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.

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.

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.

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 (AU)

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.

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.

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.

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.

Could We Safely Avoid a Second Resection in Selected Patients With T1 Non-Muscle-Invasive Bladder Cancer? Preliminary Results of Cost-Effectiveness Study From HUmanitas New Indications for ReTUR (HuNIRe) Multicenter Prospective Trial.

Objectives: The aim of this study is to assess whether restaging transurethral resection (ReTUR) could be safely replaced with urine cytology (UC) and in-office fiexible cystoscopy in selected T1 non-muscle-invasive bladder cancer (NMIBC). Materials and Methods: This is an ongoing prospective multicenter trial enrolling patients diagnosed with T1 BC from 5 Italian centers. Patients with a macroscopically incomplete initial resection or absence of detrusor muscle were subjected to ReTUR according to European Association of Urology (EAU) guidelines. Conversely, those with a complete tumor resection at initial TUR underwent UC at 3-4 weeks and in-office fiexible white-light and narrow-band cystoscopy at 4-6 weeks. In case of positive UC, or evidence of recurrence at cystoscopy, ReTUR was performed within 2 weeks. Otherwise, patients started Bacillus Calmette-Guérin (BCG) induction course without ReTUR. The primary endpoint was to determine the feasibility and the clinical utility of not performing ReTUR in selected T1 NMIBC patients. The secondary endpoint was to perform a cost-benefit analysis of this alternative approach. Results: Since May 2020, among 87 patients presenting with T1, 76 patients were enrolled. Nineteen (25%) patients underwent standard ReTUR after initial resection, 10 (13.2%) due to the absence of the detrusor muscle and 9 (11.8%) due to a macroscopically incomplete initial TUR. Overall, 57 (75%) patients initially avoided immediate ReTUR and underwent UC plus in-office flexible cystoscopy. Among them, 38 (66.7%) had no evidence of residual disease and immediately started the BCG induction course. Nineteen patients (33.3%) underwent "salvage" ReTUR due to either positive UC (7; 12.3%) or suspicious cystoscopy (12; 21%). Considering only the patients who initially avoided the ReTUR, disease recurrence was observed in 10/57. The saving of resource for each safely avoided ReTUR was estimated to be 1,759 €. Considering the entire sample, we estimated a saving of 855 € per patient if compared with the EAU guideline approach. Conclusion: The preliminary results of our trial suggested that ReTUR might be safely avoided in highly selected T1 BC patients with a complete resection at first TUR. Longer follow-up and larger sample size are needed to investigate the long-term oncological outcomes of this alternative approach.

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.

Drift compensation on electronic nose data for non-invasive diagnosis of prostate cancer by urine analysis.

Diagnostic protocol for prostate cancer (KP) is affected by poor accuracy and high false-positive rate. The most promising innovative approach is based on urine analysis by electronic noses (ENs), highlighting a specific correlation between urine alteration and KP presence. Although EN could be exploited to develop non-invasive KP diagnostic tools, no study has already introduced EN into clinical practice, most probably because of drift issues that hinder EN scaling up from research objects to large-scale diagnostic devices. This study, proposing an EN for non-invasive KP detection, describes the data processing protocol applied to a urine headspace dataset acquired over 9 months, comprising 81 patients with KP and 41 controls, for compensating the drift. It proved effective in mitigating drift on 1-year-old sensors by restoring accuracy from 55% up to 80%, achieved by new sensors not subjected to drift. The model achieved, on double-blind validation, a balanced accuracy of 76.2% (CI95% 51.9-92.3).

Optimization of training and measurement protocol for eNose analysis of urine headspace aimed at prostate cancer diagnosis.

More than one million new cases of prostate cancer (PCa) were reported worldwide in 2020, and a significant increase of PCa incidence up to 2040 is estimated. Despite potential treatability in early stages, PCa diagnosis is challenging because of late symptoms' onset and limits of current screening procedures. It has been now accepted that cell transformation leads to release of volatile organic compounds in biologic fluids, including urine. Thus, several studies proposed the possibility to develop new diagnostic tools based on urine analysis. Among these, electronic noses (eNoses) represent one of the most promising devices, because of their potential to provide a non-invasive diagnosis. Here we describe the approach aimed at defining the experimental protocol for eNose application for PCa diagnosis. Our research investigates effects of sample preparation and analysis on eNose responses and repeatability. The dependence of eNose diagnostic performance on urine portion analysed, techniques involved for extracting urine volatiles and conditioning temperature were analysed. 192 subjects (132 PCa patients and 60 controls) were involved. The developed experimental protocol has resulted in accuracy, sensitivity and specificity of 83% (CI95% 77-89), 82% (CI95% 73-88) and 87% (CI95% 75-94), respectively. Our findings define eNoses as valuable diagnostic tool allowing rapid and non-invasive PCa diagnosis.

Hope for Ostomates: A Carbon and Zeolite Impregnated Polyester Fabric Inhibits Urine Odor in Cancer Patients: A Randomized Experimental Study.

OBJECTIVE: Many individuals with bladder cancer have undergone a surgical urostomy and often complain of being self-conscious of the unpleasant smell of their own urine. The focus of this study was to test the efficacy of a pouch cover made of a carbon and zeolite containing polyester material to inhibit the smell of urine by comparing two trained dogs' response time in detecting volatile organic compounds (VOCs) in urine, with and without the fabric covering the samples. METHODS: This study used a randomized, blinded experimental design to evaluate the efficacy of a fabric to interfere with two highly trained dogs' ability to detect specific VOCs present in the urine of prostate cancer patient. Ninety urine samples were analyzed in this study. RESULTS: Prior to the experiment, both dogs accurately detected VOCs in the uncovered test urine samples of men with prostate cancer with a sensitivity and specificity of nearly 100%. Both dogs recognized the "uncovered" urine samples of men with prostate cancer within two seconds. When the test sample was covered with the study fabric, the test urine samples were detected within 30-40 seconds and in some instances the dogs were not able to identify the covered samples, whatsoever. CONCLUSION: The findings of this study demonstrate that the carbon and zeolite containing polyester fabric did significantly interfere with the ability of the dogs to detect VOCs in urine of men with prostate cancer. The fabric may show promise as a pouch cover in controlling offensive urine odor which many ostomates experience.

The kidney, COVID-19, and the chemokine network: an intriguing trio.

On December 30th 2019, some patients with pneumonia of unknown etiology were reported in the Program for Monitoring Emerging Diseases (ProMED), a program run by the International Society for Infectious Diseases (ISID), hypothesized to be related to subjects who had had contact with the seafood market in Wuhan, China. Chinese authorities instituted an emergency agency aimed at identifying the source of infection and potential biological pathogens. It was subsequently named by the World Committee on Virus Classification as 2019-nCoV (2019-novel coronavirus) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A number of studies have demonstrated that 2019-nCoV and the SARS-CoV shared the same cell entry receptor named angiotensin-converting enzyme 2 (ACE2). This is expressed in human tissues, not only in the respiratory epithelia, but also in the small intestines, heart, liver, and kidneys. Here, we examine the most recent findings on the effects of SARS-CoV-2 infection on kidney diseases, mainly acute kidney injury, and the potential role of the chemokine network.

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.