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PURPOSE: The robot-assisted laparoscopic (RALUVR) and open (OUVR) approaches have both been described for ureterovesical reimplantation to treat benign lower ureteral pathologies. Thus, we aimed to compare the perioperative and functional outcomes of RALUVR vs. OUVR. METHODS: We performed a retrospective comparative study including all consecutive patients treated with RALUVR or OUVR for benign lower ureteral pathologies between January 2013 and December 2022 at our center. Logistic regression analyses were used to assess the predictors of complication ≥ Clavien-Dindo (CD) III within 90 days, prolonged length of stay (LOS), and 90-day overall success. The Kaplan-Meier method and Cox regression analyses were used to assess vesicoureteral reflux-free (VU-RFS) and stenosis-free (SFS) survivals. RESULTS: Overall, 44 patients underwent RALUVR (n = 19; 43%) and OUVR (n = 25; 57%). In univariable logistic regression analyses, the use of RALUVR vs. OUVR was not significantly associated with postoperative complications ≥ CDIII (OR = 0.98; 95% CI=[0.17-5.09]; p = 0.98), and 90-day overall success (OR = 1.43; 95% CI=[0.24-11.28]; p = 0.7). Despite a shorter median LOS after RALUVR vs. OUVR (4 vs. 10 days, respectively; p < 0.001), multivariable logistic regression analysis showed no impact of the surgical approach on prolonged LOS (OR = 0.51, 95% CI=[0.03-13.86]; p = 0.65). No significant difference was observed in 2-year VU-RFS (72.9% vs. 100%, respectively; p = 0.2) and 2-year SFS between the RALUVR and OUVR groups (85.7% vs. 87.7%, respectively; p = 0.8). In Cox regression analysis, the use of RALUVR vs. OUVR was not significantly associated with VU-RFS (HR = 4.26; 95% CI=[0.38-47.84]; p = 0.24) or SFS (HR = 1.32; 95% CI=[0.22-8.01]; p = 0.76). CONCLUSION: We observed that RALUVR provides similar perioperative and functional outcomes as compared to OUVR, except for potentially shorter LOS.
Assuntos
Laparoscopia , Reimplante , Procedimentos Cirúrgicos Robóticos , Ureter , Doenças Ureterais , Procedimentos Cirúrgicos Urológicos , Humanos , Masculino , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Feminino , Laparoscopia/métodos , Ureter/cirurgia , Reimplante/métodos , Resultado do Tratamento , Adulto , Procedimentos Cirúrgicos Urológicos/métodos , Doenças Ureterais/cirurgia , Bexiga Urinária/cirurgia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Tempo de Internação/estatística & dados numéricosRESUMO
BACKGROUND: The aims of this narrative review were (i) to describe the current indications of SLKT, (ii) to report evolution of SLKT activity, (iii) to report the outcomes of SLKT, (iv) to explain the immune-protective effect of liver transplant on kidney transplant, (v) to explain the interest of delay kidney transplantation, using hypothermic machine perfusion (HMP), (vi) to report kidney after liver transplantation (KALT) indications and (vii) to describe the value of the increase in the use of extended criteria donors (ECD) and particular controlled donation after circulatory death (cDCD) transplant, thanks to the development of new organ preservation strategies. METHOD: Electronic databases were screened using the keywords "Simultaneous", "Combined", "kidney transplantation" and "liver transplantation". The methodological and clinical heterogeneity of the included studies meant that meta-analysis was inappropriate. RESULTS: A total of 1,917 publications were identified in the literature search. Two reviewers screened all study abstracts independently and 1,107 of these were excluded. Thus, a total of 79 full text articles were assessed for eligibility. Of these, 21 were excluded. In total, 58 studies were included in this systematic review. CONCLUSIONS: Simultaneous liver-kidney transplantation has made a significant contribution for patients with dual-organ disease. The optimization of indication and selection of SLKT patients will reduce futile transplantation. Moreover, increasing the use of transplants from extended criteria donors, in particular cDCD, should be encouraged, thanks to the development of new modalities of organ preservation.
