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1.
World J Urol ; 42(1): 233, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613608

RESUMO

PURPOSE: This study aimed to evaluate the ability of Kidney Stone Calculator (KSC), a flexible ureteroscopy surgical planning software, to predict the lithotripsy duration with both holmium:YAG (Ho:YAG) and thulium fiber laser (TFL). METHODS: A multicenter prospective study was conducted from January 2020 to April 2023. Patients with kidney or ureteral stones confirmed at non-contrast computed tomography and treated by flexible ureteroscopy with laser lithotripsy were enrolled. "Kidney Stone Calculator" provided stone volume and subsequent lithotripsy duration estimation using three-dimensional segmentation of the stone on computed tomography and the graphical user interface for laser settings. The primary endpoint was the quantitative and qualitative comparison between estimated and effective lithotripsy durations. Secondary endpoints included subgroup analysis (Ho:YAG-TFL) of differences between estimated and effective lithotripsy durations and intraoperative outcomes. Multivariate analysis assessed the association between pre- and intraoperative variables and these differences according to laser source. RESULTS: 89 patients were included in this study, 43 and 46 in Ho:YAG and TFL groups, respectively. No significant difference was found between estimated and effective lithotripsy durations (27.37 vs 28.36 min, p = 0.43) with a significant correlation (r = + 0.89, p < 0.001). Among groups, this difference did not differ (p = 0.68 and 0.07, respectively), with a higher correlation between estimated and effective lithotripsy durations for TFL compared to Ho:YAG (r = + 0.95, p < 0.001 vs r = + 0.81, p < 0.001, respectively). At multivariate analysis, the difference was correlated with preoperative (volume > 2000 mm3 (Ho:YAG), 500-750 mm3 SV and calyceal diverticulum (TFL)), operative (fragmentation setting (p > 0.001), and basket utilization (p = 0.05) (Ho:YAG)) variables. CONCLUSION: KSC is a reliable tool for predicting the lithotripsy duration estimation during flexible ureteroscopy for both Ho:YAG and TFL. However, some variables not including laser source may lead to underestimating this estimation.


Assuntos
Cálculos Renais , Litotripsia , Cálculos Ureterais , Humanos , Hólmio , Túlio , Ureteroscopia , Estudos Prospectivos , Cálculos Renais/cirurgia , Lasers
2.
World J Urol ; 41(3): 725-732, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36710292

RESUMO

INTRODUCTION: Due to medical improvements leading to increased life expectancy after renal transplantation and widened eligibility criteria allowing older patients to be transplanted, incidence of (low-risk) prostate cancer (PCa) is increasing among renal transplant recipients (RTR). It remains to be established whether active surveillance (AS) for PCa represents a safe treatment option in this setting. Therefore, we aim to compare AS discontinuation and oncological outcomes of AS for PCa of RTR vs. non-transplant patients. METHODS: Multicentre study including RTR diagnosed with PCa between 2008 and 2018 in whom AS was initiated. A subgroup of non-RTR from the St. Antonius hospital AS cohort was used as a control group. Comparison of RTR vs. non-RTR was performed by 2:1 propensity score matched survival analysis. Outcome measures included tumour progression-free survival, treatment-free survival, metastasis rates, biochemical recurrence rates and overall survival. Patients were matched based on age, year of diagnosis, PSA, biopsy ISUP grade group, relative number of positive biopsy cores and clinical stage. RESULTS: A total of 628 patients under AS were evaluated, including 17 RTRs and 611 non-RTRs. A total of 13 RTR cases were matched with 24 non-RTR cases. Median overall follow-up for the RTR and non-RTR matched cases was, respectively, 5.1 (IQR 3.2-8.7) years and 5.7 (IQR 4.8-8.1) years. There were no events of metastasis and biochemical recurrence among matched cases. The matched-pair analysis results in a 1-year and 5-year survival of the RTR and non-RTR patients were, respectively, 100 vs. 92%, and 39 vs. 76% for tumour progression, 100 vs. 91% and 59 vs. 76% for treatment-free survival and, respectively, 100 vs. 100% and 88 vs. 100% for overall survival. No significant differences in tumour progression-free survival (p = 0.07) and treatment-free survival were observed (p = 0.3). However, there was a significant difference in overall survival comparing both groups (p = 0.046). CONCLUSIONS: AS may be carefully considered in RTR with low-risk PCa. In our preliminary analysis, no major differences were present in AS outcomes between RTR and non-RTR. Overall mortality was significantly higher in the RTR subgroup.


