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The management of anal squamous cell carcinoma (ASCC) has yet to experience the transformative impact of precision medicine. Conducting genomic analyses may uncover novel prognostic biomarkers and offer potential directions for the development of targeted therapies. To that end, we assessed the prognostic and theragnostic implications of pathogenic variants identified in 571 cancer-related genes from surgical samples collected from a homogeneous, multicentric French cohort of 158 ASCC patients who underwent abdominoperineal resection treatment. Alterations in PI3K/AKT/mTOR, chromatin remodeling, and Notch pathways were frequent in HPV-positive tumors, while HPV-negative tumors often harbored variants in cell cycle regulation and genome integrity maintenance genes (e.g., frequent TP53 and TERT promoter mutations). In patients with HPV-positive tumors, KMT2C and PIK3CA exon 9/20 pathogenic variants were associated with worse overall survival in multivariate analysis (Hazard ratio (HR)KMT2C = 2.54, 95%CI = [1.25,5.17], P value = .010; HRPIK3CA = 2.43, 95%CI = [1.3,4.56], P value = .006). Alterations with theragnostic value in another cancer type was detected in 43% of patients. These results suggest that PIK3CA and KMT2C pathogenic variants are independent prognostic factors in patients with ASCC with HPV-positive tumors treated by abdominoperineal resection. And, importantly, the high prevalence of alterations bearing potential theragnostic value strongly supports the use of genomic profiling to allow patient enrollment in precision medicine clinical trials.
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Neoplasias del Ano , Carcinoma de Células Escamosas , Proctectomía , Humanos , Neoplasias del Ano/genética , Neoplasias del Ano/patología , Neoplasias del Ano/cirugía , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Fosfatidilinositol 3-Quinasa Clase I/genética , Mutación , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Fosfatidilinositol 3-Quinasas/genética , PronósticoRESUMEN
BACKGROUND: Perivascular epithelioid cell neoplasms (PEComas) encompass a heterogeneous family of mesenchymal tumors. Previously described clinicopathologic features aimed at distinguishing benign from malignant variants but lacked prognostic value. METHODS: This retrospective analysis examined clinicopathologic data from patients who had localized PEComa across French Sarcoma Network centers. The authors analyzed 12 clinicopathologic features in a Cox proportional hazard framework to derive a multivariate prognostic risk model for event-free survival (EFS). They built the PEComa prognostic score (PEC-PRO), in which scores ranged from 0 to 5, based on the coefficients of the multivariate model. Three groups were identified: low risk (score = 0), intermediate risk (score = 1), and high risk (score ≥ 2). RESULTS: Analyzing 87 patients who had a median 46-month follow-up (interquartile range, 20-74 months), the median EFS was 96.5 months (95% confidence interval [CI], 47.1 months to not applicable), with 2-year and 5-year EFS rates of 64.7% and 58%, respectively. The median overall survival was unreached, with 2-year and 5-year overall survival rates of 82.3% and 69.3%, respectively. The simplified Folpe classification did not correlate with EFS. Multivariate analysis identified three factors affecting EFS: positive surgical margins (hazard ratio [HR], 5.17; 95% CI, 1.65-16.24; p = .008), necrosis (HR, 3.94; 95% CI, 1.16-13.43; p = .030), and male sex (HR, 3.13; 95% CI, 1.19-8.27; p = 0.023). Four variables were retained in the prognostic model. Patients with low-risk PEC-PRO scores had a 2-year EFS rate of 93.7% (95% CI, 83.8%-100.0%), those with intermediate-risk PEC-PRO scores had a 2-year EFS rate of 67.4% (95% CI, 53.9%-80.9%), and those with high-risk PEC-PRO scores had a 2-year EFS rate of 2.3% (95% CI, 0.0%-18.3%). CONCLUSIONS: The PEC-PRO score reliably predicts the risk of postoperative recurrence in patients with localized PEComa. It has the potential to improve follow-up strategies but requires validation in a prospective trial.