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Transplante de Rim , Transplante de Fígado , Preservação de Órgãos , Humanos , Transplante de Rim/métodos , Preservação de Órgãos/métodos , Previsões , Sobrevivência de EnxertoRESUMO
OBJECTIVES: There is limited evidence on how opioid agonist treatment (OAT) may affect psychoactive non-opioid substance use in prescription-type opioid use disorder (POUD) and whether this effect might explain OAT outcomes. We aimed to assess the effect of methadone on non-opioid substance use compared to buprenorphine/naloxone (BUP/NX), to explore whether non-opioid substance use is associated with opioid use and retention in treatment, and to test non-opioid use as a moderator of associations between methadone with retention in OAT and opioid use compared to BUP/NX. METHODS: This is a secondary analysis of data from the OPTIMA trial, an open-label, pragmatic, parallel, two-arm, pan-Canadian, multicentre, randomized-controlled trial to compare standard methadone model of care and flexible take-home dosing BUP/NX for POUD treatment. We studied the effect of methadone and BUP/NX on non-opioid substance use evaluated by urine drug screen (UDS) and by classes of non-opioid substances (i.e., tetrahydrocannabinol [THC], benzodiazepines, stimulants) (weeks 2-24) using adjusted generalized estimation equation (GEE). We studied the association between non-opioid substance-positive UDS and opioid-positive UDS and retention in treatment, using adjusted GEE and logistic regressions. RESULTS: Overall, methadone was not associated with non-opioid substance-positive UDS compared to BUP/NX (OR: 0.78; 95%CI, 0.41 to 1.48). When non-opioid substances were studied separately, methadone was associated with lower odds of benzodiazepine-positive UDS (OR: 0.63; 95% CI: 0.40 to 0.98) and THC-positive UDS (OR: 0.47; 95% CI: 0.28 to 0.77), but not with different odds of stimulant-positive UDS (OR: 1.29; 95% CI: 0.78 to 2.16) compared to BUP/NX. Substance-positive UDS, overall and separate classes, were not associated with opioid-positive UDS or retention in treatment. CONCLUSION: Methadone did not show a significant effect on overall non-opioid substance use in POUD compared to BUP/NX treatment but was associated with lower odds of benzodiazepine and THC use in particular. Non-opioid substance use did not predict OAT outcomes. Further research is needed to ascertain whether specific patterns of polysubstance use (quantity and frequency) may affect treatment outcomes.
Assuntos
Metadona , Transtornos Relacionados ao Uso de Opioides , Humanos , Metadona/uso terapêutico , Analgésicos Opioides/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Tratamento de Substituição de Opiáceos , Canadá/epidemiologia , Combinação Buprenorfina e Naloxona/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Benzodiazepinas/uso terapêutico , PrescriçõesRESUMO
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 EsperaRESUMO
OBJECTIVE: In 2018, the sale of non-medical cannabis was authorized in the province of Quebec in Canada, within a public monopoly under the Société Québécoise du Cannabis (SQDC). The objective of this study was to offer a description of the cannabis-using population regarding the sources of cannabis supply and to explore whether at-risk individuals are purchasing cannabis at SQDC. METHOD: We used data from a cross-sectional, representative population survey (age >18 years, n = 1799), the Enquête Québécoise sur le Cannabis, which was completed between February and June 2019. Analyses involved adjusted binary logistic regressions, incorporating population weights, to assess 7 potential indicators of harm. RESULTS: The vulnerability profiles of SQDC consumers (47.8%) and those acquiring their cannabis elsewhere (52.2%) were similar in terms of frequency of cannabis use (adjusted odds ratio [aOR] = 0.46; 95% confidence interval [CI] = 0.12-1.67), motivation to use (aOR = 0.62; 95% CI = 0.16-2.46), concomitant consumption of other substances (aOR = 0.80; 95% CI = 0.14-4.75), cannabis-impaired driving behaviours (aOR = 0.93; 95% CI = 0.26-3.36), psychological distress (aOR = 0.99; 95% CI = 0.26-3.79), and problematic cannabis use (aOR = 0.46; 95% CI = 0.13-1.64). However, SQDC consumers were more likely to be aware of the cannabinoid content of the product purchased compared to those who acquired their cannabis from other sources (aOR = 4.12; 95% CI = 1.10-15.40). CONCLUSIONS: No association was detected between the source of cannabis supply and potential vulnerability indicators of cannabis-related harms, but SQDC consumers were more aware of the cannabinoid content of the products purchased. These results suggest that the regulated government supply in Quebec is reaching a substantial portion of those with potential high vulnerability to harm. Whether this knowledge translates into a reduction in the negative consequences related to consumption is still to be determined.
