PURPOSE OF REVIEWPheochromocytomas and paragangliomas (PPGL) display a strong genetic determinism with 40% of inherited forms. The purpose of this review is to provide an update on current knowledge ...on adult forms of hereditary PPGL and their management.
RECENT FINDINGSPPGL are genetically-driven in 70% of cases, with germline and/or somatic mutations identified in more than 20 genes. Although eight new susceptibility genes have recently emerged, mutations on SDHx genes remain the most frequent. In addition to SDHB, mutations in SLC25A11, FH and MDH2 may predispose to a metastatic disease and somatic alterations including TERT and ATRX mutations, and the differential expression on noncoding RNAs are also associated with the occurrence of metastases.The biochemical diagnosis remains the mainstay of functional PPGL and does not differ between hereditary PPGL while the choice of the best nuclear imaging approach is dictated by the tumor type and can be influenced by the presence of a germline mutation (18F-DOPA PET/CT for cluster 2 mutation and Ga-DOTATATE PET/CT for cluster 1 mutation).
SUMMARYA systematic genetic testing and counselling is recommended for all PPGL patients and should lead to conservative surgery and an adapted follow up, in case of hereditary form.
Highlights • The efficacy of targeted therapy (TT) after PD-1/ PD-L1 blockade is unknown in mRCC. • We conducted a retrospective analysis of mRCC patients treated with PD-1/PD-L1 blockade and ...subsequent TT. • Median time to treatment failure on subsequent TT was 6.6 months. • 1-year and 2-year OS from the initiation of subsequent TT was 58% and 36%. • Both VEGF/VEGFR and mTOR inhibitors demonstrated activity following PD-1/PD-L1 blockade.
PI-QUAL (Prostate Imaging Quality) is a new score used to standardize the assessment of multiparametric magnetic resonance imaging (mpMRI). We provide further evidence that PI-QUAL has clinical ...implications. mpMRI of insufficient quality, defined as PI-QUAL <3, results in a higher rate of pathological upstaging.
Increasing use of multiparametric magnetic resonance imaging (mpMRI) has come with heterogeneity in image quality. The Prostate Imaging Quality (PI-QUAL) score is under scrutiny to assess its usefulness in predicting clinical outcomes.
To compare upstaging of localized disease on mpMRI (mrT2) to locally invasive disease in radical prostatectomy (RP) specimens (≥pT3a) in relation to PI-QUAL.
Patients treated with RP between 2015 and 2020 who underwent 1.5–3-T mpMRI within 6 mo before surgery and had systematic and mpMRI-US targeted biopsies were included. mpMRI scans were retrospectively assigned a PI-QUAL score, and prospectively acquired Prostate Imaging-Recording and Data System (PI-RADS) scores (version 2.0 or 2.1) were used. PI-QUAL scores were categorized as nondiagnostic (PI-QUAL <3), sufficient (PI-QUAL 3), or optimal (PI-QUAL >3).
We assessed the relationship between the PI-QUAL score and upstaging using multivariate logistic regression. mpMRI, clinical, and pathological findings were compared using χ2 tests and analysis of variance.
We identified 351 patients, of whom 40 (11.4%) had PI-QUAL <3, 57 (16.3%) had PI-QUAL 3, and 254 (72.3%) had PI-QUAL >3 scores. The distribution of PI-QUAL <3 (0–33.6%; p < 0.001) and PI-QUAL >3 (37.3–100%; p < 0.001) scores varied widely among centers. PI-QUAL ≥3 in comparison to PI-QUAL <3 was associated with a lower rate of upstaging (19% vs 35%; p = 0.02), greater detection of mrT3a and mrT3b prostate cancer (17.0% vs 2.5%; p = 0.016), a higher rate of PI-RADS 5 lesions (47% vs 27.5%; p = 0.002), a higher number of suspicious lesion (PI-RADS ≥3: 34.7% vs 15%; p = 0.012), and higher detection rates for aggregated (50.7% vs 22.5%; p = 0.001) and late (21.2% vs 0%; p < 0.001) extraprostatic extension. On multivariate analysis, PI-QUAL<3 was associated with more frequent upstaging in the RP specimen (odds ratio 3.4; p = 0.01).
