Urinary symptoms in women receiving carboplatin/paclitaxel for treatment of gynecologic cancers.

OBJECTIVES: Urinary incontinence is estimated to affect up to 34% of women with gynecologic cancers. Chemotherapeutic effects on urinary symptoms have been scarcely studied. The aim of our study was to examine the impact of carboplatin/paclitaxel chemotherapy on urinary symptoms. METHODS: This was a prospective cohort study of all women undergoing adjuvant chemotherapy with carboplatin/paclitaxel after their primary debulking surgery for ovarian, fallopian tube, peritoneal, or endometrial cancers performed at a tertiary medical center by board certified gynecologic oncologists. We used validated questionnaires (incontinence impact questionnaire (IIQ-7), medical, epidemiologic, and social aspects of aging (MESA), urogenital distress inventory (UDI-6), the Sandvik severity index, and functional assessment of cancer therapy/GynecologicOncology Group-neurotoxicity (FACT/GOG-Ntx)) to assess the effects of carboplatin/paclitaxel therapy on the incidence and severity of urinary incontinence at three time points during the participants' chemotherapy regimen: start of chemotherapy (pretreatment), during the fifth chemotherapy cycle (mid-cycle), and during the 6-12 week post-chemotherapy visit (post-treatment). RESULTS: We identified 62 women with ovarian, fallopian, peritoneal, and endometrial cancer who received carboplatin/paclitaxel therapy between May 2009 and December 2012 who met all of the inclusion criteria. Analysis of median IIQ-7 scores, across all time points, showed a statistically significant difference (0.0 (0.0 to 4.8), 0.0 (0.0 to 7.1), 0.0 (0.0 to 0.0), p=0.002, respectively). Examining pairwise differences between two treatment points, IIQ-7 pretreatment versus mid-treatment and pretreatment versus post-treatment, did not achieve significance (0.0 (0.0 to 2.4), p=0.13 and 0.0 (0.0 to 0.0), p>0.999, respectively), but the decrease in IIQ-7 mid-treatment versus post-treatment was statistically significant (0.0 (-2.4 to 0.0), p=0.003). Generalized estimating equation model analysis also showed significant changes in both median MESA for urge urinary incontinence (MESA-UUI) and median MESA for stress urinary incontinence (MESA-SUI) across all time points (p=0.003 and p=0.009, respectively). MESA-UUI and MESA-SUI pretreatment versus mid-treatment analysis achieved significance (2.0 (0.0 to 4.0), p=0.003 and 0.0 (0.0 to 2.0), p=0.01, respectively), demonstrating an increase in the incidence of stress urinary incontinence and urge urinary incontinence. There was a statistically significant association between the changes in FACT and UDI-6 scores from pretreatment versus mid-treatment, with a correlation coefficient of 0.37 (95% CI 0.08 to 0.61, p=0.005). CONCLUSION: The study achieved its primary aim in demonstrating an impact of carboplatin/paclitaxel therapy on urinary incontinence severity and suggests if may be a factor leading to new onset or worsening urinary incontinence. As quality of life can be significantly impacted by these chemotherapeutic changes, further investigation is warranted to determine if the effects on urinary incontinence and neuropathy are transient or permanent.

Expression and function of PDCD1 at the human maternal-fetal interface.

The failure to reject the semiallogenic fetus by maternal T lymphocytes suggests that potent mechanisms regulate these cells. PDCD1 is a CD28 family receptor expressed by T cells, and its ligand CD274 is strongly expressed by trophoblast cells of the human placenta. In this study, we examined whether human maternal T cells express PDCD1. Immunofluorescence examination of uterine tissues revealed PDCD1 expression on CD3+ cells was low in nonpregnant endometrium but increased in first-trimester decidua and remained elevated in term decidua (P < 0.05). In addition, higher relative proportions of term decidual CD8 bright, CD4+, and regulatory T cells expressed PDCD1 in comparison to autologous peripheral blood (P < 0.05). Term decidual T cells also expressed full-length and soluble PDCD1 mRNA isoforms more abundantly than their peripheral blood counterparts (P