The prostate cancer immunome: In silico functional analysis of antigenic proteins from microarray profiling with IgG.

The study of the immunome of prostate cancer (PCa) and characterization of autoantibody signature from differentially reactive antigens can uncover disease stage proteins, reveal enriched networks and even expose aberrant cellular mechanisms during the disease process. By conducting plasma IgG profiling on protein microarrays presenting 5449 unique human proteins expressed in 15 417 E. coli human cDNA expression clones, we elucidated 471 (21 higher reactive in PCa) differentially reactive antigens in 50 PCa versus 49 patients with benign prostate hyperplasia (BPH) at initial diagnosis. Functional analyzes show that the immune-profile of PCa compared to BPH control samples is significantly enriched in features targeting Cellular assembly, Cell death and pathways involved in Cell cycle, translation, and assembly of proteins as EIF2 signaling, PCa related genes as AXIN1 and TP53, and ribosomal proteins (e.g. RPS10). An overlap of 61 (out of 471) DIRAGs with the published 1545 antigens from the SEREX database has been found, however those were higher reactive in BPH. Clinical relevance is shown when antibody-reactivities against eight proteins were significantly (p < 0.001) correlated with Gleason-score. Herewith we provide a biological and pathophysiological characterization of the immunological layer of cancerous (PCa) versus benign (BPH) disease, derived from antibody profiling on protein microarrays.

Impact of the use of bowel for urinary diversion on perioperative complications and 90-day mortality in patients aged 75 years or older.

OBJECTIVE: A potential strategy to decrease the high complication rate of radical cystectomy (RC) in the elderly is to avoid the use of bowel for urinary diversion. The aim of this study was to address this issue in a multicentre study of patients aged ≥ 75 years. PATIENTS AND METHODS: We performed a retrospective, multicentre study of a consecutive series of patients aged ≥ 75 years who underwent RC for muscle-invasive bladder cancer between 2006 and 2010. Medical, surgical and wound complications were graded according to the modified Clavien-Dindo classification. RESULTS: A total of 256 patients (68% men, mean age 79.6 years) were analysed. 204 (80%) patients received a urinary diversion with use of bowel and 52 (20%) a ureterocutaneostomy (UC). Patients with UC were older (82.0 vs. 78.9 years, p < 0.001) and had a higher ASA score (2.6 vs. 2.3, p = 0.007), while the mean Charlson score was lower (4.2 vs. 5.6, p < 0.001). Patients with UC had a shorter operating time (279 vs. 311 min, p = 0.002) and a shorter period in the intensive care unit (0.9 vs. 2.2 days). The overall rate of severe complications graded as Clavien III-V was significantly lower in the UC group (11.5%) as compared to patients receiving bowel for urinary diversion (25.0%) (p = 0.003). Severe (Clavien grade III-V) medical (3.9 vs. 10.3%) and surgical (2.1 vs. 14.1%) complications were all less frequent in the UC group. Inpatient, 30- and 90-day mortality was 5.8, 7.7 and 17.3% in the UC group as compared to 3.9, 5.9 and 6.9% in the bowel cohort, respectively. CONCLUSION: UC following RC is associated with a lower complication rate in geriatric patients. The constantly increasing cohort of geriatric, multimorbid patients requiring cystectomy might justify reconsideration of this form of diversion.

Perioperative complications and 90-day mortality of radical cystectomy in the elderly (75+): a retrospective, multicentre study.

OBJECTIVE: To assess perioperative complications and 90-day mortality of radical cystectomy (RC) in elderly patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: This is a retrospective, multicentre (n = 11) study of a consecutive series of patients ≥75 years who underwent RC for MIBC between 2006 and 2010. Medical, surgical and wound complications were graded according to the modified Clavien-Dindo classification. RESULTS: A total of 256 patients with a mean age of 79.6 years (range 75.0-86.6) were analysed. Urinary diversion with the use of bowel was performed in 79.5% and ureterocutaneostomy in 20.5%, with a higher proportion in the ≥80 cohort (32.2 vs. 14%; p = 0.001). 41.4% of patients had an uneventful postoperative course (Clavien grade 0) and 26.6% developed severe complications (Clavien grade III-V). In a multivariable regression analysis, the Charlson comorbidity index (odds ratio 1.5 per unit increase; p < 0.001) and the body mass index (odds ratio 1.13 per kg/m(2) increase; p = 0.015) were predictors for the development of complications. The 90-day mortality rate was 9% and the independent correlates thereof were the development of severe medical complications (p = 0.004), the American Society of Anesthesiologists (ASA) score (p = 0.03) and age (p = 0.005). CONCLUSIONS: Morbidity and 90-day mortality of RC in the elderly remain substantial. The interrelation between comorbidity, complication rate and 90-day mortality underlines the need for a comprehensive geriatric assessment of elderly patients with MIBC in whom RC is indicated.