Sexual function after radical hysterectomy for early-stage cervical cancer

IntroductionFor early-stage cervical cancer, treatment with radical surgery appears effective with excellent survival. However, the treatment is associated with significant morbidities. Sexual dysfunction is the leading cause of symptom-induced distress after the treatments for early-stage cervical cancer. There has been no study that evaluates the effect of surgical treatments for cervical cancer on sexual function in the Eastern/Asian patients.AimTo examine the effect of radical hysterectomy on postoperative sexual function in women with early-stage cervical cancer.Main Outcome MeasuresThe visual analog score on seven aspects of sexual function: overall satisfaction with sexual intercourse, sexual desire, vaginal lubrication, vaginal elasticity, orgasmic satisfaction, patient-perceived partner satisfaction, and associated anxiety.MethodsThirty patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy at the Chiang Mai University Hospital were recruited. All of the patients were interviewed by questionnaire on sexual function at preoperative hospital admission and then at 3 and 6 months after surgery. Relevant clinical and pathologic data were also prospectively collected.ResultsThe mean age of the patients was 45.3 ± 6 years (range 28–59). Seven (23%) of the patients were postmenopausal. Almost all (97%) had FIGO stage IB1 disease. Fourteen (46.7%) patients had bilateral salpingo-oophorectomy, and one (3.3%) patient had unilateral salpingo-oophorectomy. Squamous-cell carcinoma and adenocarcinoma were diagnosed in 83% and 17%, respectively. At 3 and 6 months after operation, 63% and 93% of the patients had sexual intercourse, respectively. Considering the overall sexual satisfaction, the patient-rated visual analog score appeared comparable at preoperative and 6-month postoperative assessment (4.2 ± 2.5 vs. 3.6 ± 2.2, P > 0.05).ConclusionRadical hysterectomy using the current technique has a minimal short-term impact on sexual function. A comparative study with long-term follow-up would provide clearer information on permanent effect of radical hysterectomy on sexual function. Jongpipan J, and Charoenkwan K. Sexual function after radical hysterectomy for early-stage cervical cancer.     

Survey of activated kinase proteins reveals potential targets for cholangiocarcinoma treatment

Improving therapy for patients with cholangiocarcinoma (CCA) presents a significant challenge. This is made more difficult by a lack of a clear understanding of potential molecular targets, such as deregulated kinases. In this work, we profiled the activated kinases in CCA in order to apply them as the targets for CCA therapy. Human phospho-receptor tyrosine kinases (RTKs) and phospho-kinase array analyses revealed that multiple kinases are activated in both CCA cell lines and human CCA tissues that included cell growth, apoptosis, cell to cell interaction, movement, and angiogenesis RTKs. Predominately, the kinases activated downstream were those in the PI3K/Akt, Ras/MAPK, JAK/STAT, and Wnt/β-catenin signaling pathways. Western blot analysis confirms that Erk1/2 and Akt activation were increased in CCA tissues when compared with their normal adjacent tissue. The inhibition of kinase activation using multi-targeted kinase inhibitors, sorafenib and sunitinib led to significant cell growth inhibition and apoptosis induction via suppression of Erk1/2 and Akt activation, whereas drugs with specificity to a single kinase showed less potency. In conclusion, our study reveals the involvement of multiple kinase proteins in CCA growth that might serve as therapeutic targets for combined kinase inhibition.     

PRKAR1A is overexpressed and represents a possible therapeutic target in human cholangiocarcinoma

The protein kinase A regulatory subunit 1 alpha (PRKAR1A/PKAI) pathway is overexpressed in varieties of tumors and cancer cell lines including cholangiocarcinoma (CCA), although its role in CCA growth modulation is unclear. In our study, we evaluated the effect of PRKAR1A/PKAI targeting on CCA cell proliferation. Real‐time PCR demonstrated an increased mRNA expression of PRKAR1A/PKAI, whereas protein kinase A regulatory subunit 2 beta (PRKAR2B/PKAII) was downregulated in human CCA tissues and CCA cell lines. Immunohistochemistry of human CCA tissues revealed increased PRKAR1A with decreased PRKAR2B protein expression. Moreover, CCA cell lines showed abundantly expressed PRKAR1A, while lacking PRKAR2B expression. Silencing PRKAR1A expression induced growth inhibition and apoptosis of CCA cells, with an associated decrease in mitogen‐activated protein kinases, PI3K/Akt, JAK/STAT and Wnt/β‐catenin pathway signaling. The inhibition of PKA using a PKA inhibitor and cAMP analogs also led to a significant cell growth inhibition. In conclusion, our study reports the overexpression as well as molecular mechanisms by which PRKAR1A/PKA regulates human CCA cell growth. Importantly, abrogation of gene expression caused significant CCA cell growth inhibition, oncogenic signaling and coupled apoptosis induction, suggesting PRKAR1A's potential as a drug target for CCA therapy.     

Do health preferences differ among Asian populations? A comparison of EQ-5D-5L discrete choice experiments data from 11 Asian studies

Introduction

Many countries have established their own EQ-5D value sets proceeding on the basis that health preferences differ among countries/populations. So far, published studies focused on comparing value set using TTO data. This study aims to compare the health preferences among 11 Asian populations using the DCE data collected in their EQ-5D-5L valuation studies.

Methods

In the EQ-VT protocol, 196 pairs of EQ-5D-5L health states were valued by a general population sample using DCE method for all studies. DCE data were obtained from the study PI. To understand how the health preferences are different/similar with each other, the following analyses were done: (1) the statistical difference between the coefficients; (2) the relative importance of the five EQ-5D dimensions; (3) the relative importance of the response levels.

Results

The number of statistically differed coefficients between two studies ranged from 2 to 16 (mean: 9.3), out of 20 main effects coefficients. For the relative importance, there is not a universal preference pattern that fits all studies, but with some common characteristics, e.g. mobility is considered the most important; the relative importance of levels are approximately 20% for level 2, 30% for level 3, 70% for level 4 for all studies.

Discussion

Following a standardized study protocol, there are still considerable differences in the modeling and relative importance results in the EQ-5D-5L DCE data among 11 Asian studies. These findings advocate the use of local value set for calculating health state utility.

     

Reviewing the evidence on effectiveness and cost-effectiveness of HIV prevention strategies in Thailand

Background  

Following universal access to antiretroviral therapy in Thailand, evidence from National AIDS Spending Assessment indicates a decreasing proportion of expenditure on prevention interventions. To prompt policymakers to revitalize HIV prevention, this study identifies a comprehensive list of HIV/AIDs preventive interventions that are likely to be effective and cost-effective in Thailand.