Disparities in the Diagnosis, Treatment, and Survival Rate of Cervical Cancer among Women with and without Disabilities.

INTRODUCTION: Not much is known regarding the disparities in cancer care between women with and without disabilities. OBJECTIVES: The aim of this study was to investigate the potential disparities in the diagnosis, treatment, and survival of women with cervical cancer with and without disabilities. METHODS: We performed a retrospective cohort study and linked the National Disability Database, Korean Central Cancer Registry, and Korean National Health Insurance claims database. Charlson comorbidity index was used for adjusting the comorbidity. The study population comprised 3 185 women with disabilities (physical/brain, communication, mental, cardiopulmonary, and other impairment) who were diagnosed with cervical cancer and 13 582 age- and sex-matched women without disability who were diagnosed with cervical cancer for comparison. RESULTS: Distant metastatic stage (7.7% vs 3.7%) and unknown stage (16.1% vs 7.0%) were more common in cervical cancer women with grade 1 disabilities, compared with women without disabilities. Women with cervical cancer with disabilities were less likely to undergo surgery (adjusted odds ratio (aOR) 0.81, 95% confidence interval (CI) 0.73-0.90) or chemotherapy (aOR 0.86, 95% CI 0.77-0.97). Lower rate of surgery was more evident in patients with physical/brain impairment (aOR 0.46, 95% CI 0.37-0.58) and severe mental impairment (aOR 0.57, 95% CI 0.41-0.81). The overall mortality risk was also higher in patients with disabilities (adjusted hazard ratio (aHR) 1.36, 95% CI 1.25-1.48). CONCLUSION: Women with cervical cancer with disabilities, especially with severe disabilities, were diagnosed at later stages, received less treatment, and had higher mortality rates, compared with patients who lacked disabilities. Social support and policies, along with education for women with disabilities, their families, and healthcare professionals, are needed to improve these disparities.

Antenatal sonographic features of persistent extrahepatic vitelline vein aneurysm confused with umbilical vein varix.

Background: The persistent vitelline vein is a portal venous system malformation arising during the embryonic period. These abnormal blood vessels frequently thrombose and can lead superior mesenteric vein obstruction or portal hypertension. Case report: We visualized a fetal intra-abdominal cystic mass with turbulent flow on prenatal ultrasound at 28 weeks' gestation. Initially diagnosed as an umbilical vein varix, it was later determined to be an extrahepatic persistent vitelline vein with an internal thrombus by postnatal ultrasound. It was successfully surgically excised. Conclusion: When an abnormal abdominal vascular structure near the umbilicus is found during prenatal ultrasonography, the persistent vitelline vein should be included in the differential diagnosis to allow prompt evaluation and treatment after birth.

Regulation of myometrial contraction by ATP-sensitive potassium (KATP) channel via activation of SUR2B and Kir 6.2 in mouse.

ATP-sensitive potassium (KATP) channels are well characterized in cardiac, pancreatic and many other muscle cells. In the present study, functional expression of the KATP channel was examined in non-pregnant murine longitudinal myometrium. Isometric contraction measurements and Western blot were used. KATP channel openers (KCOs), such as pinacidil, cromakalim, diazoxide and nicorandil, inhibited spontaneous myometrial contractions in a reversible and glibenclamide-sensitive manner. KCOs inhibited oxytocin (OXT)- and prostaglandin F2α (PGF2α)-induced phasic contractions in a glibenclamide-sensitive manner. SUR2B and Kir6.2 were detected by Western blot, whereas SUR1, SUR2A and Kir6.1 were not. These results show that pinacidl, cromakalim, diazoxide and nicorandil-sensitive KATP channels exist in murine myometrium, which are composed of SUR2B and Kir6.2. Based on the modulatory effects of the KATP channel on spontaneous contraction, OXT- and PGF2α-induced contractions, KATP channels seem to play an essential role in murine myometrial motility via activation of SUR2B and Kir6.2.

Increased expression of nuclear factor kappa-B p65 subunit in adenomyosis.

OBJECTIVE: Nuclear factor kappa-B (NF-κB) is a critical proinflammatory regulator that has been suggested to play a pivotal role in the pathogenesis and pathophysiology of endometriosis. In the present study, we aimed to evaluate whether the expression of NF-κB p65 subunit is increased in the eutopic endometrium and/or in the adenomyosis nodule of women with adenomyosis. METHODS: Thirty-three women with histologically confirmed adenomyosis after laparoscopic or transabdominal hysterectomy were recruited. Women with carcinoma in situ of uterine cervix without evidence of adenomyosis or endometriosis (n=32) served as controls. Formalin-fixed, paraffin-embedded archival tissues were sectioned and immunostained utilizing a monoclonal anti-human NF-κB p65 subunit antibody, and the immunoreactivity of NF-κB p65 subunit was compared between women with and without adenomyosis. RESULTS: The immunoreactivities of both the nuclear and the cytoplasmic NF-κB p65 subunit were significantly increased in the stromal cells in the eutopic endometrium as well as in the adenomyosis nodule of women with adenomyosis compared with controls, respectively. The nuclear expression of NF-κB p65 subunit was significantly higher in the glandular cells in the eutopic endometrium as well as the adenomyosis nodule of women with adenomyosis compared with controls, respectively. CONCLUSION: The expression of NF-κB p65 is increased in the eutopic endometrium and adenomyosis nodule of women with adenomyosis, which strongly suggest that NF-κB plays a critical role in the pathogenesis and/or pathophysiology of adenomyosis.

