Urethral recurrence in women with orthotopic bladder substitutes: A multi-institutional study.

OBJECTIVES To evaluate risk factors for urethral recurrence (UR) in women with neobladder. MATERIAL AND METHODS From 1994 to 2011, 297 women (median age = 54y; interquartile range: 47-57) underwent radical cystectomy with ileal neobladder for bladder cancer in 4 centers. None of the patients had bladder neck involvement at preoperative assessment. Univariable and multivariable analyses were used to estimate recurrence-free survival and overall survival. The median follow-up was 64 months (interquartile range: 25-116). RESULTS Of the 297 patients, 81 developed recurrence (27%). The 10- and 15-year recurrence-free survival rates were 66% and 66%, respectively. The 10- and 15-year overall survival rates were 57% and 55%, respectively. UR occurred in 2 patients (0.6%) with solitary urethral, 4 (1.2%) with concomitant urethral and distant recurrence, and 1 with concomitant urethral and local recurrence (0.3%). Bladder tumors were located at the trigone in 27 patients (9.1%). None of these patients developed UR. Lymph node tumor involvement was present in 60 patients (20.2%). On univariable and multivariable analyses, pathologic tumor and nodal stage were independent predictors for the overall risk of recurrence. UR was associated with a positive final urethral margin status (P<0.001) whereas no significant associations were found for carcinoma in situ, pathologic tumor and nodal stage, and bladder trigone involvement. CONCLUSIONS In this series, only 0.6% of women developed solitary UR. A positive final urethral margin was associated with an increased risk of UR. Women with involvement of the bladder trigone were not at higher risk of UR.

Prognostic factors and outcomes in primary urethral cancer: results from the international collaboration on primary urethral carcinoma.

PURPOSE To evaluate risk factors for survival in a large international cohort of patients with primary urethral cancer (PUC). METHODS A series of 154 patients (109 men, 45 women) were diagnosed with PUC in ten referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank test was used to investigate various potential prognostic factors for recurrence-free (RFS) and overall survival (OS). Multivariate models were constructed to evaluate independent risk factors for recurrence and death. RESULTS Median age at definitive treatment was 66 years (IQR 58-76). Histology was urothelial carcinoma in 72 (47 %), squamous cell carcinoma in 46 (30 %), adenocarcinoma in 17 (11 %), and mixed and other histology in 11 (7 %) and nine (6 %), respectively. A high degree of concordance between clinical and pathologic nodal staging (cN+/cN0 vs. pN+/pN0; p < 0.001) was noted. For clinical nodal staging, the corresponding sensitivity, specificity, and overall accuracy for predicting pathologic nodal stage were 92.8, 92.3, and 92.4 %, respectively. In multivariable Cox-regression analysis for patients staged cM0 at initial diagnosis, RFS was significantly associated with clinical nodal stage (p < 0.001), tumor location (p < 0.001), and age (p = 0.001), whereas clinical nodal stage was the only independent predictor for OS (p = 0.026). CONCLUSIONS These data suggest that clinical nodal stage is a critical parameter for outcomes in PUC.

Stereochemistry of Amino Acid Spacers Determines the Pharmacokinetics of (111)In-DOTA-Minigastrin Analogues for Targeting the CCK2/Gastrin Receptor.

The metabolic instability and high kidney retention of minigastrin (MG) analogues hamper their suitability for use in peptide-receptor radionuclide therapy of CCK2/gastrin receptor-expressing tumors. High kidney retention has been related to N-terminal glutamic acids and can be substantially reduced by coinjection of polyglutamic acids or gelofusine. The aim of the present study was to investigate the influence of the stereochemistry of the N-terminal amino acid spacer on the enzymatic stability and pharmacokinetics of (111)In-DOTA-(d-Glu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 ((111)In-PP11-D) and (111)In-DOTA-(l-Glu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 ((111)In-PP11-L). Using circular dichroism measurements, we demonstrate the important role of secondary structure on the pharmacokinetics of the two MG analogues. The higher in vitro serum stability together with the improved tumor-to-kidney ratio of the (d-Glu)6 congener indicates that this MG analogue might be a good candidate for further clinical study.

Changes in self-reported symptoms of depression and physical wellbeing in healthy individuals following a Taiji beginner course – Results of a randomized controlled trial

Introduction: Taiji is a mind-body practice being increasingly investigated for its therapeutic benefits in a broad range of mental and physical conditions. The aim of the present study was to investigate potential preventive effects of Taiji practice in healthy individuals with regard to their depressive symptomatology and physical wellbeing. Methods: A total of 70 healthy Taiji novices (mean age 35.5 years) were randomly assigned to a Taiji intervention group, i.e. Taiji beginner course (Yang-Style Taiji, 2 hours per week, 12 weeks) or a waiting control group. Self-reported symptoms of depression (CES-D) and physical wellbeing (FEW-16) were assessed at baseline, at the end of the intervention, as well as two months later. Results: Physical wellbeing in the Taiji group significantly increased when comparing baseline to follow up (FEW-16 sum scale T(27) = 3.94, p = 0.001, 95% CI 0.17 - 0.55). Pearson’s correlation coefficients displayed a strong negative relationship between self-reported symptoms of depression and physical wellbeing (p’s < 0.001, r‘s ≥ -.54). Conclusions: In this randomized controlled trial we found significant evidence that a Taiji beginner course of three months duration elicits positive effects with respect to physical wellbeing in healthy individuals, with improvements pronouncing over time. Physical wellbeing was shown to have a strong relationship with depressive symptoms. Based on these results, the consideration of Taiji as one therapeutic option in the development of multimodal approaches in the prevention of depression seems justifiable.