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.

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.

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.

Fractal nature of human gastrointestinal system: Exploring a new era.

The morphological complexity of cells and tissues, whether normal or pathological, is characterized by two primary attributes: Irregularity and self-similarity across different scales. When an object exhibits self-similarity, its shape remains unchanged as the scales of measurement vary because any part of it resembles the whole. On the other hand, the size and geometric characteristics of an irregular object vary as the resolution increases, revealing more intricate details. Despite numerous attempts, a reliable and accurate method for quantifying the morphological features of gastrointestinal organs, tissues, cells, their dynamic changes, and pathological disorders has not yet been established. However, fractal geometry, which studies shapes and patterns that exhibit self-similarity, holds promise in providing a quantitative measure of the irregularly shaped morphologies and their underlying self-similar temporal behaviors. In this context, we explore the fractal nature of the gastrointestinal system and the potential of fractal geometry as a robust descriptor of its complex forms and functions. Additionally, we examine the practical applications of fractal geometry in clinical gastroenterology and hepatology practice.

A Comprehensive Guide to Artificial Intelligence in Endoscopic Ultrasound.

BACKGROUND: Endoscopic Ultrasound (EUS) is widely used for the diagnosis of bilio-pancreatic and gastrointestinal (GI) tract diseases, for the evaluation of subepithelial lesions, and for sampling of lymph nodes and solid masses located next to the GI tract. The role of Artificial Intelligence in healthcare in growing. This review aimed to provide an overview of the current state of AI in EUS from imaging to pathological diagnosis and training. METHODS: AI algorithms can assist in lesion detection and characterization in EUS by analyzing EUS images and identifying suspicious areas that may require further clinical evaluation or biopsy sampling. Deep learning techniques, such as convolutional neural networks (CNNs), have shown great potential for tumor identification and subepithelial lesion (SEL) evaluation by extracting important features from EUS images and using them to classify or segment the images. RESULTS: AI models with new features can increase the accuracy of diagnoses, provide faster diagnoses, identify subtle differences in disease presentation that may be missed by human eyes, and provide more information and insights into disease pathology. CONCLUSIONS: The integration of AI in EUS images and biopsies has the potential to improve the diagnostic accuracy, leading to better patient outcomes and to a reduction in repeated procedures in case of non-diagnostic biopsies.

Sperm protein antigen 17 and Sperm flagellar 1 cancer testis antigens are expressed in a rare case of ciliated foregut cyst of the common hepatic duct.

INTRODUCTION: Ciliated foregut cysts (CFCs) are frequently described in liver, pancreas and gallbladder and generally considered benign although one case of squamous cell metaplasia and five cases of squamous cell carcinoma arising from a ciliated hepatic foregut cyst have been reported. Here we explore two cancer-testis antigens (CTAs), Sperm protein antigen 17 (SPA17) and Sperm flagellar 1 (SPEF1) expression in a rare case of CFC of the common hepatic duct MATERIALS AND METHODS: 3 µm-thick CFC sections were immunohistochemically treated with antibodies raised against human SPA17 or SPEF1. In silico Protein-Protein Interaction (PPI) network and differential protein expression were also investigated RESULTS: Immunohistochemistry revealed SPA17 and SPEF1 in the cytoplasm of ciliated epithelium. SPA17, but not SPEF1, was also detected in cilia. The PPI networks demonstrated that other CTAs are significantly predicted functional partners with SPA17 and SPEF1. The differential protein expression demonstrated that SPA17 was higher in breast cancer, cholangiocarcinoma, liver hepatocellular carcinoma, uterine corpus endometrial carcinoma, gastric adenocarcinoma, cervical squamous cell carcinoma, bladder urothelial carcinoma. SPEF1 expression was higher in breast cancer, cholangiocarcinoma, uterine corpus endometrial carcinoma and kidney renal papillary cell carcinoma CONCLUSIONS: Our study suggests that further characterization of SPA17 and SPEF1 in patients with CFCs might provide significant insights to understand the mechanisms underlying their potential to malignant transformation.

Evolution in Endoscopic Sinus Surgery: The Adjuvant Role of Reboot Surgery in Patients with Uncontrolled Nasal Symptoms of Eosinophilic Granulomatosis with Polyangiitis.

PURPOSE: In the era of precision medicine, target-therapy with monoclonal antibodies (mAb) has enabled new treatment options in patients affected by eosinophilic granulomatosis with polyangiitis (EGPA). Nevertheless, sometimes unsatisfactory results at a nasal level may be observed. The aim of this study is to describe reboot surgery as a potential adjuvant strategy in multi-operated, yet uncontrolled EGPA patients treated with Mepolizumab. METHODS: We performed reboot surgery on EGPA patients with refractory CRSwNP. We obtained clinical data, nasal endoscopy, nasal biopsy, and symptom severity scores two months before surgery and 12 months after it. Computed tomography (CT) prior to surgery was also obtained. RESULTS: Two patients were included in the study. Baseline sinonasal disease was severe. Systemic EGPA manifestations were under control, and the patients received previous mepolizumab treatment and previous surgery with no permanent benefits on sinonasal symptoms. Twelve months after surgery, nasal symptoms were markedly improved; endoscopy showed an absence of nasal polyps and there were fewer eosinophils at histology. CONCLUSIONS: We presented the first experience of two EGPA patients with refractory CRSwNP who underwent non-mucosa sparing (reboot) sinus surgery; our results support the possible adjuvant role of reboot surgery in this particular subset of patients.

