Assessing clinically significant prostate cancer: Diagnostic properties of multiparametric magnetic resonance imaging compared to three-dimensional transperineal template mapping histopathology.

OBJECTIVE: To evaluate the diagnostic properties of multiparametric magnetic resonance imaging in the detection, localization and characterization of prostate cancer using three-dimensional transperineal template mapping biopsy histopathology as the comparator. METHODS: A retrospective analysis of patients undergoing prostate multiparametric magnetic resonance imaging followed by three-dimensional transperineal template mapping biopsy was carried out. For imaging and pathology data, the prostate was divided in octants with the urethra being the midline. The index test properties were calculated using the biopsy histopathology as the reference test with the following end-points: any cancer, any Gleason ≥7, any Gleason ≥7 or cancer length of ≥4 mm and any Gleason ≥7 or 6 mm in any given core. The latter two definitions correspond to 0.2 and 0.5 mL of cancer volume, respectively. Diagnostic properties including sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: A total of 50 patients were included in the study. A median of 55 (interquartile range 42-63) biopsy cores were obtained per patient. Of 400 prostate octants evaluated, 28.5% had prostate cancer on mapping biopsy, whereas 23% of octants were considered suspicious for cancer on imaging. Multiparametric magnetic resonance imaging negative predictive values for Gleason ≥7 and clinically significant cancers were 84-100%. Similarly, specificity ranged between 79% and 85%. Sensitivity and positive predictive value remained moderate for all the reference test definitions. CONCLUSIONS: Multiparametric magnetic resonance imaging is a useful minimally-invasive tool for detection, localization and characterization of prostate cancer. This imaging modality has high negative predictive value and specificity, and therefore it could be used to reliably rule out clinically significant cancer, obviating the multicore mapping biopsy.

Palmitate differentially regulates the polarization of differentiating and differentiated macrophages.

The tissue accumulation of M1 macrophages in patients with metabolic diseases such as obesity and type 2 diabetes mellitus has been well-documented. Interestingly, it is an accumulation of M2 macrophages that is observed in the adipose, liver and lung tissues, as well as in the circulation, of patients who have had major traumas such as a burn injury or sepsis; however, the trigger for the M2 polarization observed in these patients has not yet been identified. In the current study, we explored the effects of chronic palmitate and high glucose treatment on macrophage differentiation and function in murine bone-marrow-derived macrophages. We found that chronic treatment with palmitate decreased phagocytosis and HLA-DR expression in addition to inhibiting the production of pro-inflammatory cytokines. Chronic palmitate treatment of bone marrows also led to M2 polarization, which correlated with the activation of the peroxisome proliferator-activated receptor-γ signalling pathway. Furthermore, we found that chronic palmitate treatment increased the expression of multiple endoplasmic reticulum (ER) stress markers, including binding immunoglobulin protein. Preconditioning with the universal ER stress inhibitor 4-phenylbutyrate attenuated ER stress signalling and neutralized the effect of palmitate, inducing a pro-inflammatory phenotype. We confirmed these results in differentiating human macrophages, showing an anti-inflammatory response to chronic palmitate exposure. Though alone it did not promote M2 polarization, hyperglycaemia exacerbated the effects of palmitate. These findings suggest that the dominant accumulation of M2 in adipose tissue and liver in patients with critical illness may be a result of hyperlipidaemia and hyperglycaemia, both components of the hypermetabolism observed in critically ill patients.

C-C Chemokine Receptor Type 2 Expression on Monocytes Before Sepsis Onset Is Higher Than That of Postsepsis in Septic Burned Patients: A New Predictor for Sepsis in Burned Injury.