Assuntos
Canabinoides , Cannabis , Humanos , Adolescente , Estudos Transversais , Canadá/epidemiologia , Quebeque/epidemiologiaRESUMO
A low anti-spike antibody response of 28.6% was observed 28 days after BNT162b2 vaccine second dose among 133 solid organ transplant recipients without previous coronavirus disease 2019 (COVID-19). No serious adverse events were recorded. Four severe COVID-19 cases were reported between or after the 2 doses. Our data suggest to change the vaccine strategy.
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COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Formação de Anticorpos , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , TransplantadosRESUMO
PURPOSE: Sarcopenia or adipose tissue distribution within obese and overweight renal transplanted have been poorly evaluated. Our objective was to evaluate morphometric markers to predict surgical complications in kidney transplantation. METHODS: We retrospectively included patients with a BMI > 25 kg/m2 undergoing kidney transplantation from 2012 to 2017. Following measurements were performed on CT-scan sections: Sub-cutaneous Adipose Tissue surface (SAT), Visceral Adipose Tissue surface (VAT), Vessel-to-Skin distance (VSK), Abdominal Perimeter (AP), and Psoas surface. A multivariable logistic regression model with BMI was compared to a model containing morphometric variables to determine the best predictive model for surgical complications. RESULTS: 248 patients were included, 15 (6%) experienced transplant nephrectomy, 18 (7.3%) urinary leakage, and 29 (11.7%) subcapsular renal hematoma. Multivariable logistic regression evidenced that sarcopenia and VSK were risk factors of surgical complication within a year post-transplantation (respectively, OR = 0.9, 95%CI (0.8-0.9), p = 0.04 and OR = 1.2, 95%CI (1.1-1.3), p = 0.002). Area under the curve for a predictive model including VSK, age and psoas surface was 0.69, whereas BMI model was 0.65. CONCLUSION: Combined morphometric parameters of obesity were associated with surgical complications in kidney transplantation. Morphometric threshold may provide a more accurate and objective criteria than BMI to evaluate kidney transplantation outcomes. External validation is needed.
Assuntos
Transplante de Rim , Sobrepeso/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Vasos Sanguíneos/anatomia & histologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Prognóstico , Estudos Retrospectivos , Medição de Risco , Pele/anatomia & histologiaRESUMO
Despite the organ shortage, a significant number of deceased donor kidneys are retrieved but not transplanted (RNTK). This study aims to describe and analyze the main causes of potential grafts discard and to propose adequate solutions. We collected data from the Cristal database of the French Biomedicine Agency about RNTK over one year. Expert opinion was taken from urologists with extensive expertise in renal transplantation. They retrospectively analyzed each record to assess the appropriateness of each graft refusal and subsequent kidney discard. Of 252 kidneys were retrieved but not transplanted in France over one year. The main reasons for discard were vascular abnormalities in 43.7% (n = 110), suspicion of malignant tumor in 18.7% (n = 47), and severe histological lesions on preimplantation biopsy in 12.3% (n = 31). The reason for kidney refusal was undetermined in 4.8% (n = 12). Iatrogenic lesions were responsible for 26.2% (n = 66). Overall, 46.0% (n = 16) and 25.0% (n = 63) of the grafts were, respectively, properly and improperly denied, and the analysis was not possible in 29.0% (n = 73). In total, 36.9% of RNTK could have been transplanted. Reduction of iatrogenic lesions, improvement of microsurgical repair skills, and proper histological examination are necessary to reduce the number of RNTK. A prospective study applying the proposed principles is undoubtedly essential to complete this work.
