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Clear cell renal cell carcinoma (ccRCC) is the most frequent histological kidney cancer subtype. Over the last decade, significant progress has been made in identifying the genetic and metabolic alterations driving ccRCC development. In particular, an integrated approach using transcriptomics, metabolomics, and lipidomics has led to a better understanding of ccRCC as a metabolic disease. The metabolic profiling of this cancer could help define and predict its behavior in terms of aggressiveness, prognosis, and therapeutic responsiveness, and would be an innovative strategy for choosing the optimal therapy for a specific patient. This review article describes the current state-of-the-art in research on ccRCC metabolic pathways and potential therapeutic applications. In addition, the clinical implication of pharmacometabolomic intervention is analyzed, which represents a new field for novel stage-related and patient-tailored strategies according to the specific susceptibility to new classes of drugs.

PurposeTo describe the vacuum-assisted mini-percutaneous nephrolithotomy (vmPCNL) technique performed via the 16Ch ClearPetra sheath, to evaluate its outcomes and to analyze intrarenal pressure (IRP) fluctuations during surgery.MethodsData from all consecutive vmPCNL procedures from September 2017 to October 2019 were prospectively collected. Data included patients’ and stones characteristics, intra and peri-operative items, post-operative complications and stone clearance. Patients undergoing vmPCNL from March to October 2019 were submitted to IRP measurement during surgery.ResultsA total of 122 vmPCNL procedures were performed. Median stone volume was 1.92 cm3. Median operative time was 90 min and median lithotripsy and lapaxy time was 28 min. Stone clearance rate was 71.3%. Thirty-one (25.2%) patients experienced post-operative complications, seven of which were Clavien 3. Postoperative fever occurred in nine (7.4%) patients and one (0.8%) needed a transfusion. No sepsis were observed. IRPs were measured in 22 procedures. Mean IRP was 15.3 cmH2O and median accumulative time with IRP > 40.78 cmH2O (pyelovenous backflow threshold) was 28.52 sec. Maximum IRP peaks were reached during the surgical steps when aspiration is closed (mainly pyelograms), whereas during lithotripsy and suction-mediated lapaxy, the threshold of 40.78 cmH2O was overcome in three procedures.ConclusionsvmPCNL is a safe procedure with satisfactory stone clearance rates. Mean IRP was always lower than the threshold of pyelo-venous backflow and the accumulative time with IRP over this limit was short in most of the procedures. During lithotripsy and vacuum-mediated lapaxy, IRP rarely raised over the threshold.

Radiomics and artificial intelligence (AI) may increase the differentiation of benign from malignant kidney lesions, differentiation of angiomyolipoma (AML) from renal cell carcinoma (RCC), differentiation of oncocytoma from RCC, differentiation of different subtypes of RCC, to predict Fuhrman grade, to predict gene mutation through molecular biomarkers and to predict treatment response in metastatic RCC undergoing immunotherapy. Neural networks analyze imaging data. Statistical, geometrical, textural features derived are giving quantitative data of contour, internal heterogeneity and gray zone features of lesions. A comprehensive literature review was performed, until July 2022. Studies investigating the diagnostic value of radiomics in differentiation of renal lesions, grade prediction, gene alterations, molecular biomarkers and ongoing clinical trials have been analyzed. The application of AI and radiomics could lead to improved sensitivity, specificity, accuracy in detecting and differentiating between renal lesions. Standardization of scanner protocols will improve preoperative differentiation between benign, low-risk cancers and clinically significant renal cancers and holds the premises to enhance the diagnostic ability of imaging tools to characterize renal lesions.

We aimed to assess the role of computerized tomography attenuation values (Hounsfield unit—HU) for differentiating pyonephrosis from hydronephrosis and for predicting postoperative infectious complications in patients with obstructive uropathy. We analysed data from 122 patients who underwent nephrostomy tube or ureteral catheter placement for obstructive uropathy. A radiologist drew the region of interest for quantitative measurement of the HU values in the hydronephrotic region of the affected kidney. Descriptive statistics and logistic regression models tested the predictive value of HU determination in differentiating pyonephrosis from hydronephrosis and in predicting postoperative sepsis. A HU cut-off value of 6.3 could diagnose the presence of pyonephrosis with 71.6% sensitivity and 71.5% specificity (AUC 0.76; 95%CI: 0.66–0.85). At multivariable logistic regression analysis HU ≥ 6.3 ( p  ≤ 0.001) was independently associated with pyonephrosis. Patients who developed sepsis had higher HU values ( p  ≤ 0.001) than those without sepsis. A HU cut-off value of 7.3 could diagnose the presence of sepsis with 76.5% sensitivity and 74.3% specificity (AUC 0.79; 95%CI: 0.71–0.90). At multivariable logistic regression analysis, HU ≥ 7.3 ( p  ≤ 0.001) was independently associated with sepsis, after accounting for clinical and laboratory parameters. Measuring HU values of the fluid of the dilated collecting system may be useful to differentiate pyonephrosis from hydronephrosis and to predict septic complications in patients with obstructive uropathy.

