The role of planetary health in urologic oncology.

INTRODUCTION: Climate change and global warming are an omnipresent topic in our daily lives. Planetary health and oncology represent two critical domains within the broader spectrum of healthcare, each addressing distinct yet interconnected aspects of human well-being. We are encouraged to do our part in saving our planet. This should include the decisions we make in our professional life, especially in uro-oncology, as the healthcare sector significantly contributes to environmental pollution. AREAS COVERED: There are many aspects that can be addressed in the healthcare sector in general, as there are structural problems in terms of energy consumption, water waste, therapeutic techniques, transportation and drug manufacturing, as well as in uro-oncology specific areas. For example, the use of different surgical techniques, forms of anesthesia and the use of disposable or reusable instruments, each has a different impact on our environment. The literature search was carried out using PubMed, a medical database. EXPERT OPINION: We are used to making decisions based on the best outcome for patients without considering the impact that each decision can have on the environment. In the present article, we outline options and choices for a more climate-friendly approach in urologic oncology.

Gross Hematuria Associated with Anticoagulants and Antiplatelet Drugs: Analysis of Current Treatment Standards and Relevance of Co-medication and Pharmacological Interactions.

BACKGROUND: Anticoagulants and antiplatelet drugs are risk factors for gross hematuria (GH). Moreover, co-medication and drug-drug interactions (DDIs) may influence GH and its clinical course. OBJECTIVE: To investigate the relationship between GH and administration of oral anticoagulants and antiplatelet drugs. DESIGN, SETTING, AND PARTICIPANTS: Hospitalized patients with GH in an academic tertiary reference center were included. The use of individual compounds and DDIs were recorded and correlated to relevant clinical outcome factors. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The association between GH, DDIs, and clinical outcome parameters was analyzed using χ2 and Kruskal-Wallis tests. DDIs were systematically evaluated using a previously published calculator. RESULTS AND LIMITATIONS: A total of 189 patients with GH were eligible for the study. Of these, 76.2% took anticoagulants or antiplatelet drugs. The mean hospitalization duration was 4.7 d. The mean bladder irrigation duration was 3.1 d and the mean volume of irrigation fluid used was 22.8 l. Overall, 30.7% of patients had a pre-existing genitourinary malignancy. DDIs were observed in 31.9% of cases. The irrigation duration (p = 0.01) and volume of irrigation fluid (p = 0.05) were significantly associated with the use of anticoagulants or antiplatelet drugs. Specific DDI patterns were not predictive of clinical outcome. CONCLUSIONS: Medication with anticoagulants or antiplatelet drugs has a significant impact on GH and its clinical course. DDIs are a relevant issue and may lead to adverse clinical events or greater drug toxicity. Critical evaluation of medication and interdisciplinary counseling for patients with GH and urinary tract disease are recommended. PATIENT SUMMARY: Drugs taken to reduce the risk of blood clotting can increase the risk of blood in the urine (called hematuria) and medical expenses for treatment. Drug-drug interactions are a relevant issue, especially in elderly patients and those with other medical conditions who are taking several drugs. Thoughtful discussion of individual risk profiles for hematuria and medication is therefore recommended.

Diagnostic benefit of multiparametric MRI over contrast-enhanced CT in patients with bladder cancer: A single-center 1-year experience.

PURPOSE: To assess the clinical applicability of local tumor staging in urinary bladder cancer (BC) with preoperative multiparametric MRI (mpMRI) using the five-point Vesical Imaging-Reporting and Data System (VI-RADS) scoring system and to compare it to dual-phase contrast-enhanced computed tomography (CECT). METHODS: 33 patients with primary untreated bladder cancer underwent CECT followed by preoperative multiparametric 3.0 T MRI between July 2019 and August 2020 and were enrolled in this retrospective study. Two radiologists initially performed staging on the CECT image data sets and - blinded to CT results - on subsequent mpMRI. BCs were staged according to the VI-RADS scoring system. Postoperative pathology was correlated to the VI-RADS score and the CECT results. The performance of VI-RADS in determining detrusor muscle invasion was analyzed using a receiver operating characteristic curve. Based on the histopathology, sensitivity, specificity and accuracy for muscle invasiveness between both image modalities were compared using the Chi square test. RESULTS: A total of 33 patients (29 male, median age 70 years, IQR: 59-81 years) were included. 10 tumors were categorized as non-muscle invasive (30%) and 23 as muscle invasive BC (70%) in final histology. Tumor stages were correctly assigned as being either muscle invasive or non-muscle invasive on both CECT and mpMRI with regard to both early and late stages of BC (Ta-Tis and T3a-T4b). T-stages bordering the histopathologic limits of muscle invasiveness (T1-T2a-b) resulted in overestimation of muscle invasion in 43% of cases (VI-RADS 3-4) for the mpMRI image data sets and in an underestimation of muscle invasion in up to 55.5% of cases analysing the CECT data. Sensitivity and specificity for the determination of muscle invasion in CECT and mpMRI were 80%/80% and 74%/61% for Radiologist#1 and 70%/90% and 83%/70% for Radiologist#2, respectively. CONCLUSIONS: There are advantages and disadvantages of both CECT and mpMRI when used in the clinical assessment of BC muscular tumor invasion. In borderline cases, only the combination of cross-sectional imaging and histopathological staging may help in making the optimal treatment decisions.

