Procoagulant Activity of Blood and Microvesicles Is Disturbed by Pneumococcal Pneumolysin, Which Interacts with Coagulation Factors.

The coagulation and contact systems are parts of the innate immune system as they prevent bleeding and dissemination of pathogens and also contribute to microbial killing by inflammatory reactions and the release of antimicrobial peptides. Here, we investigated the influence of Streptococcus pneumoniae on the coagulation and contact system. S. pneumoniae (pneumococci), but no other investigated streptococcal species, impairs coagulation of blood by autolysis and release of pneumolysin. Defective blood coagulation results from the lysis of tissue factor-producing mononuclear cells and their procoagulant microvesicles, which are the main trigger for blood coagulation during sepsis. In addition, pneumolysin binds coagulation and contact system factors, but this does not result in activation. Thus, pneumococci modulate activation of the coagulation system by releasing pneumolysin, which could potentiate lung injury during pneumonia.

The Impact of Tumor Diameter and Tumor Necrosis on Oncologic Outcomes in Patients With Urothelial Carcinoma of the Bladder Treated With Radical Cystectomy.

OBJECTIVE: To evaluate the influence of tumor diameter and tumor necrosis on oncologic outcomes in patients with urothelial carcinoma of the bladder treated with radical cystectomy (RC). MATERIALS AND METHODS: We treated 517 consecutive patients with urothelial carcinoma of the bladder treated with RC without neoadjuvant chemotherapy at our institution between 1996 and 2011. All RC specimens were meticulously re-reviewed for the largest residual tumor diameter and for the presence and extent of tumor necrosis. Cox regression models evaluated the association with disease recurrence and cancer-specific survival. RESULTS: At RC, 155 patients (30.0%) had a residual tumor diameter ≥3 cm and tumor necrosis was present in 156 patients (30.2%). Tumor diameter and necrosis were significantly correlated (P <.001). Both a tumor diameter ≥3 cm and the presence of tumor necrosis were associated with an older age, advanced tumor stage, higher tumor grade, lymph node metastasis, positive surgical margin status, lymphovascular invasion, and administration of adjuvant chemotherapy (P values ≤.009). A tumor diameter ≥3 cm and the presence of tumor necrosis were associated with disease recurrence and cancer-specific mortality in Kaplan-Meier analyses, respectively (pairwise P values <.001). In addition, a tumor diameter ≥3 cm was an independent predictor of cancer-specific mortality in multivariate analysis that adjusted for standard clinicopathologic features. CONCLUSION: Tumor diameter and necrosis are closely correlated and associated with aggressive tumor features and inferior oncologic outcomes. A residual tumor diameter ≥3 cm is an independent predictor of cancer-specific mortality. This additional information should be considered to be reported in every pathology report for consideration in patient counseling and treatment decision making. In addition, these results underscore the importance of a thorough transurethral resection of the bladder tumor before RC.

Does the extent of variant histology affect oncological outcomes in patients with urothelial carcinoma of the bladder treated with radical cystectomy?

BACKGROUND: To evaluate the effect of variant histology and its extent on oncological outcomes in patients with urothelial carcinoma of the bladder (UCB) who are treated with radical cystectomy. MATERIAL AND METHODS: Data from 485 patients with UCB who were treated with radical cystectomy without neoadjuvant chemotherapy at a single academic center between 1996 and 2011 were collected retrospectively. All pathologic specimens were meticulously re-reviewed for the presence and extent of variant UCB histologies. Cox regression models were used to evaluate the association with disease recurrence and cancer-specific survival. RESULTS: Variant histology was present in 96 patients (19.8%), with squamous cell differentiation (12.6%) being most common. In patients with variant histology, the median and mean extent was 70% and 60%, respectively. Variant histology was associated with female sex, advanced tumor stage, less presence of concomitant carcinoma in situ, and administration of adjuvant chemotherapy (P ≤ 0.001). The presence of variant histology and non-squamous cell differentiation was associated with cancer-specific mortality (pairwise P ≤ 0.02). Moreover, non-squamous cell differentiation was associated with disease recurrence (P = 0.002). The presence of variant histology, non-squamous cell differentiation, and the extent of variant histology were associated with cancer-specific mortality in univariable but not in multivariable analyses. CONCLUSIONS: The presence of variant histology, particularly non-squamous cell differentiation, and its extent are associated with inferior survival. However, they are not independent predictors of outcomes. The association of variant histology with established predictors of aggressive tumor biology is likely impairing oncological outcomes and thus has to be considered in clinical decision making.