Moreira, Daniel M.

Objective To evaluate whether elective off‐clamp laparoscopic partial nephrectomy ( LPN ) affords long‐term renal functional benefit compared with the on‐clamp approach. Patients and Methods This is a retrospective review of patients who underwent elective LPN between 2006 and 2011. Patients were followed longitudinally for up to 5 years. In all, 315 patients with radiographic evidence of a solitary renal mass and normal‐appearing contralateral kidney underwent elective LPN ; 209 were performed on‐clamp vs 106 off‐clamp. One patient who required conversion from LPN to open PN was excluded from the study. Additionally, four patients in the on‐clamp cohort who underwent subsequent radical nephrectomy for local‐regional recurrence were excluded from longitudinal functional evaluation after their procedure. The primary objective was to evaluate differences in postoperative estimated glomerular filtration rate ( eGFR ) between hilar clamping groups. Subgroup analyses were performed for patients with clamp times >30 min and those with baseline renal insufficiency ( eGFR <60 mL/min/1.73m 2 ). Risk of developing worsened or new‐onset renal insufficiency was also compared. Results The mean preoperative eGFR was similar between the on‐clamp and off‐clamp cohorts (80.7 vs 84.1 mL/min/1.73m 2 , P > 0.05). Univariable and multivariable analyses did not show significant differences in postoperative eGFR between both groups among all‐comers, those with clamp times >30 min, and patients with baseline renal insufficiency. Risk of chronic kidney disease was not diminished by the off‐clamp approach with up to 5 years of follow‐up. Conclusions Progressive recovery of renal function after hilar clamping in the elective setting eclipses short‐term functional benefit achieved with off‐clamp LPN by 6 months; there was no significant difference in eGFR or the percentage incidence of chronic kidney disease between the on‐clamp and off‐clamp cohorts with up to 5 years follow‐up. As such, eliminating transient ischaemia during elective LPN does not confer clinical benefit.

Objective To evaluate the incidence, predictors and oncological outcomes of pT 0 prostate cancer ( PC a). Methods We conducted a retrospective analysis of 20 222 patients undergoing radical prostatectomy ( RP ) for PC a at the Mayo Clinic between 1987 and 2012. Disease recurrence was defined as follow‐up PSA >0.4 ng/mL or biopsy‐proven local recurrence. Systemic progression was defined as development of metastatic disease on imaging. Comparisons of baseline characteristics between pT 0 and non‐ pT 0 groups were carried out using chi‐squared tests. Recurrence‐free survival was estimated using the Kaplan–Meier method and compared using the log‐rank test. Results A total of 62 patients (0.3%) had pT 0 disease according to the RP specimen. In univariable analysis, pT 0 disease was significantly associated with older age ( P = 0.045), lower prostate‐specific antigen ( PSA ; P = 0.002), lower clinical stage ( P < 0.001), lower biopsy Gleason score ( P = 0.042), and receipt of preoperative transurethral resection, hormonal and radiation therapies (all P < 0.001). In multivariable analysis, lower PSA levels, lower Gleason score, and receipt of preoperative treatment were independently associated with pT 0 (all P < 0.05). Seven patients (11%) with pT 0 PC a developed disease recurrence over a median follow‐up of 10.9 years. All seven patients had preoperative treatment(s) and three had recurrence with a PSA doubling time of <9 months. Compared with non‐ pT 0 disease, pT 0 disease was associated with longer recurrence‐free survival ( P < 0.05). Only one (1.6%) patient with pT 0 disease developed systemic progression. Conclusions pT 0 stage PC a is a rare phenomenon and is associated with receipt of preoperative treatment and features of low‐risk PC a. Although pT 0 has a very favourable prognosis, some men, especially those who received preoperative treatment, experience a small but non‐negligible risk of disease recurrence and systemic progression.

Abstract Both anti- and proinflammatory effects of cigarette smoking have been described. As prostate inflammation is common, we hypothesized smoking could contribute to prostate inflammation. Thus, we evaluated the association of smoking status with acute and chronic inflammation within the prostate of men undergoing prostate biopsy. We retrospectively analyzed 8,190 men ages 50 to 75 years with PSA levels between 2.5 and 10 ng/mL enrolled in the Reduction by Dutasteride of Prostate Cancer Events study. Smoking status was self-defined as never, former, or current. Prostate inflammation was assessed by systematic central review blinded to smoking status. The association of smoking with inflammation in the baseline, 2-year, and 4-year biopsies was evaluated with univariable and multivariable logistic regressions. At study enrollment, 1,233 (15%), 3,203 (39%), and 3,754 (46%) men were current, former, and never smokers, respectively. Current smokers were significantly younger and had smaller prostates than former and never smokers (all P &lt; 0.05). Former smokers were significantly heavier than current and never smokers (P &lt; 0.001). Acute and chronic prostate inflammations were identified in 1,261 (15%) and 6,352 (78%) baseline biopsies, respectively. In univariable analysis, current smokers were more likely to have acute inflammation than former (OR, 1.35; P, 0.001) and never smokers (OR, 1.36; P, 0.001). The results were unchanged at 2- and 4-year biopsies. In contrast, current smoking was linked with chronic inflammation in the baseline biopsy, but not at 2- and 4-year biopsies. In conclusion, among men undergoing prostate biopsy, current smoking was independently associated with acute and possibly chronic prostate inflammations. Cancer Prev Res; 8(4); 312–7. ©2015 AACR.