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Neoplasias de Células Epitelioides Perivasculares , Humanos , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto , Neoplasias de Células Epitelioides Perivasculares/patología , Neoplasias de Células Epitelioides Perivasculares/terapia , Neoplasias de Células Epitelioides Perivasculares/mortalidad , Neoplasias de Células Epitelioides Perivasculares/cirugía , Anciano , Adulto Joven , Adolescente , Modelos de Riesgos Proporcionales , Tasa de SupervivenciaRESUMEN
Renal cell carcinomas (RCC) represent a group of heterogeneous tumors whose classification has greatly evolved since 1981. The latest update in 2022 classifies all renal cell carcinomas into six categories according to their morphology or the detection of specific molecular alterations. Molecular disassembly of renal cell carcinomas with papillary features has enabled the identification of new entities characterized by a specific molecular alteration, such as Fumarate Hydratase (FH) deficient RCC, TFE3-rearranged RCC or TFEB-altered RCC. This new classification allows for a more accurate diagnosis but requires a thorough knowledge of the genomic alterations to search for with immunohistochemical or molecular biology techniques. According to the new WHO 2022 classification, papillary renal cell carcinoma (PRC) type 1 or type 2 classification is no longer recommended. A classification based on nucleolar ISUP grade must be preferred: low-grade PRC (ISUP 1-2) or high-grade PRC (ISUP 3-4). The other prognostic factors remain the same: the pTNM stage, lymphovascular invasion, and the presence or absence of dedifferentiated areas referring to sarcomatoid or rhabdoid features. Of note, the presence of necrosis is not currently recognized as a poor prognostic element for this type of carcinoma. The diagnosis of high-grade PRC is from now on a diagnosis of exclusion. It can only be sustained after having ruled out TFE3-rearranged RCC, TFEB-altered RCC, and FH-deficient RCC. For clinicians, the diagnosis of PRC implies suggesting an oncogenetic consultation to screen for an associated genetic tumor syndrome regardless of the patient's age.
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PURPOSE: Cytology and cystoscopy, the current gold standard for diagnosing urothelial carcinomas, have limits: cytology has high interobserver variability with moderate or not optimal sensitivity (particularly for low-grade tumors); while cystoscopy is expensive, invasive, and operator dependent. The VISIOCYT1 study assessed the benefit of VisioCyt® for diagnosing urothelial carcinoma. METHODS: VISIOCYT1 was a French prospective clinical trial conducted in 14 centers. The trial enrolled adults undergoing endoscopy for suspected bladder cancer or to explore the lower urinary tract. Participants were allocated either Group 1: with bladder cancer, i.e., with positive cystoscopy or with negative cystoscopy but positive cytology, or Group 2: without bladder cancer. Before cystoscopy and histopathology, slides were prepared for cytology and the VisioCyt® test from urine samples. The diagnostic performance of VisioCyt® was assessed using sensitivity (primary objective, 70% lower-bound threshold) and specificity (75% lower-bound threshold). Sensitivity was also assessed by tumor grade and T-staging. VisioCyt® and cytology performance were evaluated relative to the histopathological assessments. RESULTS: Between October 2017 and December 2019, 391 participants (170 in Group 1 and 149 in Group 2) were enrolled. VisioCyt®'s sensitivity was 80.9% (95% CI 73.9-86.4%) and specificity was 61.8% (95% CI 53.4-69.5%). In high-grade tumors, the sensitivity was 93.7% (95% CI 86.0-97.3%) and in low-grade tumors 66.7% (95% CI 55.2-76.5%). Sensitivity by T-staging, compared to the overall sensitivity, was higher in high-grade tumors and lower in low-grade tumors. CONCLUSION: VisioCyt® is a promising diagnostic tool for urothelial cancers with improved sensitivities for high-grade tumors and notably for low-grade tumors.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Adulto , Humanos , Carcinoma de Células Transicionales/diagnóstico , Neoplasias de la Vejiga Urinaria/diagnóstico , Inteligencia Artificial , Estudios Prospectivos , Técnicas CitológicasRESUMEN
Fumarate hydratase deficient renal cell carcinoma (FH-RCC) is a rare malignant neoplasia caused by constitutive or somatic mutations in the FH gene whose diagnosis is primordial, requiring genetic counselling. Because of histological heterogeneity, such tumors have been in the past misclassified as "type 2 papillary carcinoma", "tubulo-cystic renal cell carcinoma" or "high grade papillary carcinoma". We report here a case of FH deficient renal cell carcinoma (FH-RCC) in a 69years old patient. Through this observation, we precise the epidemiological and histological aspects and diagnosis criteria of this rare tumor.