Exploring the CXCR4/CXCR7/CXCL12 Axis in Primary Desmoid Tumors.

BACKGROUND: Desmoid tumors have an extremely variable natural history. The uncertainty behind desmoid behavior reflects the complexity, which subtends its development and non-linear advancement. Apart from Wnt- ßcatenin mutation, estrogen receptors, and COX-2 overexpression, little is known about the ability of desmoids to grow and recur while being unable to metastasize. Several tumors have been shown to express the CXCR4/CXCR7/CXCL12 axis, whose functions are essential for tumoral development. AIMS: This study aimed to investigate the expression of the CXCR4/CXCR7/CXCL12 axis in primary desmoid tumors and discuss the potential role of this key-signaling as an antiangiogenic therapeutic strategy. METHODS: In this study, 3 µm-thick consecutive sections from each formalin-fixed and paraffin-embedded tissue block were treated with mouse monoclonal antibodies developed against CD34, CXCR4, CXCR7, and CXCL12. RESULTS: Two distinct vessel populations: CXCR4+ and CXCR4- vessels, have been found. Similarly, chemokine receptor CXCR7 expression in the entire desmoid tumor series positively stained a portion of tumor-associated vessels, identifying two distinct subpopulations of vessels: CXCR7+ and CXCR7- vessels. All 8 neoplastic tissue samples expressed CXCL12. Immunohistochemical positivity was identified in both stromal and endothelial vascular cells. Compared to CXCR4 and CXCR7, the vast majority of tumor-associated vessels were found to express this chemokine. CONCLUSION: It is the first time, as per our knowledge, that CXCR4/CXCR7/CXCL12 axis expression has been identified in a desmoid type-fibromatosis series. CXCL12 expression by neoplastic cells, together with CXCR4 and CXCR7 expression by a subgroup of tumor-associated vessels, was detected in all desmoid tumor tissue samples examined. Since chemokines are known contributors to neovascularization, CXCR4/CXCR7/CXCL12 axis may play a role in angiogenesis in this soft-tissue tumor histotype, thereby supporting its growth.

High-Resolution Analysis of Mononuclear Phagocytes Reveals GPNMB as a Prognostic Marker in Human Colorectal Liver Metastasis.

Patients with colorectal liver metastasis (CLM) present with heterogenous clinical outcomes and improved classification is needed to ameliorate the therapeutic output. Macrophages (Mϕ) hold promise as prognostic classifiers and therapeutic targets. Here, stemming from a single-cell analysis of mononuclear phagocytes infiltrating human CLM, we identified two Mϕ markers associated with distinct populations with opposite clinical relevance. The invasive margin of CLM was enriched in pro-inflammatory monocyte-derived Mϕ (MoMϕ) expressing the monocytic marker SERPINB2, and a more differentiated population, tumor-associated Mϕ (TAM), expressing glycoprotein nonmetastatic melanoma protein B (GPNMB). SERPINB2+ MoMϕ had an early inflammatory profile, whereas GPNMB+ TAMs were enriched in pathways of matrix degradation, angiogenesis, and lipid metabolism and were found closer to the tumor margin, as confirmed by spatial transcriptomics on CLM specimens. In a cohort of patients, a high infiltration of SERPINB2+ cells independently associated with longer disease-free survival (DFS; P = 0.033), whereas a high density of GPNMB+ cells correlated with shorter DFS (P = 0.012) and overall survival (P = 0.002). Cell-cell interaction analysis defined opposing roles for MoMϕ and TAMs, suggesting that SERPINB2+ and GPNMB+ cells are discrete populations of Mϕ and may be exploited for further translation to an immune-based stratification tool. This study provides evidence of how multi-omics approaches can identify nonredundant, clinically relevant markers for further translation to immune-based patient stratification tools and therapeutic targets. GPNMB has been shown to set Mϕ in an immunosuppressive mode. Our high dimensional analyses provide further evidence that GPNMB is a negative prognostic indicator and a potential player in the protumor function of Mϕ populations.

Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer.

Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival (OS), prognosis in Stage I, Stage II, Stage II-high-risk, and microsatellite-stable (MSS) patients. RESULTS: High-Immunoscore presented with the lowest risk of recurrence in both cohorts. In Stage I/II, recurrence-free rates at 5 years were 78.4% (95%-CI, 74.4−82.6), 88.1% (95%-CI, 85.7−90.4), 93.4% (95%-CI, 91.1−95.8) in low, intermediate and high Immunoscore, respectively (HR (Hi vs. Lo) = 0.27 (95%-CI, 0.18−0.41); p < 0.0001). In Cox multivariable analysis, the association of Immunoscore to outcome was independent (TTR: HR (Hi vs. Lo) = 0.29, (95%-CI, 0.17−0.50); p < 0.0001) of the patient's gender, T-stage, sidedness, and microsatellite instability-status (MSI). A significant association of Immunoscore with survival was found for Stage II, high-risk Stage II, T4N0 and MSS patients. The Immunoscore also showed significant association with TTR in Stage-I (HR (Hi vs. Lo) = 0.07 (95%-CI, 0.01−0.61); P = 0.016). The Immunoscore had the strongest (69.5%) contribution χ2 for influencing survival. Patients with a high Immunoscore had prolonged TTR in T4N0 tumors even for patients not receiving chemotherapy, and the Immunoscore remained the only significant parameter in multivariable analysis. CONCLUSION: In early CC, low Immunoscore reliably identifies patients at risk of relapse for whom a more intensive surveillance program or adjuvant treatment should be considered.

