An untargeted analytical workflow based on Kendrick mass defect filtering reveals dysregulations in acylcarnitines in prostate cancer tissue.

BACKGROUND: Metabolomics is nowadays considered one the most powerful analytical for the discovery of metabolic dysregulations associated with the insurgence of cancer, given the reprogramming of the cell metabolism to meet the bioenergetic and biosynthetic demands of the malignant cell. Notwithstanding, several challenges still exist regarding quality control, method standardization, data processing, and compound identification. Therefore, there is a need for effective and straightforward approaches for the untargeted analysis of structurally related classes of compounds, such as acylcarnitines, that have been widely investigated in prostate cancer research for their role in energy metabolism and transport and ß-oxidation of fatty acids. RESULTS: In the present study, an innovative analytical platform was developed for the straightforward albeit comprehensive characterization of acylcarnitines based on high-resolution mass spectrometry, Kendrick mass defect filtering, and confirmation by prediction of their retention time in reversed-phase chromatography. In particular, a customized data processing workflow was set up on Compound Discoverer software to enable the Kendrick mass defect filtering, which allowed filtering out more than 90 % of the initial features resulting from the processing of 25 tumoral and adjacent non-malignant prostate tissues collected from patients undergoing radical prostatectomy. Later, a partial least square-discriminant analysis model validated by repeated double cross-validation was built on the dataset of 74 annotated acylcarnitines, with classification rates higher than 93 % for both groups, and univariate statistical analysis helped elucidate the individual role of the annotated metabolites. SIGNIFICANCE: Hydroxylation of short- and medium-chain minor acylcarnitines appeared to be a significant variable in describing tissue differences, suggesting the hypothesis that the neoplastic growth is linked to oxidation phenomena on selected metabolites and reinforcing the need for effective methods for the annotation of minor metabolites.

Prognostic role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with non-metastatic and metastatic prostate cancer: A meta-analysis and systematic review.

Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic diseases. Methods: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect model. Results: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: -0.03-0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16-0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78-1.88) and between high and low PLR was 1.47 (95% CI: 0.91-2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44-2.13) and between high and low PLR was 1.05 (95% CI: 0.87-1.24). Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.

Diagnostic Accuracy of Contrast-Enhanced Ultrasound (CEUS) in the Detection of Muscle-Invasive Bladder Cancer: A Systematic Review and Diagnostic Meta-Analysis.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a diagnostic tool that is gaining popularity for its ability to improve overall diagnostic accuracy in bladder cancer (BC) staging. Our aim is to determine the cumulative diagnostic performance of CEUS in predicting preoperative muscle invasiveness using a comprehensive systematic review and pooled meta-analysis. METHODS: A systematic review until October 2023 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Patients with BC suspicion were offered CEUS before the transurethral resection of the bladder tumor (TURBT). The diagnostic performance of CEUS was evaluated based on non-muscle-invasive bladder cancer (NMIBC) vs. muscle-invasive bladder cancer (MIBC) confirmed at the final histopathological examination after TURBT. The outcomes were determined through pooled sensitivity, specificity, pooled positive likelihood ratio (PLR+), negative likelihood ratio (PLR-), and area under the summary receiver operating characteristic (SROC) along with their respective 95% confidence intervals (CI). RESULTS: Overall, five studies were included. In these studies, a total of 362 patients underwent CEUS prior to TURBT. The pooled sensitivity and specificity were 0.88 (95% CI: 0.81-0.93) and 0.88 (95% CI: 0.82-0.92), respectively. SROC curve depicted a diagnostic accuracy of 0.94 (95% CI: 0.81-0.98). The pooled PLR+ and PLR- were 7.3 (95% CI: 4.8-11.2) and 0.14 (95% CI: 0.08-0.23), respectively. CONCLUSIONS: Our meta-analysis indicates that CEUS is highly accurate in the diagnosis and staging for BC. Beyond its accuracy, CEUS offers the advantage of being a cost-effective, safe, and versatile imaging tool.