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Carcinoma Papilar , Carcinoma de Células Renales , Neoplasias Renales , Leiomiomatosis , Neoplasias Cutáneas , Neoplasias Uterinas , Femenino , Humanos , Carcinoma de Células Renales/diagnóstico , Fumarato Hidratasa/genética , Inmunohistoquímica , Neoplasias Renales/patología , Leiomiomatosis/diagnóstico , Neoplasias Cutáneas/genética , AncianoRESUMEN
Testis tumors are uncommon in oncology, and testicular metastasis from distant solid tumors are even rarer. We present two cases encountered in our department of pathology in CHU de Rennes, France. Moreover, we collected all reported cases in the Medline/PubMed databases of non-hematopoietic secondary testis tumors in adults, excluding autopsy studies, to propose an integrative study on this topic. In total, we report 98 cases of secondary testis lesions to prostate (n=38, 38.77 %), colorectal (n=19, 19.39%), gastric (n=12, 12.24%), kidney (n=7, 7.14%), lung (n=6, 6.12%) and other primary cancers. The median age at diagnosis was 66.5 years. We identified significantly more prostate adenocarcinoma (P<0.0001) when the primary tumor was known and significantly more colorectal adenocarcinoma (P=0.035) and pancreatic adenocarcinoma (P=0.002) when the primary tumor was unknown. The age at diagnosis was older when the primary tumor was known (P=0.007). We present the challenges for the diagnosis and propose some elements for diagnosis orientation. Finally, we discuss the possible ways of metastatic dissemination from primary site to testis, as illustrated by the two cases we present.
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Adenocarcinoma , Neoplasias Colorrectales , Neoplasias Pancreáticas , Neoplasias Testiculares , Masculino , Adulto , Humanos , Anciano , Testículo/patología , Adenocarcinoma/patología , Neoplasias Pancreáticas/patología , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patologíaRESUMEN
AIMS: Renal cell carcinomas (RCCs) represent 2-5% of kidney malignancies in children and adolescents. Appropriate diagnostic and classification are crucial for the correct management of the patients and in order to avoid inappropriate pre-operative chemotherapy, which is usually recommended if a Wilms' tumour is suspected. METHODS AND RESULTS: A French-Italian series of 93 renal cell carcinomas collected from 1990 to 2019 in patients aged less than 18 years was reclassified according to the 2016 World Health Organization (WHO) classification and the latest literature. TFE3 and TFEB fluorescence in-situ hybridisation (FISH) analyses and a panel of immunohistochemical stains were applied. The median age at diagnosis was 11 years (range = 9 months-17 years). MiT family (MiTF) translocation RCCs accounted for 52% of the tumours, followed by papillary (20%) and unclassified RCCs (13%). Other subtypes, such as SDHB-deficient and fumarate hydratase-deficient RCCs, represented 1-3% of the cases. We also described a case of ALK-rearranged RCC with a metanephric adenoma-like morphology. CONCLUSION: A precise histological diagnosis is mandatory, as targeted therapy could be applied for some RCC subtypes, i.e. MiTF-translocation and ALK-translocation RCC. Moreover, some RCC subtypes may be associated with a predisposition syndrome that will impact patients' and family's management and genetic counselling. A precise RCC subtype is also mandatory for the clinical management of the patients and inclusion in new prospective clinical trials.
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Carcinoma de Células Renales , Neoplasias Renales , Tumor de Wilms , Adolescente , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Carcinoma de Células Renales/patología , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Translocación GenéticaRESUMEN
AIMS: First described in 2014, renal cell carcinoma (RCC) with TFEB amplification (6p21) is a rare molecular subgroup whose diagnosis is challenging. The prognosis and therapeutic implications remain unclear. METHODS: We report here the clinical, histological, immunohistochemical, and genetic features of nine novel cases. The pathological and immunohistochemical features were centrally reviewed by expert uropathologists. Fluorescence in situ hybridisation (FISH) confirmed the diagnosis and comparative genomic hybridisation (CGH) was performed to determine quantitative genomic alterations. We also performed an exhaustive review of the literature and compiled our data. RESULTS: TFEB-amplified RCC were locally advanced, with initial lymph node involvement in one case and liver metastasis in another case. They were high-grade eosinophilic tumours with papillary/pseudopapillary architecture, frequent positivity for melanocytic markers, and frequent PDL1 expression. FISH demonstrated high-level TFEB amplification in six cases. One case showed concomitant TFEB translocation. CGH analysis identified complex alterations with frequent losses of 1p, 2q, 3p, 6p, and frequent 6p and 8q gains. VEGFA coamplification was identified in all cases with a lower level than TFEB. The prognosis was poor, with five patients having lymph node or distant metastases. CONCLUSION: TFEB-amplified RCC is a rare molecular subgroup with variable morphology whose diagnosis is confirmed by FISH analysis. The complex alterations identified by CGH are consistent with an aggressive clinical behaviour. The coamplification of VEGFA and the expression of PDL1 could suggest a potential benefit from antiangiogenics and targeted immunotherapy in combination for these aggressive tumours.
