Luciano Giuliani (1928-1994): Great master and founding father of modern Italian Urology.

Luciano Giuliani was born near Arezzo, in Tuscany (Italy) in 1928. After taking his Degree cum Laude in Medicine and Surgery at the University of Florence in 1951, he became a voluntary assistant at the Institute of General Clinical Surgery and Surgical Therapy. He then took a diploma in Urology and General Surgery, having demonstrated his great technical and surgical ability, and was subsequently appointed assistant in charge and then extraordinary assistant. Endowed with uncommon surgical skills and a forceful personality, Giuliani tirelessly carried out his clinical and surgical activity, covering several roles and rapidly earning profound esteem and recognition in the field of urology. As a pupil of the great luminary of Italian surgery, Ulrico Bracci, Dr Giuliani keenly followed his master, embracing his teachings and surgical techniques, until 1969, when he was appointed to run the 2nd Urology Division at San Martino Hospital in Genoa. He subsequently took up the chair of Urology at the University of Genoa and became Director of the Specialty School in Urology. Within a few years, he earned a solid reputation both nationally and internationally through his innovative surgical techniques. He also gave considerable impetus to the Genoese School of Urology, reaching the highest echelons of the Italian and European Societies of Urology. At the beginning of the 1990s, he designed and founded a new urology clinic in Genoa; this imposing, avant-garde building was subdivided into four floors and equipped with 80 beds. In July 1994, he won the prestigious "Willy Grégoir Medal", an accolade awarded to eminent personalities in European urology. In August of the same year, he died in the Institute that he himself had created at San Martino Hospital in Genoa.

Clinical use of bioelectrical impedance analysis in patients affected by myotonic dystrophy type 1: A cross-sectional study.

OBJECTIVES: Myotonic dystrophy type 1 (DM1) is an inherited muscle disorder characterized by slowly progressive weakness due to muscle degeneration. The Muscular Impairment Rating Scale (MIRS) is validated to assess clinical muscle severity of patients with DM1, although the scale is not sensitive enough to assess disease progression in time intervals fit for clinical trials. The aim of this study was to analyze bioelectrical whole body and arm segmental parameters in patients with DM1 to explore a correlation between bioelectrical impedance analysis (BIA) parameters and disease stage. METHODS: Forty patients with DM1 were enrolled in a cross-sectional study. In all patients, MIRS, handgrip strength (HGS), and BIA were assessed. A Kruskal-Wallis test was used to assess the difference in continuous variables according to MIRS. Correlation between BIA values and HGS were made by Pearson's coefficient analysis. A linear regression analysis was performed. RESULTS: Eighteen of 40 patients were men (45%). The median age of the cohort was 42 y (30-58 y). Four patients (10%) were classified as MIRS 1; 20 (50%) MIRS 2; 11 (27.5%) MIRS 3; and 5 (12.5%) as MIRS 4. A correlation was observed between phase angle and MIRS (P = 0.0001). MIRS correlated with other BIA values such as resistance, impedance ratio, and capacitance (P = 0.005, P = 0.0001, P = 0.0006, respectively). At linear regression analysis, segmental resistance, phase angle, impedance ratio, and capacitance of both arms significantly correlated with HGS. CONCLUSIONS: Results from the study support the use of BIA as a suitable procedure for staging DM1 muscle involvement and as a measure of muscle disease outcome, in clinical practice and in clinical trial design of therapeutic drugs.

Management of kidney cancer patients: 2018 guidelines of the Italian Medical Oncology Association (AIOM).

In the past two decades, the treatment landscape for patients with metastatic renal cell carcinoma has significantly changed thanks to the approval of several targeted molecular therapies (VEGF and mTOR inhibitors) and recently immune-checkpoint inhibitors. The Italian Association of Medical Oncology (AIOM) Renal Cell Cancer (RCC) Guidelines Panel has developed clinical guidelines to provide evidence-based information and recommendations to oncologists, urologists and all professionals involved in the management of patients with renal cell cancer.