OBJECTIVE: The present study aims to investigate the alterations in monocytes (Mo) and dendritic cells (DCs) in septic burned patients with a special focus on C-C chemokine receptor type 2 (CCR2) expressions on classical Mo. BACKGROUND: The phenotypes of Mo and DCs, particularly CCR2 expression on Mo, are not fully explored in severely burned patients with sepsis. METHODS: The prospective cohort study was conducted in Ross Tilley Burn Centre and Sunnybrook Research Institute (Toronto, Canada). We enrolled 8 healthy patients and 89 burned patients with various burned sizes, of those burned patients, 12 were with sepsis. Blood was collected upon admission to the hospital and throughout their course in hospital. The expression of human leukocyte antigen-DR was determined on all DCs and Mo, along with CCR2 on CD14/CD16 Mo. RESULTS: We found a profound decrease in human leukocyte antigen-DR on Mo and DCs in burned patients with sepsis compared with healthy controls and nonseptic burned patients. In addition, septic burned patients presented an increased CCR2 expression on classical Mo (CD14/CD16), which was paralleled by greater chemokine (C-C motif) ligand 2 concentrations in the plasma when compared with controls and nonseptic burned patients. Furthermore, burned patients with sepsis had a more profound expansion of CD14/CD16 Mo when compared with nonseptic burned patients. CONCLUSION: Our results demonstrate that burned patients with sepsis have more profound impairment of monocytes and dendritic cells than burned patients without sepsis. With CCR2 level on Mo before sepsis onset being higher than postsepsis, CCR2 expression could be a new predictor of sepsis onset in severe burn injury.

Lipidomic analysis enables prediction of clinical outcomes in burn patients.

Recent discoveries have highlighted the novel metabolic functions of adipose tissue in enhancing hypermetabolism after trauma. As the exact function and expression profiles of serum lipids and free fatty acids (FFA) are essentially unknown, we determined the lipidomic expression profile after burn in correlation to clinical outcomes to identify important lipid mediators affecting post-burn outcomes. We conducted a prospective cohort study with 46 adult burn patients and 5 healthy controls at the Ross Tilley Burn Center in Toronto, Canada. Patients were stratified based on major demographic and clinical variables, including age, burn severity, mortality, and sepsis. Serum FFAs and inflammatory markers were measured during acute hospital stay. We found that FFAs were acutely elevated post-burn and returned to baseline over time. Greater burn severity and age were associated with an impaired acute response in unsaturated FFAs and pro-inflammatory cytokines. Elevations in saturated and mono-unsaturated FFAs correlated significantly to increased mortality. In summary, persistent elevation of unsaturated lipids was associated with a functionally altered inflammatory-immunological milieu and worse clinical outcomes. The present lipidomic analysis indicates profound alterations in the lipid profile after burn by characterizing key lipids as potential diagnostic and outcome indicators in critically injured patients.

Burn Induces Browning of the Subcutaneous White Adipose Tissue in Mice and Humans.

Burn is accompanied by long-lasting immuno-metabolic alterations referred to as hypermetabolism that are characterized by a considerable increase in resting energy expenditure and substantial whole-body catabolism. In burned patients, the length and magnitude of the hypermetabolic state is the highest of all patients and associated with profoundly increased morbidity and mortality. Unfortunately, the mechanisms involved in hypermetabolism are essentially unknown. We hypothesized that the adipose tissue plays a central role for the induction and persistence of hypermetabolism post-burn injury. Here, we show that burn induces a switch in the phenotype of the subcutaneous fat from white to beige, with associated characteristics such as increased mitochondrial mass and UCP1 expression. Our results further demonstrate the significant role of catecholamines and interleukin-6 in this process. We conclude that subcutaneous fat remodeling and browning represent an underlying mechanism that explains the elevated energy expenditure in burn-induced hypermetabolism.

Clinicopathological characteristics and outcomes of surgically excised renal masses in African Americans.

OBJECTIVES: In the present study, we report on the clinical and pathological characteristics of African American (AA) patients with surgically excised renal masses and assess the associations between race and oncological outcomes. METHODS AND MATERIALS: We conducted a retrospective review of patients who underwent partial or radical nephrectomy for renal masses at our institution between 2000 and 2010. Patients were divided into 2 groups based on self-reported race: AA and non-AA. Patient demographics and disease characteristics, and overall, cancer-specific, recurrence-free, distant, and local recurrence-free survival for localized renal cell carcinoma (RCC) were compared between AA and non-AA patients. Multivariable proportional hazard analyses were used to assess the associations of race with oncological outcomes. RESULTS: A total of 1,467 patients, of whom 359 (24.5%) were AA, were included. Rates of benign disease were comparable between AA patients and non-AA (18.2% vs. 17.6%, P = 0.556). AA patients presented with higher rates of localized disease (83% vs. 71%, P<0.001). Papillary subtype accounted for 40.8% of RCCs in AA patients compared with 11.6% in non-AA patients (P<0.001). The high proportion of papillary RCC in AA patients was maintained across disease stages. On univariable analyses, AA patients had better recurrence-free and cancer-specific survival. On multivariable analyses, AA race was not a significant predictor of oncological outcomes after adjusting for patient and disease characteristics. CONCLUSION: In this study, AA patients presented with more localized disease than non-AA patients, whereas rates of benign disease were comparable between the groups. Furthermore, AA patients had roughly 3 times higher rates of papillary RCC across disease stages. On univariable analyses, AA patients appeared to have more favorable oncological outcomes. However, this association is likely explained by tumor stage, grade, and histology as outcomes were similar across races when the analyses were adjusted for these and other characteristics.