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Carcinoma de Células Renales , Neoplasias Renales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Humanos , Hibridación Fluorescente in Situ , Neoplasias Renales/genética , Neoplasias Renales/patología , Translocación GenéticaRESUMEN
OBJECTIVES: To investigate the role of cancer-associated fibroblasts (CAFs) in clear cell renal cell carcinoma (ccRCC) with respect to tumour aggressiveness, metastasis development, and resistance to anti-angiogenic therapy (vascular endothelial growth factor receptor-tyrosine kinase inhibitors [VEGFR-TKI]). PATIENTS AND METHODS: Our study involved tissue samples from three distinct and independent cohorts of patients with ccRCC. The presence of CAFs and tumour lymphangiogenesis was investigated, respectively, by transcriptional signatures and then correlated with tumour development and prognosis. The effect of these CAFs on tumour cell migration and VEGFR-TKI resistance was analysed on co-cultures of ccRCC cells with CAFs. RESULTS: Results from our cohorts and from in silico investigations showed that VEGFR-TKI significantly increase the number of CAFs in tumours. In the same populations of patients with ccRCC, the proportion of intra-tumoral CAFs correlated to shorter disease-free and overall survival. The presence of CAFs was also correlated with lymphangiogenesis and lymph node metastasis. CAFs increased the migration and decreased the VEGFR-TKI-dependent cytotoxic effect of tumour cells. CONCLUSIONS: Our results show that VEGFR-TKI promote the development of CAFs, and CAFs favour tumour aggressiveness, metastatic dissemination, and resistance to treatment in ccRCC. CAFs could represent a new therapeutic target to fight resistance to treatment of ccRCC. Targeting CAF and immunotherapies combination are emerging as efficient treatments in many types of solid tumours. Our results highlight their relevance in ccRCC.
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Fibroblastos Asociados al Cáncer/patología , Carcinoma de Células Renales/patología , Resistencia a Antineoplásicos , Neoplasias Renales/patología , Neovascularización Patológica/patología , Actinas/genética , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/metabolismo , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antineoplásicos/metabolismo , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/genética , Fibroblastos Asociados al Cáncer/efectos de los fármacos , Fibroblastos Asociados al Cáncer/fisiología , Capilares/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/cirugía , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular , Supervivencia sin Enfermedad , Endopeptidasas/genética , Femenino , Humanos , Neoplasias Renales/genética , Neoplasias Renales/terapia , Linfangiogénesis , Metástasis Linfática , Masculino , Proteínas de la Membrana/genética , Ratones , Persona de Mediana Edad , Terapia Neoadyuvante , Neovascularización Patológica/tratamiento farmacológico , Nefrectomía , Estudios Retrospectivos , Sunitinib/metabolismo , Sunitinib/uso terapéutico , Tasa de Supervivencia , TranscriptomaRESUMEN
OBJECTIVES: The objective of this study was to assess the impact of complete transurethral resection of bladder tumors (TURBTs) before radical cystectomy on pathological and oncological outcomes of patients with muscle-invasive bladder cancer (MIBC) and high-risk non-MIBC. MATERIALS AND METHODS: The charts of all patients who underwent radical cystectomy for bladder cancer in 2 academic departments of urology between 1996 and 2016 were retrospectively reviewed. Patients were divided into 2 groups according to the completeness of the last endoscopic resection before radical cystectomy: macroscopically complete transurethral resection (complete) or macroscopically incomplete transurethral resection (incomplete). The primary end point was the recurrence-free survival (RFS). Secondary end points included cancer-specific survival (CSS) and rates of pT0 and downstaging. RESULTS: Out of 486 patients included for analysis, the TURBT immediately preceding radical cystectomy was considered macroscopically complete in 253 patients (52.1%) and incomplete in 233 patients (47.9%). In multivariate analysis, macroscopically complete TURBT was the strongest predictor of both pT0 disease (OR = 3.1; p = 0.02) and downstaging (OR = 7.1; p < 0.0001). After a median follow-up of 41 months, macroscopically complete TURBT was associated with better RFS (5-year RFS: 57 vs. 37%; p < 0.0001) and CSS (5-year CSS: 70.8 vs. 54.5%; p = 0.002). In multivariate analysis adjusting for multifocality, weight of endoscopic resection specimen, cT4 stage on preoperative imaging, interval between endoscopic resection and radical cystectomy, neoadjuvant chemotherapy, pT stage, and associated carcinoma in situ, macroscopically complete endoscopic resection remained the main predictor of better RFS (HR = 0.4; p = 0.0003) and the only preoperative factor associated with CSS (HR = 0.5; p = 0.01). CONCLUSION: A macroscopically complete TURBT immediately preceding radical cystectomy may improve pathological and oncological outcomes in patients with MIBC and high-risk MIBC.