Assuntos
Transplante de Rim , Neoplasias da Próstata , Masculino , Humanos , Transplante de Rim/efeitos adversos , Conduta Expectante , Neoplasias da Próstata/patologia , Risco , Incidência
3.
Eur Radiol ; 33(12): 8703-8714, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37405502

RESUMO

OBJECTIVES: Contrast enhancement by MRI done early after cryoablation for renal malignancies may suggest residual tumor (RT). However, we have observed MRI enhancement within 48 h of cryoablation in patients who had no contrast enhancement 6 weeks later. Our purpose was to identify features of 48-h contrast enhancement in patients without RT. METHODS: This single-center retrospective study included consecutive patients who underwent percutaneous cryoablation of renal malignancies in 2013-2020, exhibited cryoablation-zone MRI contrast enhancement 48 h later, and had available 6-week MRI scans. Persistent or growing CE at 6 weeks vs. 48 h was classified as RT. A washout index was calculated for each 48-h MRI, and its performance for predicting RT was assessed by receiver operating characteristic curve analysis. RESULTS: We included 60 patients with 72 cryoablation procedures and 83 cryoablation zones exhibiting 48-h contrast enhancement; mean age was 66 ± 17 years. Clear-cell renal cell carcinoma accounted for 95% of tumors. Of the 83 48-h enhancement zones, RT was observed in eight while 75 were benign. The 48-h enhancement was consistently visible at the arterial phase. Washout was significantly associated with RT (p < 0.001) and gradually increasing contrast enhancement with benignity (p < 0.009). A washout index below - 1.1 predicted RT with 88% sensitivity and 84% specificity. CONCLUSION: MRI contrast enhancement 48 h after cryoablation of renal malignancies was usually benign. Washout was associated with residual tumor, with a washout index value below - 1.1 exhibiting good performance in predicting residual tumor. These findings may help to guide decisions about repeat cryoablation. CLINICAL RELEVANCE STATEMENT: Magnetic resonance imaging contrast enhancement 48 h after cryoablation of renal malignancies rarely indicates residual tumor, which is characterized by washout with a washout index lower than - 1.1. KEY POINTS: • Contrast enhancement at the arterial phase of magnetic resonance imaging done 48 h after cryoablation of a renal malignancy is usually benign. • Residual tumor manifesting as contrast enhancement at the arterial phase is characterized by subsequent marked washout. • A washout index below - 1.1 has 88% sensitivity and 84% specificity for residual tumor.


Assuntos
Carcinoma de Células Renais , Criocirurgia , Neoplasias Renais , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Criocirurgia/métodos , Estudos Retrospectivos , Neoplasia Residual , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Imageamento por Ressonância Magnética/métodos , Meios de Contraste
4.
Clin Transplant ; 37(9): e14998, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37138463

RESUMO

Systematic screening for prostate cancer is widely recommended in candidates for renal transplant at the time of listing. There are concerns that overdiagnosis of low-risk prostate cancer may result in reducing access to transplant without demonstrated oncological benefits. The objective of the study was to assess the outcome of newly diagnosed prostate cancer in candidates for transplant at the time of listing, and its impact on transplant access and transplant outcomes according to treatment options. This retrospective study was conducted over 10 years in 12 French transplant centers. Patients included were candidates for renal transplant at the time of prostate cancer diagnosis. Demographical and clinical data regarding renal disease, prostate cancer, and transplant surgery were collected. The primary outcome of the study was the interval between prostate cancer diagnosis and active listing according to treatment options. Overall median time from prostate cancer diagnosis to active listing was 25.0 months [16.4-40.2], with statistically significant differences in median time between the radiotherapy and the active surveillance groups (p = .03). Prostate cancer treatment modalities had limited impact on access and outcome of renal transplantation. Active surveillance in low-risk patients does not seem to compromise access to renal transplantation, nor does it impact oncological outcomes.


Assuntos
Falência Renal Crônica , Transplante de Rim , Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Transplante de Rim/efeitos adversos , Falência Renal Crônica/diagnóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Listas de Espera
5.
Transpl Int ; 36: 10556, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37035106

RESUMO

Early (<14 days) renal transplant vein thrombosis posttransplant (eRVTPT) is a rare but threatening complication. We aimed to assess eRVTPT management and the rate of functional renal transplantation. Of 11,172 adult patients who had undergone transplantation between 01/1997 and 12/2020 at 6 French centres, we identified 176 patients with eRVTPT (1.6%): 16 intraoperative (Group 1, G1) and 160 postoperative (Group 2, G2). All but one patient received surgical management. Patients in group G2 had at least one imaging test for diagnostic confirmation (N = 157, 98%). During the operative management of the G2 group, transplantectomy for graft necrosis was performed immediately in 59.1% of cases. In both groups, either of two techniques was preferred, namely, thrombectomy by renal venotomy or thrombectomy + venous anastomosis repair, with no difference in the functional graft rate (FGR) at hospital discharge (p = NS). The FGR was 62.5% in G1 and 8.1% in G2 (p < 0.001). Numerous complications occurred during the initial hospitalization: 38 patients had a postoperative infection (21.6%), 5 experienced haemorrhagic shock (2.8%), 29 exhibited a haematoma (16.5%), and 97 (55.1%) received a blood transfusion. Five patients died (2.8%). Our study confirms the very poor prognosis of early renal graft venous thrombosis.


