Accuracy of a new electronic nose for prostate cancer diagnosis in urine samples.

OBJECTIVE: To evaluate the accuracy of a new electronic nose to recognize prostate cancer in urine samples. METHODS: A blind, prospective study on consecutive patients was designed. Overall, 174 subjects were included in the study: 88 (50.6%) in prostate cancer group, and 86 (49.4%) in control group. Electronic nose performance for prostate cancer was assessed using sensitivity and specificity. The diagnostic accuracy of electronic nose was reported as area under the receiver operating characteristic curve. RESULTS: The electronic nose in the study population reached a sensitivity 85.2% (95% confidence interval 76.1-91.9; 13 false negatives out of 88), a specificity 79.1% (95% confidence interval 69.0-87.1; 18 false positives out of 86). The accuracy of the electronic nose represented as area under the receiver operating characteristic curve 0.821 (95% confidence interval 0.764-0.879). CONCLUSIONS: The diagnostic accuracy of electronic nose for recognizing prostate cancer in urine samples is high, promising and susceptible to supplemental improvement. Additionally, further studies will be necessary to design a clinical trial to validate electronic nose application in diagnostic prostate cancer nomograms.

Retrotrigonal muscular layer sling associated with total anatomical reconstruction in robot-assisted radical prostatectomy and early continence.

BACKGROUND AND PURPOSE: Urinary continence (UC) represents the main non-oncological goal in patients undergoing robotic-assisted radical prostatectomy (RARP). To evaluate the efficacy in early UC achievement, we described a new sling technique using the retrotrigonal muscular layer (TZ sling) combined with total anatomical reconstruction (TAR). PATIENTS AND METHODS: We prospectively enrolled 407 consecutive prostate cancer (PC) patients undergoing RARP between May 2017 and January 2020. The first 250 patients underwent only TAR, while the following 157 patients TAR + TZ sling, by isolating and anchoring the retrotrigonal muscular layer to the pubic bone with 2 bilateral sutures. We defined UC as ≤ 1 pad/die, which was assessed after catheter removal at 1, 4 and 12wk using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score. Sling-related operative time and post-operative complications were analyzed. RESULTS: In the TAR group, the UC rates at the 1, 4 and 12wk were 58%, 66% and 86%; in the TAR + TZ sling group 72%, 76% and 88%, respectively. A statistically significant difference was observed in the two groups at 1wk (p = 0.0049) and 4wk (p = 0.035) favoring the TZ sling surgical strategy. This difference in UC rates was lost at 12wk (p ≥ 0.05). No statistically significant differences in operative time, acute urinary retentions and other complication rates were observed between the two groups (p = NS). CONCLUSIONS: We have described a new, safe, feasible modification of RARP using a sling with the retrotrigonal muscular layer associated with TAR. We have demonstrated a statistically significant improvement in early UC rate in patients who are undergoing TAR and TZ sling compared to undergoing only TAR.

Endorectal multiparametric 3-tesla magnetic resonance imaging associated with systematic cognitive biopsies does not increase prostate cancer detection rate: a randomized prospective trial.

PURPOSE: To investigate prostate cancer (PC) detection rate, employing endorectal multiparametric 3-tesla magnetic resonance imaging (MRI) driving subsequent cognitive systematic prostatic biopsy (CSPB) versus a homogenous group of patients who did not undergo endorectal MRI. MATERIALS AND METHODS: A series of patients with a first negative biopsy were enrolled in the study. Patients were randomized into two groups: Group A: patients underwent MRI and subsequent CSPB; Group B: patients that did not undergo MRI. Each patient underwent a 13-core sampling. Patients from Group A had four cores more for each MRI suspected lesion. The cancer detection rate was calculated for each group with regard to possible matches or mismatches between MRI evidence and pathological reports. RESULTS: Two hundred consecutive patients were investigated. Fifty out of 200 (25 %) patients had a diagnosis of PC, 24 in Group A and 26 in Group B. In Group A, 67 patients (67 %) were positive for suspected lesions at the MRI. The mismatch between MRI findings and the CSPB outcome was 61 % with an MRI-driven detection rate of 15 %. Group B detection rate was 26 % with no significant differences versus Group A (P = NS). Patient discomfort was higher in Group A (82 %). The accuracy of CSPB was 41 % with a positive predictive value of 22.3 %. This rate is lower in high-grade cancers (11.9 %). The cost-effectiveness was higher in Group A. CONCLUSIONS: Prostate cancer detection rate does not improve by CSPB. The accuracy of CSPB was lower in high-grade PC, and a higher cost was found with CSPB.