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Cistectomía/métodos , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Femenino , Humanos , Masculino , Invasividad Neoplásica , Estudios Retrospectivos , Resultado del Tratamiento , Uretra , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
The accurate diagnosis of Xp11-translocation renal cell carcinoma (RCC) in adults is challenging. TFE3 (located on chromosome X) fuses with a partner gene generally located on another chromosome. In rare cases TFE3 may fuse with a neighboring gene: RBM10. Because TFE3 false-positive immunostaining is a common pitfall in many laboratories, demonstration of the chromosomal rearrangement is required in order to ascertain the diagnosis. Fluorescence in situ hybridization (FISH)-that has been considered as the gold standard method-reaches its limits for detecting small Xp11 paracentric inversions. We performed a comprehensive clinical, histological and genomic study of six novel cases of RCC with RBM10-TFE3 fusion. Using FISH, TFE3 rearrangement was equivocal in one case and negative in others. RBM10-TFE3 fusion was discovered using targeted RNA sequencing (RNASeq). As all the previously reported cases (mean age: 50), the six patients were adults (mean age: 42), suggesting an epidemiologic difference between RBM10-TFE3 RCC and tumors harboring some other partner genes, such as ASPSCR1 that rather occur in children. Array-comparative genomic hybridization showed several alterations, notably a gain of 17q in four cases with papillary features and loss of 3p in one case with clear cells. Our study demonstrates that, though rare among adult cases of RCC, RBM10-TFE3 fusion is not exceptional and warrants appropriate molecular detection. Notably, it would be worthy to systemically investigate by RNASeq challenging RCC with type-2 papillary features and 17q gain.
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Carcinoma de Células Renales/genética , Neoplasias Renales/genética , Proteínas de Fusión Oncogénica/genética , Proteínas de Unión al ARN/genética , Adulto , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Femenino , Humanos , Hibridación Fluorescente in Situ , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , MasculinoRESUMEN
BACKGROUND: Prostate cancer (PCa) is more frequent and more aggressive in populations of African descent than in Caucasians. Since the fatty acid composition of peri-prostatic adipose tissue (PPAT) has been shown to differ according to the ethno-geographic origin and is involved in PCa aggressiveness, we aimed to analyze the cholesterol content of PPAT from Caucasian and African-Caribbean patients, in correlation with markers of disease aggressiveness and cholesterol metabolism in cancer tissues. METHODS: The quantification of cholesterol in PPAT was analyzed in 52 Caucasian and 52 African-Caribbean PCa patients, with in each group 26 indolent tumors (ISUP Group1 and pT2) and 26 potentially aggressive tumors (ISUP Group 3-5 and/or pT3). The expression of proteins involved in cholesterol metabolism was analyzed by immunohistochemistry on cancer tissue samples included in tissue microarrays. RESULTS: The amount of cholesterol esters was lower in PPAT from African-Caribbean patients compared with Caucasians, without any correlation with markers of disease aggressiveness. In cancer tissues from African-Caribbean patients, the expression of ABCA1 (involved in cholesterol efflux) was decreased, and that of SREBP-2 (involved in cholesterol uptake) was increased. In both groups of patients, SREBP-2 expression was strongly associated with that of Zeb1, a key player in the epithelial-to-mesenchymal transition (EMT) process. CONCLUSION: These results suggest that cholesterol metabolism differs according to the ethno-geographic origin, in both PPAT and cancer tissues. In African-Caribbeans, the orientation towards accumulation of cholesterol in cancer cells is associated with a more frequent state of EMT, which may promote PCa aggressiveness in this population.