The prevention of fragility fractures in patients with non-metastatic prostate cancer: a position statement by the international osteoporosis foundation.

Androgen deprivation therapy is commonly employed for the treatment of non-metastatic prostate cancer as primary or adjuvant treatment. The skeleton is greatly compromised in men with prostate cancer during androgen deprivation therapy because of the lack of androgens and estrogens, which are trophic factors for bone. Men receiving androgen deprivation therapy sustain variable degrees of bone loss with an increased risk of fragility fractures. Several bone antiresorptive agents have been tested in randomized controlled trials in these patients. Oral bisphosphonates, such as alendronate and risedronate, and intravenous bisphosphonates, such as pamidronate and zoledronic acid, have been shown to increase bone density and decrease the risk of fractures in men receiving androgen deprivation therapy. Denosumab, a fully monoclonal antibody that inhibits osteoclastic-mediated bone resorption, is also effective in increasing bone mineral density and reducing fracture rates in these patients. The assessment of fracture risk, T-score and/or the evaluation of prevalent fragility fractures are mandatory for the selection of patients who will benefit from antiresorptive therapy. In the future, new agents modulating bone turnover and skeletal muscle metabolism will be available for testing in these subjects.

Cost of illness of urothelial bladder cancer in Italy.

BACKGROUND: Urothelial bladder cancer (UBC) is the ninth most common cancer worldwide. In Italy, the prevalence of the disease is approximately 10%, making it the fourth most prevalent cancer in the country. The increase in prevalence requires continuous surveillance and care, resulting in a significant burden on Italian National Health Service, making any improvement to the strategy for diagnosing and treating this disease important to the medical and scientific community. The aim of this study was to evaluate the UBC cost of illness in the Italian context, collecting the total costs of the disease. METHODS: An economic analysis was carried out in the context of the National Health Service, using data collected from six centers, in order to evaluate direct costs in terms of outpatient, inpatient, and emergency care; pharmaceuticals and follow-up procedures; and indirect costs in terms of productivity losses. Data were collected through aggregated form reports, focusing on patients with an existing diagnosis of UBC who were treated in the last year. The Italian Association of Medical Oncology (AIOM) guidelines were used to identify diagnostic and therapeutic procedures. Statistical analysis was conducted to explore variations among centers. RESULTS: The weighted mean total annual cost per patient was € 3,591, where the cost for superficial disease was € 3,252 and that for metastatic disease was € 606. The analysis confirmed a proportional relation between disease severity and disability grade. The UBC cost of illness, considering prevalence and incidence data coming from the 2016 AIOM/Italian Association of Cancer Registries report, was € 1,187,036,344. Indirect costs accounted to 44%, represented by estimated productivity losses. CONCLUSION: Our analysis represents the first economic study of UBC in the Italian context, as well as the first real-life evidence of the current therapeutic algorithm. This study opens the possibility for further analysis on the indirect cost components that represent a great burden for the society, especially for those in the severest stages of the disease with high disability grades.

Chromographic Analysis and Cytotoxic Effects of Chlorhexidine and Sodium Hypochlorite Reaction Mixtures.

INTRODUCTION: The literature reveals controversies regarding the formation of para-chloroaniline (PCA) when chlorhexidine (CHX) is mixed with sodium hypochlorite (NaOCl). This study aimed to investigate the stability of PCA in the presence of NaOCl and to examine the in vitro cytotoxic effects of CHX/NaOCl reaction mixtures. METHODS: Different volumes of NaOCl were added to CHX (mix 1) or PCA (mix 2). Upon centrifugation, the supernatant and precipitate fractions collected from samples were analyzed using high-performance liquid chromatography. The cytotoxic effects of both fractions were examined on human periodontal ligament and 3T3 fibroblast cell lines. RESULTS: High-performance liquid chromatographic analysis showed no PCA signal when NaOCl was mixed with CHX (mix 1). In mix 2, the intensity of PCA was decreased when NaOCl was added to PCA, and chromatographic signals, similar to that of CHX/NaOCl, were also observed. The mortality of precipitates exerted on both cell lines was lower compared with that of supernatants. CONCLUSIONS: The discrepancy in the data from the literature could be caused by the instability of the PCA in the presence of NaOCl. The CHX/NaOCl reaction mixture exhibits a wide range of cytotoxic effects.

