Analyses of tumor microenvironment in patients with advanced renal cell carcinoma receiving immunotherapy (Meet-URO 18 study).

Introduction: The Meet-URO 18 study is a multicentric study of patients with metastatic renal cell carcinoma receiving nivolumab in the second-line and beyond, categorized as responders (progression-free survival ≥ 12 months) and non-responders (progression-free survival < 3 months). Areas covered: The current study includes extensive immunohistochemical analysis of T-lineage markers (CD3, CD4, CD8, CD8/CD4 ratio), macrophages (CD68), ph-mTOR, CD15 and CD56 expression on tumor cells, and PD-L1 expression, on an increased sample size including 161 tumor samples (113 patients) compared with preliminary presented data. Responders' tumor tissue (n = 90; 55.9%) was associated with lower CD4 expression (p = 0.014), higher CD56 expression (p = 0.046) and higher CD8/CD4 ratio (p = 0.030). Expert opinion/commentary: The present work suggests the regulatory role of a subpopulation of T cells on antitumor response and identifies CD56 as a putative biomarker of immunotherapy efficacy.

Diagnostic Biomarkers in Renal Cell Tumors According to the Latest WHO Classification: A Focus on Selected New Entities.

The fifth edition of the World Health Organization (WHO) classification for urogenital tumors, released in 2022, introduces some novelties in the chapter on renal epithelial tumors compared to the previous 2016 classification. Significant changes include the recognition of new disease entities and adjustments in the nomenclature for certain pathologies. Notably, each tumor entity now includes minimum essential and desirable criteria for reliable diagnosis. This classification highlights the importance of biological and molecular characterization alongside traditional cytological and architectural features. In this view, immunophenotyping through immunohistochemistry (IHC) plays a crucial role in bridging morphology and genetics. This article aims to present and discuss the role of key immunohistochemical markers that support the diagnosis of new entities recognized in the WHO classification, focusing on critical topics associated with single markers, in the context of specific tumors, such as the clear cell capillary renal cell tumor (CCPRCT), eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), and so-called "other oncocytic tumors", namely the eosinophilic vacuolated tumor (EVT) and low-grade oncocytic tumor (LOT). Their distinctive characteristics and immunophenotypic profiles, along with insights regarding diagnostic challenges and the differential diagnosis of these tumors, are provided. This state-of-the-art review offers valuable insights in biomarkers associated with novel renal tumors, as well as a tool to implement diagnostic strategies in routine practice.

2012 Briganti nomogram predict prostate cancer progression in EAU intermediate risk with unfavorable tumor grade: A single center experience.

BACKGROUND: To investigate the potential prognostic impact of Briganti's 2012 nomogram in EAU intermediate-risk patients presenting with an unfavorable tumor grade and treated with robot-assisted radical prostatectomy, eventually associated with extended pelvic lymph node dissection. MATERIALS AND METHODS: From January 2013 to December 2021, the study included 179 EAU intermediate-risk patients presenting with an unfavorable tumor grade (ISUP 3), eventually associated with a PSA of 10-20 ng/ml and/or cT-2b. Briganti's 2012 nomogram was assessed as both a continuous and dichotomous variable, categorized according to the median (risk score ⩾7% vs <7%). Disease progression, defined as biochemical recurrence and/or metastatic progression, was evaluated using Cox proportional hazards in both univariate and multivariate analyses. RESULTS: Disease progression occurred in 43 (24%) patients after a median (95% CI) follow-up of 78 (65.7-88.4) months. The nomogram risk score predicted disease progression, evaluated both as a continuous variable (hazard ratio, HR = 1.064; 95% CI: 1.035-1.093; p < 0.0001) and as a categorical variable (HR = 3.399; 95% CI: 1.740-6.638; p < 0.0001). This association was confirmed in multivariate analysis, where hazard ratios remained consistent even after adjusting for clinical and pathological factors. CONCLUSIONS: In EAU intermediate-risk PCa cases presenting with an unfavorable tumor grade and treated surgically, Briganti's 2012 nomogram was associated with disease progression after surgery. Consequently, as the nomogram risk score increased, patients were more likely to experience PCa progression, facilitating the stratification of the patient population into distinct prognostic subgroups.