Assuntos
Nefropatias , Transplante de Rim , Trombose Venosa , Adulto , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Trombose Venosa/etiologia , Trombose Venosa/cirurgia , Rim , Nefropatias/etiologia , Trombectomia/efeitos adversos , Trombectomia/métodos , Estudos Retrospectivos
6.
Mod Pathol ; 35(3): 352-360, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34531523

RESUMO

Low-grade oncocytic renal tumor (LOT) is an emerging provisional entity, described as rare solid renal oncocytic/eosinophilic tumor sharing diffuse CK7 and negative CD117 immunoprofile. The links between LOT and other eosinophilic chromophobe like-renal cell carcinomas (RCC) are currently discussed. We sequenced tumoral DNA with a next generation sequencing panel for kidney cancer and carried out immunohistochemical analyses with CK7, CD117, SDHB, 4EBP1-P, S6K-P, and FOXI1 antibodies in a series of ten cases of LOT (9 females, 1 male; mean age at surgery: 66 years, 42.3 to 83.4) retrospectively diagnosed from a cohort of 272 tumors initially classified as chromophobe RCC (CHRCC). All LOT were single, without known hereditary predisposition, classified stage pT1 (70%), pT2 (20%) or pT3a (10%). Morphological features were similar to previous descriptions and clinical behavior was indolent for the six cases with available follow-up. We identified genetic variations in mTOR pathway related genes in 80% of cases, MTOR (7 cases) or TSC1 (1 case). Expression of FOXI1 was absent in all cases. In 9 LOT, 4EBP1-P and S6K-P were overexpressed, suggesting mTOR pathway activation.Our data highlights the major role of mTOR pathway in tumorigenesis of LOT mostly due to activating MTOR gene variations. Absence of FOXI1 expression is a strong argument to distinguish LOT from eosinophilic CHRCC and to bring them closer to other recently described FOXI1 negative eosinophilic-CHRCC like with MTOR/TSC mutations. Altogether, our data argue to consider LOT as a distinct entity with a favorable clinical outcome. However, in case of metastasis, an accurate diagnosis of LOT would be essential for the patient's management and could allow targeted therapy.


Assuntos
Adenoma Oxífilo , Carcinoma de Células Renais , Neoplasias Renais , Adenoma Oxífilo/patologia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Feminino , Fatores de Transcrição Forkhead , Humanos , Neoplasias Renais/patologia , Masculino , Mutação , Estudos Retrospectivos , Serina-Treonina Quinases TOR/genética
7.
BJU Int ; 129(2): 225-233, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34114727

RESUMO

OBJECTIVES: To assess the impact of expanded criteria donors (ECD) on urinary complications in kidney transplantation. PATIENTS AND METHODS: The UriNary Complications Of Renal Transplant (UNyCORT) is a cohort study based on the French prospective Données Informatisées et VAlidées en Transplantation/Computerized and VAlidated Data in Transplantation (DIVAT) cohort. Data were extracted between 1 January 2002 and 1 January 2018 with 1-year minimum follow-up, in relation to 44 pre- and postoperative variables. ECD status was included according to United Network for Organ Sharing (UNOS) definition. The primary outcome of the UNyCORT study was the association between the donor's ECD/standard criteria donors (SCD) status and urinary complications at 1 year in uni- and multivariate analysis. Sub-group analysis, stratified analysis on ECD/SCD donor's status and transplant failure analysis were then conducted. RESULTS: Between 1 January 2002 and 1 January 2018, 10 279 kidney transplants in adult recipients were recorded within the DIVAT network. A total of 8559 (83.4%) donors were deceased donors and 1699 (16.6%) were living donors (LD). Among donation after circulatory death (DCD) donors, 224 (2.85%) were uncontrolled DCD and 93 (1.09%) were controlled DCD donors. A total of 3617 (43.9%) deceased donors were ECD. The overall urological complication rate was 16.26%. The donor's ECD status was significantly associated with an increased risk of urological complications at 1 year in multivariate analysis (odds ratio: 1.50, 95% CI 1.31-1.71; P < 0.001) and especially with stenosis and ureteric fistulae at 1 year. There is no association with LD, uncontrolled and controlled DCD. The placement of an endo-ureteric stent was beneficial in preventing urinary complications in all donors and particularly in ECD donors. CONCLUSION: The donor's ECD status is associated with a higher likelihood of stenosis and ureteric fistulae at 1 year. Recipients of grafts from ECD donors should probably be considered for closer urological monitoring and systematic preventive measures.


