Sharon Hanley

Risk factors for persistent low bladder compliance after radical hysterectomy.

Introduction: Bladder compliance deteriorates immediately after radical hysterectomy (RH), and low bladder compliance causes upper urinary tract dysfunctions such as progressive hydronephrosis. The aims of this study were to clarify risk factors for persistent low bladder compliance after RH and to propose a postsurgical management protocol for improved recovery of bladder function. Methods: A total of 113 consecutive patients who underwent RH with the intention to preserve the pelvic autonomic nerve system were included in this prospective study. Urodynamic studies were performed according to a planned schedule: presurgery and 1, 3, 6, and 12 months after surgery. Autonomic nerves were preserved at least unilaterally in 95 (84.1%) of the 113 patients, but this was not possible in the remaining 18 patients (15.9%). Postoperative adjuvant radiation therapy (RT) was performed in 14 patients. The relationships between bladder compliance and various clinical factors were investigated using logistic regression analysis. Covariates included age, nerve-sparing procedure, adjuvant RT, and maximum abdominal pressure during the voiding phase. Bladder compliance at 12 months after surgery was used as the dependent variable. Results: Radical hysterectomy with a non-nerve-sparing procedure (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.1-11.0), adjuvant RT (OR, 10.3; 95% CI, 2.5-43.5), and voiding with abdominal pressure at 3 months after surgery (OR, 2.9; 95% CI, 1.1-7.2) were risk factors for persistent low bladder compliance. Conclusions: A nerve-sparing procedure and prohibition of voiding with abdominal strain during the acute and subacute phases after RH resulted in improved recovery of bladder compliance. Adjuvant RT should be avoided in patients who undergo nerve-sparing RH if an alternative postoperative strategy is possible.

An Exploratory Study of Japanese Fathers' Knowledge of and Attitudes towards HPV and HPV Vaccination: Does Marital Status Matter?

BACKGROUND No studies on male attitudes towards HPV and HPV vaccination have been conducted in Japan, and little is known globally whether attitudes of single fathers differ to those living with a female partner. This exploratory study assessed whether Japanese fathers were likely to have their daughter vaccinated against HPV in a publically funded program and whether any differences existed regarding attitudes and knowledge about HPV according to marital status. MATERIALS AND METHODS Subjects were 27 fathers (16 single; 11 married) who took part in a study on HPV vaccine acceptability aimed at primary caregivers of girls aged 11-14 yrs in three Japanese cities between July and December 2010. RESULTS Knowledge about HPV was extremely poor (mean score out of 13 being 2.74 ± 3.22) with only one (3.7%) participant believing he had been infected with HPV and most (81.4%) believing they had no or low future risk. No difference existed regarding knowledge or awareness of HPV according to marital status. Concerning perceived risk for daughters, single fathers were significantly more likely to believe their daughter was at risk for both HPV (87.5% versus 36.4%; p=0.01) and cervical cancer (75.0% versus 27.3%; p=0.02). Acceptability of free HPV vaccination was high at 92% with no difference according to marital status, however single fathers were significantly more likely (p=0.01) to pay when vaccination came at a cost. Concerns specific to single fathers included explaining the sexual nature of HPV and taking a daughter to a gynecologist to be vaccinated. CONCLUSIONS Knowledge about HPV among Japanese fathers is poor, but HPV vaccine acceptability is high and does not differ by marital status. Providing sexual health education in schools that addresses lack of knowledge about HPV as well as information preferences expressed by single fathers, may not only increase HPV vaccine acceptance, but also actively involve men in cervical cancer prevention strategies. However, further large-scale quantitative studies are needed.

Tumor-Intrinsic PD-L1 Signaling in Cancer Initiation, Development and Treatment: Beyond Immune Evasion

Although the role of PD-L1 in suppressing the anti-tumor immune response is extensively documented, recent discoveries indicate a distinct tumor-intrinsic role for PD-L1 in modulating epithelial-to-mesenchymal transition (EMT), cancer stem cell (CSC)-like phenotype, metastasis and resistance to therapy. In this review, we will focus on the newly discovered functions of PD-L1 in the regulation of cancer development, describe underlying molecular mechanisms responsible for PD-L1 upregulation and discuss current insights into novel components of PD-L1 signaling. Furthermore, we summarize our current understanding of the link between PD-L1 signaling and the EMT program as well as the CSC state. Tumor cell-intrinsic PD-L1 clearly contributes to cancer stemness, EMT, tumor invasion and chemoresistance in multiple tumor types. Conversely, activation of OCT4 signaling and upregulation of EMT inducer ZEB1 induce PD-L1 expression in cancer cells, thereby suggesting a possible immune evasion mechanism employed by cancer stem cells during metastasis. Our meta-analysis demonstrated that PD-L1 is co-amplified along with MYC, SOX2, N-cadherin and SNAI1 in the TCGA endometrial and ovarian cancer datasets. Further identification of immune-independent PD-L1 functions and characterization of crucial signaling events upstream or downstream of PD-L1 in diverse cancer types and specific cancer subtypes, would provide additional targets and new therapeutic approaches.

Long Non-coding RNA NEAT1: A Novel Target for Diagnosis and Therapy in Human Tumors

The nuclear paraspeckle assembly transcript 1 (NEAT1, a long non-coding RNA) is frequently overexpressed in human tumors, and higher NEAT1 expression is correlated with worse survival in cancer patients. NEAT1 drives tumor initiation and progression by modulating the expression of genes involved in the regulation of tumor cell growth, migration, invasion, metastasis, epithelial-to-mesenchymal transition, stem cell-like phenotype, chemoresistance and radioresistance, indicating the potential for NEAT1 to be a novel diagnostic biomarker and therapeutic target. Mechanistically, NEAT1 functions as a scaffold RNA molecule by interacting with EZH2 (a subunit of the polycomb repressive complex) to influence the expression of downstream effectors of EZH2, it also acts as a microRNA (miRNA) sponge to suppress the interactions between miRNAs and target mRNAs, and affects the expression of miR-129 by promoting the DNA methylation of the miR-129 promoter region. Knockdown of NEAT1 via small interfering RNA or short hairpin RNA inhibits the malignant behavior of tumor cells. In this review, we highlight the latest insights into the expression pattern, biological roles and mechanisms underlying the function and regulation of NEAT1 in tumors, and especially focus on its clinical implication as a new diagnostic biomarker and an attractive therapeutic target for cancers.