"In-bore" MRI-guided Prostate Biopsy Using an Endorectal Nonmagnetic Device: A Prospective Study of 70 Consecutive Patients.

INTRODUCTION: We investigated the diagnostic performance of in-bore endorectal magnetic resonance imaging-guided biopsy (MRI-GB) with a 1.5-T MRI scanner using a 32-channel coil in patients with suspected prostate cancer (PCa). PATIENTS AND METHODS: Seventy patients with ≥ 1 suspicious area found on the preliminary multiparametric MRI scan were enrolled. The index lesion was defined as the lesion with the greatest Prostate Imaging Reporting and Data System, version 2 (PIRADS-v2), score. MRI-GBs were performed with a nonmagnetic biopsy device, needle guide, and titanium double-shoot biopsy gun with dedicated software for needle tracking. Clinically significant PCa was defined as the presence of Gleason score ≥ 7 in the biopsy specimen. RESULTS: Seventy index lesions were scheduled for MRI-GB. The median PIRADS-v2 score and the median number of cores per patient was 4 of 5 (interquartile range, 3-5) and 2 (interquartile range, 1-3), respectively. The PCa detection rate was 45.7%. Of the 70 patients, 24 (75%) had clinically significant PCa, with a significant correlation between the PIRADS-v2 score and the Gleason score in the MRI-GB cores (r = 0.839; 95% confidence interval, 0.535-0.951; P = .003). According to the PIRADs-v2 scheme, the proportion of PCa in the central and anterior regions of the gland was greater in the entire population and in the subgroup of patients with a history of negative transrectal ultrasound-guided biopsy findings (P ≤ .01 for all). On multivariate analysis, a PIRADS-v2 score of 5 of 5 correlated significantly with the likelihood of PCa at biopsy (hazard ratio, 4.69; 95% confidence interval, 0.92-23.74; P = .04). No major complications were recorded. CONCLUSION: MRI-GB has a high detection rate for PCa, especially for lesions located in the central and anterior regions of the prostate.

Body mass index and the clinicopathological characteristics of clinically localized renal masses-An international retrospective review.

OBJECTIVES: To investigate the potential association between body mass index (BMI) and clinicopathological features of clinically localized renal masses. MATERIALS AND METHODS: An international, multi-institutional retrospective review of patients who underwent surgery for clinically localized renal masses between 2000 and 2010 was undertaken after an institutional review board approval. Patients were divided into 4 absolute BMI groups based on the entire cohort׳s percentiles and 4 relative BMI groups based on their respective population (American or Italian). Renal mass pathological diagnosis, renal cell carcinoma (RCC) subtype, Fuhrman grade (low and high), and clinical stage were compared among groups using Fisher׳s exact test, Kruskal-Wallis test, and the Cochran-Armitage trend test. A multivariate logistic analysis was performed to evaluate independent association between tumor and patient characteristics with tumor pathology (Fuhrman grade). RESULTS: A total of 1,748 patients having a median BMI of 28 (interquartile range 25-32) were evaluated. Benign masses and RCC cases had similar proportion across BMI groups (P = 0.4). The most common RCC subtype was clear cell followed by papillary carcinoma, chromophobe, and other subtypes. Their distribution was comparable across BMI groups (P = 0.7). Similarly, clinical stage distribution was comparable with the overall cohort. The distribution of Fuhrman grade in RCC, however, demonstrated an increased proportions of low grade with increasing BMI (P<0.05). This trend was maintained in subgroups according to gender, stage and age (P<0.05 in all subgroup analysis). In a multivariable model that included potential confounders (i.e., age, sex, and tumor size) higher BMI groups had lower odds of presenting a high Fuhrman grade. CONCLUSION: In this study, higher BMI was associated with lower grade of RCC in clinically localized renal masses. This may, in part, explain better survival rates in patients with higher BMI and may correlate with a possible link between adipose tissue and RCC biology.