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Tejido Adiposo , Colesterol/metabolismo , Próstata/patología , Neoplasias de la Próstata , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/análisis , Transportador 1 de Casete de Unión a ATP/análisis , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Población Negra/estadística & datos numéricos , Transición Epitelial-Mesenquimal , Francia/epidemiología , Humanos , Inmunohistoquímica , Metabolismo de los Lípidos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proteína 2 de Unión a Elementos Reguladores de Esteroles/análisis , Población Blanca/estadística & datos numéricosRESUMEN
INTRODUCTION: Kidney biopsies (KBs) are performed in patients with type 2 diabetes (T2D) to diagnose non-diabetic or hypertensive kidney disease (NDHKD) potentially requiring specific management compared to diabetic and or hypertensive nephropathy (absence of NDHKD). Indications for KB are based on the presence of atypical features compared to the typical course of diabetic nephropathy. In this study, we assessed the association of different patterns of atypical features, or KB indications, with NDHKD. METHODS: Native KBs performed in patients with T2D were analyzed. Data were collected from the patients' records. KB indications were determined according to the presence of different atypical features considered sequentially: (1) presence of any feature suggesting NDHKD which is not among the following ones, (2) recent onset of nephrotic syndrome, (3) low or rapidly declining estimated glomerular filtration rate (eGFR), (4) rapid increase in proteinuria, (5) short duration of diabetes, (6) presence of hematuria, or (7) normal retinal examination. RESULTS: Among the 463 KBs analyzed, NDHKD was diagnosed in 40% of the total population and 54, 40, 24, and 7% of the KBs performed for indications 1-4 respectively. Conversely, no patient who underwent KB for indications 5-7 displayed NDHKD. Logistic regression analyses identified eGFRCKD-EPI >15 mL/min/1.73 m2, urinary protein-to-Cr ratio <0.3 g/mmol, hematuria, HbA1c <7%, and diabetes duration <5 years as predictors of NDHKD, independently from the indication group. CONCLUSION: NDHKD is frequent in T2D. Despite the association of hematuria with NDHKD, our results suggest that presence of hematuria and absence of DR are insufficient to indicate KB in the absence of concurrent atypical features. Conversely, rapid progression of proteinuria and rapid deterioration of eGFR are major signals of NDHKD.
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Diabetes Mellitus Tipo 2/complicaciones , Enfermedades Renales/diagnóstico , Enfermedades Renales/patología , Riñón/patología , Selección de Paciente , Anciano , Biopsia , Estudios Transversales , Femenino , Tasa de Filtración Glomerular , Hematuria/patología , Humanos , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Proteinuria/patología , Estudios Retrospectivos , Factores de TiempoRESUMEN
Engaging in exercise while undergoing radiotherapy (RT) has been reported to be safe and achievable. The impact of exercise training (ET) on RT efficiency is however largely unknown. Our study aims to investigate the interactions between ET and RT on prostate cancer growth. Athymic mice received a subcutaneous injection of PPC-1 cells and were randomly assigned to either cancer control, cancer ET, cancer RT, or cancer RT combined with ET (CaRT-ET). Mice were sacrificed 24 days post-injection. All three intervention groups had reduced tumor size, the most important decrease being observed in CaRT-ET mice. Apoptotic marker cleaved caspase-3 was not modified by ET, but enhanced with RT. Importantly, this increase was the highest when the two strategies were combined. Furthermore, NK1.1 staining and gene expression of natural killer (NK) cell receptors Klrk1 and Il2rß were not affected by ET alone but were increased with RT, this effect being potentiated when combined with ET. Overall, our study shows that (a) ET enhances RT efficiency by potentiating NK cell infiltration, and (b) while ET alone and ET combined with RT both reduce tumor growth, the mechanisms mediating these effects are different.