An observational study of the use of beclomethasone dipropionate suppositories in the treatment of lower urinary tract inflammation in men.

BACKGROUND: Nonbacterial prostatitis, together with chronic pelvic pain syndrome, accounts for 90-95 % of prostatitis cases. Anti-inflammatory medications are commonly used to reduce storage/inflammatory symptoms that can deteriorate quality of life. The purpose of this study was to observe the efficacy and safety of beclomethasone dipropionate rectal suppositories (Topster®) in inflammations of the lower urinary tract in men. METHODS: Patients underwent diagnostic and therapeutic protocols according to current evidence-based practice. Efficacy assessments: voiding parameters, perineal pain, International Prostate Symptom Score (IPSS), digital rectal examination (DRE). Adverse events and patient compliance were recorded throughout the study. RESULTS: One hundred eighty patients were enrolled, mean age 52 ± 14.97. Most frequent diagnosis: nonbacterial prostatitis (85 %). All patients completed visits 1 and 2. All patients were treated with beclomethasone dipropionate (BDP) suppositories, 136/180 also with Serenoa repens (SR) extract. Antibiotics were rarely required. 162/180 patients presented clinically significant improvements and terminated treatment. Mean change vs. baseline in voiding frequency: -3.55 ± 2.70 n/day in patients taking only BDP and -3.68 ± 2.81 n/day in those taking both BDP and SR (P<.0001 in both groups). Uroflowmetry improved significantly; change from baseline 3.26 ± 5.35 ml/s in BDP only group and 5.61 ± 7.32 ml/s in BDP + SR group (P = 0.0002 for BDP, P<.0001 for BDP + SR). Urine stream normal in 35 % of patients at visit 1 and 57.22 % of patients at visit 2. Mean change in perineal pain, on 0-10 VAS, -0.66 ± 2.24 for BDP only group (P = 0.0699) and -1.37 ± 2.40 for BDP + SR group (P<.0001). IPSS increased at visit 2. No adverse events were reported. For all parameters, none of the comparisons between groups was found to be statistically significant. CONCLUSION: This study confirmed the drug's good safety profile. We also observed an improvement in the main storage symptoms and clinical findings associated with lower urinary tract inflammation in patients treated with beclomethasone dipropionate suppositories.

Application and Uses of Electronic Noses for Clinical Diagnosis on Urine Samples: A Review.

The electronic nose is able to provide useful information through the analysis of the volatile organic compounds in body fluids, such as exhaled breath, urine and blood. This paper focuses on the review of electronic nose studies and applications in the specific field of medical diagnostics based on the analysis of the gaseous headspace of human urine, in order to provide a broad overview of the state of the art and thus enhance future developments in this field. The research in this field is rather recent and still in progress, and there are several aspects that need to be investigated more into depth, not only to develop and improve specific electronic noses for different diseases, but also with the aim to discover and analyse the connections between specific diseases and the body fluids odour. Further research is needed to improve the results obtained up to now; the development of new sensors and data processing methods should lead to greater diagnostic accuracy thus making the electronic nose an effective tool for early detection of different kinds of diseases, ranging from infections to tumours or exposure to toxic agents.

Olfactory system of highly trained dogs detects prostate cancer in urine samples.