The 2012 Briganti nomogram not only predicts lymph node involvement but also disease progression in surgically treated intermediate-risk prostate cancer patients with PSA <10 ng/mL, ISUP grade group 3, and clinical stage up to cT2b.

PURPOSE: We assessed the prognostic impact of the 2012 Briganti nomogram on prostate cancer (PCa) progression in intermediate-risk (IR) patients presenting with PSA <10ng/mL, ISUP grade group 3, and clinical stage up to cT2b treated with robot assisted radical prostatectomy eventually associated with extended pelvic lymph node dissection. MATERIALS AND METHODS: From January 2013 to December 2021, data of surgically treated IR PCa patients were retrospectively evaluated. Only patients presenting with the above-mentioned features were considered. The 2012 Briganti nomogram was assessed either as a continuous and a categorical variable (up to the median, which was detected as 6%, vs. above the median). The association with PCa progression, defined as biochemical recurrence, and/or metastatic progression, was evaluated by Cox proportional hazard regression models. RESULTS: Overall, 147 patients were included. Compared to subjects with a nomogram score up to 6%, those presenting with a score above 6% were more likely to be younger, had larger/palpable tumors, presented with higher PSA, underwent tumor upgrading, harbored non-organ confined disease, and had positive surgical margins at final pathology. PCa progression, which occurred in 32 (21.7%) cases, was independently predicted by the 2012 Briganti nomogram both considered as a continuous (Hazard Ratio [HR]:1.04, 95% Confidence Interval [CI]:1.01-1.08;p=0.021), and a categorical variable (HR:2.32; 95%CI:1.11-4.87;p=0.026), even after adjustment for tumor upgrading. CONCLUSIONS: In IR PCa patients with PSA <10ng/mL, ISUP grade group 3, and clinical stage up to cT2b, the 2012 Briganti nomogram independently predicts PCa progression. In this challenging subset of patients, this tool can identify prognostic subgroups, independently by upgrading issues.

Analyses of tumor microenvironment in patients with advanced renal cell carcinoma receiving immunotherapy (Meet-URO 18 study).

Introduction: The Meet-URO 18 study is a multicentric study of patients with metastatic renal cell carcinoma receiving nivolumab in the second-line and beyond, categorized as responders (progression-free survival ≥ 12 months) and non-responders (progression-free survival < 3 months). Areas covered: The current study includes extensive immunohistochemical analysis of T-lineage markers (CD3, CD4, CD8, CD8/CD4 ratio), macrophages (CD68), ph-mTOR, CD15 and CD56 expression on tumor cells, and PD-L1 expression, on an increased sample size including 161 tumor samples (113 patients) compared with preliminary presented data. Responders' tumor tissue (n = 90; 55.9%) was associated with lower CD4 expression (p = 0.014), higher CD56 expression (p = 0.046) and higher CD8/CD4 ratio (p = 0.030). Expert opinion/commentary: The present work suggests the regulatory role of a subpopulation of T cells on antitumor response and identifies CD56 as a putative biomarker of immunotherapy efficacy.

[Box: see text].

Forensic value of soft tissue detachments from the hyoid bone in death due to strangulation asphyxia.

