ABSTRACT
Patients with prostate cancer frequently show resistance to androgen-deprivation therapy, a condition known as castration-resistant prostate cancer (CRPC). Acquiring a better understanding of the mechanisms that control the development of CRPC remains an unmet clinical need. The well-established dependency of cancer cells on the tumour microenvironment indicates that the microenvironment might control the emergence of CRPC. Here we identify IL-23 produced by myeloid-derived suppressor cells (MDSCs) as a driver of CRPC in mice and patients with CRPC. Mechanistically, IL-23 secreted by MDSCs can activate the androgen receptor pathway in prostate tumour cells, promoting cell survival and proliferation in androgen-deprived conditions. Intra-tumour MDSC infiltration and IL-23 concentration are increased in blood and tumour samples from patients with CRPC. Antibody-mediated inactivation of IL-23 restored sensitivity to androgen-deprivation therapy in mice. Taken together, these results reveal that MDSCs promote CRPC by acting in a non-cell autonomous manner. Treatments that block IL-23 can oppose MDSC-mediated resistance to castration in prostate cancer and synergize with standard therapies.
Subject(s)
Interleukin-23/antagonists & inhibitors , Interleukin-23/metabolism , Myeloid-Derived Suppressor Cells/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/therapy , Androgen Receptor Antagonists/pharmacology , Androgen Receptor Antagonists/therapeutic use , Androgens/deficiency , Animals , Benzamides , Cell Proliferation , Cell Survival , Humans , Interleukin-23/blood , Interleukin-23/immunology , Male , Mice , Myeloid-Derived Suppressor Cells/cytology , Myeloid-Derived Suppressor Cells/immunology , Nitriles , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Phenylthiohydantoin/analogs & derivatives , Phenylthiohydantoin/pharmacology , Phenylthiohydantoin/therapeutic use , Prostatic Neoplasms, Castration-Resistant/blood , Prostatic Neoplasms, Castration-Resistant/metabolism , Receptors, Androgen/metabolism , Receptors, Interleukin/metabolism , Signal TransductionABSTRACT
PURPOSE: COVID-19 pandemic represents a novel challenge for healthcare systems, and it affects even the daily urological practice. Italy was the first country after China to experience a lock-down period. Our objective is to determine whether, during the COVID-19 period, there has been any modification in urological emergencies. METHODS: we retrospectively reviewed urgent urological consultations requested by the Emergency Department (ED) of Padua University Hospital in the 36-day period between February 22nd and March 30th, 2020 and compared them to the prior year cases within a similar time frame (February 24th to March 31st, 2019). Pediatric population (age < 15 years); surgical complications and traumas were excluded to avoid confounding from the reduction of activities during the lockdown. The number of daily consultations, the number of invasive procedures performed and admissions were evaluated, together with the predictors of admission were identified through multivariate logistic regression models. RESULTS: The final sample resulted in 107 consultations performed in 2020 and 266 in 2019. A higher number of daily consultations was performed during 2019 (7.33 vs 2.97, p < 0.001). Similarly, the number of daily-invasive procedures was higher in 2019 (p = 0.006), while there was no difference in the number of daily admissions (15 vs 12, p = 0.80). On multivariate analysis, the year (2020 vs 2019, OR 2.714, 95% CI 1.096-6.757, p = 0.0297) was a significant predictor of admission. CONCLUSIONS: Urgent urology practice was affected during COVID-19 pandemic with a remarkable reduction in urgent urological consultations; furthermore, a higher risk of admissions was observed in 2020. The consequences of a potentially delayed diagnosis remain to be determined.