PURPOSE: We established diagnostic accuracy in terms of the sensitivity and specificity with which a rigorously trained canine olfactory system could recognize specific volatile organic compounds of prostate cancer in urine samples. MATERIALS AND METHODS: Two 3-year-old female German Shepherd Explosion Detection Dogs were trained to identify prostate cancer specific volatile organic compounds in urine samples. They were tested on 362 patients with prostate cancer (range low risk to metastatic) and on 540 healthy controls with no nonneoplastic disease or nonprostatic tumor. This cross-sectional design for diagnostic accuracy was performed at a single Italian teaching hospital and at the Italian Ministry of Defense Military Veterinary Center. RESULTS: For dog 1 sensitivity was 100% (95% CI 99.0-100.0) and specificity was 98.7% (95% CI 97.3-99.5). For dog 2 sensitivity was 98.6% (95% CI 96.8-99.6) and specificity was 97.6% (95% CI 95.9-98.7). When considering only men older than 45 years in the control group, dog 1 achieved 100% sensitivity and 98% specificity (95% CI 96-99.2), and dog 2 achieved 98.6% sensitivity (95% CI 96.8-99.6) and 96.4% specificity (95% CI 93.9-98.1). Analysis of false-positive cases revealed no consistent pattern in participant demographics or tumor characteristics. CONCLUSIONS: A trained canine olfactory system can detect prostate cancer specific volatile organic compounds in urine samples with high estimated sensitivity and specificity. Further studies are needed to investigate the potential predictive value of this procedure to identify prostate cancer.

Sky is no limit for ureteroscopy: extending the indications and special circumstances.

PURPOSE: To critically review and synthesize data of ureteroscopy (URS) in different circumstances that all urologists may encounter during everyday clinical practice, such as pregnancy, obesity, bleeding diathesis, renal stones larger than 2 cm, calyceal diverticula, and kidney malformations. METHODS: According to PRISMA guidelines, a systematic literature review was performed to identify articles published between 1990 and December 2013 that reported different indications and special circumstances for URS. Articles were separated into the following categories: pregnancy, obesity, bleeding diathesis, stones larger than 2 cm in diameter, calyceal diverticula, and kidney malformations. We used a narrative synthesis for the analyses of the studies, including a description of the characteristics and main outcomes reported in the articles. RESULTS: Records identified through database searching were 1396; at the end of study selection, articles included were 57. The majority of these are retrospective studies and involve small cohorts of patients. There does not exist a consensus about important parameters in ureterorenoscopy like stone size, stone free status and complication rate. CONCLUSION: Ureteroscopy is effective and reliable tool capable of treating the majority of stones even in the most complicated clinical scenarios and will have more fundamental roles in endourology. The lack of definitive conclusions is due to the great heterogeneity in collecting study's results; multicentric randomized trials that define in advance the parameters to be studied should be encouraged.

Inflammation and prostate cancer: friends or foe?

INTRODUCTION: Prostate cancer is the most common non-cutaneous malignancy diagnosed in men. Moving from histological observations since a long time, it has been recognized that innate and adaptive immunity actively participates in the pathogenesis, surveillance, and progression of prostate cancer. MATERIALS AND METHODS: A PubMed and Web of Science databases search was performed for studies providing evidence on the roles of the innate and adaptive immunity during the development and progression of prostate cancer. CONCLUSIONS: There are growing evidences that chronic inflammation is involved in the regulation of cellular events in prostate carcinogenesis, including disruption of the immune response and regulation of the tumor microenvironment. This review discusses the role played by the innate and adaptive immune system in the local progression of prostate cancer, and the prognostic information that we can currently understand and exploit.

Is retrograde intrarenal surgery for the treatment of renal stones with diameters exceeding 2 cm still a hazard?

INTRODUCTION: Major kidney stones have traditionally been treated with percutaneous nephrolithotomy. However, retrograde intrarenal surgery (RIRS), which until a few years ago was considered inappropriate for this purpose, is becoming a viable, attractive alternative. The aim of the current study was to assess the efficacy and safety of RIRS combined with holmium laser lithotripsy for the treatment of stones > 2 cm in diameter in a large series of patients, reporting complications according to the Clavien-Dindo classification. MATERIALS AND METHODS: By retrospective analysis, we identified a total of 162 patients who were affected by stones greater than 2 cm in diameter and who had undergone RIRS. We reviewed demographic and stone characteristics, intraoperative and postoperative outcomes, and complications. RESULTS: The mean stone size was 2.7 cm +/- 0.6 cm. The primary, secondary, and tertiary stone-free rates were 66%, 80.9%, and 87.7%, respectively. The mean number of procedures per patient was 1.48. The complication rates according to the Clavien-Dindo classification were Clavien I in 20.4% of patients, Clavien II in 0%, Clavien III in 4.9%, Clavien IV in 0.6%, and Clavien V in 0%. CONCLUSIONS: As an alternative to standard procedures for the treatment of renal calculi greater than 2 cm in diameter, RIRS is safe and effective, with a low complication rate.