Primary prostate cancer presents with multifocal lesions and unpredictable clinical behavior, posing significant challenges for effective prognosis. To address this, we investigate the epigenomic landscape of prostate tumor biopsies from 25 treatment-naïve male patients by analyzing chromatin compartmentalization patterns. Our analysis reveals two distinct molecular subtypes: one with a Low Degree of Decompartmentalization (LDD) and another with a High Degree of Decompartmentalization (HDD). Here we show that the HDD subgroup exhibits extensive chromatin reorganization associated with diminished oncogenic potential. This subtype shows repression of molecular pathways involved in extracellular matrix remodeling and cellular plasticity. From this distinction, we derive an 18-gene transcriptional signature capable of differentiating HDD from LDD cases. Importantly, we validate the prognostic relevance of this signature in multiple independent cohorts totaling over 900 patients. Our findings suggest that epigenetic-derived signature at the time of diagnostic biopsy can offer a powerful tool for risk stratification in prostate cancer. Prostate cancer (PCa) evaluation remains challenging due to its heterogenous and multifocal nature. Here, the authors reconstruct the nuclear chromatin compartmentalization of PCa patients-derived biopsies distinguishing two epigenetic subtypes and deriving an 18-gene signature with prognostic value on TCGA samples that is further validated with multiple independent PCa cohorts.

To evaluate anthropometric variables, energy expenditure by physical activity and nutrient intake of uric acid stone formers (UA-RSFs) compared to non-forming subjects (C). The study included 33 consecutive male patients with a diagnosis of “pure” stones of anhydrous uric acid at infrared spectroscopy and 49 male control subjects with no history of urinary stones. A personal interview was conducted including questionnaires for physical activity and dietary intakes. Anthropometric parametric and blood pressure were measured. Mean age, weight, height, waist circumference, body mass index, systolic and diastolic blood pressure values, dietary energy, carbohydrate intake, lipid intake, dietary acid load, time spent for different physical activities and total energy expenditure for physical activity were not different in UA-RSFs with respect to C. Mean dietary protein (76.2 ± 19.6 vs 65.4 ± 14.7 g/day, P = 0.006) and ethanol intake (10.4 ± 8.8 vs 4.1 ± 8.6, P = 0.002) were higher in UA-RSFs than in C. History of renal disease, heart disease and treatment with thiazides or allopurinol were more frequent and mean serum glucose and triglycerides (104 ± 12 vs 97 ± 11 mg/dl, P = 0.043) (172 ± 77 vs 123 ± 52 mg/dl, P = 0.023) were higher in UA-RSFs. Metabolic syndrome was more frequent in UA-RSFs (57% vs 39%) but not significant (p = 0.09). Increased dietary animal protein (and ethanol) intake can act as co-factors for uric acid stone formation although a more complex and not fully elucidated metabolic background can have an even more crucial role in the pathogenesis of this disease even in the absence of overweight.

Bipolar Transurethral Enucleation of the Prostate (B-TUEP) is recommended as a first-choice treatment for benign prostatic obstruction in prostates >80 ml. Differently, B-TUEP is only considered as an alternative option after TURP for smaller prostates (30-80 ml). The aim of our study is to assess the relation between prostate size and surgical outcomes after B-TUEP. We performed a retrospective analysis of data collected from 172 patients submitted to B-TUEP. Patients were segregated according to tertiles of prostate volume (PV) ([less than or equal to]60 ml, 61-110 ml, >110 ml). For each group we evaluated enucleation efficacy (enucleated weight/enucleation time), complication rates, urinary and sexual function parameters. Functional and sexual parameters were compared between groups at baseline, 1 and 3 months follow up. Descriptive statistics and linear and logistic regression models tested the association between PV and postoperative complications/outcomes. Operative time and weight of enucleated adenomas increased along with prostate volumes (all p[less than or equal to]0.01). Enucleation efficacy was higher in men with PV >110 ml compared to other groups (p[less than or equal to]0.001). Length of hospital stay, catheterization time and rates of postoperative complications, such as transfusion and clot evacuation rates and bladder neck/urethral strictures, were comparable between groups. Urinary symptoms improved at 1-and 3-months in each group as compared to baseline evaluation (all p<0.01) but they did not differ according to PV. In each group maximum urinary flow and post-void residual volume significantly improved at 3 months compared to baseline (all p[less than or equal to]0.01), without differences according to PV. Sexual symptoms were similar between groups at each follow up assessment. At multivariable linear and logistic regression analysis, prostate volume was not associated with postoperative functional outcomes and complications. Conversely, patient's comorbid status and antiplatelet/anticoagulation use were independently associated with postoperative complications. According to our findings, B-TUEP should be considered a \"size independent procedure\" as it can provide symptom relief in men with prostates of all sizes with the same efficacy and safety profile.