Subject(s)
COVID-19 , Diagnostic Techniques, Urological/statistics & numerical data , Emergencies/epidemiology , Emergency Service, Hospital , Referral and Consultation , Urologic Diseases , Aged , COVID-19/epidemiology , COVID-19/prevention & control , Delayed Diagnosis/prevention & control , Emergency Service, Hospital/statistics & numerical data , Emergency Service, Hospital/trends , Female , Humans , Infection Control/methods , Infection Control/organization & administration , Italy/epidemiology , Male , Patient Admission/statistics & numerical data , Referral and Consultation/statistics & numerical data , Referral and Consultation/trends , Risk Assessment , SARS-CoV-2 , Urologic Diseases/diagnosis , Urologic Diseases/epidemiology , Urology Department, Hospital/statistics & numerical dataABSTRACT
BACKGROUND: Open radical cystectomy (ORC) with pelvic lymph-node dissection (PLND) for bladder cancer (BCa) and urinary diversion is a morbid procedure, and advanced age has been associated with a higher incidence of Clavien-Dindo ≥ 3 complications. AIM: To investigate the association between chronological age, survival outcomes, incidence of perioperative complications, and quality parameters in patients undergoing ORC. METHODS: We reviewed 413 patients who underwent ORC and PLND at a single academic centre between December 2009 and June 2018 for cT2-T4N0M0 BCa. Complete clinical, demographic, and pathological data were collected in the preoperative, preoperative, and postoperative setting. Patients were categorized as ≥ 75 years or < 75 years and statistical analysis was performed accordingly. Besides descriptive statistics, Kaplan-Meier log-rank test was used. Cox regression univariate and multivariate analyses were used to assess any potential predictor of OS and CSS. RESULTS: There were 285 (69%) patients < 75 years and 128 (31%) patients ≥ 75 years old. There was no significant difference between the two age groups neither in terms of distribution of pathological stage nor in terms of overall incidence of postoperative complications. Chronological age was not significantly associated with survival outcomes on multivariate analysis. Finally, the comorbidity index was the only significant risk factor for the incidence of any complications (OR = 0.83, p = 0.002) at multivariate binary logistic regression. CONCLUSION: Open radical cystectomy (ORC) is a feasible and safe procedure in patients with high-risk non-metastatic bladder cancer. Uro-oncologists should consider evaluating elderly patients for surgery according to a thorough geriatric assessment despite chronological age.
Subject(s)
Robotic Surgical Procedures , Urinary Bladder Neoplasms , Aged , Cystectomy/adverse effects , Humans , Lymph Node Excision/adverse effects , Morbidity , Postoperative Complications/epidemiology , Retrospective Studies , Treatment Outcome , Urinary Bladder Neoplasms/surgeryABSTRACT
BACKGROUND: Multiparametric-magnetic resonance imaging (mpMRI) can accurately detect high-grade and larger prostate cancers (PC). AIMS: To evaluate the ability of 1.5 T magnetic field mpMRI-targeted Prostate Biopsies (PBx) in predicting PC in comparison with blind 24-core saturation PBx (sPBx). METHODS: We prospectively collected data from patients undergoing transrectal sPBx and, if needed, targeted PBx of suspected lesions based on the 16-'region-of-interest' (ROI) PI-RADS graph. Data remodeling: for each 'target' (each suspected lesion at mpMRI), we identified all the 16 'ROIs' into which the lesion extended: these single 'ROIs' were identified as 'macro-targets'. For each 'ROI' and 'macro-target', we compared the mpMRI result with that of a saturation and targeted biopsy (if performed). RESULTS: 1.5T mpMRI showed a PI-RADS value ≥ 3 in 101 patients (82.1%). We found a PC in 50 (40.6%). Negative-positive predictive values for mpMRI were 82-45%, respectively. Of the 22 patients with normal mpMRI, four had a PC, but none had a clinically significant cancer. After the data remodeling, we demonstrated the presence of PC in 228 'ROIs': (a) only in targeted biopsies in 15 'ROIs'/'macro-targets' (6.6%); (b) only in sPBx in 177 'ROIs' (77.6%); (c) in both targeted and sPBx in 36 'ROIs' (15.8%). DISCUSSION: 81.8% of patients with normal 1.5T mpMRI were negative at PBx. Performing only targeted PBx may lead to lack of PC diagnosis in about 50% of patients. CONCLUSIONS: In patients with suspected PC and a previous negative PBx, a normal mpMRI may exclude a clinically significant PC, avoiding sPBx.