Intermittent Versus Continuous Androgen Deprivation Therapy for Biochemical Progression After Primary Therapy in Hormone-Sensitive Nonmetastatic Prostate Cancer: Comparative Analysis in Terms of CRPC-M0 Progression.

INTRODUCTION: To analyze whether the use of an intermittent (IAD) versus continuous (CAD) androgen deprivation therapy for the treatment of biochemical progression after primary treatments in prostate cancer can influence the development of nonmetastatic castration resistant prostate cancer (CRPC-M0). PATIENTS: 170 male patients with an histologically confirmed diagnosis of PC, presenting a biochemical progression after primary treatments (82 after radical prostatectomy and 88 after external radiation therapy), nonmetastatic at imaging were considered for continuous (85 cases) or intermittent (85 cases) administration of androgen deprivation therapy. METHODS: we retrospectively collect all data regarding histological diagnosis, primary treatment, imaging for M0-M1 staging, PSA at progression, time to biochemical progression from primary therapy, ADT used, IAD cycles, so to compare in 2 groups (IAD vs. CAD) time for progression from the beginning of ADT treatment and type of progression in terms of CRPC-M0 versus CRPC-M1 cases. RESULTS: no significant (P= .4955) difference in the whole CRPC progression was found between IAD (25.8%) and CAD (30.5%) treatment at a mean of 32.7 ± 7.02 months and 35.6 ± 13.1 months respectively (P= .0738). Mean PSA at CRPC development was significantly higher in the IAD group (5.16 ± 0.68 ng/mL) than in the CAD group (3.1 ± 0.7 ng/mL) (P < .001). In all cases, imaging to detect M status at CRPC development was PET TC scan. At univariate analysis CAD administration significantly increases the RR for CRPC-M0 progression (RR 3.48; 95%CI 1.66-7.29; P = .01) when compared to the IAD administration, and this effect at multivariate analysis remained significant and independent to the other variables (RR 2.34, 95%CI 1.52-5.33; P = .03). CONCLUSIONS: in our population with biochemical progression after primary treatment for PC, the intermittent administration of ADT significantly reduces the risk to develop CRPC-M0 disease when compared to a continuous administration of ADT, whereas no difference between the 2 strategies in terms of CRPC-M1 progression exists.

Regenerative Medicine-Based Treatment of Stress Urinary Incontinence with Mesenchymal Stem Cells: A Systematic Review and Meta-analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis is to analyze clinical trials on the use of autologous stem cell [SC] injection for the treatment of stress urinary incontinence [SUI] in humans. METHODS: We analyzed the effect in terms of UI improvement and continence recovery after treatment. A literature search was performed following the PRISMA guidelines. Entry into the analysis was restricted to data collected from clinical prospective trials on humans, including female and male patients with SUI. We performed a cumulative meta-analysis to explore the trend in the effect size across different groups at follow-up. Available data were compared in terms of Event Rate [ER] for the percentage of pad-free patients. RESULTS: 12 trials were enclosed in the analysis. The sample size of patients with SUI ranged from 5 to 123 cases, mainly female cases. Autologous muscle-derived stem cells [MDSCs] were used in 9 and adipocyte- derived SCs [ADSC] in 3 trials. Considering a random effect model, ER of continence recovery was 0.41 [95%CI 0.29 - 0.54], with similar results between the ADSC [ER, 0.40;95%CI 0.12 - 0.69] and the MDSC group [ER 0.41; 95%CI 0.27-0.55] [I2 84.69%; Q 104.69 - p<0.01] [Test of group differences p=0.96]. CONCLUSION: Autologous MDSC or ADSC injection to treat SUI is demonstrated to be a safe procedure and a 41% mean rate of continence recovery is described. A higher effort should be produced to design better clinical trials, objectively evaluating either modifications inside the urethral sphincter or long-term functional results in terms of pad test and UI questionnaires.

Comparative Prospective and Longitudinal Analysis on the Platelet-to-Lymphocyte, Neutrophil-to-Lymphocyte, and Albumin-to-Globulin Ratio in Patients with Non-Metastatic and Metastatic Prostate Cancer.