Assuntos
Transplante de Rim , Obtenção de Tecidos e Órgãos , Adulto , Estudos de Coortes , Constrição Patológica/etiologia , Sobrevivência de Enxerto , Humanos , Rim , Transplante de Rim/efeitos adversos , Doadores Vivos , Estudos Prospectivos , Estudos Retrospectivos , Doadores de Tecidos , Resultado do Tratamento
8.
World J Urol ; 40(12): 2931-2937, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36342512

RESUMO

PURPOSE: The aim was to evaluate the prognostic role of sub-categories of ISUP 4 prostate cancer (PCa) on final pathology, and assess the tumor architecture prognostic role for predicting biochemical recurrence (BCR) after radical prostatectomy. METHODS: From a prospectively-maintained database, we included 370 individuals with ISUP 4 on final pathology. The main outcomes were to evaluate the relationship between different ISUP patterns within the group 4 with pathological and oncological outcomes. Binary logistic regression and Kaplan-Meier estimator were used to evaluate the role of the different categories (3 + 5, 4 + 4, 5 + 3) and tumor architecture (intraductal and/or cribriform) on pathological and oncological outcomes. RESULTS: Among the 370 individuals with ISUP considered for the study, 9, 85 and 6% had grade 3 + 5, 4 + 4 and 5 + 3 PCa, respectively. Overall, 74% had extracapsular extension, while lymph node invasion (LNI) was documented in 9%. A total of 144 patients experienced BCR during follow-up. After adjusting for PSA, pT, grade group, LNI and positive surgical margins (PSM), grade 3 + 5 was a protective factor (HR: 0.30, 95% CI: 0.13,0.68, p = 0.004) in predicting BCR relative to grade 4 + 4. Intraductal or cribriform architecture was correlated with BCR (HR: 5.99, 95% CI: 2.68, 13.4, p < 0.001) after adjusting for PSA, pT, grade group, LNI and PSM. CONCLUSIONS: Patients with tumor grade 3 + 5 had better pathological and prognostic outcomes compared to 4 + 4 or 5 + 3. When accounting for tumor architecture, the sub-stratification into subgroups lost its prognostic role and tumor architecture was the sole predictor of poorer prognosis in terms of biochemical recurrence.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Prostatectomia , Gradação de Tumores , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Próstata/patologia , Margens de Excisão , Recidiva Local de Neoplasia/patologia
9.
Eur Surg Res ; 63(4): 155-164, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35944490

RESUMO

BACKGROUND: High-fidelity repair of DNA damage repair (DDR) (either single-strand- [SSBs] or double-strand breaks [DSBs]) is necessary for maintaining genomic integrity and cell survival. DDR alterations are commonly found in genitourinary malignancies involving either DSB repair by the homologous recombination (HR) repair (HRR) system (BRCA1/2 pathway) or the SSB repair through the poly (ADP-ribose) polymerase (PARP) pathway. PARP inhibitors (PARPi) exploit defects in the DNA repair pathway through synthetic lethality, DSBs being repaired only in HR-proficient cells but not in HR-deficient (HRD) cells. SUMMARY: A growing body of evidence supports the need for identification of germinal and somatic DDR alterations in patients with genitourinary malignancies. PARPi have already shown significant survival benefits in patients harboring HRR mutations in advanced settings, paving the way for precision medicine. KEY MESSAGES: In advanced prostate cancer (PCa), somatic mutations in HRR pathway are observed in up to 27% of metastatic resistant-to-castration PCa (mCRPC), although occurring early in PCa development, and mainly involving BRCA2, ATM, CHEK2, and BRCA1. Overall, germinal alterations are present in roughly 30-50% of cases of HRR alterations, and relative risk of PCa in germinal BRCA2 alteration carriers is 4.65-fold higher compared to noncarriers. Determination of DDR gene status is recommended in metastatic patients, a fortiori in mCRPC setting, since it could be a putative biomarker of response to first line of treatment (androgen-receptor signaling inhibitors [ARSI] vs. taxane-based chemotherapy) and allows to assess eligibility for PARPi use. Thus, olaparib (combined with androgen deprivation therapy) recently improved overall survival in mCRPC HRD patients, after new hormonal therapy (NHT) and led to its approvement for patients with an alteration in 14 of 15 prespecified HRR genes. Moreover, since preclinical data suggested synergic action between PARPi and ARSI, the use of either olaparib or niraparib has also been proposed in combination with NHT, with a radiological progression-free survival improvement when used with abiraterone. In urothelial carcinoma, a DDR gene alteration is identified in 23-54% of patients mostly in muscle-invasive bladder cancer, with a strong association between DDR gene mutation and a higher tumor mutation burden and sensitivity to cisplatin-based chemotherapy and immunotherapy. Recent phase 2 trials supported the use of HRR status to select patients for PARPi treatment in advanced urothelial carcinoma. Finally, in renal cell carcinomas (RCCs), pathogenic germline variants in DDR genes were identified in 7.3% of the cases, and deleterious somatic alterations have also been described as recurrent genomic events in patients with advanced RCC.