Topoisomerases and Anthracyclines: Recent Advances and Perspectives in Anticancer Therapy and Prevention of Cardiotoxicity.

Topoisomerases are ubiquitous enzymes involved in maintaining genomic stability of the cell by regulating the over- or underwinding of DNA strands. Besides their customary functions, topoisomerases are important cellular targets of widely used anticancer drugs. In particular, topoisomerase IIα (Top2α) has been postulated as the primary molecular target of anthracycline's anticancer activity, whereas topoisomerase IIß (Top2ß), the only Top2 present in heart tissue, seems to be involved in the development of anthracycline-induced cardiotoxicity. Noteworthy, cardiotoxicity is the most frequent adverse effect of both conventional and modern anticancer targeted therapy, representing the leading noncancer-related cause of morbidity and mortality in long-term survivors. The molecular mechanisms of anthracyclineinduced cardiotoxicity have been investigated for decades and, despite the numerous mechanistic hypotheses put forward, its aetiology and pathogenesis still remain controversial. This review is aimed at focusing on the double edge sword of topoisomerase-anthracycline interaction, and, in particular, on the potential role of topoisomerases in anthracyclines anticancer activity as well as in the pathogenesis of anthracycline-induced cardiotoxicity.

PADUA and R.E.N.A.L. nephrometry scores correlate with perioperative outcomes of robot-assisted partial nephrectomy: analysis of the Vattikuti Global Quality Initiative in Robotic Urologic Surgery (GQI-RUS) database.

OBJECTIVES: To evaluate and compare the correlations between Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) and R.E.N.A.L. [Radius (tumour size as maximal diameter), Exophytic/endophytic properties of the tumour, Nearness of tumour deepest portion to the collecting system or sinus, Anterior (a)/posterior (p) descriptor and the Location relative to the polar line] nephrometry scores and perioperative outcomes and postoperative complications in a multicentre, international series of patients undergoing robot-assisted partial nephrectomy (RAPN) for masses suspicious for renal cell carcinoma (RCC). PATIENTS AND METHODS: We retrospectively evaluated the clinical records of patients who underwent RAPN between 2010 and 2013 for clinical N0M0 renal tumours in four international centres that completed all the data required for the Vattikuti Global Quality Initiative in Robotic Urologic Surgery (GQI-RUS) database. All patients underwent preoperative computed tomography or magnetic resonance imaging to define the clinical stage and anatomical characteristics of the tumours. PADUA and R.E.N.A.L. scores were retrospectively assessed in each centre. Univariate and multivariate analyses were used to evaluate the correlations between age, gender, Charlson comorbidity index, clinical tumour size, PADUA and R.E.N.A.L. complexity group categories and warm ischaemia time (WIT) of >20 min, urinary calyceal system closure, and grade of postoperative complications. RESULTS: Overall, 277 patients were evaluated. The median (interquartile range) tumour size was 33.0 (22.0-43.0) mm. The median PADUA and R.E.N.A.L. scores were eight and seven, respectively; 112 (40.4%), 86 (31.0%) and 79 (28.5%) patients were classified in the low-, intermediate- or high-complexity group according to PADUA score, while 118 (42.5%), 139 (50.1%) and 20 (7.2%) were classified in the low-, intermediate- or high-complexity group according to R.E.N.A.L. score, respectively. Both nephrometry tools significantly correlated with perioperative outcomes at univariate and multivariate analyses. CONCLUSION: A precise stratification of patients before PN is recommended to consider both the potential threats and benefits of nephron-sparing surgery. In our present analysis, both PADUA and R.E.N.A.L. were significantly associated with predicting prolonged WIT and high-grade postoperative complications after RAPN.

