Análise dos fatores de risco para o diagnóstico do carcinoma incidental da próstata em pacientes com hiperplasia prostática benigna

PURPOSE: To determine the occurence of incidental carcinoma of the prostate, its characteristics, and the risk factors for this diagnosis in a group of patients surgically treated for benign prostatic hyperplasia. METHODS: The study comprised a retrospective analysis of 218 patients. After surgical treatment, patients with the finding of incidental carcinoma of the prostate were compared to those without this finding. The preoperative variables analyzed were patient age, digital rectal examination, PSA, PSA density, prostate volume, and preoperative prostate biopsy. We also determined the sensitivity, specificity, positive predictive value, and negative predictive value of digital rectal examination and PSA for the finding of incidental carcinoma of the prostate at surgical specimen analysis. RESULTS: Thirteen (6.2%) out of the 218 patients presented incidental carcinoma of the prostate. Eight (61.5%) of these tumors were classified as T1a and 5 (38.5%) as T1b. Only advanced age (P = 0.003) and the presence of a suspect digital rectal examination (P = 0. 016) were statistically related to the findings of the surgical specimen analysis. The sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of incidental carcinoma were 23.0%, 96.6%, 30.0%, and 95.2% for a suspect digital rectal examination and 85.0%, 34.1%, 7.5%, and 97.2% for a PSA greater than 4.0 ng/mL. The accuracy for these methods was 92.2% and 37.1%, respectively. CONCLUSIONS: Advanced age and the presence of a suspect digital rectal examination represent the most important risk factors for the diagnosis of an incidental carcinoma of the prostate. However, the low positive predictive values reflect the weak correlations among these variables.OBJETIVO: Determinar a ocorrência do carcinoma incidental da próstata, suas características e fatores de risco para o diagnóstico em um grupo de pacientes tratados cirurgicamente para hiperplasia prostática benigna. MÉTODOS: O estudo compreendeu a análise retrospectiva de 218 pacientes. Após o tratamento cirúrgico, os pacientes com achado de carcinoma incidental da próstata foram comparados com os pacientes sem este achado. As variáveis pré-operatórias analisadas foram idade, toque retal, PSA, densidade do PSA, volume prostático e biópsia prostática pré-operatória. Também foram determinados a sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo do toque retal e do PSA para o diagnóstico do carcinoma incidental da próstata. RESULTADOS: Treze (6.2%) dos 218 pacientes apresentaram carcinoma incidental da próstata. Oito (61.5%) deles foram classificados com T1a e 5 (38.5%) como T1b. Apenas a idade avançada (p=0.003) e a presença de um toque retal suspeito (p=0.016) se relacionaram estatisticamente com este achado na peça cirúrgica. A sensibilidade, especificidade, valore preditivo positivo e negativo para o diagnóstico de carcinoma incidental da próstata foram de 23.0%, 96.6%, 30.0%, 95.2% para a presença de um toque retal suspeito e 85.0%, 34.1%, 7.5% e 97.2% para um valor de PSA maior que 4.0 ng/ml respectivamente. A exatidãos dois métodos foi de 92.2% e 37.1% respectivamente. CONCLUSÕES: A idade avançada e a presença de um toque retal suspeito representam os fatores de risco mais importantes para o diagnóstico de carcinoma incidental da próstata

Analysis of the risk factors for incidental carcinoma of the prostate in patients with benign prostatic hyperplasia

PURPOSE: To determine the occurence of incidental carcinoma of the prostate, its characteristics, and the risk factors for this diagnosis in a group of patients surgically treated for benign prostatic hyperplasia. METHODS: The study comprised a retrospective analysis of 218 patients. After surgical treatment, patients with the finding of incidental carcinoma of the prostate were compared to those without this finding. The preoperative variables analyzed were patient age, digital rectal examination, PSA, PSA density, prostate volume, and preoperative prostate biopsy. We also determined the sensitivity, specificity, positive predictive value, and negative predictive value of digital rectal examination and PSA for the finding of incidental carcinoma of the prostate at surgical specimen analysis. RESULTS: Thirteen (6.2%) out of the 218 patients presented incidental carcinoma of the prostate. Eight (61.5%) of these tumors were classified as T1a and 5 (38.5%) as T1b. Only advanced age (P = 0.003) and the presence of a suspect digital rectal examination (P = 0. 016) were statistically related to the findings of the surgical specimen analysis. The sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of incidental carcinoma were 23.0%, 96.6%, 30.0%, and 95.2% for a suspect digital rectal examination and 85.0%, 34.1%, 7.5%, and 97.2% for a PSA greater than 4.0 ng/mL. The accuracy for these methods was 92.2% and 37.1%, respectively. CONCLUSIONS: Advanced age and the presence of a suspect digital rectal examination represent the most important risk factors for the diagnosis of an incidental carcinoma of the prostate. However, the low positive predictive values reflect the weak correlations among these variables.OBJETIVO: Determinar a ocorrência do carcinoma incidental da próstata, suas características e fatores de risco para o diagnóstico em um grupo de pacientes tratados cirurgicamente para hiperplasia prostática benigna. MÉTODOS: O estudo compreendeu a análise retrospectiva de 218 pacientes. Após o tratamento cirúrgico, os pacientes com achado de carcinoma incidental da próstata foram comparados com os pacientes sem este achado. As variáveis pré-operatórias analisadas foram idade, toque retal, PSA, densidade do PSA, volume prostático e biópsia prostática pré-operatória. Também foram determinados a sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo do toque retal e do PSA para o diagnóstico do carcinoma incidental da próstata. RESULTADOS: Treze (6.2%) dos 218 pacientes apresentaram carcinoma incidental da próstata. Oito (61.5%) deles foram classificados com T1a e 5 (38.5%) como T1b. Apenas a idade avançada (p=0.003) e a presença de um toque retal suspeito (p=0.016) se relacionaram estatisticamente com este achado na peça cirúrgica. A sensibilidade, especificidade, valore preditivo positivo e negativo para o diagnóstico de carcinoma incidental da próstata foram de 23.0%, 96.6%, 30.0%, 95.2% para a presença de um toque retal suspeito e 85.0%, 34.1%, 7.5% e 97.2% para um valor de PSA maior que 4.0 ng/ml respectivamente. A exatidãos dois métodos foi de 92.2% e 37.1% respectivamente. CONCLUSÕES: A idade avançada e a presença de um toque retal suspeito representam os fatores de risco mais importantes para o diagnóstico de carcinoma incidental da próstata

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting & Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (<60, 60-69, and >_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 & PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages <60, 60-69, and >_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791