Assuntos
Carcinoma de Células de Transição , Neoplasias de Próstata Resistentes à Castração , Neoplasias da Bexiga Urinária , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Carcinoma de Células de Transição/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , DNA/uso terapêutico
10.
Eur Surg Res ; 63(1): 19-24, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34289472

RESUMO

INTRODUCTION: Indeterminate renal cysts may require several imaging modalities before clinical decision. The aim of this study was to investigate the effect of the imaging modality used to characterize indeterminate renal cysts on the pathological findings after surgical resection. METHODS: From our institutional database, we identified all patients surgically treated for Bosniak III renal masses between January 2008 and January 2018. All complex renal cysts were characterized with a combination of computed tomography (CT) and/or magnetic resonance imaging (MRI), and/or contrast-enhanced ultrasound (CEUS) and discussed during a multidisciplinary tumor board. Potential association between clinical/radiological characteristics and the pathological findings were investigated, using univariate and multivariate analyses. RESULTS: Of the 52 renal cystic lesions surgically removed, with a preoperative diagnosis of Bosniak III renal cyst, 19 (37%) were malignant and 33 (63%) were benign. The proportion of malignant lesions decreased from 47% when the renal cyst was characterized with cross-sectional imaging (CT and/or MRI) to 17% when the diagnosis required CEUS in addition to cross-sectional imaging. In multivariate analysis, prior history of renal cell carcinoma was associated with a higher risk of malignancy (p = 0.016) and diagnosis made with CEUS was associated with a lower risk of malignancy (p = 0.040). CONCLUSION: We found that using CEUS in addition to cross-sectional imaging to characterize indeterminate renal cysts tends to redefine Bosniak III as lesions with a lower risk of malignancy and can lead to overclassification.


Assuntos
Cistos , Doenças Renais Císticas , Estudos de Casos e Controles , Meios de Contraste , Humanos , Doenças Renais Císticas/diagnóstico por imagem , Doenças Renais Císticas/patologia , Ultrassonografia/métodos
11.
N Engl J Med ; 379(5): 417-427, 2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-29860937

RESUMO

BACKGROUND: Cytoreductive nephrectomy has been the standard of care in metastatic renal-cell carcinoma for 20 years, supported by randomized trials and large, retrospective studies. However, the efficacy of targeted therapies has challenged this standard. We assessed the role of nephrectomy in patients with metastatic renal-cell carcinoma who were receiving targeted therapies. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with confirmed metastatic clear-cell renal-cell carcinoma at presentation who were suitable candidates for nephrectomy to undergo nephrectomy and then receive sunitinib (standard therapy) or to receive sunitinib alone. Randomization was stratified according to prognostic risk (intermediate or poor) in the Memorial Sloan Kettering Cancer Center prognostic model. Patients received sunitinib at a dose of 50 mg daily in cycles of 28 days on and 14 days off every 6 weeks. The primary end point was overall survival. RESULTS: A total of 450 patients were enrolled from September 2009 to September 2017. At this planned interim analysis, the median follow-up was 50.9 months, with 326 deaths observed. The results in the sunitinib-alone group were noninferior to those in the nephrectomy-sunitinib group with regard to overall survival (stratified hazard ratio for death, 0.89; 95% confidence interval, 0.71 to 1.10; upper boundary of the 95% confidence interval for noninferiority, ≤1.20). The median overall survival was 18.4 months in the sunitinib-alone group and 13.9 months in the nephrectomy-sunitinib group. No significant differences in response rate or progression-free survival were observed. Adverse events were as anticipated in each group. CONCLUSIONS: Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic renal-cell carcinoma who were classified as having intermediate-risk or poor-risk disease. (Funded by Assistance Publique-Hôpitaux de Paris and others; CARMENA ClinicalTrials.gov number, NCT00930033 .).


