2000 to 2022, using the keywords "prostate cancer", "germline mutations", "family history", and "inheritance" was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.The search identified 980 publications. Of these, 200 papers were removed before screening (duplicates, non-English literature, and publication year before 2000) and 245 records were excluded after title/abstract screening. Finally, 50 articles were included in the final analysis. We analyze the latest evidence on the genetic basis of PCa predisposition and clinical implications for more personalized screening protocols and therapeutic management of this high-prevalent cancer.Emerging data show that germline mutations in homologous recombination genes (BRCA1/2, ATM, CHECK2), in mismatch repair genes (MLH1, MLH2, MSH6), and other additional genes are associated with the development and aggressiveness of PCa. Germline testing and genetic counseling have increasingly important implications in cancer screening and therapeutic decisions making for patients affected by PCa. Patients with localized PCa and some gene mutations are more likely to develop aggressive cancer, so active treatment may be preferable to active surveillance for these patients. Moreover, in patients with metastatic PCa, these gene alterations may be useful biomarkers for predicting response to specific therapy such as PARP inhibitors, recently approved for the treatment of metastatic castration-resistant PCa. The evidence supports recent guidelines and recommendations considering germline genetic testing for patients with a positive family history of PCa or men with high risk or metastatic disease.

The correct N-staging in breast cancer is crucial to tailor treatment and stratify the prognosis. N-staging is based on the number and the localization of suspicious regional nodes on physical examination and/or imaging. Since clinical examination of the axillary cavity is associated with a high false negative rate, imaging modalities play a central role. In the presence of a T1 or T2 tumor and 0–2 suspicious nodes, on imaging at the axillary level I or II, a patient should undergo sentinel lymph node biopsy (SLNB), whereas in the presence of three or more suspicious nodes at the axillary level I or II confirmed by biopsy, they should undergo axillary lymph node dissection (ALND) or neoadjuvant chemotherapy according to a multidisciplinary approach, as well as in the case of internal mammary, supraclavicular, or level III axillary involved lymph nodes. In this scenario, radiological assessment of lymph nodes at the time of diagnosis must be accurate. False positives may preclude a sentinel lymph node in an otherwise eligible woman; in contrast, false negatives may lead to an unnecessary SLNB and the need for a second surgical procedure. In this review, we aim to describe the anatomy of the axilla and breast regional lymph node, and their diagnostic features to discriminate between normal and pathological nodes at Ultrasound (US) and Magnetic Resonance Imaging (MRI). Moreover, the technical aspects, the advantage and limitations of MRI versus US, and the possible future perspectives are also analyzed, through the analysis of the recent literature.

Partial nephrectomy (PN) is the gold standard treatment for localized renal masses. Robot-assisted PN (RAPN) has overcome laparoscopy’s technical limitations, greatly expanding the indications of minimally invasive PN, which is dominated by renal artery clamping in almost all published series. We compared off-clamp RAPN (OFFC-RAPN) with the open approach (OFFC-OPN) using propensity score (PS) matching. A favourable pentafecta outcome was defined as a combination of no positive surgical margins (PSM), no complications of Clavien–Dindo (CD) grade ≥ 3, post-operative eGFR loss 2 complication rate (4.2% vs. 2.8%, p = 1.00) and mean ± SD eGFR change (−0.06 ± 0.3 vs. −0.8 ± 0.3, p = 0.5). Pentafecta was achieved in 56.3% and 21.1% in the OFFC-RAPN and OFFC-OPN series, respectively (p < 0.0001). On multivariable analysis, surgical approach and BMI proved to be independent predictors of achieving pentafecta. After adjusting for potential treatment selection bias, OFFC-RAPN outperformed OFFC-OPN for important peri-operative outcomes, without compromising oncological and functional safety.