Subject(s)
Magnetic Resonance Imaging, Interventional/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Aged , Humans , Image-Guided Biopsy , Male , Middle Aged , Prospective StudiesABSTRACT
BACKGROUND: Lower urinary tract symptoms (LUTS) and prostate specific antigen-based parameters seem to have only a limited utility for the differential diagnosis of prostate cancer (PCa). MALDI-TOF/MS peptidomic profiling could be a useful diagnostic tool for biomarker discovery, although reproducibility issues have limited its applicability until now. The current study aimed to evaluate a new MALDI-TOF/MS candidate biomarker. METHODS: Within- and between-subject variability of MALDI-TOF/MS-based peptidomic urine and serum analyses were evaluated in 20 and 15 healthy donors, respectively. Normalizations and approaches for accounting below limit of detection (LOD) values were utilized to enhance reproducibility, while Monte Carlo experiments were performed to verify whether measurement error can be dealt with LOD data. Post-prostatic massage urine and serum samples from 148 LUTS patients were analysed using MALDI-TOF/MS. Regression-calibration and simulation and extrapolation methods were used to derive the unbiased association between peptidomic features and PCa. RESULTS: Although the median normalized peptidomic variability was 24.9%, the within- and between-subject variability showed that median normalization, LOD adjustment, and log2 data transformation were the best combination in terms of reliability; in measurement error conditions, intraclass correlation coefficient was a reliable estimate when the LOD/2 was substituted for below LOD values. In the patients studied, 43 peptides were shared by the urine and serum, and several features were found to be associated with PCa. Only few serum features, however, show statistical significance after the multiple testing procedures were completed. Two serum fragmentation patterns corresponded to the complement C4-A. CONCLUSIONS: MALDI-TOF/MS serum peptidome profiling was more efficacious with respect to post-prostatic massage urine analysis in discriminating PCa.
ABSTRACT
STUDY QUESTION: To investigate whether sperm recovery is related to clinical features, hormone parameters and testosterone replacement therapy (TRT) in patients with Klinefelter syndrome (KS). SUMMARY ANSWER: This study provides three interesting insights: (i) the probability to retrieve sperm is not related to testicular volume; (ii) TRT does not affect sperm retrieval rate (SRR); and (iii) reduced levels of LH and FSH represent a negative predictor of sperm retrieval in patients with TRT. WHAT IS KNOWN ALREADY: Classical KS shows a karyotype with one extra X chromosome in all of somatic cells and clinical manifestations characterized by hypergonadotropic hypogonadism and infertility. STUDY DESIGN, SIZE AND DURATION: We performed a retrospective cohort study. Data from 111 consecutive KS azoospermic patients undergoing testicular sperm extraction (TESE) were collected from 2005 to 2016. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Data on anthropometric parameters, reproductive hormones and testicular volumes were collected. SRR was related to clinical characteristics and compared between TRT and untreated patients. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 38 patients (34.2%) had successful sperm recovery. The comparison of clinical characteristics did not differ between patients with and without sperm recovery. Sperm retrieval was successful also in subjects with smaller testes. The comparison of SRR in patients with or without TRT was not different (33.3% vs 34.6%). In TRT group, LH and FSH levels were significantly lower in subjects with no sperm retrieval (P values, respectively, <.05 and <.001). LIMITATIONS AND REASONS FOR CAUTION: Well-designed controlled studies are necessary to confirm these data aimed to set the best therapeutic approach for fertility management in hypogonadal patients with nonmosaic KS. WIDER IMPLICATIONS OF THE FINDINGS: Age at TESE, anthropometric measures, testis volume, sex hormones levels and semen parameters are not predictive parameters of SRR. Among TRT patients, reduced gonadotropin is related to failure in sperm retrieval.