BACKGROUND: There are no unequivocal histopathological findings for the diagnosis of fatal asphyxia due to neck compression. From the observation of a series of asphyxiation cases, we noted, during microscopic analysis, a high frequency of "detachment" of soft tissues from the hyoid bone. This specifically refers to the presence of an optical space between the surface of the hyoid bone and soft tissues. OBJECTIVES: We aimed to evaluate the detachment of soft tissues from the hyoid bone as specific histological evidence of death due to strangulation asphyxia. MATERIAL AND METHODS: Ten blocks were taken from deaths due to external mechanical compression of the neck (strangulation asphyxia, group A), 22 blocks were taken from deaths for other causes without trauma to the neck (group B), and 38 blocks were obtained from living subjects that have undergone laryngectomies (group C). The presence/absence of detachments were compared between the 3 groups (A, B and C) using Fisher's exact test. RESULTS: The detachment of soft tissues from the hyoid bone was observed in 5 cases (50%) in group A, 6 cases (27.2%) in group B, and 17 cases (44.3%) in group C. The sensitivity and specificity of the presence of the detachment in group A were 0.5 (95% confidence interval (95% CI): 0.38-0.62) and 0.57 (95% CI: 0.45-0.69), respectively. The comparison between the 3 groups and the presence/absence of soft tissue detachment showed no statistically significant differences between the groups (p = 0.329), clarifying that soft tissue detachment is a nonspecific variable for all 3 situations. CONCLUSIONS: Detachment of soft tissues has poor value as a single element to favor the diagnosis of asphyxia due to violent compression of the neck and should be interpreted as an artifactual finding, unrelated to the neck injury or injury vitality.

Tumor upgrading among very favorable intermediate-risk prostate cancer patients treated with robot-assisted radical prostatectomy: how can it impact the clinical course?

PURPOSE: We sought to investigate predictors of unfavorable tumor upgrading in very favorable intermediate-risk (IR) prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy, in addition to evaluate how it may affect the risk of disease progression. METHODS: A very favorable subset of IR PCa patients presenting with prostate-specific antigen (PSA) < 10 ng/mL, percentage of biopsy positive cores (BPC) < 50%, and either International Society of Urological Pathology (ISUP) grade group 1 and clinical stage T2b or ISUP grade group 2 and clinical stage T1c-2b was identified. Unfavorable pathology at radical prostatectomy was defined as the presence of ISUP grade group > 2 (unfavorable tumor upgrading), extracapsular extension (ECE), and seminal vesicle invasion (SVI). Disease progression was defined as the event of biochemical recurrence and/or local recurrence and/or distant metastases. Associations were evaluated by Cox regression and logistic regression analyses. RESULTS: Overall, 210 patients were identified between January 2013 and October 2020. Unfavorable tumor upgrading was detected in 71 (33.8%) cases, and adverse tumor stage, including ECE or SVI in 18 (8.6%) and 11 (5.2%) patients, respectively. Median (interquartile range) follow-up was 38.5 (16-61) months. PCa progression occurred in 24 (11.4%) patients. Very favorable IR PCa patients with unfavorable tumor upgrading at final pathology showed a persistent risk of disease progression, which hold significance after adjustment for all factors (Hazard Ratio [HR]: 5.95, 95% Confidence Interval [CI]: 1.97-17.92, p = 0.002) of which PSA was an independent predictor (HR: 1.52, 95% CI 1.12-2.08, p = 0.008). Moreover, these subjects were more likely to belong to the biopsy ISUP grade group 2. CONCLUSIONS: Very favorable IR PCa patients hiding unfavorable tumor upgrading were more likely to experience disease progression. Unfavorable tumor upgrading involved about one-third of cases and was less likely to occur in patients presenting with biopsy ISUP grade group 1. Tumor misclassification is an issue to discuss, when counseling this subset of patients for active surveillance because of the risk of delayed active treatment.

Optomechanical realization of the bosonic Kitaev chain.