Adverse Features and Competing Risk Mortality in Patients With High-Risk Prostate Cancer.

PURPOSE: To assess survival and competing causes of mortality in prostate cancer (PCa) patients referred to radical prostatectomy through a combination of unfavorable characteristics. PATIENTS AND METHODS: We evaluated 615 PCa patients referred to radical prostatectomy and pelvic lymph node dissection at single tertiary-care center with at least one adverse feature (AF): preoperative prostate-specific antigen ≥ 20 ng/mL, pathologic Gleason score 8 to 10, and no organ-confined disease at final pathology (seminal vesicle involvement, positive surgical margins, and/or lymph node invasion). Kaplan-Meier analyses were used to assess cancer-specific mortality (CSM)-free survival rates by stratifying patients into 3 risk categories according to the number of AFs (namely, 1, 2, and 3 AFs). Multivariable competing risk Cox regression analyses were used to assess CSM and other cause of mortality. RESULTS: Significant differences were found in terms of preoperative and pathologic tumor characteristics, adjuvant therapies, and biochemical recurrence (BCR). Men with 1 AF had higher CSM-free survival estimates compared to those with 2 and 3 AFs (92.8% vs. 84.2% vs. 27.7% at 10 years' follow-up, P < .001). Moreover, the presence of 3 AFs (hazard ratio [HR], 2.96), postoperative adjuvant treatment status (HR, 2.44), and time to BCR (HR, 0.96) were all independent predictors of CSM (P ≤ .04). Age at surgery and time to BCR were the only independent predictors of other causes of mortality (P ≤ .0009). CONCLUSION: The risk group stratification according to the number of AFs could help physicians to accurately predict oncologic outcomes and to select PCa patients for the most appropriate postoperative strategies.

Can the multiphasic computed tomography be useful in the clinical management of small renal masses?

Background Small renal masses (SRMs; ≤4 cm) represent a challenging issue. Computed tomography (CT) is widely used for investigating renal tumors even if its ability to differentiate among the different subtypes has not yet been definitively established. Purpose To assess the potential role of the morphological features and angiodynamic behavior on multiphasic CT in the preoperative evaluation of SRMs. Material and Methods The CT images of 80 patients with SRMs who underwent surgical resection at our institution were retrospectively reviewed. The morphological features, the pattern, and the quantitative analysis of enhancement were assessed for each lesion and were correlated with the histological subtypes. Results Overall, 81 SRMs were evaluated. Final pathological examination showed 30 (37%) oncocytomas, 22 (27.2%) clear cell renal cell carcinomas (ccRCCs), 16 (19.8%) papillary RCCs (pRCCs), and 13 (16%) chromophobe RCCs (chRCCs). Of the morphological features, only necrosis was significantly associated with ccRCC ( P = 0.047). The analysis of enhancement allowed the identification of two groups of lesions, based on arterial behavior: hypervascular (oncocytomas/ccRCC) and hypovascular (chRCC/pRCC) lesions. A significant difference between the two groups in terms of degree of enhancement on CT phases was found ( P < 0.05); this was also confirmed by the receiver operating characteristic (ROC) analysis. Conclusion Except for necrosis, the morphological features are not useful in making a correct diagnosis in the case of SRMs. The angiodynamic behavior on multiphasic CT showed high accuracy in differentiating between hypovascular and hypervascular tumors; this differentiation could be useful for deciding on the most appropriate clinical management of SRMs.

Predicting survival in node-positive prostate cancer after open, laparoscopic or robotic radical prostatectomy: A competing risk analysis of a multi-institutional database.