Subject(s)
Klinefelter Syndrome/drug therapy , Sperm Retrieval , Testis/pathology , Testosterone/therapeutic use , Adolescent , Adult , Cohort Studies , Humans , Hypogonadism/drug therapy , Infertility, Male/drug therapy , Karyotype , Male , Middle Aged , Retrospective Studies , Spermatozoa/physiology , Young AdultABSTRACT
BACKGROUND: Prostate cancer (PC) represents the second most frequent cancer in the male population worldwide. It is mandatory to have a very accurate staging to choice the best possible treatment. AIMS: To test the possibility of improving the performance of Partin's tables in predicting the pathological staging of PC by introducing bioptic parameters through an innovative statistic tool (Fagan's two-step nomogram). METHODS: We prospectivelly collected data of all 1048 consecutive patients undergoing saturation 24-core transrectal prostate biopsy. Then, in eligible 94 patients, we compared the prediction of presence/absence of extracapsular extension of neoplasm (EPE+/-), with pathological assessment of invasion through (pseudo)capsule in the prostatectomy specimens. Starting from the probability of EPE- (pre-test probability, calculated with formula "100%-risk of EPE+"), we used Fagan's nomogram to examine the diagnostic sensitivity (DSe) and specificity (DSp) of negative "lateral" bioptic cores. RESULTS: We specifically analyzed the status of "lateral" cores in each side (94 patients × 2 sides = 188 sides). "Lateral" cores were negative in 42.5% of sides (80/188) with a DSe and DSp of 91.7 and 45.4%, respectively. In these sides, the mean probability of EPE+ according to Partin's tables was 21.6%. With Fagan's nomogram, the post-test probability of EPE+ when all "lateral" cores were negative was 14.1%, with a substantial gain of 7.5%. DISCUSSION: The spatial distribution of bioptic positive cores allowed us to demonstrate the role Fagan's nomogram in increasing the accuracy of already existing, predictive tools for PC. CONCLUSIONS: This pioneering study may justify the use of the above nomogram in testing "local" predictive parameters in combination with pre-existing nomograms.
Subject(s)
Neoplasm Staging/methods , Nomograms , Prostatic Neoplasms/pathology , Aged , Biopsy , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , ProstatectomyABSTRACT
INTRODUCTION: Spermatic cord tumors represent 4% of scrotal tumors. The most common neoplasms are lipomas. Spermatic cord sarcomas (SCS) of the genitourinary tract account for 2% of all urological tumors. Herein we presented our experience in the treatment of these tumors and a review of the literature. PATIENTS AND METHODS: A review of the literature was performed using the Medline database with no restriction on language and date of published papers. The literature search used the following terms: epidemiology, surgery, chemotherapy, radiotherapy and spermatic cord sarcomas. Four cases treated from December 2009 to May 2010 are described. RESULTS: All patients were treated with radical orchiectomy. The final pathological report showed different types of sarcomas. Two of the patients were treated with adjuvant chemotherapy. 12 months after surgery, 2/4 patients were alive without signs of relapse. CONCLUSION: SCS are very rare tumors with a poor prognosis. SCS's prognostic factors have been identified in grading, size, depth of invasion and surgical margin status. Age and performance status of the patient are however very important. Lymphatic and hematogenous dissemination is uncommon. Surgery is the most important treatment both in the first approach and in local relapse. The role of adjuvant chemotherapy and radiation therapy is still debated.