Investigating the Spatial Distribution of Proliferating Cells in Primary Ovarian Cancers.

BACKGROUND: Ovarian cancer (OC) accounts for about 4% of female cancers globally. While Ki67-immunopositive (Ki67+) cell density is commonly used to assess proliferation in OC, the two-dimensional (2D) distribution pattern of these cells is poorly understood. This study explores the 2D distribution pattern of Ki67+ cells in primary OC tissues and models the proliferation process to improve our understanding of this hallmark of cancer. METHODS: A total of 100 tissue cores, included in a tissue microarray (TMA) representing 5 clear cell carcinomas, 62 serous carcinomas, 10 mucinous adenocarcinomas, 3 endometrioid adenocarcinomas, 10 lymph node metastases from OC, and 10 samples of adjacent normal ovary tissue, were stained using a standardized immunohistochemical protocol. The computer-aided image analysis system assessed the 2D distribution pattern of Ki67+ proliferating cells, providing the cell number and density, patterns of randomness, and cell-to-cell closeness. Three computer models were created to simulate behavior and responses, aiming to gain insights into the variations in the proliferation process. RESULTS: Significant differences in Ki67+ cell density were found between low- and high-grade serous carcinoma/mucinous adenocarcinomas (p = 0.003 and p = 0.01, respectively). The Nearest Neighbor Index of Ki67+ cells differed significantly between high-grade serous carcinomas and endometrioid adenocarcinomas (p = 0.01), indicating distinct 2D Ki67+ distribution patterns. Proxemics analysis revealed significant differences in Ki67+ cell-to-cell closeness between low- and high-grade serous carcinomas (p = 0.002). Computer models showed varied effects on the overall organization of Ki67+ cells and the ability to preserve the original 2D distribution pattern when altering the location and/or density of Ki67+ cells. CONCLUSIONS: Cell proliferation is a hallmark of OCs. This study provides new evidence that investigating the Ki67+ cell density and 2D distribution pattern can assist in understanding the proliferation status of OCs. Moreover, our computer models suggest that changes in Ki67+ cell density and their location are critical for maintaining the 2D distribution pattern.

Recapitulating COVID-19 detection methods: RT-PCR, sniffer dogs and electronic nose.

In December 2019, a number of subjects presenting with an unexplained pneumonia-like illness were suspected to have a link to a seafood market in Wuhan, China. Subsequently, this illness was identified as the 2019-novel coronavirus (2019-nCoV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the World Committee on Virus Classification. Since its initial identification, the virus has rapidly sperad across the globe, posing an extraordinary challenge for the medical community. Currently, the Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is considered the most reliable method for diagnosing SARS-CoV-2. This procedure involves collecting oro-pharyngeal or nasopharyngeal swabs from individuals. Nevertheless, for the early detection of low viral loads, a more sensitive technique, such as droplet digital PCR (ddPCR), has been suggested. Despite the high effectiveness of RT-PCR, there is increasing interest in utilizing highly trained dogs and electronic noses (eNoses) as alternative methods for screening asymptomatic individuals for SARS-CoV-2. These dogs and eNoses have demonstrated high sensitivity and can detect volatile organic compounds (VOCs), enabling them to distinguish between COVID-19 positive and negative individuals. This manuscript recapitulates the potential, advantages, and limitations of employing trained dogs and eNoses for the screening and control of SARS-CoV-2.

Prostate cancer risk stratification via eNose urine odor analysis: a preliminary report.