The fermionic Kitaev chain is a canonical model featuring topological Majorana zero modes1. We report the experimental realization of its bosonic analogue2 in a nano-optomechanical network, in which the parametric interactions induce beam-splitter coupling and two-mode squeezing among the nanomechanical modes, analogous to hopping and p-wave pairing in the fermionic case, respectively. This specific structure gives rise to a set of extraordinary phenomena in the bosonic dynamics and transport. We observe quadrature-dependent chiral amplification, exponential scaling of the gain with system size and strong sensitivity to boundary conditions. All these are linked to the unique non-Hermitian topological nature of the bosonic Kitaev chain. We probe the topological phase transition and uncover a rich dynamical phase diagram by controlling interaction phases and amplitudes. Finally, we present an experimental demonstration of an exponentially enhanced response to a small perturbation3,4. These results represent the demonstration of a new synthetic phase of matter whose bosonic dynamics do not have fermionic parallels, and we have established a powerful system for studying non-Hermitian topology and its applications for signal manipulation and sensing.

TROP-2, NECTIN-4 and predictive biomarkers in sarcomatoid and rhabdoid bladder urothelial carcinoma.

Introduction: The surface protein TROP-2/TACSTD2 and the cell adhesion protein NECTIN-4/NECTIN4 are responsible for the efficacy of anticancer therapies based on antibody-drug conjugates (ADC) targeting intracellular microtubules. In contrast with common histologic subtypes of bladder urothelial carcinoma (BUC), little is known of TROP-2 and NECTIN-4 expression in sarcomatoid and rhabdoid BUC. Aims: In this study, we aimed to analyze TROP-2 and NECTIN-4 expression and additional predictive biomarkers by immunohistochemistry and fluorescence in situ hybridization (FISH) on 35 undifferentiated BUC (28 sarcomatoid and 7 rhabdoid). Wide genomic investigation was also performed on 411 BUC cases of the PanCancer Atlas, focusing on genes related to the microtubule pathways. Results: Seven of 35 (20%) undifferentiated BUC showed expression of TROP-2. NECTIN-4 was expressed in 10 cases (29%). Seven cases (20%) co-expressed TROP-2 and NECTIN-4. HER-2 FISH was amplified in 5 cases (14%) while HER-2 immunoexpression was observed in 14 cases (40%). PD-L1 scored positive for combined proportion score (CPS) in 66% of cases and for tumor proportion score (TPS) in 51% of cases. Pan-NTRK1-2/3 was elevated in 9 cases (26%) and FGFR-2/3 was broken in 7 of 35 cases (20%). Of 28 sarcomatoid BUC, 9 (32%) were negative for all (TROP-2, NECTIN-4, PD-L1, HER-2, FGFR and pan-NTRK) biomarkers and 3 (11%) expressed all five biomarkers. Among cases with rhabdoid dedifferentiation, 1 of 7 (14%) showed activation of all biomarkers, whereas 2 of 7 (28%) showed none. The mRNA analysis identified microtubule-related genes and pathways suitable for combined ADC treatments in BUC. Conclusion: Sarcomatoid and rhabdoid BUC do harbor positive expression of the ADC targets TROP-2 or NECTIN-4 in a relatively modest subset of cases, whereas the majority do not. Different combinations of other positive biomarkers may help the choice of medical therapies. Overall, these findings have important clinical implications for targeted therapy for BUC.

Avelumab Plus Intermittent Axitinib in Previously Untreated Patients with Metastatic Renal Cell Carcinoma. The Tide-A Phase 2 Study.

