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1.
Can J Psychiatry ; 69(4): 252-263, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-37899716

RESUMEN

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.


Asunto(s)
Metadona , Trastornos Relacionados con Opioides , Humanos , Metadona/uso terapéutico , Analgésicos Opioides/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Tratamiento de Sustitución de Opiáceos , Canadá/epidemiología , Combinación Buprenorfina y Naloxona/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Benzodiazepinas/uso terapéutico , Prescripciones
2.
Clin Transplant ; 37(9): e14998, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37138463

RESUMEN

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.


Asunto(s)
Fallo Renal Crónico , Trasplante de Riñón , Neoplasias de la Próstata , Masculino , Humanos , Estudios Retrospectivos , Trasplante de Riñón/efectos adversos , Fallo Renal Crónico/diagnóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/epidemiología , Listas de Espera
3.
Can J Psychiatry ; 68(2): 109-118, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36168206

RESUMEN

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.


Asunto(s)
Cannabinoides , Cannabis , Humanos , Adolescente , Estudios Transversales , Canadá/epidemiología , Quebec/epidemiología
4.
Clin Infect Dis ; 74(6): 1093-1096, 2022 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-34166499

RESUMEN

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.


Asunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Formación de Anticuerpos , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Receptores de Trasplantes
5.
World J Urol ; 39(6): 2223-2230, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32785765

RESUMEN

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.


Asunto(s)
Trasplante de Riñón , Sobrepeso/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Vasos Sanguíneos/anatomía & histología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Piel/anatomía & histología
6.
Transpl Int ; 34(10): 1845-1852, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33570752

RESUMEN

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.


Asunto(s)
Selección de Donante , Obtención de Tejidos y Órganos , Supervivencia de Injerto , Humanos , Riñón , Estudios Prospectivos , Estudios Retrospectivos , Donantes de Tejidos
7.
Am J Transplant ; 20(6): 1729-1738, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32012441

RESUMEN

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.


Asunto(s)
Trasplante de Riñón , Soluciones Preservantes de Órganos , Supervivencia de Injerto , Humanos , Riñón , Preservación de Órganos , Oxígeno , Perfusión , Donantes de Tejidos
8.
Prostate ; 79(1): 73-80, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30141208

RESUMEN

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.


Asunto(s)
Estudios de Asociación Genética/métodos , Variación Genética/genética , Polimorfismo de Nucleótido Simple/genética , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Anciano , Estudios de Cohortes , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico , Tasa de Supervivencia/tendencias
9.
Clin Transplant ; 33(5): e13536, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30869162

RESUMEN

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.


Asunto(s)
Funcionamiento Retardado del Injerto/mortalidad , Hipotermia Inducida/métodos , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/mortalidad , Preservación de Órganos/mortalidad , Perfusión/métodos , Donantes de Tejidos/provisión & distribución , Anciano , Criopreservación/métodos , Funcionamiento Retardado del Injerto/etiología , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Rechazo de Injerto/mortalidad , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia
11.
Rev Prat ; 68(2): 152-156, 2018 Feb.
Artículo en Francés | MEDLINE | ID: mdl-30801140

RESUMEN

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.


Asunto(s)
Lesión Renal Aguda , Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Biomarcadores , Creatinina/sangre , Creatinina/orina , Hematuria , Humanos , Proteinuria
12.
BJU Int ; 119(2): 268-275, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27322735

RESUMEN

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.


Asunto(s)
Nefrectomía , Nomogramas , Complicaciones Posoperatorias/epidemiología , Uréter/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nefrectomía/efectos adversos , Nefrectomía/métodos , Cuidados Preoperatorios , Estudios Retrospectivos , Factores de Tiempo
13.
World J Urol ; 35(2): 293-298, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27277477

RESUMEN

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.