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Nefrectomia , Pirróis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Indóis/efeitos adversos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nefrectomia/efeitos adversos , Seleção de Pacientes , Complicações Pós-Operatórias , Prognóstico , Pirróis/efeitos adversos , Medição de Risco , Sunitinibe , Análise de Sobrevida
12.
Curr Opin Oncol ; 33(1): 23-32, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33186184

RESUMO

PURPOSE OF REVIEW: Pheochromocytomas 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 FINDINGS: PPGL 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). SUMMARY: A 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.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/terapia , Paraganglioma/genética , Paraganglioma/terapia , Feocromocitoma/genética , Feocromocitoma/terapia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Testes Genéticos , Humanos , Paraganglioma/cirurgia , Feocromocitoma/cirurgia
13.
Mod Pathol ; 34(3): 647-659, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32770124

RESUMO

Biphasic squamoid alveolar papillary renal cell carcinoma (BSA-PRCC) is a recently studied lesion considered a morphologic variant of papillary renal cell carcinoma (RCC), more closely related to type 1. Considering the role of proto-oncogene MET in both sporadic type 1 papillary RCC and hereditary papillary RCC, we aimed to explore the role of MET activation in the oncogenesis of BSA-PRCC. We identified 17 patients with either unique (n = 14) or multiple (n = 3) BSA-PRCC, all localized, and performed an integrative analysis of MET status in 18 formalin-fixed paraffin-embedded tumors combining next-generation sequencing analysis, fluorescent in situ hybridization and immunohistochemistry. Trisomy 7 was found in 86% of tumors (14/16) without MET amplification at 7q31 (15/15). A pathogenic MET genetic variant was identified in 60% (9/15) of cases, at the germline level in 57% (4/7) of tested patients or at the somatic level (5/11). MET expression was observed in all tumors with a higher value of combined score in large cells (mean 97%, range 80-100%) than in small cells (mean 74%, range 10-100%) and was lower in two cases without MET copy number gain. In conclusion, our study provides additional evidence to consider biphasic squamoid alveolar papillary RCC as a morphological variant of type 1 papillary renal RCC. Our data strongly suggest that MET represents a major oncogenic driver gene in BSA-PRCC, harboring a higher frequency of MET mutation that encourages to further explore the benefice of anti-MET targeted therapies for aggressive BSA-PRCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Papilar/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Mutação , Proteínas Proto-Oncogênicas c-met/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Feminino , Dosagem de Genes , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Paris , Fenótipo , Proto-Oncogene Mas
14.
World J Urol ; 39(9): 3607-3614, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33779821

RESUMO

INTRODUCTION: Kidney Stone Calculator (KSC) is a free, three-dimensional (3D) planning software for flexible ureteroscopy(fURS) with Holmium:YAG(Ho:YAG) endocorporeal lithotripsy (EL). KSC provides the stone volume (SV) and expected duration of lithotripsy (ExDL) estimations based on non-enhanced-CT scan (NECT) DICOM series. We aimed to provide a preclinical and clinical evaluation of KSC. PATIENTS AND METHODS: A preclinical evaluation measured the SV by three operators (resident, endourology expert and research engineer) among 17 NECT cases. Between January and March 2020, a multicentric, prospective, observational double-blind clinical evaluation was conducted in patients presenting with renal stones treated with Ho:YAG-EL during fURS and preoperative NECT. Demographic and surgical data were collected. The primary endpoint was a significant median difference between ExDL and EffectiveDL (EfDL). Second, efficiency (J/mm3) and efficacy (mm3/min) ratios were calculated. RESULTS: The preclinical evaluation showed no significant difference in the SV measurements among operators (p > 0.05). Pearson and Kendall coefficients of 0.99 and 0.98, respectively, were found. Twenty-six patients were included in the clinical evaluation, with a median age of 55 years. In 66% of cases, there was a single stone located in the lower pole, with a density > 1000 Hounsfield Unit observed in 42% and 85% of cases. A 14% [Q1-Q3 (5.4-24.8); p = 0.36] median difference between ExDL and EfDL was noted, which was greater in the case of lower pole stones with no possible relocation (p = 0.008). Median values of 17.6 J/mm3 and 0.4 (0.32-0.56) mm3/s EL were also noted. CONCLUSIONS: Kidney Stone Calculator is a reproducible and accurate software that allows for an estimation of the stone burden and provides an ExDL for URSf. Defining the influencing factors of EL will improve its ExDL.