In comparison to PI-QUAL ≥3, PI-QUAL <3 was significantly associated with a higher rate of upstaging from organ-confined disease on mpMRI to locally advanced disease on pathology, lower detection rates for PI-RADS 5 lesions and extraprostatic extension, and a lower number of suspicious lesions.
Poor image quality for magnetic resonance imaging (MRI) scans of the prostate is associated with underestimation of the stage of prostate cancer.
Abstract
To describe clinical outcomes of patients aged 75 years and above after partial nephrectomy (PN), and to assess independent factors of postoperative complications. We retrospectively ...reviewed information from our multi-institutional database. Every patient over 75 years old who underwent a PN between 2003 and 2016 was included. Peri-operative and follow up data were collected. Multivariate logistic regression was performed to determine independent predictive factors of postoperative complications. We reviewed 191 procedures including 69 (40%) open-surgery, and 122 (60%) laparoscopic procedures, of which 105 were robot-assisted. Median follow-up was 25 months. The mean age was 78 75–88. The American Society of Anesthesiologist’s score was 1, 2, 3 and 4 in 10.5%, 60%, 29% and 0.5% of patients respectively. The mean tumor size was 4.6 cm. Indication of PN was elective in 122 (65%) patients and imperative in 52 patients (28%). The median length of surgery was 150(± 60) minutes, and the median estimated blood loss 200 ml. The mean glomerular filtration rate was 71.5 ml/minute preoperatively, and 62 ml/min three months after surgery. The severe complications (Clavien III-V) rate was 6.2%. On multivariate analysis, the robotic-assisted procedure was an independent protective factor of medical postoperative complications (Odds Ration (OR) = 0.31 0.12–0.80, p = 0.01). It was adjusted for age and RENAL score, robotic-assisted surgery (OR = 0.22 0.06–0.79, p = 0.02), and tumor size (OR = 1.13 1.02–1.26, p = 0.01), but the patients age did not forecast surgical complications. Partial nephrectomy can be performed safely in elderly patients with an acceptable morbidity, and should be considered as a viable treatment option. Robotic assistance is an independent protective factor of postoperative complications.
Background: The molecular and cellular mechanisms that drive castration-resistant prostate cancer (CRPC) remain poorly understood. LSCmed cells defines an FACS-enriched population of ...castration-tolerant luminal progenitor cells that has been proposed to promote tumorigenesis and CRPC in Pten-deficient mice. The goals of this study were to assess the relevance of LSCmed cells through the analysis of their molecular proximity with luminal progenitor-like cell clusters identified by single-cell (sc)RNA-seq analyses of mouse and human prostates, and to investigate their regulation by in silico-predicted growth factors present in the prostatic microenvironment. Methods: Several bioinformatic pipelines were used for pan-transcriptomic analyses. LSCmed cells isolated by cell sorting from healthy and malignant mouse prostates were characterized using RT-qPCR, immunofluorescence and organoid assays. Results: LSCmed cells match (i) mouse luminal progenitor cell clusters identified in scRNA-seq analyses for which we provide a common 15-gene signature including the previously identified LSCmed marker Krt4, and (ii) Club/Hillock cells of the human prostate. This transcriptional overlap was maintained in cancer contexts. EGFR/ERBB4, IGF-1R and MET pathways were identified as autocrine/paracrine regulators of progenitor, proliferation and differentiation properties of LSCmed cells. The functional redundancy of these signaling pathways allows them to bypass the effect of receptor-targeted pharmacological inhibitors. Conclusions: Based on transcriptomic profile and pharmacological resistance to monotherapies that failed in CRPC patients, this study supports LSCmed cells as a relevant model to investigate the role of castration-tolerant progenitor cells in human prostate cancer progression.