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Condicionamiento Físico Animal/métodos , Neoplasias de la Próstata/radioterapia , Radioterapia/métodos , Animales , Antígenos Ly/genética , Antígenos Ly/metabolismo , Apoptosis , Caspasa 3/genética , Caspasa 3/metabolismo , Línea Celular Tumoral , Terapia Combinada , Humanos , Subunidad beta del Receptor de Interleucina-2/genética , Subunidad beta del Receptor de Interleucina-2/metabolismo , Masculino , Ratones , Subfamilia B de Receptores Similares a Lectina de Células NK/genética , Subfamilia B de Receptores Similares a Lectina de Células NK/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/genética , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/terapiaRESUMEN
To investigate the association of adherent perinephric fat (APF) with perioperative outcomes, we conducted a systematic review and meta-analysis of the literature to clarify the impact of APF in patients undergoing partial nephrectomy. A systematic literature search using the Medline, Scopus, and Cochrane databases was performed in April 2019 and updated in November 2019 to identify studies investigating the effect of APF on perioperative outcomes in patients treated with partial nephrectomy with the aim of evaluating its impact on intraoperative, postoperative and oncological outcomes. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. A total of 1534 patients in nine nonrandomized, observational studies met our inclusion criteria. Patients with APF were significantly older (p = 0.0001), had a higher BMI (p = 0.0001) and were predominately male (p = 0.003). APF was associated with a higher operative time (p = 0.001) and higher blood loss (p = 0.002). No significant impact of APF was found in terms of postoperative complications, positive margins or length of stay. APF was also found to be associated with malignant renal histology of RCC on final pathology (p = 0.005). APF was associated with some adverse perioperative outcomes, especially a prolonged operating time and higher blood loss. In addition, APF was also associated with underlying renal malignancy, but the precise causal mechanism requires further exploration.
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Neoplasias Renales , Procedimientos Quirúrgicos Robotizados , Tejido Adiposo , Índice de Masa Corporal , Humanos , Riñón , Neoplasias Renales/cirugía , Masculino , Nefrectomía , Complicaciones Posoperatorias , Resultado del TratamientoRESUMEN
We previously demonstrated that mast cells expressing HLA-G are associated with regions of hepatitis C virus-induced liver fibrosis. Here, we aimed to determine whether HLA-G expression in mast cells is specific to viral etiology, the liver, or to the general process of fibrosis. We enumerated HLA-G+ cells and mast cells by the immunohistochemistry of (i) liver blocks from 41 cases of alcoholic cirrhosis, (ii) 10 of idiopathic pulmonary fibrosis (IPF), and (iii) 10 of renal fibrosis. The nature of the HLA-G+ cells was specified by multiplex immunofluorescence using software. More than half of all HLA-G+ cells were mast cells in fibrotic areas of alcoholic cirrhosis and IPF. In the kidneys, subjected to fibrosis, the HLA-G+ cells were indeed mast cells but could not be counted. Moreover, in certain cases of the liver and lung, we observed a number of cellular nodes, which were secondary or tertiary follicles, in which HLA-G was highly expressed by B lymphocytes. In conclusion, HLA-G+ mast cells could be observed in the fibrotic regions of all organs studied. Previous studies suggest a protective role for HLA-G+ mast cells against inflammation and fibrosis. The observed follicles with B lymphocytes that express HLA-G may also reinforce their antifibrotic role.
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Fibrosis/genética , Antígenos HLA-G/genética , Riñón/metabolismo , Hígado/metabolismo , Pulmón/metabolismo , Anciano , Linfocitos B/metabolismo , Linfocitos B/patología , Recuento de Células , Femenino , Fibrosis/metabolismo , Fibrosis/patología , Regulación de la Expresión Génica/genética , Humanos , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Riñón/patología , Hígado/patología , Pulmón/patología , Masculino , Mastocitos/metabolismo , Mastocitos/patología , Persona de Mediana EdadRESUMEN
Renal cell carcinoma with leiomyomatous stroma is a rare and poorly described histopathological entity. Here we report a unique case with osseous metaplasia, in a 31-year-old man recently diagnosed with a tuberous sclerosis complex (TSC2 gene mutation). Partial nephrectomy was performed. Histologically, the epithelial component was made up of papillary and alveolar structures with clear to eosinophilic cytoplasm, and basally located nuclei. The cells are surrounded by an abundant smooth muscle stroma with focally osseous metaplasia. The tumor was positive for carbonic anhydrase IX, cytokeratin 7, cytokeratin 20, and CD10, and negative for TFE3. This emerging entity is highly correlated to tuberous sclerosis complex, which justifies a screening for the syndrome when this diagnosis is made.