Assuntos
Seleção do Doador , Obtenção de Tecidos e Órgãos , Sobrevivência de Enxerto , Humanos , Rim , Estudos Prospectivos , Estudos Retrospectivos , Doadores de TecidosRESUMO
The medical device M101 is an extracellular hemoglobin featuring high oxygen-carrying capabilities. Preclinical studies demonstrated its safety as an additive to organ preservation solutions and its beneficial effect on ischemia/reperfusion injuries. OXYgen carrier for Organ Preservation (OXYOP) is a multicenter open-label study evaluating for the first time the safety of M101 added (1 g/L) to the preservation solution of one of two kidneys from the same donor. All adverse events (AEs) were analyzed by an independent data and safety monitoring board. Among the 58 donors, 38% were extended criteria donors. Grafts were preserved in cold storage (64%) or machine perfusion (36%) with a mean cold ischemia time (CIT) of 740 minutes. At 3 months, 490 AEs (41 serious) were reported, including two graft losses and two acute rejections (3.4%). No immunological, allergic, or prothrombotic effects were reported. Preimplantation and 3-month biopsies did not show thrombosis or altered microcirculation. Secondary efficacy end points showed less delayed graft function (DGF) and better renal function in the M101 group than in the contralateral kidneys. In the subgroup of grafts preserved in cold storage, Kaplan-Meier survival and Cox regression analysis showed beneficial effects on DGF independent of CIT (P = .048). This study confirms that M101 is safe and shows promising efficacy data.
Assuntos
Transplante de Rim , Soluções para Preservação de Órgãos , Sobrevivência de Enxerto , Humanos , Rim , Preservação de Órgãos , Oxigênio , Perfusão , Doadores de TecidosRESUMO
BACKGROUND: We previously identified a blood RNA transcript-based model consisting of six immune or inflammatory response genes (ABL2, SEMA4D, ITGAL, C1QA, TIMP1, and CDKN1A) that was prognostic for survival in cohorts of men with castration-resistant prostate cancer (CRPC). We investigated whether inherited variation in these six genes was associated with overall survival (OS) in men with CRPC. METHODS: The test cohort comprised 600 patients diagnosed with CRPC between 1996 and 2011 at Dana-Farber Cancer Institute. Genotyping of 66 tagging single nucleotide polymorphisms (SNPs) spanning the six genes was performed on blood derived DNAs. For the top four SNPs (P < 0.05), validation was conducted in an independent cohort of 223 men diagnosed with CRPC between 2000 and 2014. Multivariable Cox regression adjusting for known prognostic factors estimated hazard ratios (HR) and 95% confidence intervals (CI) of the association of genetic variants with OS. RESULTS: Two thirds of patients in both cohorts had metastases at CRPC diagnosis. Median OS from CRPC diagnosis was 3.6 (95%CI 3.3-4.0) years in the test cohort and 4.6 (95%CI 3.8-5.2) years in the validation cohort. Fifty-nine SNPs in Hardy-Weinberg equilibrium were analyzed. The major alleles of rs1318056 and rs1490311 in ABL2, and the minor alleles of rs2073917 and rs3764322 in ITGAL were associated with increased risk of death in the test cohort (adjusted-HRs 1.27-1.39; adjusted-p <0.05; false discovery rate <0.35). In the validation cohort, a similar association with OS was observed for rs1318056 in ABL2 (adjusted-HR 1.44; 95%CI 0.89-2.34) and rs2073917 in ITGAL (adjusted-HR 1.41; 95%CI 0.82-2.42). The associations did not reach statistical significance most likely due to the small sample size of the validation cohort (adjusted-p = 0.142 and 0.209, respectively). Additional eQTL analysis indicated that minor alleles of rs1318056 and rs1490311 in ABL2 are associated with a lower ABL2 expression in blood. CONCLUSIONS: These findings corroborate our initial work on the RNA expression of genes involved in immunity and inflammation from blood and clinical outcome and suggest that germline polymorphisms in ABL2 and ITGAL may be associated with the risk of death in men with CRPC. Further studies are needed to validate these findings and to explore their functional mechanisms.
Assuntos
Estudos de Associação Genética/métodos , Variação Genética/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/mortalidade , Idoso , Estudos de Coortes , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Taxa de Sobrevida/tendênciasRESUMO
In 2012, an expert working group from the French Transplant Health Authority recommended the use of hypothermic machine perfusion (HMP) to improve kidney preservation and transplant outcomes from expanded criteria donors, deceased after brain death. This study compares HMP and cold storage (CS) effects on delayed graft function (DGF) and transplant outcomes. We identified 4,316 kidney transplants from expanded criteria donors (2011-2014) in France through the French Transplant Registry. DGF occurrence was analyzed with a logistic regression, excluding preemptive transplants. One-year graft failure was analyzed with a Cox regression. A subpopulation of 66 paired kidneys was identified: one preserved by HMP and the other by CS from the same donor. Kidneys preserved by HMP (801) vs CS (3515) were associated with more frequent recipient comorbidities and older donors and recipients. HMP had a protective effect against DGF (24% in HMP group and 38% in CS group, OR = 0.49 [0.40-0.60]). Results were similar in the paired kidneys (OR = 0.23 [0.04-0.57]). HMP use decreased risk for 1-year graft failure (HR = 0.77 [0.60-0.99]). Initial hospital stays were shorter in the HMP group (P < 0.001). Our results confirm the reduction in DGF occurrence among expanded criteria donors kidneys preserved by HMP.