Subject(s)
Genital Neoplasms, Male/therapy , Orchiectomy , Sarcoma/therapy , Spermatic Cord/surgery , Adolescent , Aged, 80 and over , Biomarkers, Tumor/analysis , Biopsy , Chemotherapy, Adjuvant , Fatal Outcome , Genital Neoplasms, Male/chemistry , Genital Neoplasms, Male/pathology , Humans , Immunohistochemistry , Lung Neoplasms/secondary , Male , Middle Aged , Neoplasm Recurrence, Local , Radiotherapy, Adjuvant , Sarcoma/chemistry , Sarcoma/secondary , Spermatic Cord/chemistry , Spermatic Cord/pathology , Time Factors , Treatment OutcomeABSTRACT
PURPOSE: Of serum prostate specific antigen variability 40% depends on inherited factors. We ascertained whether the knowledge of KLK3 genetics would enhance prostate specific antigen diagnostic performance in patients with clinical suspicion of prostate cancer. MATERIALS AND METHODS: We studied 1,058 men who consecutively underwent prostate biopsy for clinical suspicion of prostate cancer. At histology prostate cancer was present in 401 cases and absent in 657. Serum total prostate specific antigen and the free-to-total prostate specific antigen ratio were determined. Four polymorphisms of the KLK3 gene (rs2569733, rs2739448, rs925013 and rs2735839) and 1 polymorphism of the SRD5A2 gene (rs523349) were studied. The influence of genetics on prostate specific antigen variability was evaluated by multivariate linear regression analysis. The performance of total prostate specific antigen and the free-to-total prostate specific antigen ratio alone or combined with a genetically based patient classification were defined by ROC curve analyses. RESULTS: For prostate cancer diagnosis the free-to-total prostate specific antigen ratio index alone (cutoff 11%) was superior to total prostate specific antigen (cutoff 4 ng/ml) and to free-to-total prostate specific antigen ratio reflex testing (positive predictive value 61%, 43% and 54%, respectively). Prostate specific antigen correlated with KLK3 genetics (rs2735839 polymorphism p = 0.001, and rs2569733, rs2739448 and rs925013 haplotype combination p = 0.003). In patients with different KLK3 genetics 2 optimal free-to-total prostate specific antigen ratio cutoffs (11% and 14.5%) were found. For free-to-total prostate specific antigen ratio values between 11% and 14.5% the prostate cancer probability ranged from 30.0% to 47.4% according to patient genetics. CONCLUSIONS: The free-to-total prostate specific antigen ratio is superior to total prostate specific antigen for prostate cancer diagnosis, independent of total prostate specific antigen results. Free-to-total prostate specific antigen ratio findings below 11% are positively associated with prostate cancer and those above 14.5% are negatively associated with prostate cancer, while the interpretation of those between 11% and 14.5% is improved by patient KLK3 genetic analysis.
Subject(s)
Kallikreins/genetics , Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnosis , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics , Aged , Aged, 80 and over , Cross-Sectional Studies , Humans , Male , Membrane Proteins/genetics , Middle Aged , Prostatic Neoplasms/blood , Prostatic Neoplasms/geneticsABSTRACT
INTRODUCTION: The gold standard treatment for high-risk NMIBC is BCG immunotherapy. Some studies suggested an immomodulatory effects for commonly used drugs (ie, ACE-I and ARBs). We aimed to determine whether these drugs impact the prognosis of patients with high-risk NMIBC treated with BCG. MATERIALS AND METHODS: Retrospective analysis on 208 patients from a single academic center with primary high-risk NMIBC treated with transurethral resection followed by 6 weekly instillations of BCG and up to 12 monthly maintenance instillations. ARBs or ACE-I use at the time of treatment initiation was recorded. Inverse probability of treatment weighting (IPTW) was used to adjust for clinical and pathological covariates. IPTW-adjusted Kaplan-Meier curves and weighted Cox proportional hazards regression were used to compare 2-yr failure-free (2-yr FFS), failure-free (FFS), overall recurrence-free (RFS) and progression-free survival (PFS). RESULTS: A total of 68 patients were on ACE-I, and 38 on ARBs and treatment respectively. At a median follow-up of 26 months, ACE-I treatment had no significant impact on cancer-related outcomes. Conversely, patients treated with ARBs experienced significant improvements in 2-yr FFS (HR 0.3; 0.1-0.9, P = .004), FFS (HR 0.4, 0.1-0.9, P = .005), and PFS (HR 0.001; < 0.001-0.001, P < .001). No significant impact was found for ARB use in RFS (HR 0.6; P = .09). Sensitivity analyses confirmed these results. CONCLUSIONS: our findings support a potential role of the angiotensin-renin system in bladder cancer development. We identified ARBs as potential beneficial drugs that seems to act in synergy with BCG-immunotherapy.