Recently, it was reported that the Bladder EpiCheck test is likely to represent a valid tool in the diagnostic process of patients who have suspected bladder carcinoma, with some controversial management decisions because of the technical limitations of cytology.Two hundred ninety patients with a diagnosis of nonmuscle-invasive bladder carcinoma who were admitted at the authors' department from March 2019 to December 2019 were treated and followed for 1 year. During follow-up, all patients were evaluated by voided urine cytology, white-light cystoscopy (according to European Association of Urology guidelines), and the Bladder EpiCheck test.The cytologic diagnoses of high-grade urothelial carcinoma (HGUC) and suspicious for HGUC were histologically confirmed in 5 of 20 patients (25%) who had quantitative Bladder EpiCheck scores (EpiScores) from 60 to 69, in 23 of 36 patients (64%) who had EpiScores from 70 to 79, and in 42 of 56 patients (75%) and 57 of 63 patients (90%) who had EpiScores between 80 and 89 and EpiScores90, respectively. Of 48 patients who had a cytologic diagnosis of HGUC or suspicious for HGUC with EpiScores ≥60 and negative histology, 20 (42%) had a recurrence of HGUC, which was cytologically and histologically confirmed, at 6-12 months during follow-up.To the best of the authors' knowledge, this is the first study in which patients at high risk for HGUC were stratified using the Bladder EpiCheck EpiScore. The results validate this methylation analysis tool as a useful method for predicting recurrent HGUC during the follow-up of patients with nonmuscle-invasive bladder carcinoma.

DOG1 is a transmembrane protein originally discovered on gastrointestinal stromal tumors and works as a calcium-activated chloride channel protein. There are a limited number of articles on the potential utility of this antibody in the diagnosis of salivary gland tumors in routine practice. In this study, we aimed to investigate the role of DOG1 as an immunohistochemical marker in patients with salivary acinic cell carcinoma (ACC) through meta-analysis. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2010 to September 2021. The literature search revealed 148 articles, of which 20 were included in the study. The overall rate of DOG1 expression in salivary acinic cell carcinoma was 55% (95% CI = 0.43–0.58). Although ACC is a challenging diagnosis, paying careful attention to the cytomorphological features in conjunction with DOG1 immunostaining can help to reach an accurate diagnosis.

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.

Hereditary and sporadic renal cell carcinomas (RCCs) are often associated with Von Hippel-Lindau (VHL)-gene inactivation. Patients with VHL disease have an increased risk of RCC, leading to bilateral nephrectomy and dialysis. In patients with advanced RCC, no standard second-lines are available after progression to immune checkpoint inhibitors (ICIs), and new agents are required to manage progression. HIFs have emerged as a promising target for metastatic RCC patients who have progressed to ICI-based combinations, as well as for those with RCC and VHL syndrome where the goal is to delay surgery and/or and preserve kidney function and avoid dialysis. This review describes the available evidence supporting the use of the small-molecule HIF-2 alpha inhibitor, belzutifan (MK-6482), as well as other new anti-HIF molecules that have demonstrated significant efficacy in VHL disease-related RCCs as well as for sporadic RCC that has progressed after the use of ICI-based combinations.

The purpose of this study was to prospectively evaluate the capability of diffusion tensor imaging (DTI) of the lumbosacral plexus to identify parametrial invasion by uterine cervical cancer.Twenty-seven women with biopsy-proven cervical cancer were prospectively enrolled and underwent DTI at 1.5 TMRI. Fractional anisotropy (FA) values were calculated at the level of right and left L5 and S1 roots. The two sides of each patient were considered independently in two groups, according to the presence or absence of parametrial invasion. Differences between FA values of invaded parametria and those of non-invaded parametria were searched using Student t-test. Receiver operating characteristic (ROC) analysis was performed to identify the cut-off value of FA that yielded best sensitivity, specificity and accuracy for the diagnosis of parametrial invasion.A total of 54 parametria in 27 participants (mean age, 52.9 ± 12 years; age range, 30-81 years) were analyzed. Invasion was present in 37/54 (68%) parametria and absent in 17/54 (31%) parametria. FA was greater in parametrial invasion (mean, 0.321 ± 0.036; range: 0.285-0.357) than in the absence of parametrial invasion (0.292 ± 0.02; range: 0.272-0.312) (P = 0.01). At ROC analysis, best cut-off value of FA for the diagnosis of parametrial invasion was0.3099 (AUC, 0.681; 95% CI: 0.583- 0.768), yielding 62% sensitivity (95% CI: 50.3-73.64), 73% specificity (95% CI: 50.6-85.27) and 66% accuracy (95% CI: 54.62-73.91).Using0.3099 as cut off-value for FA of L5-S1 roots, DTI has an accuracy of 73% in the diagnosis of parametrial invasion by uterine cervical cancer.