Assuntos
Cálculos Renais/cirurgia , Lasers de Estado Sólido/uso terapêutico , Planejamento de Assistência ao Paciente , Software , Ureteroscopia/métodos , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
15.
World J Urol ; 39(2): 621-627, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32363451

RESUMO

PURPOSE: Laparoscopic living-donor nephrectomy (LLDN) is the gold-standard procedure for kidney procurement. Ipsilateral orchialgia has barely been described. Some authors reported that ligation of gonadal vein (GV) above iliac vessel bifurcation could prevent orchialgia. We aimed to assess incidence and duration of orchialgia after LLDN in male donors despite distal ligation of GV. METHODS: Patients who underwent LLDN from 2014 to 2017 were included. Standard procedure consisted in distal ligation of GV, close to the renal vein confluence and proximal ureteral ligation. Patients' demographics, per-operative data, and post-operative consultation reports were retrospectively reviewed. Orchialgia and scrotal symptoms were assessed through a non-validated questionnaire by phone interview. RESULTS: Sixty-nine donors were included. Orchialgia incidence and testicular swelling were 31.9% (n = 22) and 15.9% (n = 11), respectively. Median symptom duration was 15.5 months. Orchialgia led to medical consultation in 41.7% (n = 10) of cases. All patients declared having been informed, prior to donation, about possible residual pain but not specifically orchialgia. CONCLUSION: Orchialgia after LLDN affects more than 30% of donors, despite distal ligation of GV and led less than 50% of them to medical consultation, suggesting a large underestimation in clinical practice. Emphasis should be put on this complication during pre-donation information.


Assuntos
Transplante de Rim , Laparoscopia , Nefrectomia/métodos , Dor/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Doenças Testiculares/epidemiologia , Coleta de Tecidos e Órgãos/métodos , Adulto , Humanos , Incidência , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
16.
Future Oncol ; 17(14): 1811-1823, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33543650

RESUMO

Aim: Comparison of the efficacy/safety/health-related quality of life of apalutamide, enzalutamide and darolutamide in Phase III clinical trials involving patients with nonmetastatic castration-resistant prostate cancer was performed. Materials & methods: Relevant studies were identified by searching PubMed as well as conference abstracts reporting updated overall survival. Three pivotal trials were identified, SPARTAN (apalutamide), PROSPER (enzalutamide) and ARAMIS (darolutamide), and form the basis of this analysis. Results: All three drugs significantly prolonged metastasis-free survival, prostate-specific antigen response and overall survival versus placebo, and were generally well tolerated. Conclusion: Drug selection will likely be influenced by tolerability/safety and other factors, such as the propensity for drug-drug interactions and the presence of comorbidities, that affect the risk-benefit balance in individual patients.


Assuntos
Benzamidas/administração & dosagem , Nitrilas/administração & dosagem , Feniltioidantoína/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Pirazóis/administração & dosagem , Tioidantoínas/administração & dosagem , Benzamidas/efeitos adversos , Benzamidas/farmacocinética , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Interações Medicamentosas , Humanos , Calicreínas/sangue , Estimativa de Kaplan-Meier , Masculino , Nitrilas/efeitos adversos , Nitrilas/farmacocinética , Feniltioidantoína/efeitos adversos , Feniltioidantoína/farmacocinética , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Pirazóis/efeitos adversos , Pirazóis/farmacocinética , Qualidade de Vida , Tioidantoínas/efeitos adversos , Tioidantoínas/farmacocinética , Fatores de Tempo
17.
Am J Transplant ; 20(12): 3462-3476, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32342614

RESUMO

The urinary chemokines CXCL9 and CXCL10 are promising noninvasive diagnostic markers of acute rejection (AR) in kidney recipients, but their levels might be confounded by urinary tract infection (UTI) and BK virus (BKV) reactivation. Multiparametric model development and validation addressed these confounding factors in a training set of 391 samples, optimizing the diagnostic performance of urinary chemokines. CXCL9/creatinine increased in UTI and BKV viremia with or without nephropathy (BKVN) (no UTI/leukocyturia/UTI: -0.10/1.61/2.09, P = .0001 and no BKV/viremia/BKVN: -0.10/1.90/2.29, P < .001) as well as CXCL10/creatinine (1.17/2.09/1.98, P < .0001 and 1.13/2.21/2.51, P < .001, respectively). An optimized 8-parameter model (recipient age, sex, estimated glomerular filtration rate, donor specific antibodies, UTI, BKV blood viral load, CXCL9, and CXCL10) diagnosed AR with high accuracy (area under the curve [AUC]: 0.85, 95% confidence interval [CI]: 0.80-0.89) and remained highly accurate at the time of screening (AUC: 0.81, 95% CI: 0.48-1) or indication biopsies (AUC: 0.85, 95% CI: 0.81-0.90) and within the first year (AUC: 0.86, 95% CI: 0.80-0.91) or later (AUC: 0.90, 95% CI: 0.84-0.96), achieving AR diagnosis with an AUC of 0.85 and 0.92 (P < .0001) in 2 external validation cohorts. Decision curve analyses demonstrated the clinical utility of the model. Considering confounding factors rather than excluding them, we optimized a noninvasive multiparametric diagnostic model for AR of kidney allografts with unprecedented accuracy.