Subject(s)
Urinary Bladder Neoplasms , Administration, Intravesical , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , BCG Vaccine/therapeutic use , Disease-Free Survival , Humans , Neoplasm Invasiveness , Neoplasm Recurrence, Local/pathology , Renin-Angiotensin System , Retrospective Studies , Urinary Bladder Neoplasms/pathologyABSTRACT
Immunotherapy may provide valid alternative therapy for patients with hormone-refractory metastatic prostate cancer. However, if the tumor environment exerts a suppressive action on antigen-specific tumor-infiltrating lymphocytes (TIL), immunotherapy will achieve little, if any, success. In this study, we analyzed the modulation of TIL responses by the tumor environment using collagen gel matrix-supported organ cultures of human prostate carcinomas. Our results indicate that human prostatic adenocarcinomas are infiltrated by terminally differentiated cytotoxic T lymphocytes that are, however, in an unresponsive status. We demonstrate the presence of high levels of nitrotyrosines in prostatic TIL, suggesting a local production of peroxynitrites. By inhibiting the activity of arginase and nitric oxide synthase, key enzymes of L-arginine metabolism that are highly expressed in malignant but not in normal prostates, reduced tyrosine nitration and restoration of TIL responsiveness to tumor were achieved. The metabolic control exerted by the tumor on TIL function was confirmed in a transgenic mouse prostate model, which exhibits similarities with human prostate cancer. These results identify a novel and dominant mechanism by which cancers induce immunosuppression in situ and suggest novel strategies for tumor immunotherapy.
Subject(s)
Adenocarcinoma/immunology , Arginase/antagonists & inhibitors , CD8-Positive T-Lymphocytes/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Nitric Oxide Synthase/antagonists & inhibitors , Prostatic Neoplasms/immunology , T-Lymphocyte Subsets/immunology , Tyrosine/analogs & derivatives , Adenocarcinoma/blood , Adenocarcinoma/enzymology , Animals , Arginine/antagonists & inhibitors , Arginine/metabolism , Cell Line, Tumor , Humans , Interferon-gamma/biosynthesis , Lymphocyte Count , Lymphocytes, Tumor-Infiltrating/chemistry , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Organ Culture Techniques , Prostatic Neoplasms/blood , Prostatic Neoplasms/enzymology , T-Lymphocyte Subsets/chemistry , Tyrosine/biosynthesisABSTRACT
The AngioVac system (AngioDynamics, Latham, NY) has already been described for treatment of thrombotic formations concerning the venous district and the tricuspid valve. We describe an innovative application of the AngioVac system to treat the inferior vena cava thrombosis associated with renal cell carcinoma. In a high surgical risk patient, we utilized a microinvasive and a modified venoarterial AngioVac circuit to remove the atrial thrombus, ensure temporary circulatory support during abdominal surgery, and prevent pulmonary embolism.
Subject(s)
Carcinoma, Renal Cell/secondary , Heart Diseases/etiology , Heart Diseases/surgery , Kidney Neoplasms/pathology , Neoplastic Cells, Circulating , Thrombosis/etiology , Thrombosis/surgery , Vena Cava, Inferior , Aged , Carcinoma, Renal Cell/surgery , Humans , Kidney Neoplasms/surgery , Male , Nephrectomy , Proof of Concept Study , SuctionABSTRACT
Cholesterol is a ubiquitous sterol with many biological functions, which are crucial for proper cellular signaling and physiology. Indeed, cholesterol is essential in maintaining membrane physical properties, while its metabolism is involved in bile acid production and steroid hormone biosynthesis. Additionally, isoprenoids metabolites of the mevalonate pathway support protein-prenylation and dolichol, ubiquinone and the heme a biosynthesis. Cancer cells rely on cholesterol to satisfy their increased nutrient demands and to support their uncontrolled growth, thus promoting tumor development and progression. Indeed, transformed cells reprogram cholesterol metabolism either by increasing its uptake and de novo biosynthesis, or deregulating the efflux. Alternatively, tumor can efficiently accumulate cholesterol into lipid droplets and deeply modify the activity of key cholesterol homeostasis regulators. In light of these considerations, altered pathways of cholesterol metabolism might represent intriguing pharmacological targets for the development of exploitable strategies in the context of cancer therapy. Thus, this work aims to discuss the emerging evidence of in vitro and in vivo studies, as well as clinical trials, on the role of cholesterol pathways in the treatment of cancer, starting from already available cholesterol-lowering drugs (statins or fibrates), and moving towards novel potential pharmacological inhibitors or selective target modulators.