BACKGROUND: Combinations of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitor (ICI) against PD1/PD-L1 are the standard first-line therapy for patients with metastatic renal cell carcinoma (mRCC), irrespective of the prognostic class. OBJECTIVE: To investigate the feasibility and safety of withdrawing VEGFR-TKI but continuing anti-PD1/PD-L1 in patients who achieve a response to their combination. DESIGN, SETTING, AND PARTICIPANTS: This was a single-arm phase 2 trial in patients with treatment-naïve mRCC with prior nephrectomy, without symptomatic/bulky disease and no liver metastases. INTERVENTION: Enrolled patients received axitinib + avelumab; after 36 wk of therapy those who achieved a tumour response interrupted axitinib and continued avelumab maintenance until disease progression. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the rate of patients without progression 8 wk after the axitinib interruption. The secondary endpoints were the median value for progression-free (mPFS) and overall (mOS) survival and the safety in the overall population. RESULTS AND LIMITATIONS: Seventy-nine patients were enrolled and 75 were evaluated for efficacy. A total of 29 (38%) patients had axitinib withdrawn, as per the study design, with 72% of them having no progression after 8 wk and thus achieving the primary endpoint. The mPFS of the overall population was 24 mo, while the mOS was not reached. The objective response rate was 76% (12% complete response and 64% partial response), with 19% of patients having stable disease. In the patients who discontinued axitinib, the incidence of adverse events of any grade was 59% for grade 3 and 3% for grade 4. This study was limited by the lack of a comparative arm. CONCLUSIONS: The TIDE-A study demonstrates that the withdrawal of VEGFR-TKI with ICI maintenance is feasible for selected mRCC patients with evidence of a response to the VEGFR-TKI + ICI combination employed in first-line therapy. Axitinib interruption with avelumab maintenance leads to decreased side effects and should be investigated further as a new strategy to delay tumour progression. PATIENT SUMMARY: We evaluated whether certain patients with advanced kidney cancer treated with the fist-line combination of axitinib plus avelumab can interrupt the axitinib in case of a tumour response after 36 wk of therapy. We found that axitinib interruption improved the safety of the combination, while the maintenance with avelumab might delay tumour progression.

The 2012 Briganti nomogram predicts disease progression in surgically treated intermediate-risk prostate cancer patients with favorable tumor grade group eventually associated with some adverse factors.

To evaluate the prognostic potential of the 2012 Briganti nomogram for pelvic lymph node invasion on disease progression after surgery in intermediate-risk (IR) prostate cancer (PCa) patients with favorable tumor grade (International Society of Urological Pathology grade group 1 or 2), eventually associated with adverse clinical features as PSA between 10 and 20 ng/mL and/or clinical stage T2b. All IR PCa patients treated with robot-assisted radical prostatectomy and eventually extended pelvic lymph node dissection at the Department of Urology of the Integrated University Hospital of Verona between 2013 and 2021, with the abovementioned features, and available follow-up were considered. The 2012 Briganti nomogram score was assessed both as a continuous and dichotomous variable, where a mean risk score of 4% was used a threshold. The independent predictor status of the nomogram score on disease progression defined as the occurrence of biochemical recurrence and/or metastatic progression was evaluated using the Cox regression analysis. Overall, 348 patients were enrolled in the study. Median (interquartile range) follow-up was 98 (83.5-112.4) months. At multivariable Cox regression analysis, PCa progression, which occurred in 65 (18.7%) cases, was independently predicted only by the 2012 Briganti nomogram score evaluated as a continuous variable, among all considered clinical features (HR 1.16; 95%CI 1.08-1.24; p < 0.001). In addition, patients presenting with a nomogram score ≥ 4% were more likely to experience disease progression even after adjustment for clinical (HR 2.22, 95%CI 1.02-4.79; p = 0.043) and pathological (HR 1.80; 95%CI 1.06-3.05; p = 0.031) factors. In the examined patient population, the 2012 Briganti nomogram predicted PCa progression after surgery. Accordingly, as the risk score increased, patients were more likely to progress, independently by the occurrence of adverse pathology in the surgical specimen. The 2012 Briganti nomogram score categorized according to the mean value allowed to identify prognostic subgroups.

External validation of a red cell-based blood prognostic score in patients with metastatic renal cell carcinoma treated with first-line immunotherapy combinations.