PURPOSE: To prospectively evaluate the albumin/globulin ratio (AGR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) diagnostic and prognostic predictive value in a stratified population of prostate cancer (PC) cases. METHODS: Population was divided based on the clinical and histologic diagnosis in: Group A: benign prostatic hyperplasia (BPH) cases (494 cases); Group B: all PC cases (525 cases); Group B1: clinically significant PC (426 cases); Group B2: non-metastatic PC (416 cases); Group B3: metastatic PC (109 cases). NLR, PLR, and AGR were obtained at the time of the diagnosis, and only in cases with PC considered for radical prostatectomy, determinations were also repeated 90 days after surgery. For each ratio, cut-off values were determined by receiver operating characteristics curve (ROC) analysis and fixed at 2.5, 120.0, and 1.4, respectively, for NLR, PLR, and AGR. RESULTS: Accuracy in predictive value for an initial diagnosis of clinically significant PC (csPC) was higher using PLR (0.718) when compared to NLR (0.220) and AGR (0.247), but, despite high sensitivity (0.849), very low specificity (0.256) was present. The risk of csPC significantly increased only according to PLR with an OR = 1.646. The percentage of cases with metastatic PC significantly increased according to high NLR and high PLR. Accuracy was 0.916 and 0.813, respectively, for NLR and PLR cut-off, with higher specificity than sensitivity. The risk of a metastatic disease increased 3.2 times for an NLR > 2.5 and 5.2 times for a PLR > 120 and at the multivariate analysis. CONCLUSION: PLR and NLR have a significant predictive value towards the development of metastatic disease but not in relation to variations in aggressiveness or T staging inside the non-metastatic PC. Our results suggest an unlikely introduction of these analyses into clinical practice in support of validated PC risk predictors.

Prognostic Value of Albumin to Globulin Ratio in Non-Metastatic and Metastatic Prostate Cancer Patients: A Meta-Analysis and Systematic Review.

The aim of our meta-analysis is to analyze data available in the literature regarding a possible prognostic value of the albumin to globulin ratio (AGR) in prostate cancer (PC) patients. We distinguished our analysis in terms of PC staging, histologic aggressiveness, and risk of progression after treatments. A literature search process was performed ("prostatic cancer", "albumin", "globulin", "albumin to globulin ratio") following the PRISMA guidelines. In our meta-analysis, the pooled Event Rate (ER) estimate for each group of interest was calculated using a random effect model. Cases were distinguished in Low and High AGR groups based on an optimal cut-off value defined at ROC analysis. Four clinical trials were enclosed (sample size range from 214 to 6041 cases). The pooled Risk Difference for a non-organ confined PC between High AGR and Low AGR cases was −0.05 (95%CI: −0.12−0.01) with a very low rate of heterogeneity (I2 < 0.15%; p = 0.43) among studies (test of group differences p = 0.21). In non-metastatic PC cases, the pooled Risk Difference for biochemical progression (BCP) between High AGR and Low AGR cases was −0.05 (95%CI: −0.12−0.01) (I2 = 0.01%; p = 0.69) (test of group differences p = 0.12). In metastatic PC cases, AGR showed an independent significant (p < 0.01) predictive value either in terms of progression free survival (PFS) (Odds Ratio (OR): 0.642 (0.430−0.957)) or cancer specific survival (CSS) (OR: 0.412 (0.259−0.654)). Our meta-analysis showed homogeneous results supporting no significant predictive values for AGR in terms of staging, grading and biochemical progression in non-metastatic PC.

Bilateral and Ipsilateral Central Neck Dissection in Total Thyroidectomy: a Long Term Comparison of Complications.

