IL-6 Signaling Link between Inflammatory Tumor Microenvironment and Prostatic Tumorigenesis

Benign prostatic hyperplasia and prostate cancer are tumoral pathologies characterized by the overexpression of inflammatory processes. The exploration of tumor microenvironment and understanding the sequential events that take place in the stromal area of the prostate could help for an early management of these pathologies. This way, it is feasible the hypothesis that normalizing the stromal environment would help to suppress or even to reverse tumor fenotype. A number of immunological and genetic factors, endocrine dysfunctions, metabolic disorders, infectious foci, nutritional deficiencies, and chemical irritants could be involved in prostate tumor development by maintaining inflammation, affecting local microcirculation, and promoting oxidative stress. Inflammatory processes activate hyperproliferative programs that ensure fibromuscular growth of the prostate and a number of extracellular changes. Acute and chronic inflammations cause accumulation of immunocompetent cells in affected prostate tissue (T cells, macrophages, mastocytes, dendritic cells, neutrophils, eosinophils, monocytes). Prostate epithelial and stromal cells, peri-prostatic fat cells, prostatic microvascular endothelial cells, and inflammatory cells produce cytokines, generating a local inflammatory environment. Interleukin-6 (IL-6) proved to be involved in the prostate tumor pathogenesis. IL-6 ability to induce pro- and anti-inflammatory responses by three mechanisms of signal transduction (classical signaling, transsignaling, cluster signaling), to interact with a diversity of target cells, to induce endocrine effects in an autocrine/paracrine manner, and the identification of an IL-6 endogenous antagonist that blocks the transmission of IL-6 mediated intracellular signals could justify current theories on the protective effects of this cytokine or by alleviating inflammatory reactions or by exacerbating tissue damage. This analysis presents recent data about the role of the inflammatory process as a determining factor in the development of benign and malign prostate tumors. The presented findings could bring improvements in the field of physiopathology, diagnosis, and treatment in patients with prostate tumors. Modulation of the expression and activity of interleukin-6 could be a mean of preventing or improving these pathologies

Dynamic Soluble IL-6R/Soluble gp130 Ratio as a Potential Indicator for the Prostate Malignancy Phenotype—A Multicenter Case–Control Study

Objective: Prostate tumors, if prostate cancer or adenoma, represent a major public health challenge. Progress in research on inflammation has revealed a connection between inflammation, immunity, and cancer. In this context, this study aimed to find IL-6 signaling systemic abnormalities in the inflammatory tumor microenvironment. Material and methods: This study was case–controlled, multicentered, and included 86 patients, 43 diagnosed with BPH and 43 diagnosed with PCa, between January 2019 and January 2020. The study group was homogenous and the studied parameters were IL-6 complex (IL-6, soluble receptor IL-6R, soluble glycoprotein gp130), acute phase proteins (C reactive protein—CRP, acid alpha1 glycoprotein—AGPA, ferritin, albumin, transferrin), and oxidative stress-associated variables (malondialdehyde—MDA, carbonylated protein—PCO, 8-hydroxy-deoxy guanosine-8-OHdG, total antioxidant status—bTAS). Results: The inflammatory microenvironment determined IL-6 signaling alterations (over-regulation of sIL-6R and suppression of sgp130 in PCa versus BPH), changes in acute phase reaction markers (increased serum levels of CRP, AGPA, ferritin, and decreased serum levels of albumin, transferrin) that were much more evident in PCa compared to BPH, an imbalance between macromolecular oxidative damage (MDA, PCO, 8-OHdG) and endogenous antioxidants (TAS) that was more accentuated in PCa compared with BPH, and a representative association between the sIL-6R/sgp130 ratio and inflammatory/oxidative stress-related factors only in PCa patients. Conclusions: Our study reconfirms the anterior concept that IL-6 promotes prostatic tumorigenesis. In this study, we first demonstrated that a high sIL-6R/sgp130 ratio facilitates prostate malignancy

IL-6 Signaling Link between Inflammatory Tumor Microenvironment and Prostatic Tumorigenesis

Benign prostatic hyperplasia and prostate cancer are tumoral pathologies characterized by the overexpression of inflammatory processes. The exploration of tumor microenvironment and understanding the sequential events that take place in the stromal area of the prostate could help for an early management of these pathologies. This way, it is feasible the hypothesis that normalizing the stromal environment would help to suppress or even to reverse tumor fenotype. A number of immunological and genetic factors, endocrine dysfunctions, metabolic disorders, infectious foci, nutritional deficiencies, and chemical irritants could be involved in prostate tumor development by maintaining inflammation, affecting local microcirculation, and promoting oxidative stress. Inflammatory processes activate hyperproliferative programs that ensure fibromuscular growth of the prostate and a number of extracellular changes. Acute and chronic inflammations cause accumulation of immunocompetent cells in affected prostate tissue (T cells, macrophages, mastocytes, dendritic cells, neutrophils, eosinophils, monocytes). Prostate epithelial and stromal cells, peri-prostatic fat cells, prostatic microvascular endothelial cells, and inflammatory cells produce cytokines, generating a local inflammatory environment. Interleukin-6 (IL-6) proved to be involved in the prostate tumor pathogenesis. IL-6 ability to induce pro- and anti-inflammatory responses by three mechanisms of signal transduction (classical signaling, transsignaling, cluster signaling), to interact with a diversity of target cells, to induce endocrine effects in an autocrine/paracrine manner, and the identification of an IL-6 endogenous antagonist that blocks the transmission of IL-6 mediated intracellular signals could justify current theories on the protective effects of this cytokine or by alleviating inflammatory reactions or by exacerbating tissue damage. This analysis presents recent data about the role of the inflammatory process as a determining factor in the development of benign and malign prostate tumors. The presented findings could bring improvements in the field of physiopathology, diagnosis, and treatment in patients with prostate tumors. Modulation of the expression and activity of interleukin-6 could be a mean of preventing or improving these pathologies.</jats:p