We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3–G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.

The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection of a bladder tumor consists of adjuvant intravesical therapy and strict and long surveillance with urine cytology and cystoscopy. The Bladder EpiCheck test (Nucleix Ltd) (BE) is a newly developed urinary markers based on DNA methylation changes in a panel of 15 genomic biomarkers, with a promising performance in term of non-invasive NMIBC detection.In this study we prospectively enrolled 151 consecutive patients with high grade NMIBC, treated with intravesical BCG and mitomycin C therapy and evaluated during the follow-up by voided urine cytology and white-light cystoscopy, according to the European Association of Urology Guidelines. The Bladder EpiCheck test was performed at the same time of urine cytology in voided specimen. In all cases with positive cytology the diagnosis was confirmed by histology and a diagnosis was made according to the 2017 tumor, node, metastasis (TNM) classification and graded using both the 1973 and the 2004 World Health Organization (WHO) classifications.At three months of follow-up, we reported similar overall specificity rates for BE and urine cytology (85,1% vs 86,3%). In the group of patients with carcinoma in situ (CIS), we found the same specificity for BE and urine cytology (81,4%), while in the groups of patients with papillary high grade NMIBC, the specificity of BE was higher compared to cytology (96,3% vs 90,4%). The sensitivity of BE was always higher compared to cytology during all the follow-up both for papillary NMIBC and CIS.In the early follow-up of NMIBC the EpiCheck test might replace urinary cytology.

Costello syndrome (CS) is a rare disorder affecting development and growth characterized by cancer predisposition and caused by mutations in HRAS proto-oncogene. Somatic HRAS mutations drive bladder carcinogenesis. The aim of this study was to analyze prevalence and histological characterization of bladder cancer (BC) in a cohort of patients with CS to help clinicians plan effective management strategies. This study included 13 patients above 10 years of age with molecular diagnosis of CS. Screening cystoscopies (31 total procedures) were performed to exclude BC. Any lesion was analyzed through cold-cup biopsy or trans-urethral resection of the bladder. According to histology, patients were followed-up with urinalysis and abdominal ultrasound yearly, and cystoscopies every 12-24 months. During study enrollment, bladder lesions (often multifocal) were detected in 11/13 patients. Histological analysis documented premalignant lesions in 90% of cystoscopies performed, epithelial dysplasia in 71%, and papillary urothelial neoplasm of low-malignant potential in 19%. BC G1/low grade (Ta) were removed in 10%. Overall, 76% of patients showed a bladder lesion at first cystoscopy. The present findings document that individuals with CS aged 10 years and older have high prevalence of bladder lesions (premalignant/malignant), highlighting the importance of personalized screening protocols.

The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) promotes growth and progression in prostate cancer (PCa); however, little is known about its possible impact in PCa metabolism. The aim of this work has been the assessment of the metabolic reprogramming associated with MALAT1 silencing in human PCa cells and in an ex vivo model of organotypic slice cultures (OSCs). Cultured cells and OSCs derived from primary tumors were transfected with MALAT1 specific gapmers. Cell growth and survival, gene profiling, and evaluation of targeted metabolites and metabolic enzymes were assessed. Computational analysis was made considering expression changes occurring in metabolic markers following MALAT1 targeting in cultured OSCs. MALAT1 silencing reduced expression of some metabolic enzymes, including malic enzyme 3, pyruvate dehydrogenase kinases 1 and 3, and choline kinase A. Consequently, PCa metabolism switched toward a glycolytic phenotype characterized by increased lactate production paralleled by growth arrest and cell death. Conversely, the function of mitochondrial succinate dehydrogenase and the expression of oxidative phosphorylation enzymes were markedly reduced. A similar effect was observed in OSCs. Based on this, a predictive algorithm was developed aimed to predict tumor recurrence in a subset of patients. MALAT1 targeting by gapmer delivery restored normal metabolic energy pathway in PCa cells and OSCs.