Active surveillance (AS) in prostate cancer (PCa) represents a curative alternative for men with localised low-risk PCa. Continuous improvement of AS patient's selection and surveillance modalities ...aims at reducing misclassification, simplifying modalities of surveillance and decreasing need for invasive procedures such repeated biopsies. Biomarkers represent interesting tools to evaluate PCa diagnosis and prognosis, of which many are readily available or under evaluation. The aim of this review is to investigate the biomarker performance for AS selection and patient outcome prediction. Blood, urinary and tissue biomarkers were studied and a brief description of use was proposed along with a summary of major findings. Biomarkers represent promising tools which could be part of a more tailored risk AS strategy aiming to offer personalized medicine and to individualize the treatment and monitoring of each patient. The usefulness of biomarkers has mainly been suggested for AS selection, whereas few studies have investigated their role during the monitoring phase. Randomized prospective studies dealing with imaging are needed as well as larger prospective studies with long-term follow-up and strong oncologic endpoints.
BHD syndrome is characterized by an increased risk of bilateral and multifocal renal cell carcinoma (RCCs), but is rarely metastatic. Our report aims to analyze the outcome of patients with BHD ...syndrome who underwent percutaneous thermal ablation (TA). The present report included six BHD syndrome patients (five men) with a mean age of 66 ± 11 (SD) years who had a proven germline FLCN gene mutation and underwent TA for a renal tumor. Nineteen renal tumors (median two tumors per patient; range: 1–3), including seven chromophobe RCCs, five clear-cell RCCs, four papillary RCCs, two clear-cell papillary RCC, and one hybrid oncocytic/chromophobe tumor were treated in 14 ablation sessions. The mean size of the tumors was 21 ± 11 (SD) mm (median: 20 mm; interquartile range (IQR): 14–25 mm) for a mean volume of 7 ± 11 (SD) mL (median: 3; IQR: 1–5 mL). Technical success was achieved in all ablation sessions (primary success rate, 100%). The procedure was well tolerated under conscious sedation with no significant Clavien–Dindo complication (grade 2, 3, 4). All patients were alive with no distant metastasis during a median follow-up period of 74 months (range: 33–83 months). No local tumor progression was observed. The mean decrease in estimated glomerular filtration rate was 8 mL/min/1.73 m2. No patients required dialysis or renal transplantation. In this case series, percutaneous TA appeared as a safe and efficient nephron-sparing treatment for treating RCCs associated with BHD syndrome, even in the case of advanced chronic kidney disease.
Abstract Objectives The complexity of partial nephrectomy (PN) is partly anticipated by morphometric tumor-based scores that do not consider patient-related issues such as adherent perinephric fat ...(APF). Also, the objective is to prospectively assess the predictive factors of APF during PN, its effect on complications, and to correlate it to the histological reality. Methods A total of 125 consecutive patients undergoing robotic or open PN were prospectively included. The Mayo adhesive probability score (MAP score) was compared to the peroperative presence of APF defined by a score≥2. Adipose tissue was analyzed histologically for fibrosis and inflammatory infiltrate of CD68+macrophages. Univariate and multivariate logistic regression analyses were performed to evaluate predictive factors of APF, and outcomes were compared using chi-square and Kruskal-Wallis tests. Results APF was present in 51 patients (40.8%) and associated with slight longer operating time and increased blood loss. Warm ischemia time, margins, transfusion, and the Clavien-Dindo score were not different. In multivariate analysis, only male sex, age, waist circumference, fat density on computed tomography, and MAP score were significant predictors of APF. A radioclinical score was more predictive of APF than MAP score alone. Histologically, there was no macrophage infiltration but larger adipocytes in APF without significant differences in fibrosis. Conclusions APF can be accurately predicted using radioclinical data as the MAP score, combined with sex, age, and waist circumference. APF is associated with increased operative time and blood loss without postoperative complications. Histological analysis finds larger adipocytes in APF without inflammatory infiltrate, and no difference in fibrosis.
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