The role of prophylactic central compartment neck dissection (CCND) in total thyroidectomy (TT) is controversial in patients without clinically evident lymph nodes metastasis (cN0) because of association with transient and permanent hypoparathyroidism (HPT) as well as transient and permanent recurrent laryngeal nerve (RLN) injury. Instead of bilateral central neck dissection (bCCND), ipsilateral central compartment neck dissection (iCCND) has recently been proposed as a safer, alternative treatment for selected patients. The aim of this study is to characterize the morbidity that CCND (ipsilateral and bilateral) adds to TT. We enrolled 453 patients: Group A (316 patients) underwent TT alone, Group B (86 patients) underwent TT + iCCND, Group C (51 patients) underwent TT + bCCND. We compared the rates of RLN injury and HPT in three groups and data analysis showed that iCCND was associated with increased rate of transient HPT but not permanent HPT and bCCND was associated with increased rate of transient and permanent HPT, when compared with TT alone. Further studies are needed to evaluate the clear advantages of CCND (both ipsilateral and bilateral), but this should be considered in the context of an higher risk of surgical complications (especially transient and permanent hypoparathyroidism), in comparison with TT alone.

Total Versus Completion Thyroidectomy: A Multidimensional Evaluation of Long-Term Vocal Alterations.

BACKGROUND: Total thyroidectomy (TT) and completion thyroidectomy (CT) are two common surgical operations that are frequently followed by vocal symptoms despite preservation of the recurrent laryngeal nerve (RLN) and of the external branch of superior laryngeal nerve (EBSLN). The aim of this study was to analyze vocal alterations through endoscopic findings, videolaryngostroboscopy (VLS), acoustic vocal parameters and impact on patients' quality of life after surgery in the absence of laryngeal nerve injury. METHODS: We enrolled 198 patients who underwent thyroidectomy by the same surgeon. One hundred twenty-six patients underwent TT (group TT) while 72 underwent CT (group CT). All patients underwent preoperative VLS and Voice Handicap Index (VHI) assessment and postoperative VHI, VLS and Acoustic Voice Analysis with Multidimensional Voice Program Analysis 12 to 18 months after surgery. RESULTS: We observed a statistically significant higher rate of EBSLN injury in CT compared to TT. Even in the absence of RLN and EBSLN injury, patients who underwent TT and CT presented slightly worse acoustic vocal parameters and VHI scores compared to healthy controls. Interestingly, some acoustic vocal parameters and VHI scores were significantly worse in group CT compared to group TT. CONCLUSIONS: The higher rate of EBSLN injury in CT rather than in TT suggests a higher surgical risk in CT. The vocal parameters of loudness and self-perception of voice were significantly worse after CT, suggesting a larger trauma in patients' vocal outcome in CT if compared to TT, although these alterations were not reported as psychologically limiting daily life of patients. Nevertheless, the existence of multiple factors contributing to vocal alterations after thyroidectomy highlight the importance of a routine comprehensive functional voice analysis before and after surgery.

Influence of operative time and blood loss on surgical margins and functional outcomes for laparoscopic versus robotic-assisted radical prostatectomy: a prospective analysis.

INTRODUCTION: The aim of this article was to analyze whether operative time and blood loss during radical prostatectomy (RP) can significantly influence surgical margins (SM) status and post-operative functional outcomes. MATERIAL AND METHODS: We prospectively analyzed prostate cancer (PC) patients undergoing RP, using robot-assisted (RARP) or laparoscopic (LRP) procedures. Blood loss was defined using the variation in hemoglobin (Hb, g/dl) values from the day before surgery and no later than 4 hours after surgery. RESULTS: From a whole population of 413 cases considered for RP, 67% underwent LRP and 33.0% RARP. Positive SM (SM+) were found in 33.9% of cases. Mean surgical operative time was 172.3 ±76 min (range 49-485), whereas blood loss was 2.3 ±1.2 g/dl (range 0.3-7.6). Operative time and blood loss at RP were not significantly correlated (r = -0.028275; p = 0.684). SM+ rates significantly (p = 0.002) varied by operative time; a higher SM+ rate was found in cases with an operative time <120 min (41.2%) and >240 min (53.4%). The risk of SM+ significantly increased 1.70 and 1.94 times in cases with an operative time <120 min and >240 min, respectively, independently to the surgical approach. The rate of erectile disfunction (ED) varied from 22.4% to 60.3% between <120 min and >240 min procedures (p = 0.001). According to blood loss, SM+ rates slightly but significantly (p = 0.032) varied; a higher rate of SM+ was found in cases with a Hb variation between 2-4 g/dl (35.9%). CONCLUSIONS: Independently to the surgical approach, operative time, more than blood loss at RP, represents a significant variable able to influence SM status and post-operative ED.