Assuntos
Função Retardada do Enxerto/mortalidade , Hipotermia Induzida/métodos , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Preservação de Órgãos/mortalidade , Perfusão/métodos , Doadores de Tecidos/provisão & distribuição , Idoso , Criopreservação/métodos , Função Retardada do Enxerto/etiologia , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
A diagnostic procedure for acute kidney injury. The definition of acute kidney injury (AKI) is universal since 2011. It is simple, based on the increase in serum creatinine on a short time period. AKI may be life-threatening, which is why the priority is to rule out hyperkalemia, pulmonary edema, or severe acidosis. Then, a panel of clinical, biological and radiological analyses is required to establish the mechanism of AKI and treat it appropriately. Basically, a three steps process is suggested: an obstruction of the urinary cavities is looked for; circumstances of renal hypoperfusion are considered, and urinary electrolytes measured; by elimination, a diagnosis of parenchymal AKI is eventually made. In that case AKI is in most cases due to an acute tubular necrosis, which implies to collect positive and negative signs: a recent history of hypotension, intake of toxic drugs, etc.; proteinuria should be low, i.e. less than 1 g/L, and urinary cells in normal count. In the presence of extra-renal symptoms, and of urinary abnormalities such as abundant proteinuria and hematuria or leucocyturia, a specialized care is urgently needed and a renal biopsy often indicated.
Démarche diagnostique devant une insuffisance rénale aiguë. L'insuffisance rénale aiguë a aujourd'hui une définition simple et universelle, fondée sur l'élévation de la créatininémie sur un temps court. Elle peut représenter une menace vitale, et il est prioritaire de l'évaluer avant toute démarche étiologique. Cette dernière requiert une analyse clinique, biologique et radiologique, et elle est stéréotypée : on cherche dans un premier temps un obstacle sur les voies urinaires, puis une insuffisance rénale par défaut de perfusion efficace, et enfin, par élimination, on aboutit au diagnostic d'insuffisance rénale aiguë « organique ¼. Le cas échéant, la cause la plus fréquente, a fortiori en réanimation médicale, est la nécrose tubulaire aiguë ischémique qui est un diagnostic par défaut qui implique la présence d'un contexte évocateur, et de plusieurs signes négatifs : absence de signes extrarénaux, protéinurie faible et sédiment urinaire inactif. Dans tous les autres cas, un avis néphrologique est urgent, et la biopsie rénale est discutée.
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Injúria Renal Aguda , Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Biomarcadores , Creatinina/sangue , Creatinina/urina , Hematúria , Humanos , ProteinúriaRESUMO
OBJECTIVES: To construct a nomogram based on preoperative variables to better predict the likelihood of complications occurring within 30 days of radical nephroureterectomy (RNU). PATIENTS AND METHODS: The charts of 731 patients undergoing RNU at eight academic medical centres between 2002 and 2014 were reviewed. Preoperative clinical, demographic and comorbidity indices were collected. Complications occurring within 30 days of surgery were graded using the modified Clavien-Dindo scale. Multivariate logistic regression determined the association between preoperative variables and post-RNU complications. A nomogram was created from the reduced multivariate model with internal validation using the bootstrapping technique with 200 repetitions. RESULTS: A total of 408 men and 323 women with a median age of 70 years and a body mass index of 27 kg/m2 were included. A total of 75% of the cohort was white, 18% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2, 20% had a Charlson comorbidity index (CCI) score >5 and 50% had baseline chronic kidney disease (CKD) ≥ stage III. Overall, 279 patients (38%) experienced a complication, including 61 events (22%) with Clavien grade ≥ III. A multivariate model identified five variables associated with complications, including patient age, race, ECOG performance status, CKD stage and CCI score. A preoperative nomogram incorporating these risk factors was constructed with an area under curve of 72.2%. CONCLUSIONS: Using standard preoperative variables from this multi-institutional RNU experience, we constructed and validated a nomogram for predicting peri-operative complications after RNU. Such information may permit more accurate risk stratification on an individual cases basis before major surgery.