A Modified Neobladder Technique: The "I-Pouch" - Illustration of Surgical Approach and Tricks.

OBJECTIVE: Various techniques for orthotopic neobladder (ONB) are currently used and have shown satisfactory oncological and functional outcomes.3 Among the relevant oncological and functional aspects for long-term follow up is the easy accessibility of the upper urinary tract in urinary diversion for endoscopic monitoring. In addition, variety exists in the amount of ileum needed to create a urinary reservoir. Depending on the ONB technique, up to 60 cm of ileum are required, and bowel dysfunction may be a consequence especially when the ileocecal valve is used for the urinary diversion. We previously reported the technique, functional and oncologic results of the I-pouch, a modified ONB made of 40 cm of ileum, combining an antirefluxive ureter implantation technique with easy access to the uretero-intestinal anastomosis.1,2 The present video is intended to illustrate key surgical steps and pitfalls during the procedure. METHODS: The technique, surgical tips, and functional results in a as compared to a institutional control group receiving conventional Studer -Pouch-procedure are outlined. RESULTS: In a follow up series of 33 I-pouch and 23 S-pouch patients, there were no differences according to ONB type for 30-day major- (P = .33) and minor (P = 0.96) complication rates although 90-day major (P = 0.08) and minor (P = 0.08) complication rates tended to be associated with less complications in I-pouch patients. CONCLUSION: The I-pouch can be used for neobladder substitution providing easy access to the upper urinary tract, reduced demand of ileum length along with a complication profile not distinct from Studer neobladder formation.

Treatment and resistance mechanisms in castration-resistant prostate cancer: new implications for clinical decision making?

Introduction: The armamentarium of treatment options in metastatic and non-metastatic CRPC is rapidly evolving. However, the question of how individual treatment decisions should be balanced by available predictive clinical parameters, pharmacogenetic and drug interaction profiles, or compound-associated molecular biomarkers is a major challenge for clinical practice.Areas covered: We discuss treatment and resistance mechanisms in PC with regard to their association to drug efficacy and tolerability. Current efforts of combination treatment and putative predictive biomarkers of available and upcoming compounds are highlighted with regard to their implication on clinical decision-making.Expert opinion: Several treatment approaches are delineated, where identification of resistance mechanisms in CRPC may guide treatment selection. To date, most of these candidate biomarkers will however be found only in a small subset of patients. While current approaches of combination treatment in CRPC are proving synergistic effects on cancer biology, higher complexity with regard to biomarker analysis and interaction profiles of the respective compounds may be expected. Among other aspects of personalized treatment, consideration of drug-drug interaction and pharmacogenetics is an underrepresented issue. However, the non-metastatic castration resistant prostate cancer situation may be an example for treatment selection based on drug interaction profiles in the future.

Penicillin G Induces H+, K+-ATPase via a Nitric Oxide-Dependent Mechanism in the Rat Colonic Crypt.

BACKGROUND/AIMS: The colonic H+, K+ ATPase (HKA2) is a heterodimeric membrane protein that exchanges luminal K+ for intracellular H+ and is involved in maintaining potassium homeostasis. Under homeostatic conditions, the colonic HKA2 remains inactive, since most of the potassium is absorbed by the small intestine. In diarrheal states, potassium is secreted and compensatory potassium absorption becomes necessary. This study proposes a novel mechanism whereby the addition of penicillin G sodium salt (penG) to colonic crypts stimulates potassium uptake in the presence of intracellular nitric oxide (NO), under sodium-free (0-Na+) conditions. METHODS: Sprague Dawley rat colonic crypts were isolated and pHi changes were monitored through the ammonium prepulse technique. Increased proton extrusion in 0-Na+ conditions reflected heightened H+, K+ ATPase activity. Colonic crypts were exposed to penG, L-arginine (a NO precursor), and N-nitro l-arginine methyl ester (L-NAME, a NO synthase inhibitor). RESULTS: Isolated administration of penG significantly increased H+, K+ ATPase activity from baseline, p 0.0067. Co-administration of arginine and penG in 0-Na+ conditions further upregulated H+, K+ ATPase activity, p <0.0001. Crypt perfusion with L-NAME and penG demonstrated a significant reduction in H+, K+ ATPase activity, p 0.0058. CONCLUSION: Overall, acute exposure of colonic crypts to penG activates the H+, K+ ATPase in the presence of NO. This study provides new insights into colonic potassium homeostasis.

Enzalutamide plus androgen-deprivation therapy in hormone-sensitive prostate cancer: new perspectives from a current Phase III clinical trial.

Prostate cancer is a major health issue with an incidence of 1,100,000 worldwide. Eventually, 20-40% of curatively treated patients will face a biochemical recurrence. Lately, the treatment options in metastasized hormone sensitive prostate cancer (mHSPC) were rapidly evolving after years of stagnation. Encouraging results in clinical trials of combination treatment of androgen deprivation therapy with either chemotherapy or second-generation hormonal treatment indicate a paradigm shift in this clinical scenario. In the light of this, the current review is focusing on the concept and initial results of the Phase III (ARCHES) trial investigating enzalutamide plus androgen deprivation therapy in mHSPC. Moreover, a comprehensive appraisal of the expanding landscape of systemic therapies for mHSPC is provided.