ABSTRACT
Resistance of cancer cells to chemotherapy is the first cause of cancer-associated death. Thus, new strategies to deal with the evasion of drug response and to improve clinical outcomes are needed. Genetic and epigenetic mechanisms associated with uncontrolled cell growth result in metabolism reprogramming. Cancer cells enhance anabolic pathways and acquire the ability to use different carbon sources besides glucose. An oxygen and nutrient-poor tumor microenvironment determines metabolic interactions among normal cells, cancer cells and the immune system giving rise to metabolically heterogeneous tumors which will partially respond to metabolic therapy. Here we go into the best-known cancer metabolic profiles and discuss several studies that reported tumors sensitization to chemotherapy by modulating metabolic pathways. Uncovering metabolic dependencies across different chemotherapy treatments could help to rationalize the use of metabolic modulators to overcome therapy resistance.
ABSTRACT
The recent COVID-19 pandemic represents a worldwide emergency and it is affecting healthcare at every level, including also urological care and especially oncologic patients. Recent epidemiological models show that, without effective treatment or vaccine, there will be a long-lasting phase of cohabitation with the virus. Current experts' opinions recommend performing only non-deferrable uro-oncological surgery and postponing other activities until the end of the emergency, with particular concerns regarding the safety laparoscopy. Veneto Region and Padua Province represent one of the first site of the pandemic spread of the virus outside China, thus we present our experience as a Urological Referral Center in applying a segregated-team work model of organization during the month of March 2020, with a stratified organization of activities, adequate screening and protection for patients and staff were adopted. Compared to the same period of last year even if a 19.5% reduction was experienced in overall surgical activity while maintaining a comparable proportion of oncologic robotic and laparoscopic surgery and guaranteeing care also for high priority non-oncological patients. No cases of COVID-19 infection were reported in staff members nor in patients and the number of surgical complications was comparable to that of last year. Therefore, in our opinion the recommended significant reduction in urological care, including surgical activities, is likely unrealistic in the long period with unknown effects affecting mostly oncological patients. Our experience introducing a segregated-team work model might represent a model for future planning.
ABSTRACT
Introduction: Spermatic cord sarcomas represent a rare genitourinary malignancy with a challenging diagnostic and therapeutic pathway. Different histotypes have been described and prognostic factors remain poorly defined due to the paucity of data presented in literature. Methods: Retrospective chart review of 22 adult patients treated for spermatic cord sarcoma in a single institution in the last 20 years was performed. Clinicopathological characteristics of the tumors were collected with primary and subsequent treatment. Survival analysis was performed in order to identify prognostic factors of disease-specific survival. Results: The median age at diagnosis was 68 years (58-78), the most common histotype was liposarcoma (14/22), and most patients (63.6%) were found to have positive surgical margins after surgery. The 5-year cancer specific survival was 91.3%. Grading (p = 0.480), histotype (p = 0.327), and type of intervention (p = 0.732) were not associated with survival. All patients dead of disease had positive surgical margins (p = 0.172). Conclusion: We report a good prognosis at 5 years. Wide radical resection remains the first and probably the most important step; thus, according also to literature, negative surgical margins should be aimed.