Short-term functional outcomes and complications associated with transperineal template prostate mapping biopsy.

OBJECTIVE: To assess the complications and erectile and urinary functional outcomes of transperineal template mapping biopsy (TTMB) of the prostate. METHODS: We retrospectively reviewed the records of 84 patients undergoing TTMB at our institution and recorded complications and functional outcomes. Erectile and urinary functions were measured at baseline, 2 weeks, and 6 ± 2 weeks after TTMB using the International Index of Erectile Function short version (IIEF-5) and International Prostate Symptom Score questionnaires. Erectile and urinary function parameters were compared between baseline and 2 and 6 weeks after TTMB in a paired fashion. A subanalysis of erectile function was performed in preoperatively potent men (IIEF-5 >17). RESULTS: Sixteen patients (19%) experienced complications. The most common events were transient urinary retention (6%), prostatitis (4%) and local events, including perineal hematoma, bruising, or perineal pain (5%). One patient with hematuria required intervention. IIEF-5 scores at baseline, 2 weeks, and 6 weeks were 20 (interquartile range [IQR], 16-23), 18 (IQR, 12-22), and 18 (IQR, 12-22), respectively (P = .096 and P = .034). Among preoperatively potent men, IIEF-5 scores at baseline, 2 weeks, and 6 weeks were 22 (IQR, 20-24), 21 (IQR, 18-24), and 22 (IQR, 18-24), respectively (P = .011 and P = .018). International Prostate Symptom Scores were 6 (IQR, 3.5-11) at baseline, rose to 10 (IQR, 4.8-15) at 2 weeks (P = .012), and returned to 7 (IQR, 3.5-13) at 6 weeks (P = .628). CONCLUSION: TTMB has a favorable morbidity profile, with mostly mild and transient complications. Urinary retention occurred in 6%, and only 1 patient required intervention with bladder irrigation. Despite a statistically significant decline in erectile function from baseline, the median change in IIEF-5 score was 1 point. Urinary symptoms worsened initially but returned to baseline within 6 weeks.

Long-term oncological outcomes of men undergoing radical prostatectomy with preoperative prostate-specific antigen <2.5 ng/ml and 2.5-4 ng/ml.

OBJECTIVES: Prostate-specific antigen (PSA) screening has increased the detection of small, organ-confined tumors, and studies suggest that these patients may have favorable outcomes following radical prostatectomy (RP). To date, there are limited data available on the outcomes of patients diagnosed with low PSA (≤ 4 ng/ml) who underwent RP. This study aimed to evaluate long-term oncological outcomes of patients undergoing RP with preoperative PSA <2.5 and 2.5-4 ng/ml compared with PSA 4.1-10 ng/ml. MATERIALS AND METHODS: Data were analyzed from 3,621 men who underwent RP between 1988 and 2010 at our institution. Patients were stratified into 3 PSA groups: <2.5 ng/ml (n = 280), 2.5-4 ng/ml (n = 563), and 4.1-10 ng/ml (n = 2,778). Patient and disease characteristics were compared. Overall, biochemical disease-free (bDFS), and PCa-specific survivals were analyzed and compared between the groups. Multivariable analyses were conducted using proportional hazards model. RESULTS: Compared with the 4.1-10 ng/ml PSA group, Gleason score >7, extracapsular extension, and non-organ-confined disease were less common in patients with PSA ≤ 4 ng/ml (all P < 0.001). The incidence of organ-confined disease was similar between the PSA < 2.5 and 2.5-4 ng/ml groups while perineural invasion (P = 0.050) and Gleason score ≥ 7 (P = 0.026) were more common in the 2.5-4 ng/ml PSA group. Estimated 10-year overall and PCa-specific survivals were comparable across all PSA groups, whereas bDFS was significantly lower in PSA 4.1-10 group (P < 0.001). bDFS was not statistically different between PSA <2.5 and 2.5-4 groups (P = 0.300). 10-year bDFS were 59.0%, 70.1%, and 76.4% in PSA 4.1-10, 2.5-4, and <2.5, respectively. For the PSA ≤ 4 ng/ml groups, age, race, margin status, pathologic stage, but not PSA were independent predictors of bDFS, whereas age, pathologic Gleason, and biochemical recurrence were associated with overall survival. CONCLUSIONS: Long-term oncological outcomes (overall, bDFS, PCa-specific survivals) of patients presenting with low PSA (≤ 4 ng/ml) were excellent in this study. Compared with PSA 4.1-10 ng/ml, patients presenting with PSA ≤ 4 ng/ml had better bDFS outcomes. However, there was no difference in long-term outcomes between PSA <2.5 and 2.5-4 ng/ml.