Assuntos
Vírus BK , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Aloenxertos , Quimiocina CXCL10 , Quimiocina CXCL9 , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Humanos , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/diagnóstico
18.
AJR Am J Roentgenol ; 214(3): 579-587, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31770020

RESUMO

OBJECTIVE. Clear cell papillary renal cell carcinoma (RCC), an entity with strikingly indolent behavior, recently was added to the World Health Organization classification of renal tumors and represents the fourth most common histologic type of renal cell carcinoma. This article aims to describe the imaging features of clear cell papillary RCC along with its clinical and pathologic characteristics. MATERIALS AND METHODS. This retrospective study consisted of 27 patients with 44 clear cell papillary RCC tumors. The inclusion criteria were a pathologically proven clear cell papillary RCC and the availability of preoperative imaging including at least CT or MRI. Two experienced radiologists performed the imaging analysis independently. RESULTS. Patients (mean age, 62 years old) presented with renal failure in 26% of cases, and four had a tumor-predisposing disease. Multiple clear cell papillary RCC tumors occurred in 5 of the 27 patients. Two imaging patterns were recognizable. Solid clear cell papillary RCC (n = 23, 52%) presented as heterogeneous tumors with minor cystic changes (74%) and rarely exhibited calcifications (10%). All solid tumors showed hyperintensity on T2-weighted images compared with renal cortex and maximal enhancement on corticomedullary phase with a delayed washout. Cystic clear cell papillary RCC (n = 21, 48%) were classified as Bosniak IV (57%), III (33%), or IIF (10%), with a predominant unilocular pattern (76%). Pathologic stage according to TNM classification was mostly pT1a and low grade on nucleolar grade. All patients were alive at the date of last follow-up after treatment with no metastasis or recurrence. CONCLUSION. Clear cell papillary RCC exhibits two imaging patterns including cystic and solid in almost equal proportion. Imaging characteristics of solid clear cell papillary RCC including high signal T2 intensity and early arterial enhancement are unexpectedly distinct from papillary RCC and very similar to clear cell RCC.


Assuntos
Carcinoma Papilar/diagnóstico por imagem , Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Meios de Contraste , Feminino , Humanos , Neoplasias Renais/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
19.
Clin Transplant ; 33(7): e13615, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31215696

RESUMO

Simultaneous heart-kidney transplant (HKTx) is a valid treatment for patients with coexisting heart and renal failure. The aim of this study was to assess renal outcome in HKTx and to identify predictive factors for renal loss. A retrospective study was conducted among 73 HKTx recipients: Donors' and recipients' records were reviewed to evaluate patients' and renal transplants' survival and their prognostic factors. The mean follow-up was 5.36 years. Renal primary non-function occurred in 2.7%, and complications Clavien IIIb or higher were observed in 67.1% including 16 (22%) postoperative deaths. Five-year overall survival and renal survival were 74.5% and 69.4%. Among survivors, seven returned to dialysis during follow-up. The postoperative use of ECMO (HR = 6.04, P = 0.006), dialysis (HR = 1.04/day, P = 0.022), and occurrence of complications (HR = 31.79, P = 0.022) were independent predictors of postoperative mortality but not the history of previous HTx or KTx nor renal function prior to transplantation. History of KTx (HR = 2.52, P = 0.026) and increased delay between the two transplantations (HR = 1.25/hour, P = 0.018) were associated with renal transplant failure. HKTx provides good renal transplant survival and function, among survivors. Early mortality rate of 22% underlines the need to identify perioperative risk factors that would lead to more judicious and responsible allocation of a scarce resource.


Assuntos
Rejeição de Enxerto/diagnóstico , Sobrevivência de Enxerto , Transplante de Coração/efeitos adversos , Transplante de Rim/efeitos adversos , Rim/fisiopatologia , Adolescente , Adulto , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
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