Small Diameter (7.5 Fr) Single-Use Flexible Ureteroscopy with Direct In-Scope Suction (DISSTM) in Conjunction with Aspiration-Assisted Flexible Access Sheath: A New Hype for Real Stone-Free?

Background: Renal lithiasis continues to represent a great challenge for modern urology in terms of minimally invasive management of lithotripsy procedures. The recent revolution of endoscopes with the miniaturization of instruments and the development of improved disposable ureteroscopes combined with recent suction methods such as suction access sheaths or direct in-scope suction (DISSTM) systems promise to further improve the outcome of renal stone treatment. Methods: Considering this technological advance, this study aims to evaluate the results obtained by combining these methods in three groups: Group 1&mdash;Single-use 7.5 Fr flexible ureteroscope with standard access sheath, Group 2&mdash;Single-use 7.5 Fr flexible ureteroscope with direct in-scope suction (DISSTM) with standard access sheath, Group 3&mdash;Single-use 7.5 Fr flexible ureteroscope with DISSTM with suction access sheath. A total number of 105 consecutive patients were enrolled in the study, divided equally in each group. Several parameters were followed, such as size and location of the stones, operative time, duration of hospitalization, the need for ureteral stent insertion, residual fragments, and subjective evaluation of the lithotripsy environment visualization. Results: The best results were highlighted in Group 3 for almost all evaluated parameters. Significant improvements were indicated in terms of stone-free rates. Conclusions: Additional large studies are needed to support these initial results, but preliminary data indicate a valuable advantage for every urologist who treats urolithiasis

Detection of Urinary Molecular Marker Test in Urothelial Cell Carcinoma: A Review of Methods and Accuracy

Early detection of bladder cancer has a positive impact on prognosis. A variety of biomarkers have been developed to detect bladder tumors in urine early and reduce the need for cystoscopy. To detect bladder cancer, several methods are available, but their accuracy varies according to the sensitivity and specificity of each method. This review aims to highlight the established detection methods for bladder cancer based on the available literature. In addition, we aim to identify the combination of different effective detection methods that provides the highest degree of accuracy. In our study, a keyword retrieval method was used to search for appropriate English-language references. This bibliography has been indexed in PubMed and Scopus or has been found through systematic searches from 2015 to 2022. Based on an analysis of international guidelines, it has been revealed that there are numerous discrepancies and unresolved issues. The discovery of an ideal detection method for urothelial cell carcinoma biomarkers has been the subject of numerous efforts. In recent years, a wide range of off-label, experimental, novel, and combined approaches have been published on this topic. This review can contribute to the identification of accurate methods of detecting bladder cancer and highlight areas for future research that can be improved

Update on Urinary Tract Infection Antibiotic Resistance&mdash;A Retrospective Study in Females in Conjunction with Clinical Data

Urinary tract infections (UTIs) represent a frequent pathology among the female population that has become more and more difficult to treat in the past decade, considering the increase in antibiotic resistance&mdash;a serious global public health problem. A cross-sectional retrospective study was conducted for six months to report an update regarding the rates of resistance and susceptibility of uropathogens necessary for optimal treatment. A total of 5487 patients were screened, of which 524 (9.54%) were female patients who met the criteria for inclusion in the study. Escherichia coli was the most common pathogen, representing 290 cases (55.34%), followed by Enterococcus spp. 82 (15.64%). Escherichia coli presented the highest resistance to amoxicillin-clavulanic acid (R = 33.1%), followed by trimethoprim-sulfamethoxazole (R = 32.41%) and levofloxacin (R = 32.06%). The highest sensitivity rates were observed for fosfomycin (S = 96.55%), followed by imipenem (S = 93.1%). Enterococcus spp. showed the highest resistance to levofloxacin (R = 50.0%), followed by penicillin (R = 39.02%). The highest sensitivity was observed for fosfomycin (S = 90.24%), linezolid (S = 89.02%), and nitrofurantoin (S = 86.58%). The second most frequent Gram-negative uropathogen was represented by Klebsiella spp., which had the highest resistance to amoxicillin-clavulanic acid (R = 35.89%), followed by levofloxacin (R = 25.64) and trimethoprim-suflamethoxazole (R = 24.35%). The most frequently associated pathology was an episode of UTI in the previous year, followed by diabetes and chronic kidney disease. Antibiotic resistance is a serious problem for all clinicians who treat UTIs. An up-to-date knowledge of antibiotic resistance rates is a major necessity to stop its evolution. Overall, the highest resistance rates were observed for aminopenicillins, fluoroquinolones, and trimethoprim-sulfamethoxazole. The best susceptibility rates were observed for fosfomycin, nitrofurantoin, and carbapenems. Our report aims to guide clinicians whenever they are forced to prescribe antibiotics empirically