Immunotherapy combinations with tyrosine-kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) had significantly improved outcomes of patients with mRCC. Predictive and prognostic factors are crucial to improve patients' counseling and management. The present study aimed to externally validate the prognostic value of a previously developed red cell-based score, including hemoglobin (Hb), mean corpuscular volume (MCV) and red cell distribution width (RDW), in patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI). We performed a sub-analysis of a multicentre retrospective observational study (ARON-1 project) involving patients with mRCC treated with first-line immunotherapy combinations. Uni- and multivariable Cox regression models were used to assess the correlation between the red cell-based score and progression-free survival (PFS), and overall survival (OS). Logistic regression were used to estimate the correlation between the score and the objective response rate (ORR). The prognostic impact of the red cell-based score on PFS and OS was confirmed in the whole population regardless of the immunotherapy combination used [median PFS (mPFS): 17.4 vs 8.2 months, HR 0.66, 95% CI 0.47-0.94; median OS (mOS): 42.0 vs 17.3 months, HR 0.60, 95% CI 0.39-0.92; p < 0.001 for both]. We validated the prognostic significance of the red cell-based score in patients with mRCC treated with first-line immunotherapy combinations. The score is easy to use in daily clinical practice and it might improve patient counselling.

The impact of prognostic group classification on prostate cancer progression in intermediate-risk patients according to the European Association of Urology system: results in 479 patients treated with robot-assisted radical prostatectomy at a single tertiary referral center.

Background: Treatment outcomes in intermediate-risk prostate cancer (PCa) may be impaired by adverse pathology misclassification including tumor upgrading and upstaging. Clinical predictors of disease progression need to be improved in this category of patients. Objectives: To identify PCa prognostic factors to define prognostic groups in intermediate-risk patients treated with robot-assisted radical prostatectomy (RARP). Design: Data from 1143 patients undergoing RARP from January 2013 to October 2020 were collected: 901 subjects had available follow-up, of whom 479 were at intermediate risk. Methods: PCa progression was defined as biochemical recurrence and/or local recurrence and/or distant metastases. Study endpoints were evaluated by statistical methods including Cox's proportional hazards, Kaplan-Meyer survival curves, and binomial and multinomial logistic regression models. Results: After a median (interquartile range) of 35 months (15-57 months), 84 patients (17.5%) had disease progression, which was independently predicted by the percentage of biopsy-positive cores ⩾ 50% and the International Society of Urological Pathology (ISUP) grade group 3 for clinical factors and by ISUP > 2, positive surgical margins and pelvic lymph node invasion for pathological features. Patients were classified into clinical and pathological groups as favorable, unfavorable (one prognostic factor), and adverse (more than one prognostic factor). The risk of PCa progression increased with worsening prognosis through groups. A significant positive association was found between the two groups; consequently, as clinical prognosis worsened, the risk of detecting unfavorable and adverse pathological prognostic clusters increased in both unadjusted and adjusted models. Conclusion: The study identified factors predicting disease progression that allowed the computation of highly correlated prognostic groups. As the prognosis worsened, the risk of PCa progression increased. Intermediate-risk PCa needs more prognostic stratification for appropriate management.

A study on 479 patients looked at how prognostic group classification affects progression in patients with intermediate-risk prostate cancer treated with robot-assisted radical prostatectomy Prostate cancer is a serious health concern in men, and those with intermediate-risk prostate cancer may experience disease progression. Urologists use various methods to predict the risk of progression in these patients. However, sometimes the predictions are not accurate. Therefore, researchers conducted a study to identify factors that could help predict disease progression in patients with intermediate-risk prostate cancer who underwent robot-assisted surgery. This study on 479 patients found that a percentage of biopsy-positive cores ⩾ 50% and the International Society of Urological Pathology (ISUP) grade group 3 were predictive factors of disease progression. Additionally, factors like ISUP > 2, positive surgical margins, and pelvic lymph node invasion also predicted disease progression. Patients were classified into three groups based on their clinical and pathological features: favorable, unfavorable (one negative prognostic factor), and adverse (more than one negative prognostic factor). The risk of prostate cancer progression increased as the prognosis worsened through these groups. The study concluded that a more accurate stratification of intermediate-risk prostate cancer patients is needed to manage the disease effectively.