Asunto(s)
Polimorfismo de Nucleótido Simple , Próstata/patología , Hiperplasia Prostática/genética , Hiperplasia Prostática/patología , Transducción de Señal/genética , Adulto , Anciano , Hormonas Esteroides Gonadales/fisiología , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Prostatectomía , Hiperplasia Prostática/cirugía
14.
Prostate ; 76(14): 1338-41, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27325180

RESUMEN

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.


Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Variación Genética/genética , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Superóxido Dismutasa/genética , Estudios de Cohortes , Estudios de Seguimiento , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico , Superóxido Dismutasa/biosíntesis , Resultado del Tratamiento
15.
Can J Urol ; 22(2): 7703-8, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25891333

RESUMEN

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.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Recurrencia Local de Neoplasia/prevención & control , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Anciano , Biopsia , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Próstata/patología , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Resultado del Tratamiento
16.
BJU Int ; 114(2): 177-84, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24410904

RESUMEN

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.


Asunto(s)
Cistectomía , Inmunomodulación , Desnutrición/complicaciones , Desnutrición/terapia , Apoyo Nutricional , Neoplasias de la Vejiga Urinaria/complicaciones , Humanos , Neoplasias de la Vejiga Urinaria/cirugía
17.
World J Urol ; 32(2): 475-9, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23455886

RESUMEN

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.


Asunto(s)
Tiempo de Tratamiento , Neoplasias Urológicas/cirugía , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/cirugía , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/cirugía , Cistectomía/métodos , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Masculino , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/mortalidad , Neoplasias de Células Germinales y Embrionarias/cirugía , Nefrectomía/métodos , Orquiectomía/métodos , Neoplasias del Pene/diagnóstico , Neoplasias del Pene/mortalidad , Neoplasias del Pene/cirugía , Prostatectomía/métodos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/cirugía , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/mortalidad , Neoplasias Testiculares/cirugía , Factores de Tiempo , Neoplasias Ureterales/diagnóstico , Neoplasias Ureterales/mortalidad , Neoplasias Ureterales/cirugía , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/mortalidad
18.
World J Urol ; 32(2): 489-93, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23723015

RESUMEN

PURPOSE: To assess the surgical approach using the pathological specimen obtained after open radical prostatectomy (ORP) or robot-assisted radical prostatectomy (RALRP). METHODS: A prospective study has been performed in patients who underwent either ORP or RALRP for localized prostate cancer. Two dedicated uro-pathologists, blinded to the surgeons and the operating rooms' schedules, analyzed the pathological specimens according to the Stanford protocol. Both pathologists also determined the surgical approach used based on several criteria pertaining to the pathological specimen. RESULTS: Overall, 117 patients with a median age of 63 years were included. The main characteristics (i.e., Gleason score, pTNM stage, preoperative PSA and margin) were comparable in both groups (p > 0.05). Pathologists 1 and 2 were able to significantly assess the surgical procedure from the pathological specimen provided (in 76.1 and 69.2 % of cases, respectively). Pathologist 1 had a better performance than pathologist 2 (AUC 0.75, IC 95 % [0.67-0.83] vs. AUC = 0.68 IC 95 % [0.59-0.77]) (p = 0.017). The κ index of the inter-observer agreement was satisfactory (0.76). In a univariate analysis, the criteria linked to the pathologist's assessment were as follows: macroscopic integrity of the specimen (p = 0.04), presence of periprostatic fat (p = 0.04), width of periprostatic tissue (p < 0.001) and nerve-sparing status (p < 0.001). CONCLUSION: It was possible to determine the surgical procedure from the analysis of the specimen obtained after a radical prostatectomy. In view of these data and from this perspective, one could infer that there are indeed oncological differences between the robotic and open approaches to radical prostatectomy.