Radiation exposure associated with dedicated renal mass computed tomography protocol: impact of patient characteristics.

BACKGROUND AND PURPOSE: Renal mass protocol CT (RMP-CT) using multiphase abdomen and pelvis CT imaging is the mainstay for diagnosis, characterization, and follow-up for renal masses; however, it is associated with ionizing radiation to the patient. We sought to quantify the effective dose associated with RMP-CT and to determine how patient factors affect radiation exposure. MATERIAL AND METHODS: We retrospectively reviewed the records of 247 patients undergoing management of a small renal mass (cT1a) between 2005 and 2011 at our institution. Body mass index (BMI) was categorized as normal weight, overweight, obese, and morbidly obese (≤25, 25.1-30, 30.1-35 and >35, respectively). Effective dose of RMP-CT was calculated through the dose-length-product multiplied by a factor coefficient (0.015). Effective doses in milliSieverts (mSv) were correlated to patient characteristics. RESULTS: Patients' median age was 61 years, and median BMI was 28.7 kg/m(2); 72% were Caucasian and 56% were male. Median effective dose was 26.1 mSv (interquartile range 20.6-35.3). When stratified by BMI, the median effective doses were 18.9, 25.2, 27.7, and 36.2mSv for normal weight, overweight, obese, and morbidly obese patients, respectively. On multivariable analyses, BMI and male sex were significantly associated with increased radiation dose. CONCLUSIONS: In this series, the median effective dose for RMP-CT was 26.1 mSv. Obesity was independently associated with markedly increased radiation exposure, with morbidly obese patients being exposed to almost twice the amount of radiation compared with normal weight persons. These findings should be considered when devising management strategies in patients with a renal mass and strategies should be developed to reduce medical ionizing radiation exposure.

The effect of noise-cancelling headphones or music on pain perception and anxiety in men undergoing transrectal prostate biopsy.

OBJECTIVE: To assess the effect of noise-cancelling headphones with or without music on patient pain and anxiety associated with routine, office-based transrectal ultrasound (TRUS)-guided prostate biopsy in a prospective randomized study. METHODS: Patients scheduled for prostate biopsy as a result of elevated prostate-specific antigen and/or abnormal digital rectal examination were prospectively enrolled and randomized into a control, noise-cancelling headphones, or music-headphones group. Patients completed pain and anxiety questionnaires and had their physiological parameters assessed before and after the procedure and compared across groups. RESULTS: Eighty-eight patients were enrolled. Pain scores increased from baseline across all study groups, with the lowest mean score in the music group. No appreciable change was noted in anxiety scores after the procedure between groups (P>.05). Although postbiopsy systolic blood pressure values remained comparable with baseline levels in all groups, postbiopsy diastolic blood pressure increased in the control and headphones groups (P=.062 and .088, respectively) but remained stable in the music group (P=.552) after biopsy, indicating lesser physiological response to anxiety and pain in this group. CONCLUSION: Music-induced attention shift during prostate biopsy may have a beneficial impact on procedural anxiety and pain perception, but no apparent effect was noted for use of headphones alone. Further studies are necessary to explore strategies to reduce perceived anxiety and pain in men undergoing prostate biopsy.