PARP Inhibitors in Metastatic Prostate Cancer: A Comprehensive Systematic Review and Meta-analysis of Existing Evidence.

Poly (ADP-ribose) polymerase inhibitors (PARPi) represent an option in selected cases of metastatic castration-resistant prostate cancer (mCRPC). The aim of the present systematic review and meta-analysis is to evaluate the efficacy and safety of approved (Olaparib, Rucaparib) and investigational (Talazoparib, Niraparib, Veliparib) PARPi in mCRPC patients. Three databases were queried for studies analyzing oncological outcomes and adverse events of mCRPC patients receiving PARPi. Primary outcome was a PSA decline ≥ 50% from baseline. Secondary outcomes were objective response rate, progression-free survival (PFS), radiological PFS, overall survival (OS), conversion of circulating tumor cell count, and time to PSA progression. The number and rate of any grade adverse events (AEs), grade ≥ 3 AEs, and most common grade ≥ 3 AEs were registered. A subanalysis of outcomes per mutation type, prospective trials, and studies adopting combination therapies was performed. Overall, 31 studies were included in this systematic review, 28 of which are available for meta-analysis. The most frequently investigated drug was Olaparib. The most frequent mutation was BRCA2. A PSA decline rate of 43% (95% CI 0.32-0.54) was observed in the overall population. Mean OS was 15.9 (95% CI 12.9-19.0) months. In BRCA2 patients, PSA decline rate was 66% (95% CI 0.57-0.7) and OS 23.4 months (95% CI 22.8-24.1). Half of the patients suffered from grade 3 and 4 AEs (0.50 [95% CI 0.39-0.60]). Most common AEs were hematological, the most frequent being anemia (21.5%). PARP inhibitors represent a viable option for mCRPC patients. Current evidence suggests an increased effectiveness in homologous recombination repair (HRR) gene mutation carriers, especially BRCA2.

Robot-assisted excision of hemangioma of the right renal vein.

Hemangiomas, benign vascular masses, occasionally occur in the kidneys, presenting as rare, small, unilateral, and solitary growths. Venous hemangiomas, a renal subtype, are atypical. While clinically nonspecific, they are typically asymptomatic and may be incidentally discovered during unrelated clinical workups. Diagnosing renal hemangioma preoperatively is challenging due to rarity, lacking standard radiographic criteria, and poor differentiation from aggressive renal neoplasms on contrast-enhanced imaging. These tumors commonly follow a benign course, with no documented recurrence. This video article showcases the robot-assisted excision of a renal vein hemangioma, addressing the expertise needed in managing this uncommon condition robotically.

Positive independent association between preoperative endogenous testosterone density and tumor load density in surgical specimen of patients undergoing radical prostatectomy.

OBJECTIVE: To evaluate the influence of endogenous testosterone density (ETD) and tumor load density (TLD) in the surgical specimen of prostate cancer (PCa) patients. METHODS: ETD was assessed as the ratio of endogenous testosterone (ET) to prostate volume (PV). TLD was calculated as the ratio of tumor load (TL) to prostate weight. Preoperative prostate-specific antigen relative densities (PSAD) and percentage of biopsy-positive cores (BPCD) were also assessed. The association of high TLD (above the first quartile) with clinical and pathological factors was assessed by the logistic regression model (univariate and multivariate analysis). RESULTS: Between November 2014 and December 2019, ET was measured in 805 cases treated with radical prostatectomy (RP). Median (IQR) of ET and ETD was 412 (321.4-519 ng/dL) and 9.8 (6.8-14.4 ng/(dLxmL)) as well as for TL and TLD was 20 (10-30%) and 0.33 (0.17-0.58%/gr), respectively. As a result, high TLD was detected in 75% of cases. A positive independent association was found between high TLD and ETD. Accordingly, as ETD levels increased, the risk of detecting high TLD in the surgical specimen increased, regardless of PSAD and BPCD. CONCLUSIONS: At diagnosis of PCa, a positive independent association was found between ETD and risk of high TLD. Subjects with increasing ETD levels were more likely to have high TLD, associated with unfavorable pathology features. The positive association between ETD and TLD in the prostate microenvironment might adversely influence PCa's natural history.