Nasal cytology as a reliable non-invasive procedure to phenotype patients with type 2 chronic rhinosinusitis with nasal polyps.

Background: The identification of type-2 inflammation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) acquires a crucial role in the endotypization needed for selecting patients for biological drugs targeting type-2 inflammation: to date, the parameters used include systemic and histological biomarkers. The aim of this study was to investigate whether nasal cytology could identify type-2 inflammation in patients with CRSwNP. Methodology: Thirty-three consecutive patients with CRSwNP underwent nasal cytology sampling at the level of the lower nasal turbinate, and of the polypoid tissue, and surgical polyp tissue sample was collected. The cellularity of the 3 collected samples were compared. Results: Mean nasal polyp tissue, nasal polyps cytology and inferior turbinate cytology eosinophils counts were 43.7 ± 39.6 cells/HPF, 32.8 ± 44.7 cells/HPF and 27.6 ± 58.0 cells/HPF respectively with inferior turbinate cytology eosinophils significantly lower than nasal polyp tissue count (p = 0.007). Both mean nasal polyps cytology eosinophils and mean inferior turbinate cytology eosinophils were significantly higher in patients with type-2 CRSwNP (52.5 ± 67.0 cells/HPF vs 12.2 ± 17.3 cells/HPF, p = 0.012, and 32.0 ± 62.1 cells/HPF vs 2.9 ± 2.9 cells/HPF, p = 0.020 respectively). Conclusions: Nasal cytology is suitable tool for assessing local biomarkers of type-2 inflammation in CRSwNP.

Enhanced endoscopic ultrasound imaging for pancreatic lesions: The road to artificial intelligence.

Early detection of pancreatic cancer has long eluded clinicians because of its insidious nature and onset. Often metastatic or locally invasive when symptomatic, most patients are deemed inoperable. In those who are symptomatic, multi-modal imaging modalities evaluate and confirm pancreatic ductal adenocarcinoma. In asymptomatic patients, detected pancreatic lesions can be either solid or cystic. The clinical implications of identifying small asymptomatic solid pancreatic lesions (SPLs) of < 2 cm are tantamount to a better outcome. The accurate detection of SPLs undoubtedly promotes higher life expectancy when resected early, driving the development of existing imaging tools while promoting more comprehensive screening programs. An imaging tool that has matured in its reiterations and received many image-enhancing adjuncts is endoscopic ultrasound (EUS). It carries significant importance when risk stratifying cystic lesions and has substantial diagnostic value when combined with fine needle aspiration/biopsy (FNA/FNB). Adjuncts to EUS imaging include contrast-enhanced harmonic EUS and EUS-elastography, both having improved the specificity of FNA and FNB. This review intends to compile all existing enhancement modalities and explore ongoing research around the most promising of all adjuncts in the field of EUS imaging, artificial intelligence.

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.

Tumor-associated macrophages and risk of recurrence in stage III colorectal cancer.

Tumor-associated macrophages (TAMs) have a unique favorable effect on the prognosis of colorectal cancer (CRC), although their association with stage-specific outcomes remains unclear. We assessed the densities of CD68+ and CD163+ TAMs at the invasive front of resected CRC stage III CRC from 236 patients, 165 of whom received post-surgical FOLFOX treatment, and their relationship with disease-free survival (DFS). Associations between macrophage mRNAs and clinical outcome were investigated in silico in 59 stage III CRC and FOLFOX-treated patients from The Cancer Genome Atlas (TCGA). Biological interactions of SW480 and HT29 cells and macrophages with FOLFOX were tested in co-culture models. Low TAM densities were associated with shorter DFS among patients receiving FOLFOX (CD68+ , p = 0.0001; CD163+ , p = 0.0008) but not among those who were untreated. By multivariate Cox analysis, only low TAM (CD68+ , p = 0.001; CD163+ , p = 0.002) and nodal status (CD68+ , p = 0.009; CD163+ , p = 0.007) maintained an independent predictive value. In the TCGA cohort, high CD68 mRNA levels were associated with better outcome (p = 0.02). Macrophages enhanced FOLFOX cytotoxicity on CRC cells (p < 0.01), and drugs oriented macrophage polarization from M2- to M1-phenotype. Low TAM densities identify stage III CRC patients at higher risk of recurrence after adjuvant therapy, and macrophages can augment the chemo-sensitivity of micro-metastases.

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).