Introduction: Prostate cancer (PCa) is known for its highly diverse clinical behavior, ranging from low-risk, slow-growing tumors to aggressive and life-threatening forms. To avoid over-treatment of low-risk PCa patients, it would be very important prior to any therapeutic intervention to appropriately classify subjects based on tumor aggressiveness. Unfortunately, there is currently no reliable test available for this purpose. The aim of the present study was to evaluate the ability of risk stratification of PCa subjects using an electronic nose (eNose) detecting PCa-specific volatile organic compounds (VOCs) in urine samples. Methods: The study involved 120 participants who underwent diagnostic prostate biopsy followed by robot assisted radical prostatectomy (RARP). PCa risk was categorized as low, intermediate, or high based on the D'Amico risk classification and the pathological grade (PG) assessed after RARP. The eNose's ability to categorize subjects for PCa risk stratification was evaluated based on accuracy and recall metrics. Results: The study population comprised 120 participants. When comparing eNose predictions with PG an accuracy of 79.2% (95%CI 70.8 - 86%) was found, while an accuracy of 74.2% (95%CI 65.4 - 81.7%) was found when compared to D'Amico risk classification system. Additionally, if compared low- versus -intermediate-/high-risk PCa, the eNose achieved an accuracy of 87.5% (95%CI 80.2-92.8%) based on PG or 90.8% (95%CI 84.2-95.3%) based on D'Amico risk classification. However, when using low-/-intermediate versus -high-risk PCa for PG, the accuracy was found to be 91.7% (95%CI 85.2-95.9%). Finally, an accuracy of 80.8% (95%CI72.6-87.4%) was found when compared with D'Amico risk classification. Discussion: The findings of this study indicate that eNose may represent a valid alternative not only for early and non-invasive diagnosis of PCa, but also to categorize patients based on tumor aggressiveness. Further studies including a wider sample population will be necessary to confirm the potential clinical impact of this new technology.

Is Artificial Intelligence the Key to Revolutionizing Benign Prostatic Hyperplasia Diagnosis and Management?

Benign prostatic hyperplasia (BPH) is a prevalent condition among older men that is characterized by the enlargement of the prostate gland and compression of the urethra, which often results in lower urinary tract symptoms, such as frequent urination, difficulty in starting urination, and incomplete bladder emptying. The development of BPH is thought to be primarily due to an imbalance between cell proliferation and apoptosis, underlying inflammation, epithelial-to-mesenchymal transition, and local paracrine and autocrine growth factors, although the exact molecular mechanisms are not yet fully understood. Anatomical structures considered natural and benign observations can occasionally present multi-parametric magnetic resonance imaging appearances that resemble prostate cancer (PCa), posing a risk of misinterpretation and generating false-positive outcomes and subsequently, unnecessary interventions. To aid in the diagnosis of BPH, distinguish it from PCa, and assist with treatment and outcome prediction, various Artificial Intelligence (AI)-based algorithms have been proposed to assist clinicians in the medical practice. Here, we explore the results of these new technological advances and discuss their potential to enhance clinicians' cognitive abilities and expertise. There is no doubt that AI holds extensive medical potential, but the cornerstone for secure, efficient, and ethical integration into diverse medical fields still remains well-structured clinical trials.

Off-clamp robotic-assisted partial nephrectomy: surgical experience from a single centre.

Introduction: Robot-assisted partial nephrectomy (RAPN) is a minimally invasive treatment for localized renal tumours, which can sometimes result in extended warm ischaemic time and serious complications. This study reports on surgical outcomes including feasibility, positive margins, and complications during and after surgery. Material and methods: From January 2011 to November 2022, a single centre performed off-clamp sutureless RAPN on 287 patients. The study recorded preoperative patient characteristics, estimated glomerular filtration rate, and tumour features according to the preoperative aspects and dimensions used for an anatomical (PADUA) classification, and utilized the RENAL nephrometry scoring system. Intraoperative details and complications were documented. Postoperative complications within 30 days were classified according to the Clavien-Dindo system. Follow-up appointments were scheduled at 1, 3, and 6 months in the first year, followed by subsequent appointments every 6 months, and then annually. Results: The study included 145 males and 142 females, with a mean age of 58.9 years and a mean body mass index of 26.7 kg/m2. The mean PADUA score was 8.3, the average console time was 83 minutes, and the estimated blood loss was 280 mL. The average hospital stay was 3 days, and no intraoperative complications were observed. However, 4 patients (1.4%) experienced post-operative haemorrhage that required laparotomy (Clavien-Dindo stage IIIB), and 4 patients (1.4%) had positive surgical margins. Conclusions: Off-clamp selective arterial clamping during minimally invasive partial nephrectomy is a safe and feasible approach for small renal tumours. Further randomized prospective studies are required to confirm if RAPN without clamping offers any renal functional benefits and reduces perioperative bleeding complications.

Prostate Cancer Microvascular Routes: Exploration and Measurement Strategies.