PurposeTo evaluate the balance between existing evidence and expert opinions on the safety and efficacy of new technological improvements in lithotripsy techniques for percutaneous nephrolithotomy (PCNL).MethodsA scoping review approach was applied to search literature in Pubmed, Embase, and Web of Science. Consensus by key opinion leaders was reached at a 2-day meeting entitled “Consultation on Kidney Stones: Aspects of Intracorporeal Lithotripsy” held in Copenhagen, Denmark, in September 2019.ResultsNew-generation dual-mode single-probe lithotripsy devices have shown favourable results compared with use of ballistic or ultrasonic lithotripters only. However, ballistic and ultrasonic lithotripters are also highly effective and safe and have been the backbone of PCNL for many years. Compared with standard PCNL, it seems that mini PCNL is associated with fewer bleeding complications and shorter hospital admissions, but also with longer operating room (OR) time and higher intrarenal pressure. Use of laser lithotripsy combined with suction in mini PCNL is a promising alternative that may improve such PCNL by shortening OR times. Furthermore, supine PCNL is a good alternative, especially in cases with complex renal stones and large proximal ureteric stones; in addition, it facilitates endoscopic combined intrarenal surgery (ECIRS).ConclusionRecent technological improvements in PCNL techniques are promising, but there is a lack of high-level evidence on safety and efficacy. Different techniques suit different types of stones and patients. The evolution of diverse methods has given urologists the possibility of a personalized stone approach, in other words, the right approach for the right patient.

Testicular volume (TV) is considered a good clinical marker of hormonal and spermatogenic function. Accurate reference values for TV measures in infertile and fertile men are lacking. We aimed to assess references values for TV in white-European infertile men and fertile controls. We analyzed clinical and laboratory data from 1940 (95.0%) infertile men and 102 (5.0%) fertile controls. Groups were matched by age using propensity score weighting. TV was assessed using a Prader orchidometer (PO). Circulating hormones and semen parameters were investigated in every male. Descriptive statistics, Spearman's correlation, and logistic regression models tested potential associations between PO-estimated TV values and clinical variables. Receiver operating characteristic (ROC) curves were used to find TV value cutoffs for oligoasthenoteratozoospermia (OAT) and nonobstructive azoospermia (NOA) status in infertile men. The median testicular volume was smaller in infertile than that of fertile men (15.0 ml vs 22.5 ml; P < 0.001). TV positively correlated with total testosterone, sperm concentration, and progressive sperm motility (all P ≤ 0.001) in infertile men. At multivariable logistic regression analysis, infertile status (P < 0.001) and the presence of left varicocele (P < 0.001) were associated with TV < 15 ml. Testicular volume thresholds of 15 ml and 12 ml had a good predictive ability for detecting OAT and NOA status, respectively. In conclusion, infertile men have smaller testicular volume than fertile controls. TV positively correlated with total testosterone, sperm concentration, and progressive motility in infertile men, which was not the case in the age-matched fertile counterparts.

We performed a narrative review with the focus on laser settings and surgical procedure with thulium laser. Our primary goal was to define the most valid settings of each surgical procedure to overcome the inconsistency about nomenclature of thulium surgery and to ensure comparability of future publications. A literature search of articles on thulium laser treatment of benign prostatic hyperplasia (BPH) was conducted between 2009 and 2019. We proposed a new classification standard for laser settings and associated surgical procedure. Each article was analyzed and categorized as concordant or discordant referring to the new classification. In total, 74 papers were included in this narrative review. Overall, 43% and 42% of included studies reported discordant laser parameters and surgical description, respectively. Most of the studies on vaporization were categorized as discordant because they reported a medium/low laser setting instead of high power. Conversely, 93.3% of studies on enucleation were deemed as discordant for laser setting because they reported high power parameters instead of medium-low power setting. Most of the studies on laser enucleation and vapo/enucleation were considered discordant for surgical procedure since authors did not mention the use of mechanical vs. laser method for enucleation. The current literature lacks a uniform definition and standardization of the terminology of thulium laser settings and surgical techniques to guarantee comparability between different approaches. We found a huge heterogeneity in 10 years of surgery with thulium laser. We proposed a new classification of laser setting and procedural description for categorization of thulium laser surgery for BPH.