Asunto(s)
Próstata/patología , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Manejo de Especímenes/métodos , Anciano , Humanos , Laparoscopía/métodos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Próstata/patología , Robótica/métodos
19.
World J Urol ; 32(2): 481-7, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23619479

RESUMEN

PURPOSE: To assess whether the PSA level (threshold 4 ng/mL) is a prognostic factor in biochemical recurrence-free survival in men with prostate cancer (PCa) with an initial PSA level <10 ng/mL who underwent robotic-assisted laparoscopic radical prostatectomy (RARLP). METHODS: We prospectively recruited data for consecutive patients treated by RARLP for PCa with an initial PSA level below 10 ng/mL between 2003 and 2011 at our institution. We divided the population into two groups: patients with a PSA level below 4 ng/mL (G1; n = 53) and patients with a PSA level between 4 and 10 ng/mL (G2; n = 371). Biochemical recurrence was defined as a single increase in PSA greater than 0.2 ng/mL after surgery. Multivariate analysis was used to assess prognostic factors of recurrence-free survival. RESULTS: Overall, 424 patients were included, and the median age was 62 (58-67) years. The median PSA was 5.8 ng/mL (4.8-7.7 ng/mL). Overall, 6 patients from G1 and 34 patients from G2 experienced a biochemical recurrence. Overall, the 5-year recurrence-free survival rate was 86.6 %. The PSA level at diagnosis (under or over 4 ng/mL) was not significantly linked to recurrence-free survival (HR = 0.59, p = 0.25). However, positive margins and a Gleason score >7 on the specimen were significantly linked to recurrence-free survival with respective hazard ratios of 4.30 (p < 0.0001) and 6.18 (p < 0.0001), respectively. CONCLUSION: A PSA level <4 ng/mL alone appears to be obsolete as a cut-off to define a population of men likely to have indolent disease.


Asunto(s)
Calicreínas/sangre , Recurrencia Local de Neoplasia/sangre , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Anciano , Estudios de Cohortes , Supervivencia sin Enfermedad , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Prostatectomía , Neoplasias de la Próstata/cirugía , Robótica , Resultado del Tratamiento
20.
World J Urol ; 32(2): 545-50, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24166289

RESUMEN

PURPOSE: To investigate the impact of 3-month androgen deprivation therapy (st-ADT) a secondary chemoprevention of indolent-localized prostate cancer (PCa). METHODS: A prospective phase II study enrolled men over 4 years with low-risk PCa and the following characteristics: PSA < 10 ng/mL, Gleason score of 6 (3 + 3) or less, three positive cores or less, and tumor stage T2a or less. Patients received a single sub-cutaneous injection of 22.5 mg of leuprolide acetate with Atrigel 3-month depot associated with a daily oral intake of bicalutamide 50 mg/day during 15 days around the injection. Follow-up included PSA and bioavailable testosterone blood tests every 3 months and yearly surveillance biopsies. Primary end point was the presence of PCa on biopsy at last follow-up. Secondary end points were detailed pathological features and adverse events. RESULTS: Overall, 98 men were included and 45 of them (45.9 %) had a negative biopsy after a median follow-up of 13 months [11-19.5]. Of the 53 patients with positive biopsy, 17 had pathologic progression because of upgraded Gleason score (11 patients), four or more positive cores (three patients) or both (three patients). The only significant predictive factor biopsy outcome was the number of positive cores at diagnosis. CONCLUSIONS: Secondary chemoprevention by st-ADT for localized PCa could be useful to pinpoint indolent tumors suitable for AS. Indeed, after st-ADT nearly one patient out of two had negative biopsies and 17 % had pathological progression. This is an innovative option to consider as an alternative to current AS protocols contingent upon confirmation in subsequent studies.


Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Anilidas/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Leuprolida/uso terapéutico , Nitrilos/uso terapéutico , Próstata/patología , Neoplasias de la Próstata/tratamiento farmacológico , Compuestos de Tosilo/uso terapéutico , Anciano , Biopsia con Aguja Gruesa , Quimioprevención , Preparaciones de Acción Retardada , Humanos , Calicreínas/sangre , Masculino , Persona de Mediana Edad , Proyectos Piloto , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Prevención Secundaria , Resultado del Tratamiento , Espera Vigilante/métodos
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