714 Background: Intermediate IMDC group is the largest and most heterogeneous group of mRCC. Current first-line (1L) therapy options for these patients (pts) are based on either an anti-angiogenic agent (VEGFR-TKI) combined with immunotherapy (IO), or a combo of IO (ipilimumab+nivolumab [I/N]). No biomarkers (BM) for selecting the most effective regimen have been identified so far. Methods: Immunohistochemical expression of PBRM1, PD-L1, CD31, and CD4/CD8 ratio was evaluated on histological samples of intermediate-risk mRCC pts treated with VEGFR-TKI monotherapy, and then in pts receiving a VEGFR-TKI-based therapy or the immune doublet I/N. PBRM1 positivity score was based on the percentage of positive cells and on the intensity of nuclear expression; PD-L1 positivity was defined as CPS≥10; CD31 high-density had moderate to strong nuclear staining; and the CD4/CD8 ratio cut-off for positivity was >0.2. Cox model was used to assess the correlation between BM and outcomes; PFS and OS were estimated by Kaplan-Meier method. Results: After screening of tumor tissues from 150 pts, a total of 111 were included in the final analysis (Table). In pts treated with VEGFR-TKI monotherapy, a significant correlation with PFS was observed with loss of PBRM1 expression (HR 0.58, p=0.035), PD-L1 negativity (HR 0.44, p=0.048), and high CD4/CD8 ratio (HR 0.62, p=0.073). CD31 density did not significantly correlate with PFS. A profile potentially predictive of angiogenesis (AP+) was defined based on the PBRM1 loss, PD-L1 negative, and high CD4/CD8. In pts treated with VEGFR-TKI monotherapy, tumors with the AP+ (43% of all cases) had a significantly longer median PFS (mPFS 23.8 vs. 11.8 months, p=0.003) and mOS (41.5 vs. 26.9 months, p=0.024) compared to the others. The AP+ retained its significant correlation with PFS (mPFS 23.8 vs. 11.1 months, p

Introduction: Prostate cancer (PCa) is one of the most common adult malignancies worldwide, and a major leading cause of cancer-related death in men in Western societies. In the last years, the prognosis of advanced PCa patients has been impressively improved thanks to the development of different therapeutic agents, including taxanes (docetaxel and cabazitaxel), second-generation anti-hormonal agents (abiraterone and enzalutamide), and the radiopharmaceutical Radium-223. However, great efforts are still needed to properly select the most appropriate treatment for each single patient.Areas covered: Several prognostic or predictive biomarkers have been studied, none of which has an established validated role in daily clinical practice. This paper analyzed the major biomarkers (including PSA, androgen receptor (AR) splice variants, βIII-tubulin, ALP, circulating tumor cells, and DNA repair genes) with a potential prognostic and/or predictive role in advanced PCa patients.Expert commentary: Surrogate biomarkers - measurable, reproducible, closely associated with tumor behavior and linked to relevant clinical outcomes - are urgently needed to improve PCa patient management.

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.

De-novo metastatic castration sensitive prostate cancer (mCSPC) is a subgroup of prostate cancer associated with poor prognosis. Recently, the treatment of mCSPC has been enriched by new life-prolonging options, including the combination of docetaxel or abiraterone acetate with androgen deprivation therapy (ADT). Of note, the advantage of chemohormonal therapy was more relevant in the subgroup of high-volume disease compared to low-volume, while the survival prolongation of abiraterone was observed only in high-risk patients. Choosing the most appropriate therapy is one of the most debated issues. This review describes the latest news on de-novo mCSPC to better outline patients' management. At the ESMO 2018 Congress two novel studies focused on this setting have been presented, trying to define the role of radiotherapy to the primary tumour and the efficacy of abiraterone acetate in the subset of low-risk patients. We have analysed these results in light of the evidence already available.