The Impact of Transurethral Enucleation Therapeutic Approach in All-Size Benign Prostatic Obstruction Pathology: From Contemporary Technological Advances to Evidence-Based Clinical Progresses

Transurethral enucleation (TUE) has revolutionized the management of benign prostatic obstruction (BPO), offering a minimally invasive solution with superior efficacy across all prostate sizes. This review explores the advancements in TUE techniques, including Holmium Laser Enucleation of the Prostate (HoLEP), Thulium Laser Enucleation of the Prostate (ThuLEP), and bipolar enucleation, highlighting their clinical benefits, safety profiles, and long-term outcomes. Compared to traditional approaches such as transurethral resection of the prostate (TURP) and open prostatectomy, TUE has been associated with reduced complication rates, shorter recovery times, and durable symptom relief. The manuscript also examines patient-centered considerations, such as quality of life improvements and preservation of sexual function, which contribute to high patient satisfaction. Furthermore, the economic advantages of TUE, driven by reduced retreatment rates and healthcare costs, underscore its value for both patients and healthcare systems. Emerging innovations, including artificial intelligence (AI), promise to further enhance procedural planning, surgical precision, and training pathways. Efforts to expand global access through cost-effective adaptations like bipolar enucleation and targeted training initiatives are paving the way for wider adoption of TUE. With its adaptability, technological advancements, and focus on patient outcomes, TUE is poised to become the global standard of care in BPO management

Chronic Kidney Disease&mdash;An Underestimated Risk Factor for Antimicrobial Resistance in Patients with Urinary Tract Infections

(1) Background: Chronic kidney disease (CKD), as well as antimicrobial resistance (AMR) represent major global health problems, with important social and economic implications. It was reported that CKD is a risk factor for antimicrobial resistance, but evidence is scarce. In addition, CKD is recognized to be a risk factor for complicated urinary tract infections (UTIs). (2) Methods: We conducted an observational study on 564 adult in-hospital patients diagnosed with urinary tract infections. The aim of the study was to identify the risk factors for AMR, as well as multiple drug resistance (MDR) and the implicated resistance patterns. (3) Results: The mean age was 68.63 &plusmn; 17.2 years. The most frequently isolated uropathogens were Escherichia coli strains (68.3%) followed by Klebsiella species (spp. (11.2%). In 307 cases (54.4%)), the UTIs were determined by antibiotic-resistant bacteria (ARBs) and 169 cases (30%) were UTIs with MDR strains. Increased age (&ge;65) OR 2.156 (95% CI: 1.404&ndash;3.311), upper urinary tract obstruction OR 1.666 (1.083&ndash;2.564), indwelling urinary catheters OR 6.066 (3.919&ndash;9.390), chronic kidney disease OR 2.696 (1.832&ndash;3.969), chronic hemodialysis OR 4.955 (1.828&ndash;13.435) and active malignancies OR 1.962 (1.087&ndash;3.540) were independent risk factors for MDR UTIs. In a multivariate logistic regression model, only indwelling urinary catheters (OR 5.388, 95% CI: 3.294&ndash;8.814, p &lt; 0.001), CKD (OR 1.779, 95% CI: 1.153&ndash;2.745, p = 0.009) and chronic hemodialysis (OR 4.068, 95% 1.413&ndash;11.715, p = 0.009) were risk factors for UTIs caused by MDR uropathogens. (4) Conclusions: CKD is an important risk factor for overall antimicrobial resistance, but also for multiple-drug resistance

Rare Onset of Tubercular Peritonitis Amidst Chronic Renal Dysfunction

Tuberculosis Peritonitis is a serious condition, whose diagnosis is established late due to the nonspecific nature of the clinical features, which delays the performance of imaging investigations and, implicitly, the setting of the diagnosis through biopsy and histopathological examination. We report the case of a 49-year-old man who presented in our clinic with nonspecific symptoms and significant nitrogen retention, with ascites fluid detected during the clinical&ndash;paraclinical examination, ultimately confirming the diagnosis of bacillary peritonitis. Confirmation of tuberculous etiology through biopsy and/or bacteriological examination is sovereign for the diagnosis. The therapeutic protocol includes three anti-tuberculostatic drugs, for a period of at least 6 months, with or without the combination of corticosteroid therapy during the first months of treatment. The patient evolution under treatment was initially favorable, but due to peritoneal adhesions, it underwent complications later