OBJECTIVES: To investigate cancer-specific mortality and other-cause mortality in prostate cancer patients with nodal metastases. METHODS: The study included 411 patients treated with radical prostatectomy and pelvic lymph node dissection for prostate cancer with lymph node metastases at 10 tertiary care centers between 1995 and 2014. Kaplan-Meier analyses were used to assess cancer-specific mortality-free survival rates at 8 years' follow up in the overall population, and after stratifying patients according to clinical and pathological parameters. Uni- and multivariable competing risk Cox regression analyses were used to assess cancer-specific mortality and other-cause mortality. Finally, cumulative-incidence plots were generated for cancer-specific mortality and other-cause mortality after stratifying patients according to the number of positive lymph nodes and the median age at surgery, according to the competing risks method. RESULTS: Men with prostate-specific antigen ≤40 ng/mL and those with one to three positive lymph nodes showed higher cancer-specific mortality-free survival estimates as compared with their counterparts with prostate-specific antigen >40 ng/mL and >3 metastatic lymph nodes, respectively (all P < 0.001). At multivariable Cox regression analyses, preoperative prostate-specific antigen >40 ng/mL, >3 lymph node metastases and pathological Gleason score 8-10 were all independent predictors of cancer-specific mortality (all P-values ≤0.001). On competing risk analysis, when patients were stratified according to the number of positive lymph nodes (namely, ≤3 vs >3), the 8-year cancer-specific mortality rates were 27.4% versus 44.8% for patients aged <65 years, and 15.2% versus 52.6% for patients aged ≥65 years, respectively. CONCLUSIONS: Three positive lymph nodes represent the best prognostic cut-off in node-positive prostate cancer patients. In those individuals with >3 positive lymph nodes, the overall mortality rate is completely related to prostate cancer in young patients.

(18)F-FACBC (anti1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid) versus (11)C-choline PET/CT in prostate cancer relapse: results of a prospective trial.

PURPOSE: To compare the accuracy of (18)F-FACBC and (11)C-choline PET/CT in patients radically treated for prostate cancer presenting with biochemical relapse. METHODS: This prospective study enrolled 100 consecutive patients radically treated for prostate cancer and presenting with rising PSA. Of these 100 patients, 89 were included in the analysis. All had biochemical relapse after radical prostatectomy (at least 3 months previously), had (11)C-choline and (18)F-FACBC PET/CT performed within 1 week and were off hormonal therapy at the time of the scans. The two tracers were compared directly in terms of overall positivity/negativity on both a per-patient basis and a per-site basis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for both the tracers; follow-up at 1 year (including correlative imaging, PSA trend and pathology when available) was considered as the standard of reference. RESULTS: In 51 patients the results were negative and in 25 patients positive with both the tracers, in eight patients the results were positive with (18)F-FACBC but negative with (11)C-choline, and in five patients the results were positive with (11)C-choline but negative with (18)F-FACBC. Overall in 49 patients the results were false-negative (FN), in two true-negative, in 24 true-positive (TP) and in none false-positive (FP) with both tracers. In terms of discordances between the tracers: (1) in one patient, the result was FN with (11)C-choline but FP with (18)F-FACBC (lymph node), (2) in seven, FN with (11)C-choline but TP with (18)F-FACBC (lymph node in five, bone in one, local relapse in one), (3) in one, FP with (11)C-choline (lymph node) but TP with (18)F-FACBC (local relapse), (4) in two, FP with (11)C-choline (lymph nodes in one, local relapse in one) but FN with (18)F-FACBC, and (5) in three, TP with (11)C-choline (lymph nodes in two, bone in one) but FN with (18)F-FACBC. With (11)C-choline and (18)F-FACBC, sensitivities were 32 % and 37 %, specificities 40 % and 67 %, accuracies 32 % and 38 %, PPVs 90 % and 97 %, and NPVs 3 % and 4 %, respectively. Categorizing patients by PSA level (<1 ng/ml 28 patients, 1 - <2 ng/ml 28 patients, 2 - <3 ng/ml 11 patients, ≥3 ng/ml 22 patients), the number (percent) of patients with TP findings were generally higher with (18)F-FACBC than with (11)C-choline: six patients (21 %) and four patients (14 %), eight patients (29 %) and eight patients (29 %), five patients (45 %) and four patients (36 %), and 13 patients (59 %) and 11 patients (50 %), respectively. CONCLUSION: (18)F-FACBC can be considered an alternative tracer superior to (11)C-choline in the setting of patients with biochemical relapse after radical prostatectomy.