(1) Background: PTTG1 sustains the EMT process and the invasiveness of several neoplasms. We previously showed the role of nuclear PTTG1 in promoting invasiveness, through its transcriptional target MMP2, in seminoma in vitro models. Here, we investigated the key players involved in PTTG1-mediated EMT in human seminoma. (2) Methods: Two seminoma cell lines and four human seminoma tumor specimens were used. E-Cadherin gene regulation was investigated using Western blot, real-time PCR, and luciferase assay. Immunoprecipitation, ChIP, RE-ChIP, and confocal microscopy analysis were performed to evaluate the interplay between PTTG1 and ZEB1. Matrigel invasion and spheroid formation assays were applied to functionally investigate PTTG1 involvement in the EMT of seminoma cell lines. RNA depletion and overexpression experiments were performed to verify the role of PTTG1/ZEB1 in E-Cadherin repression and seminoma invasiveness. E-Cadherin and ZEB1 levels were analyzed in human testicular tumors from the Atlas database. (3) Results: PTTG1 transcriptionally represses E-Cadherin in seminoma cell lines through ZEB1. The cooperation of PTTG1 with ZEB1 has a significant impact on cell growth/invasion properties involving the EMT process. Analysis of the Atlas database of testicular tumors showed significantly lower E-Cadherin levels in seminoma, where PTTG1 showed nuclear staining. Finally, PTTG1 and ZEB1 strongly localize together in the periphery of the tumors. (4) Conclusions: These results strengthen the evidence for a role of PTTG1 in the EMT process in human seminomas through its cooperation with the transcriptional repressor ZEB1 on the E-Cadherin gene. Our data enrich the molecular characterization of seminoma, suggesting that PTTG1 is a prognostic factor in seminoma clinical management.

Numerous studies showed that bladder urothelial carcinoma and upper urothelial tract carcinoma (UTUC) display clinical and genomic similarities. In order to analyze that the same panel of biomarkers used in the diagnosis of bladder urothelial carcinoma could be suitable for early detection of UTUC, we performed a retrospective study in which we analyzed Bladder EpiCheck scores in the urinary samples obtained by selective ureteral catheterization in a high-grade UTUC cohort, correlating the results with urinary cytology and diagnostic urethral biopsies. The present study represents a retrospective analysis of 82 patients with clinically localized high-grade UTUC (60 renal pelvis UTUC, 22 ureter UTUC) who had undergone a radical nephroureterectomy (RNU) at our Urology department from June 2018 to November 2020. Before any surgical procedure, one sample of urine, obtained by selective ureteral catheterization, was collected for each patient for cytological examination, and the remaining material was stored for the Bladder EpiCheck test. Our results showed that the sensitivity of the methylation test for high-grade UTUC was about 97.4%, significantly higher than the sensitivity of urinary cytology either considering the HGUC cytological diagnosis or including in the positive cases the SHGUC cytological diagnosis (97.4% versus 59% or 70.5%). The methylation analysis of urinary samples may represent a valid tool in the diagnostic process of patients with suspected UTUC. In cases with a difficult clinical decision after upper urinary tract biopsy and cytology, the methylation test could assist in the clinical management of UTUC patients.

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) represent a group of hematological disorders that are traditionally considered as indistinct slow progressing conditions; still, a subset of cases shows a rapid evolution towards myelofibrotic bone marrow failure. Specific abnormalities in the megakaryocyte lineage seem to play a central role in this evolution, especially in the bone marrow fibrosis but also in the induction of myeloproliferation. In this review, we analyze the current knowledge of prognostic factors of MPNs related to their evolution to myelofibrotic bone marrow failure. Moreover, we focused the role of the megakaryocytic lineage in the various stages of MPNs, with updated examples of MPNs in vitro and in vivo models and new therapeutic implications.

Machine learning (ML) is the subfield of artificial intelligence (AI), born from the marriage between statistics and computer science, with the unique purpose of building prediction algorithms able to improve their performances by automatically learning from massive data sets. The availability of ever-growing computational power and highly evolved pattern recognition software has led to the spread of ML-based systems able to perform complex tasks in bioinformatics, medical imaging, and diagnostics. These intelligent tools could be the answer to the unmet need for non-invasive and patient-tailored instruments for the diagnosis and management of bladder cancer (BC), which are still based on old technologies and unchanged nomograms. We reviewed the most significant evidence on ML in the diagnosis, prognosis, and management of bladder cancer, to find out if these intelligent technologies are ready to be introduced into the daily clinical practice of the urologist.