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Nefrectomia , Nomogramas , Complicações Pós-Operatórias/epidemiologia , Ureter/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Cuidados Pré-Operatórios , Estudos Retrospectivos , Fatores de TempoRESUMO
OBJECTIVES: A few preliminary studies have suggested a link between some genetics variants and benign prostatic hyperplasia (BPH). Our goal was to study the link between a set of single nucleotide polymorphisms (SNPs) implicated in the steroid pathway and accurate measurement of prostate volume in a cohort of men who underwent radical prostatectomy. METHODS: Clinical and pathological data including prostate weight were obtained from 611 Caucasian patients with small volume, localized prostate cancer treated by radical prostatectomy. Patients were genotyped for 90 SNPs located inside or nearby genes implicated in the steroid pathway (Sequenom iPLEX). Correlation between prostate weight and genotypes from each SNP was studied by analysis of covariance, adjusted on age and tumor stage. A Bonferroni correction was applied, and the SNPs implicated were then incorporated in a multivariable model. RESULTS AND LIMITATIONS: Seven SNPs located in or nearby genes implicated in steroid hormone metabolism were significantly associated with prostate volume: HSD17B2 (rs1119933), ESR2 (rs8006145), SULT2B1 (rs279451), NQO1 (rs2917670), ESR1 (rs1569788), GSTP1 (rs1138272), and CYP19A1 (rs17523880). Significant association was maintained after multivariate analysis for four SNPs, indicating their independent association with prostate volume. The power of the association of each SNP with prostate volume was comparable to the effect of age. The strongest associations were found with variants in ESR1, ESR2, HSD17B2, and CYP19A1 genes, indicating a potential role of the estrogen signaling pathway in genesis of BPH. CONCLUSIONS: Our results are in favor of an implication of estrogen biotransformation and signaling pathways in the pathophysiology of BPH.
Assuntos
Polimorfismo de Nucleotídeo Único , Próstata/patologia , Hiperplasia Prostática/genética , Hiperplasia Prostática/patologia , Transdução de Sinais/genética , Adulto , Idoso , Hormônios Esteroides Gonadais/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Prostatectomia , Hiperplasia Prostática/cirurgiaRESUMO
BACKGROUND: Silencing SOD2 expression upregulates androgen receptor (AR) signaling and expression of SOD2 is downregulated in CRPC, compared with untreated tumors. The decreased SOD2 activity could lead to AR gain-of-function and the development of castration-resistance. METHODS: We genotyped SOD2-rs4880 in a cohort of 753 prostate cancer patients receiving androgen deprivation therapy (ADT) between 1996 and 2010. The rs4880 encodes Ala16Val in SOD2 and the Val variant has been demonstrated to be functionally less efficient than the Ala variant. We assessed the impact of SOD2-rs4880 variants on the time to progression (TTP) and overall survival (OS) on ADT using multivariable Cox regression. RESULTS: Four hundred thirty-two out of 753 (57%) had metastases at the time of ADT initiation. Overall, median TTP on ADT was 18.4 (95%CI: 15.8, 20.9) months and median overall survival (OS) from ADT initiation was 6.3 (95%CI: 5.8, 6.8) years. In unadjusted and adjusted analyses, there was no association between SOD-rs4880 and TTP or OS on ADT (P > 0.05). Results were similarly negative among patients with and without metastatic disease at ADT initiation. CONCLUSIONS: Our result suggests that a functional genetic variant in SOD2 does not determine the efficacy of ADT for prostate cancer. It is possible that the drastic downregulation of SOD2 in advanced prostate cancer cells may have overridden any influence of the genetic variation of SOD2. This study suggests the need for careful consideration about timing if the application of SOD2 mimetics for prostate cancer therapy is considered. Prostate 76:1338-1341, 2016. © 2016 Wiley Periodicals, Inc.