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Carcinoma de Células Renales , Neoplasias Renales , Esclerosis Tuberosa , Adulto , Biomarcadores de Tumor , Humanos , Masculino , Metaplasia , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/diagnósticoRESUMEN
Apolipoprotein A1 amyloidosis (ApoAI) results from specific mutations in the APOA1 gene causing abnormal accumulation of amyloid fibrils in diverse tissues. The kidney is a prominent target tissue in ApoAI amyloidosis with a remarkable selectivity for the renal medulla. Here, we investigated six French families with ApoAI Glu34Lys, p.His179Profs∗47, and a novel p.Thr185Alafs∗41 variant revealing unprecedented clinical association of a glomerular with a retinal disease. Comprehensive clinicopathological, molecular and proteomics studies of numerous affected tissues ensured the correlation between clinical manifestations, including novel unrecognized phenotypes, and apoA-I amyloid deposition. These ophthalmic manifestations stemmed from apoA-I amyloid deposition, highlighting that the retina is a previously unrecognized tissue affected by ApoAI amyloidosis. Our study provides the first molecular evidence that a significant fraction of ApoAI amyloidosis cases with no family history result from spontaneous neomutations rather than variable disease penetrance. Finally, successful hepatorenal transplantation resulted in a life- and vision-saving measure for a 32-year-old man with a hitherto unreported severe ApoAI amyloidosis caused by the very rare Glu34Lys variant. Our findings reveal new modes of occurrence and expand the clinical spectrum of ApoAI amyloidosis. The awareness of glomerular and ocular manifestations in ApoAI amyloidosis should enable earlier diagnosis and avoid misdiagnosis with other forms of renal amyloidosis. Thus, documented apoA-I amyloid deposition in the retina offers new biological information about this disease and may change organ transplantation practice to reduce retinal damage in patients with ApoAI amyloidosis.
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Amiloidosis Familiar , Amiloidosis , Enfermedades Renales , Adulto , Amiloidosis/diagnóstico , Amiloidosis/genética , Amiloidosis Familiar/genética , Apolipoproteína A-I/genética , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/genética , Masculino , RetinaRESUMEN
Renal cell carcinoma is the third type of urologic cancer and has a poor prognosis with 30% of metastatic patients at diagnosis. The antiangiogenics and targeted immunotherapies led to treatment remodeling emphasizing the role of the tumour microenvironment. However, long-term responses are rare with a high rate of resistance. New strategies are emerging to improve the efficacy and the emerging drugs are under evaluation in ongoing trials. With the different treatment options, there is an urgent need to identify biomarkers in order to predict the efficacy of drugs and to better stratify patients. Owing to the limitations of programmed death-ligand 1 (PD-L1), the most studied immunohistochemistry biomarkers, and of the tumor mutational burden, the identification of more reliable markers is an unmet need. New technologies could help in this purpose.
Asunto(s)
Carcinoma de Células Renales/terapia , Inmunoterapia/métodos , Neoplasias Renales/terapia , Animales , Carcinoma de Células Renales/inmunología , Ensayos Clínicos como Asunto , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéuticoRESUMEN
INTRODUCTION: Lysozyme-induced nephropathy is a rare and unknown complication of chronic myelomonocytic leukemia with overproduction of lysozyme by tumoral cells leading to proximal tubular cells injuries. The present case reports a lysozyme nephropathy secondary to chronic myelomonocytic leukemia. OBSERVATION: We reported a case of a 82-years-old woman who presented an acute renal failure in a context of diarrhea and vomiting. Her background was characterized by untreated chronic myelomonocytic leukemia and high blood pressure. Despite rehydration, renal function deteriorated. Renal biopsy revealed a tubulo-interstitial lysozyme-induced nephropathy with a vacuolization of the tubular epithelium by eosinophilic droplets stained by anti-lysozyme antibody, without tumoral infiltration of the renal parenchyma. CONCLUSION: Lysozyme-induced nephropathy is a rare disease which can be suspected biologically and needs histologic confirmation. Other causes of renal failure secondary to chronic myelomonocytic leukemia have to be eliminated first in these patients. The treatment is symptomatic and is associated with treatments of the underlying hematologic pathology.