Alveolar rhabdomyosarcoma (ARMS) commonly occurring in children and adolescents, is a rare and aggressive soft tissue malignancy demonstrating rapid growth and dissemination. Although their histopathologic and immunohistochemical findings are well known, cytomorphological features on serous effusions have not been well documented. A case of metastatic rhabdomyosarcoma diagnosed on cytological examination of the pericardial fluid cytology and discuss the diagnostic difficulties that were encountered in this case has been presented.

The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) promotes growth and progression in prostate cancer (PCa), however, little is known about its possible impact in PCa metabolism. The aim of this work has been the assessment of the metabolic reprogramming associated with MALAT1 silencing in human PCa cells and in an ex vivo model of organotypic slice cultures (OSCs). Cultured cells and OSCs derived from primary tumors were transfected with MALAT1 specific gapmers. Cell growth and survival, gene profiling, and evaluation of targeted metabolites and metabolic enzymes were assessed. Computational analysis was made considering expression changes occurring in metabolic markers following MALAT1 targeting in cultured OSCs. MALAT1 silencing reduced expression of some metabolic enzymes, including malic enzyme 3, pyruvate dehydrogenase kinases 1 and 3, and choline kinase A. Consequently, PCa metabolism switched toward a glycolytic phenotype characterized by increased lactate production paralleled by growth arrest and cell death. Conversely, the function of mitochondrial succinate dehydrogenase and the expression of oxidative phosphorylation enzymes were markedly reduced. A similar effect was observed in OSCs. Based on this, a predictive algorithm was developed aimed to predict tumor recurrence in a subset of patients. MALAT1 targeting by gapmer delivery restored normal metabolic energy pathway in PCa cells and OSCs.

AimsBladder EpiCheck is one of several urinary tests studied to identify bladder tumours and analyses 15 methylation biomarkers determining bladder cancer presence on the basis of methylation profile.Methods374 patients diagnosed with high-grade non-muscle invasive bladder cancer were treated and followed for 1 year with voided urine cytology and white-light cystoscopy and biopsies according to European Association of Urology Guidelines. 268 cases were diagnosed with high-grade papillary carcinoma, while 106 cases were carcinoma in situ. Bladder EpiCheck test was performed together with cytology in all cases.ResultsComparing cytological categories of negative for high-grade urothelial carcinoma (NHGUC) and atypical urothelial cells (AUCs), we found that an EpiScore ConclusionsAnalysing methylation study results, we demonstrated that different TPS cytological categories also carry a distinct molecular signature. Moreover, our results confirm that cytological categories SHGUC and HGUC are different entities also from a molecular point of view and should continue to represent distinct groups in TPS.

Biopsy proven Gleason score is essential to decide treatment modalities for prostate cancer, either surgical (radical prostatectomy) or non-surgical (active surveillance, watchful waiting, radiation therapy and hormone therapy). Several studies indicated that biopsy proven Gleason score may underestimate Gleason score at radical prostatectomy, hence we aimed to calculate the minimum length of biopsy cores needed to have Gleason score agreement. We evaluated 115 prostate cancer patients who underwent multiparametric magnetic resonance/transperineal ultrasonography fusion biopsy and subsequently, radical prostatectomy. Biopsy proven Gleason score was consistent with Gleason score at subsequent radical prostatectomy in 82.6% of patients, while in 17.4% of patients, Gleason score was higher at radical prostatectomy. Gleason score agreement showed a strong direct association with a ratio &gt, 0.05 between the total volume of biopsies performed in tumor area and the volume of the corresponding tumor at radical prostatectomy. A significant association was also found with a ratio &ge, 0.0034 between the tumor volume in the biopsy and the volume of the corresponding tumor at radical prostatectomy and with a ratio &ge, 0.086 between the tumor volume in the biopsy and the total volume of biopsies performed in the tumor area. These results could be exploited to calculate the minimum length of biopsy cores needed to have a correct Gleason score estimation and therefore be used in fusion targeted biopsies with volume adjustments.