Role of Inter-Observer Variability and Quantification of Muscularis Propria in the Pathological Staging of Bladder Cancer.

INTRODUCTION: Pathological staging of bladder cancer (BC) on trans-urethral bladder resection (TURB) specimens is critical for the indication of radical cystectomy (RC). MATERIALS AND METHODS: We aimed to assess the inter-observer variability among dedicated and not dedicated genito-urinary pathologists (GUP) and the predictive value of the amount of muscularis propria (MP) in the TURB specimens to predict accurate staging in RC. We selected 101 patients with at least 1 diagnosis of pT1 high grade BC who underwent RC during the history of disease. All the pathological TURB and RC specimens were reviewed by 3 GUPs, and concordance among them and with the original pathology report (OPR) was made. The presence and the extent of MP was measured in all the TURB specimens and correlated to stage at RC. RESULTS: Excellent (0.90 ≥ K ≥ 0.74) diagnostic concordance was reached among GUP while only good (0.77 ≥ K ≥ 0.67) with the OPR on stage and grade in TURBs. We found a general up-stage in the OPR compared with the GUP review. After histological review, 34.4% cases were downstaged to pT1 from pT2 and 10.1% from pT1 to pTa. The presence of MP was associated with a better discrimination of the stage at RC (P = .00065), and a trend towards correlation was found with its extent (area under the curve-receiver operator characteristic = 0.752; best cut-off 3.69 mm). CONCLUSION: The implementation of dedicated GUP can improve diagnostic sensitivity and specificity in BC diagnosis. The amount of MP and perhaps its extent in pT1 TURB speciments can predict more accurate cancer stage at RC.

Cancer Biomarkers Discovery and Validation: State of the Art, Problems and Future Perspectives.

Cancer is one of the major public health problems worldwide representing the leading cause of morbidity and mortality in industrialized countries. To reduce cancer morbidity and mortality as well as to facilitate the evolution from the traditional "one size fits all" strategy to a new "personalized" cancer therapy (i.e., the right drug to the right patient at the right time, using the right dose and schedule), there is an urgent need of reliable, robust, accurate and validated cancer biomarker tests.Unfortunately, despite the impressive advances in tumor biology research as well as in high-powerful "omics" technologies, the translation of candidate cancer biomarkers from bench to bedside is lengthy and challenging and only a few tumor marker tests have been adopted successfully into routine clinical care of oncologic patients.This chapter provides an updated background on biomarkers research in oncology, including biomarkers clinical uses, and discusses the problems of discovery pipeline, biomarkers failures and future perspectives.

Inhibition of Anthracycline Alcohol Metabolite Formation in Human Heart Cytosol: A Potential Role for Several Promising Drugs.

The clinical efficacy of anthracyclines (e.g., doxorubicin and daunorubicin) in cancer therapy is limited by their severe cardiotoxicity, the etiology of which is still not fully understood. The development of anthracycline-induced cardiomyopathy has been found to correlate with myocardial formation and accumulation of anthracycline secondary alcohol metabolites (e.g., doxorubicinol and daunorubicinol) that are produced by distinct cytosolic NADPH-dependent reductases. The aim of the current study is to identify chemical compounds capable of inhibiting myocardial reductases implied in anthracycline reductive metabolism in an attempt to decrease the production of cardiotoxic C-13 alcohol metabolites. Among the variety of tested compounds (metal chelators, radical scavengers, antioxidants, ß-blockers, nitrone spin traps, and lipid-lowering drugs), ebselen, cyclopentenone prostaglandins, nitric oxide donors, and short-chain coenzyme Q analogs resulted in being effective inhibitors of both doxorubicinol and daunorubicinol formation. In particular, ebselen (as well as ebselen diselenide, its storage form in the cells) was the most potent inhibitor of cardiotoxic anthracycline alcohol metabolites with 50% inhibition of doxorubicinol formation at 0.2 mol Eq of ebselen with respect to doxorubicin concentration. The high efficacy, together with its favorable pharmacological profile (low toxicity, lack of adverse effects, and metabolic stability) portends ebselen as a promising cardioprotective agent against anthracycline-induced cardiotoxicity.