Fatal cardiac air embolism after CT-guided percutaneous needle lung biopsy: medical complication or medical malpractice?

Computed tomography (CT)-guided percutaneous needle biopsy of the lung is a well-recognized and relatively safe diagnostic procedure for suspicious lung masses. Systemic air embolism (SAE) is a rare complication of transthoracic percutaneous lung biopsies. Herein, we present a case of an 81-year-old man who underwent CT-guided percutaneous needle biopsy of a suspicious nodule in the lower lobe of the right lung. Shortly after the procedure, the patient coughed up blood which prompted repeat CT imaging. He was found to have a massive cardiac air embolism. The patient became unresponsive and, despite resuscitation efforts, was pronounced dead. The pathophysiology, risk factors, clinical features, radiological evidence, and autopsy findings associated with SAE are discussed, which may, in light of the current literature, assist with the dilemma between assessing procedural complications and medical liability. Given the instances of SAE in the setting of long operative procedures despite careful technical execution, providing accurate and in-depth information, including procedure-related risks, even the rarest but potentially fatal ones, is recommended for informed consent to reduce medicolegal litigation issues.

mTOR eosinophilic renal cell carcinoma: a distinctive tumor characterized by mTOR mutation, loss of chromosome 1, cathepsin-K expression, and response to target therapy.

In the spectrum of oncocytic renal neoplasms, a subset of tumors with high-grade-appearing histologic features harboring pathogenic mutations in mammalian target of rapamycin (mTOR) and hitherto clinical indolent behavior has been described. Three cases (2F,1 M) with histologically documented metastases (lymph node, skull, and liver) were retrieved and extensively investigated by immunohistochemistry, FISH, and next-generation sequencing. Tumors were composed of eosinophilic cells with prominent nucleoli (G3 by ISUP/WHO) arranged in solid to nested architecture. Additionally, there were larger cells with perinuclear cytoplasmic shrinkage and sparse basophilic Nissl-like granules, superficially resembling the so-called spider cells of cardiac rhabdomyomas. The renal tumors, including the skull and liver metastases, showed immunoexpression PAX8, CK8-18, and cathepsin-K, and negativity for vimentin. NGS identified mTOR genetic alterations in the three cases, including the skull and liver metastases. One patient was then treated with Everolimus (mTOR inhibitors) with clinical response (metastatic tumor shrinkage). We present a distinct renal tumor characterized by high-grade eosinophilic cells, cathepsin-K immunohistochemical expression, and harboring mTOR gene mutations demonstrating a malignant potential and showing responsiveness to mTOR inhibitors.

Digital pathology world tour.

Objective: Digital pathology (DP) is currently in the spotlight and is rapidly gaining ground, even though the history of this field spans decades. Despite great technological progress, the adoption of DP for routine clinical diagnostic use remains limited. Methods: A systematic search was conducted in the electronic databases Pubmed-MEDLINE and Embase. Inclusion criteria were all published studies that encompassed any application of DP. Results: Of 4888 articles retrieved, 4041 were included. Relevant articles were categorized as "diagnostic" (147/4041, 4%) where DP was utilized for routine diagnostic workflow and "non-diagnostic" (3894/4041, 96%) for all other applications. The "non-diagnostic" articles were further categorized according to DP application including "artificial intelligence" (33%), "education" (5%), "narrative" (17%) for reviews and editorials, and "technical" (45%) for pure research publications. Conclusion: This manuscript provided temporal and geographical insight into the global adoption of DP by analyzing the published scientific literature.