Predictive markers of long-term recurrence in chronic rhinosinusitis with nasal polyps.

BACKGROUND: In last years, many attempts were made to recognize chronic rhinosinusitis with nasal polyps (CRSwNP) phenotypes focusing on identifying relevant key pathogenic molecules. Polyps recurrence rate ranges from 4% to 60%, so it's clear that not all clinical and immunologic factors associated with recurrence are known. OBJECTIVE: We investigate the inflammatory profile in patients with long term recurrent and non-recurrent CRSwNPs and if a specific profile is associated with recurrence, comparing eosinophilic, neutrophilic and lymphocytic infiltration, as well as IL-5 and IL-8 expression to long term recurrence rate. METHODS: This prospective study included 44 adult patients with CRSwNP treated with endoscopic sinus surgery between 2008 and 2010. Long term follow-up data (8-10 years) indicated that among 44 patients, 18 (40.1%) experienced long term recurrence of nasal polyposis needing maximal medical treatment or revision surgery. We realized two groups: one with patients who didn't present long term recurrence (26 patients) and another with patients who presented long term recurrence (18 patients) and in both groups eosinophilic, neutrophilic and lymphocytic infiltration and IL-5 and IL-8 expression were measured. RESULTS: The parameters that reached statistical significance (p < 0.05) comparing the two groups were eosinophilic infiltration and IL-5 expression, whereas neutrophilic and lymphocytic infiltration, as IL-8 expression didn't show any significant difference. Asthma and aspirin intolerance seemed significantly more frequent in patients with recurrence, while allergy presented not statistically significant difference between two groups. CONCLUSIONS: We can conclude that high eosinophilic infiltration and high IL-5 expression in CRSwNP correlate with higher rate of long term recurrence, while neutrophilic and lymphocytic infiltration, and IL-8 expression don't correlate with it. These findings provide the opportunity to improve our ability to predict the prognosis of surgical intervention, although it is still needed to explore the optimal predictor of outcome in CRSwNP.

The prognostic role of E-cadherin and ß-catenin overexpression in laryngeal squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: Epithelial-to-mesenchymal transition (EMT) consists of a rapid and reversible change in the cellular phenotype toward the mesenchymal cell phenotype that facilitates cell migration and invasion of the tumor into surrounding tissues followed by metastasis. In the present study, we sought to determine the clinical significance of E-cadherin, N-cadherin, ß-catenin, α-catenin, γ-catenin, caveolin-1, and vimentin in a cohort of patients with stage I to IVA laryngeal squamous cell carcinoma (LSCC) treated with surgery with or without adjuvant therapy using immunohistochemical analyses. STUDY DESIGN: Individual retrospective cohort study. METHODS: E-cadherin, N-cadherin, ß-catenin, α-catenin, γ-catenin, caveolin-1, and vimentin immunohistochemical expression were evaluated in a cohort of 82 patients with stages I to IVA LSCC. The Fisher exact test was used for categorical variables, and the Mann-Whitney test where appropriate for continuous variables. Survival comparisons was performed using the log-rank test. A multivariate analysis using the Cox proportional hazards model was performed and considered all EMT markers. RESULTS: In multivariate analysis, T stage was an independent risk factor for adverse disease-specific survival (DSS) and overall survival (OS) (P = .025 and .019, respectively). Cytoplasmic ß-catenin overexpression was independently associated with a longer DSS (P = .0007), and E-cadherin overexpression was found to be an independent risk factor for poor OS (P = .030). CONCLUSIONS: E-cadherin and ß-catenin pathways could represent future therapeutic targets in the treatment of LSCC. However, validation of our results in prospective cohorts of patients with LSCCs is required before their clinical implementation. LEVEL OF EVIDENCE: NA.