The Prognostic Impact of Tumor Size on Cancer-Specific and Overall Survival Among Patients With Pathologic T3a Renal Cell Carcinoma.

BACKGROUND: We aimed to determine the prognostic role of tumor size in patients with stage pT3a renal cell carcinoma (RCC). PATIENTS AND METHODS: We analyzed our database of patients who underwent radical nephrectomy for RCC between July 2000 and December 2013. Clinical and pathologic data were obtained for each patient. Patients with stage pT3a disease were divided into 2 subgroups according to the most informative threshold for pathologic tumor dimension that was able to predict survival outcomes (group 1, ≤ 8 cm; group 2, > 8 cm). RESULTS: Globally, 185 consecutive patients were evaluated. The median (interquartile range [IQR]) follow-up was 32 months (18-62 months). The median (IQR) pathologic tumor size was 7.5 cm (5.7-10 cm). Seventy (34.3%) patients died of RCC during the follow-up period. Patients in group 2 experienced worse cancer-specific survival (CSS) rates compared with those in group 1, (5- and 10- year CSS, 52% and 40% vs. 67% and 63%, respectively; P = .001). Overall survival (OS) rates were significantly lower for patients included in group 2 compared with patients in group 1 (5- and 10- year OS rates, 46% and 38% vs. 60% and 57%, respectively; P = .01). Subgroup stratification (hazard ratio [HR], 3.65; P < .001), presence of positive surgical margins (HR, 3.86; P = .22), high Fuhrman grade (HR, 4.33; P < .001), and the presence of sarcomatoid cells (HR, 2.61; P = .02) were found to be independent predictors of CSS. CONCLUSION: Worse oncologic outcomes are observed in patients with stage pT3a RCC tumors > 8 cm. The current TNM classification still does not precisely correlate with CSS. Tumor size should be taken into account in a future revision of the TNM staging system.

18F-Fluciclovine PET/CT for the Detection of Prostate Cancer Relapse: A Comparison to 11C-Choline PET/CT.

PURPOSE: In recent years, a new PET compound (anti-3-(18)F-FACBC or (18)F-fluciclovine) was tested for the detection of prostate cancer relapse. Despite very promising results, only preliminary data were available with regard to the comparison to (11)C-choline. The aim of this study was to compare the detection rate of (18)F-FACBC and (11)C-choline in patients presenting a biochemical relapse. PATIENTS AND METHODS: Fifty patients radically treated for prostate cancer and presenting with rising prostate-specific antigen (PSA) levels were consecutively and prospectively enrolled. All the patients were out of hormonal therapy and underwent both (11)C-choline PET/CT and (18)F-fluciclovine PET/CT within 1 week. The results were compared in terms of detection rate on a patient and lesion basis. Furthermore, a more detailed analysis regarding local, lymph node, and bone relapse was performed. RESULTS: On a patient-based analysis, (18)F-fluciclovine detection turned out to be significantly superior to (11)C-choline (P < 0.000001). This result was also true on lesion, lymph node, bone lesion, and local relapse analysis (P < 0.0001 in all the cases). There was no significant difference in terms of target to background of positive lesions between (11)C-choline and (18)F-fluciclovine. When the patients were divided into groups with different PSA levels, (18)F-fluciclovine had a superior detection rate for low, intermediate, and high PSA levels. CONCLUSIONS: In our experimental conditions, (18)F-fluciclovine provided a statistically significant better performance in terms of lesion detection rate as compared with (11)C-choline. However, more studies are required to evaluate the clinical significance of these results in terms of sensitivity, specificity, and accuracy.