Abstract Purpose: A recent meta-analysis showed that aspirin was associated with reduced prostate cancer risk. As anti-inflammatory medications lower PSA levels, whether these findings reflect reduced prostate cancer detection or lower prostate cancer risk is unknown. We tested the association between aspirin and nonaspirin NSAID use on prostate cancer diagnosis in REDUCE, where all men received biopsies at 2 and 4 years largely independent of PSA. REDUCE tested dutasteride for prostate cancer risk reduction in men with a PSA of 2.5 to 10.0 ng/mL and a negative prestudy biopsy. Experimental Design: We examined the association between aspirin, NSAIDs, or both and total, low-grade (Gleason &lt; 7), or high-grade (Gleason ≥ 7) prostate cancer versus no prostate cancer using multinomial logistic regression among 6,390 men who underwent ≥1 on-study biopsy. Multivariable analyses were adjusted for age, race, geographic region, PSA, prostate volume, digital rectal examination, body mass index, treatment arm, smoking, alcohol, statins, hypertension, diabetes, and cardiovascular disease. Results: Overall, 3,169 men (50%) were nonusers, 1,368 (21%) used aspirin, 1,176 (18%) used NSAIDs, and 677 (11%) used both. In unadjusted models, aspirin was associated with reduced prostate cancer risk (OR = 0.85, P = 0.036). In multivariable analyses, aspirin was associated with reduced total prostate cancer risk (OR = 0.81, P = 0.015). Use of NSAIDs or NSAIDs and aspirin was not associated with total, low-grade, or high-grade prostate cancer, though all ORs were &lt;1 (all P ≥ 0.08). Therefore, we created a dichotomous variable of aspirin and/or NSAID users versus nonusers. On multivariable analysis, the use of aspirin and/or NSAIDs was significantly associated with decreased total (OR = 0.87, P = 0.030) and high-grade (OR = 0.80, P = 0.040), but not with low-grade, prostate cancer risk (OR = 0.90, P = 0.15). Results were similar in placebo and dutasteride arms. Conclusions: Among men with a negative biopsy, aspirin and/or NSAID use was associated with decreased prostate cancer risk. Additional studies are warranted. Clin Cancer Res; 21(4); 756–62. ©2014 AACR.

Abstract Background: Studies suggest that obesity is associated with lower risk of prostate cancer but more aggressive cancers. As obesity lowers PSA levels, these observations may be influenced by detection bias. We examined the association between obesity and risk of low- and high-grade prostate cancer in REDUCE, in which biopsies were largely independent of PSA. Methods: The REDUCE study tested dutasteride for prostate cancer risk reduction in men with a PSA of 2.5 to 10.0 ng/mL and a negative biopsy. Study participants included 6,729 men who underwent at least one on-study biopsy. The association between baseline body mass index (BMI &lt;25 kg/m2 normal weight; 25–29.9 kg/m2 overweight; and ≥30 kg/m2 obese) and risk of high-grade (Gleason ≥7) or low-grade prostate cancer (Gleason &lt;7) versus no prostate cancer was examined using multinomial logistic regression. Results: Overall, 1,739 men (27%) were normal weight, 3,384 (53%) overweight, and 1,304 (20%) were obese. Obesity was associated with lower risk of low-grade prostate cancer in both univariable (OR, 0.74; P = 0.001) and multivariable analyses (OR, 0.79; P = 0.01). In univariable analysis, obesity was not associated with high-grade prostate cancer (OR, 1.08; P = 0.50). However, in multivariable analysis, obesity was associated with increased risk of high-grade prostate cancer (OR, 1.28; P = 0.042). This analysis was not able to address how obesity may influence prostate cancer progression. Conclusions: Obesity is associated with decreased risk of low-grade and increased risk of high-grade prostate cancer. These data provide further support to the hypothesis that obesity is associated with aggressive prostate cancer. Impact: Obesity is linked with aggressive prostate cancer. Avoiding obesity may prevent the risk of developing high-grade prostate cancer. Cancer Epidemiol Biomarkers Prev; 23(12); 2936–42. ©2014 AACR.