Angiogenesis is acknowledged as a pivotal feature in the pathology of human cancer. Despite the absence of universally accepted markers for gauging the comprehensive angiogenic activity in prostate cancer (PCa) that could steer the formulation of focused anti-angiogenic treatments, the scrutiny of diverse facets of tumoral blood vessel development may furnish significant understanding of angiogenic processes. Malignant neoplasms, encompassing PCa, deploy a myriad of strategies to secure an adequate blood supply. These modalities range from sprouting angiogenesis and vasculogenesis to intussusceptive angiogenesis, vascular co-option, the formation of mosaic vessels, vasculogenic mimicry, the conversion of cancer stem-like cells into tumor endothelial cells, and vascular pruning. Here we provide a thorough review of these angiogenic mechanisms as they relate to PCa, discuss their prospective relevance for predictive and prognostic evaluations, and outline the prevailing obstacles in quantitatively evaluating neovascularization via histopathological examinations.

Prospective Validation of the ROL System in Substaging pT1 High-Grade Urothelial Carcinoma: Results from a Mono-Institutional Confirmatory Analysis in BCG Treated Patients.

Patients with pT1 high-grade (HG) urothelial carcinoma (UC) and a very high risk of progression might benefit from immediate radical cystectomy (RC), but this option remains controversial. Validation of a standardized method to evaluate the extent of lamina propria (LP) invasion (with recognized prognostic value) in transurethral resection (TURBT) specimens is still needed. The Rete Oncologica Lombarda (ROL) system showed a high predictive value for progression after TURBT in recent retrospective studies. The ROL system was supposed to be validated on a large prospective series of primary urothelial carcinomas from a single institution. From 2016 to 2020, we adopted ROL for all patients with pT1 HG UC on TURBT. We employed a 1.0-mm threshold to stratify tumors in ROL1 and ROL2. A total of 222 pT1 HG UC were analyzed. The median age was 74 years, with a predominance of men (73.8%). ROL was feasible in all cases: 91 cases were ROL1 (41%), and 131 were ROL2 (59%). At a median follow-up of 26.9 months (IQR 13.8-40.6), we registered 81 recurrences and 40 progressions. ROL was a significant predictor of tumor progression in both univariable (HR 3.53; CI 95% 1.56-7.99; p < 0.01) and multivariable (HR 2.88; CI 95% 1.24-6.66; p = 0.01) Cox regression analyses. At Kaplan-Meier estimates, ROL showed a correlation with both PFS (p = 0.0012) and RFS (p = 0.0167). Our results confirmed the strong predictive value of ROL for progression in a large prospective series. We encourage the application of ROL for reporting the extent of LP invasion, substaging T1 HG UC, and improving risk tables for urological decision-making.

Clinical and pathological predictors of persistent T1 HG at second resection.

BACKGROUND: T1 high-grade (HG) non-muscle invasive bladder cancer (NMIBC) has a significant risk of recurrence and progression, and the European Association of Urology recommends a second transurethral resection of the bladder (ReTUR). Stage at ReTUR has been shown to be a reliable predictor of survival, therefore, we sought to assess clinical and pathological predictors associated with the persistence of T1 at ReTUR in our retrospective multicentric cohort. METHODS: This is a retrospective multicentric study of T1 HG patients at transurethral resection of the bladder (TURB) who underwent subsequent ReTUR. All histological samples were sub-classified according to Rete Oncologica Lombarda (ROL) T1 sub-staging system. RESULTS: One hundred and sixty-six patients were enrolled. Forty-four (26.5%) had T1 HG tumor at ReTUR while 93 (56%) had residual tumor of any stage. Lesion size was significantly greater in T1 HG patients at ReTUR, as well as the prevalence of multifocality. The multivariable logistic regression model showed lesion dimension and multifocality as predictors of T1 HG at ReTUR, after adjusting for significant covariables (CIS and detrusor muscle presence). ROL sub-staging system was not a significant predictor, but ROL2 prevalence was higher in the T1 HG at ReTUR group. CONCLUSIONS: Lesion size and multifocality were independent predictors of T1 HG persistence at ReTUR, and patients at risk should be promptly identified and treated accordingly. Our results could help physicians make patient-tailored decisions by identifying those most likely to benefit from a second resection.