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

Impalpable Testicular Seminoma Identified on Sonoelastography

The role of sonoelastography in diagnosing cancerous masses has increased since the advent of elastography as an ultrasound modality. Its ability to display differences in the mechanical properties of cancerous masses compared to normal surrounding tissue has shown benefit in increasing the accuracy of diagnosing malignant breast and thyroid masses and has shown early potential in accomplishing better targeted prostate biopsies. To date, the literature is limited in the number of studies describing the use of sonoelastography for testicular masses. We describe a 34-year-old man who presented with an incidental finding of an impalpable hypoechoic testicular mass on grayscale ultrasound during an infertility work-up. Sonoelastography was performed displaying intermediate testicular elastic properties. Upon frozen section of the mass during surgical exploration, classic testicular seminoma was diagnosed and subsequent radical orchiectomy was performed. We would like to use this atypical presentation of testicular seminoma to review the potential role of elastography for diagnosing testicular cancer

Aggressive Renal Angiomyolipoma of the Lipomatous Variant With Inferior Vena Cava Thrombus: A Case Report and Review of the Literature

Two variants of renal angiomyolipoma (AML)—classic and epithelioid—have been described. Although the epithelioid variant has been reported to demonstrate an aggressive clinical behavior, classic AML is usually benign. Herein, we report a case of a 42-year-old asymptomatic woman with a lipomatous variant of renal AML associated with an inferior vena cava thrombus managed with radical nephrectomy and caval thrombectomy

Multi-parametric MRI of the prostate: Factors predicting extracapsular extension at the time of radical prostatectomy

Objective: Extracapsular extension (ECE) of prostate cancer is a poor prognostic factor associated with progression, recurrence after treatment, and increased prostate cancer-related mortality. Accurate staging prior to radical prostatectomy is crucial in avoidance of positive margins and when planning nerve-sparing procedures. Multi-parametric magnetic resonance imaging (mpMRI) of the prostate has shown promise in this regard, but is hampered by poor sensitivity. We sought to identify additional clinical variables associated with pathologic ECE and determine our institutional accuracy in the detection of ECE amongst patients who went on to radical prostatectomy. Methods: mpMRI studies performed between the years 2012 and 2014 were cross-referenced with radical prostatectomy specimens. Predictive properties of ECE as well as additional clinical and biochemical variables to identify pathology-proven prostate cancer ECE were analyzed. Results: The prevalence of ECE was 32.4%, and the overall accuracy of mpMRI for ECE was 84.1%. Overall mpMRI sensitivity, specificity, positive predictive value, and negative predictive value for detection of ECE were 58.3%, 97.8%, 93.3%, and 81.5%, respectively. Specific mpMRI characteristics predictive of pathologic ECE included primary lesion size ((20.73 ± 9.09) mm, mean ± SD, p < 0.001), T2 PIRADS score (p = 0.009), overall primary lesion score (p < 0.001), overall study suspicion score (p = 0.003), and MRI evidence of seminal vesicle invasion (SVI) (p = 0.001). Conclusion: While mpMRI is an accurate preoperative assessment tool for the detection of ECE, its overall sensitivity is poor, likely related to the low detection rate of standard protocol MRI for microscopic extraprostatic disease. The additional mpMRI findings described may also be considered in surgical margin planning prior to radical prostatectomy

Role of multi-parametric MRI of the prostate for screening and staging: Experience with over 1500 cases

Objective: Contemporary prostate cancer (PCa) screening modalities such as prostate specific antigen (PSA) and digital rectal examination (DRE) are limited in their ability to predict the detection of clinically significant disease. Multi-parametric magnetic resonance imaging (mpMRI) of the prostate has been explored as a staging modality for PCa. Less is known regarding its utility as a primary screening modality. We examined our experience with mpMRI as both a screening and staging instrument. Methods: mpMRI studies performed between 2012 and 2014 in patients without PCa were cross-referenced with transrectal ultrasonography (TRUS) biopsy findings. Statistical analyses were performed to determine association of mpMRI findings with overall cancer diagnoses and clinically significant (Gleason score ≥7) disease. Subgroup analyses were then performed on patients with a history of prior negative biopsy and those without a history of TRUS biopsy. mpMRI studies were also cross-referenced with RP specimens. Statistical analyses determined predictive ability of extracapsular extension (ECE), seminal vesicle involvement (SVI), and pathologic evidence of clinically significant disease (Gleason score ≥7). Results: Four hundred biopsy naïve or prior negative biopsy patients had positive mpMRI studies. Overall sensitivity, specificity, positive and negative predictive values were 94%, 37%, 58%, and 87%, respectively and 95%, 31%, 42%, and 93%, respectively for overall cancer detection and Gleason score ≥7 disease. In patients with no prior biopsy history, mpMRI sensitivity, specificity, positive and negative predictive values were 94%, 36%, 65%, and 82%, for all cancers, and 95%, 30%, 50%, and 89% for Gleason score≥7 lesions, respectively. In those with prior negative biopsy sensitivity, specificity, positive and negative predictive values were 94%, 37%, 52%, and 90% for all cancers, and 96%, 32%, 36%, and 96% for Gleason score ≥7 lesions, respectively. Seventy-four patients underwent radical prostatectomy (RP) after mpMRI. Lesion size on mpMRI correlated with the presence of Gleason score ≥7 cancers (p = 0.005). mpMRI sensitivity, specificity, positive and negative predictive values were 84%, 39%, 81%, and 44% respectively, for Gleason ≥7 cancer. For ECE and SVI, sensitivity and specificity were 58% and 98% and 44% and 97%, respectively. Conclusion: mpMRI is an accurate predictor of TRUS biopsy and RP outcomes. mpMRI has significant potential to change PCa management, particularly in the screening population, in whom a significant proportion may avoid TRUS biopsy. Further studies are necessary to determine how mpMRI should be incorporated into the current PCa screening and staging paradigms

Positive Surgical Margins Increase Risk of Recurrence after Partial Nephrectomy for High Risk Renal Tumors

PurposeThe clinical significance of a positive surgical margin after partial nephrectomy remains controversial. The association between positive margin and risk of disease recurrence in patients with clinically localized renal neoplasms undergoing partial nephrectomy was evaluated.Materials and methodsA retrospective multi-institutional review of 1,240 patients undergoing partial nephrectomy for clinically localized renal cell carcinoma between 2006 and 2013 was performed. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of positive surgical margin with the log rank test and Cox models adjusting for tumor size, grade, histology, pathological stage, focality and laterality. The relationship between positive margin and risk of relapse was evaluated independently for pathological high risk (pT2-3a or Fuhrman grades III-IV) and low risk (pT1 and Fuhrman grades I-II) groups.ResultsA positive surgical margin was encountered in 97 (7.8%) patients. Recurrence developed in 69 (5.6%) patients during a median followup of 33&nbsp;months, including 37 (10.3%) with high risk disease (eg pT2-pT3a or Fuhrman grade III-IV). A positive margin was associated with an increased risk of relapse&nbsp;on multivariable analysis (HR 2.08, 95% CI 1.09-3.97, p=0.03) but not with site of recurrence. In a stratified analysis based on pathological features, a&nbsp;positive surgical margin was significantly associated with a higher risk of recurrence in cases considered high risk (HR 7.48, 95% CI 2.75-20.34, p &lt;0.001) but not low risk (HR 0.62, 95% CI 0.08-4.75, p=0.647).ConclusionsPositive surgical margins after partial nephrectomy increase the risk of disease recurrence, primarily in patients with adverse pathological features