ABSTRACT
OBJECTIVE: The aim of the study was to assess results and quality of life after kidney transplant in adult patients with previously bladder augmentation or urinary diversion due to significant lower urinary tract dysfunction. MATERIALS AND METHODS: This cross-sectional study examines the outcome of 19 renal allografts transplanted in patients with augmented bladder or urinary diversion over a ten years period; moreover we submitted SF36 questionnaire to evaluate quality of life of these patients and compared the results with the general population. RESULT: Between January 1, 2005 and 31 December 2015 we performed 19/1093 renal transplantations in patients with abnormal lower urinary tract previously treated with bladder augmentation or bladder recycling. Current post-transplant follow-up was 47 months (range 18-188). No patient developed any episode of acute or chronic rejection. Mean serum creatinine after one year from transplant was 102 umol/L. Overall survival is 94.8% at the end of follow-up and graft survival is 89.6%. No significant differences emerged between patients undergoing transplant with lower urinary tract dysfunction and patients without, regarding to recurrent urinary tract infection. There was not statistically significant difference for vitality (p = 0.8088) and mental health (p = 0.8668). CONCLUSIONS: Presence of a previously augmented bladder or other lower urinary tract dysfunction treated in kidney transplant patients doesn't worsen the final outcome. Mental health and the vitality of these patients are similar to the general population.
Subject(s)
Kidney Transplantation , Quality of Life , Treatment Outcome , Urinary Bladder/surgery , Urinary Diversion , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies , Young AdultABSTRACT
Erythroplasia of Queyrat (EQ) is an intraepidermal carcinoma in situ presenting clinically as a sharply demarcated, slightly raised erythematosus plaque on the glans penis or the inner side of the foreskin. Various treatment modalities for EQ have been proposed, including electrocautery and curettage, topical 5-floururacil cream, imiquimod cream, isotretinoin, cryotherapy, laser therapy, radiotherapy, ingenol mebutate gel and Photodynamic Therapy (PDT). Most of these treatments are limited by low clearance rates and frequent relapses. Surgical treatment including local excision, Mohs micrographic surgery and partial or total penectomy, ensures adequate healing rates. However, discomfort consequent to surgical treatment might be unacceptable. Topical PDT using the methyl ester of 5- aminolaevulinic acid (MAL) is an established non-surgical treatment of cutaneous precancerous lesions and skin cancers. We present the case of a 60-year-old uncircumcised man affected by EQ of the penis successfully treated with MAL-PDT, performed five times, two weeks apart, with no recurrences after 6 years.
ABSTRACT
BACKGROUND: No compelling evidence is available about surveillance and follow-up of patients with testicular germ cell tumour (TGCT). METHODS: In the light of the best clinical evidence, the Italian Germ cell cancer Group (IGG) and the Associazione Italiana di Oncologia Medica (AIOM) set up a multidisciplinary national consensus conference, involving 42 leading experts and 3 TGCT survivors. A minimum of 50% of votes was required in order to achieve a consensus recommendation on 29 questions. RESULTS: Recommendations have been summarized in three tables, divided by stage I seminoma, stage I nonseminoma and the advanced disease, which may be useful for clinicians to appropriately choose the clinical investigation and its timing during the surveillance and follow-up of TGCT patients based on an accurate estimation of their risk of disease relapse. CONCLUSIONS: The IGG-AIOM consensus recommendations may help clinicians to choose appropriate clinical investigations for the surveillance and follow-up of TGCT patients.
Subject(s)
Neoplasms, Germ Cell and Embryonal/diagnosis , Testicular Neoplasms/diagnosis , Consensus , Follow-Up Studies , Humans , Male , Practice Guidelines as Topic , Seminoma/diagnosisABSTRACT
BACKGROUND: The only available method to detect prostate cancer is prostate biopsy; however, to our knowledge, no evidence-based clinical practice guidelines have been established on this topic. MATERIALS AND METHODS: A three-year project was elaborated in which experts in the field worked to define the controversies existing in clinical practice regarding prostatic biopsies and then to develop guidelines by means of a systematic search of all the English-language literature using online databases and a consensus conference. RESULTS AND CONCLUSION: The guidelines were formulated to help practitioners in making clinical decisions regarding the appropriate time the patient should undergo prostate biopsy, the type of antibiotic prophylaxis and anaesthesia, the biopsy approach, the method for processing and reporting prostatic needle cores, the biopsy technique, when to repeat a biopsy after a prior negative biopsy, radiotherapy or radical prostatectomy and the accuracy of biopsies in staging prostate cancer.