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Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Variação Genética/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Superóxido Dismutase/genética , Estudos de Coortes , Seguimentos , Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Superóxido Dismutase/biossíntese , Resultado do TratamentoRESUMO
INTRODUCTION: To assess the impact of statin use on biochemical recurrence (BCR) of prostate cancer after radical prostatectomy (RP). MATERIALS AND METHODS: Data from all men treated with robot-assisted laparoscopic RP (RALRP) for localized prostate cancer between 2009 and 2014 at our institution were prospectively collected: age, body mass index (BMI), statin-use status, preoperative prostate-specific antigen (PSA) level, clinical T stage, biopsy Gleason score (bGS), D'Amico risk group, pathological T stage, specimen Gleason score (sGS), multifocality, peri neural invasion, positive surgical margins and time to BCR. Univariate and multivariate analysis were performed to test associations between statin use and prognostic factors of prostate cancer and/or BCR. RESULTS: Overall, 591 patients with a median follow up of 42.3 months [25.8-59.9] were included in the current study and split in two cohorts: statin users (n = 156) and statin non-users (n = 435). When comparing statin user and non-users, no significant difference was found in terms of clinical, biochemical and pathological characteristics except for BMI (median 29 versus 26, respectively; p = 0.04). Regarding BCR, there was no significant difference between men using statin versus those not using them (4.5% versus 4.6%, p = 0.65). In univariate analysis, statin use was not significantly correlated to any prognostic factors of prostate cancer recurrence. Furthermore, there was no significant difference in the 5 years biochemical-free survival rates between statin users and non-users (75% versus 73%; p = 0.7). CONCLUSIONS: From the current study, statin daily intake was not significantly associated with any prognostic factors of prostate cancer and with BCR after RARLP.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Recidiva Local de Neoplasia/prevenção & controle , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Idoso , Biópsia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The 'gold standard' treatment for patients with carcinoma invading the bladder muscle is radical cystectomy (RC). Such patients are known to be at risk of malnutrition because of age and disease factors. Current evidence has established the nutritional and immunological benefits of immune-enhancing nutritional supplements in upper gastrointestinal surgery. There are currently no guidelines for immunonutrition (IM) use in urology and bladder cancer specifically. We carried out a systematic review of the available literature in the MEDLINE/Embase database. We assessed the rates of malnutrition in RC cohorts and analysed the clinical impacts of nutritional deficiency. The impact of immune-enhancing supplements was also investigated in RC cohorts with regard to postoperative outcomes. The prevalence of severe malnutrition was found to be 16-22%. There was a consistent association of malnourished patients with adverse postoperative outcomes in terms of mortality and morbidity. There is a paucity of data regarding IM in urological cohorts. Postoperative IM in RC was not found to have significant benefits beyond early return to a normal diet. There is not enough evidence in malnourished urological study cohorts to establish a consensus on IM. Until there are more well-controlled comparative effective studies or randomized trials, the role of IM should be considered investigational in patients with bladder cancer.
Assuntos
Cistectomia , Imunomodulação , Desnutrição/complicações , Desnutrição/terapia , Apoio Nutricional , Neoplasias da Bexiga Urinária/complicações , Humanos , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
OBJECTIVE: Our aim was to assess the effect of surgical wait time on the survival of patients with urological neoplasms, including prostate, bladder, penile, and testicular cancers and upper tract tumours (UTUC). MATERIALS AND METHODS: Current, relevant studies were identified from the literature. Keywords used for article retrieval were as follows: delay; surgery; prostate cancer; urothelial carcinoma; renal cell carcinoma; testicular cancer; bladder; renal pelvis; ureter; and survival. RESULTS: Regarding the length of surgical wait time, it does not matter in cases of incidental T1a renal cell carcinomas. In other cases of renal cell carcinomas, surgery should be considered within <1 month; it is of crucial importance in bladder cancer and should be <1 month for a TURBT in cases of non-muscle-invasive bladder cancer and <1 month for a radical cystectomy in cases of muscle-invasive bladder cancer; it is important in invasive UTUC and should be <1 month for a radical nephroureterectomy; it is not crucial in cases of low-risk prostate cancer. In any other case, radical prostatectomy should be considered within <2 months; it is important in testicular cancer and should be fewer than 10 days for an orchiectomy. CONCLUSION: Prolonged surgical wait times have an impact on the overall quality of life and anxiety of the patient. Extending the wait time beyond a given threshold can also have a negative impact on the patient's clinical outcomes, but this threshold differs between urological neoplasms.