Comparison of HE4, CA125, and Risk of Ovarian Malignancy Algorithm in the Prediction of Ovarian Cancer in Korean Women.

This study is a multi-center clinical study, which aimed to compare CA125, HE4, and risk of ovarian malignancy algorithm (ROMA) in predicting epithelial ovarian cancer of Korean women with a pelvic mass. Prospectively, serum from 90 Korean women with ovarian mass was obtained prior to surgery. For control group, serum from 79 normal populations without ovarian mass was also obtained. The HE4 and CA125 data were registered and evaluated separately and ROMA was calculated for each sample. Total 67 benign tumors and 23 ovarian cancers were evaluated. Median serum levels of HE4 and CA125, and ROMA score were significantly higher in patients with ovarian cancer than those with benign ovarian tumor and normal population (P < 0.001). In ROC curve analysis for women with a pelvic mass, area under the curve (AUC) for HE4 and ROMA was higher than CA125. Statistical differences in each study compared to CA125 were marginal (P compared to CA125; 0.082 for HE4 and 0.069 for ROMA). Sub-analysis revealed that AUC for HE4 and ROMA was higher than AUC for CA125 in post-menopausal women with a pelvic mass, but there were no statistically significant differences (P compared to CA125; 0.160 for HE4 and 0.127 for ROMA). Our data suggested that both HE4 and ROMA score showed better performance than CA125 for the detection of ovarian cancer in women with a pelvic mass. HE4 and ROMA can be a useful independent diagnostic marker for epithelial ovarian cancer in Korean women.

Development of an in vitro antigen-detection test as an alternative method to the in vivo plaque reduction neutralization test for the quality control of Japanese encephalitis virus vaccine.

Japanese encephalitis virus (JEV) causes diseases that attack the human central nervous system. Traditionally, the quality control for JEV vaccines, in which the plaque reduction neutralization (PRN) titer is measured by the national control laboratories before the vaccine batches are marketed, has required laboratory animal testing. However, classical animal tests have inherent problems, including the very fact that animals are used, ethical issues, and the possibility of error. In this study, JEV antigen was measured in an in vitro assay to assess the feasibility of replacing in vivo assays that measure the PRN titers of JEV vaccines. We constructed a double-sandwich enzyme-linked immunosorbent assay (DS-ELISA) that could detect JEV envelope (E). Initially, monoclonal antibodies (mAbs) directed against the JEV E protein were generated and characterized. We isolated 18 mAbs against JEV E protein, and most were the IgG1 or IgG2a isotype. The mAbs (5F15 and 7D71) were selected as the most suitable mAb pair to detect JEV E protein. DS-ELISA with this pair detected as little as approximately 3 µg/mL JEV E protein and demonstrated a relationship between the amount of JEV E protein and the PRN titer. From these results, we surmise that this DS-ELISA may be useful, not only in terms of measuring the amount of JEV E protein, but also as a substitute for the PRN test for JEV vaccine evaluation.

Validation of a HeLa Mx2/Luc reporter cell line for the quantification of human type I interferons.

Although antiviral assays have been the most widely available biological assays for interferons (IFNs), they are less sensitive and provide considerable interassay variation. In this study, we demonstrate a new reporter cell line, which is based on HeLa cells transfected with a plasmid containing a human Mx2 promoter driving a luciferase (Luc) cDNA. To characterize the specific gene expression profiles induced by interferon alpha, we analyzed the microarray results of interferon response gene expression induced by IFN-alpha2a or IFN-alpha2b treatment with HeLa cells. We found that the Mx2 gene increased the most by treatment with both IFN-alpha2a and IFN-alpha2b. Based on this result, we designed a reporter cell line, HeLa-Mx2, suitable for determination of IFN-alpha. HeLa cells were stably transfected with the luciferase gene under the control of Mx2 promoter. The expression of luciferase can be easily measured for luminescence using a 96-well luminometer and has been correlated with the concentration of added IFN and cell density. In the validation results, our reporter cell line had specificity for type I IFN, but the significant effects of a number of other cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-2, IL-5, IL-6 and GM-CSF, or type II interferon (IFN-gamma) were not observed. Moreover, the robustness of our cell line is demonstrated by the lack of an effect of the HeLa-Mx2 cell culture's age on the performance of the reporter gene assay. The reporter gene assay demonstrated reproducible dose-response curves for IFN-alpha2a in the range of 1-10,000 IU/ml. The 95% confidential limit and total coefficient of variation estimates ranged between 96 and 116 and 10.51% in the reducible range mentioned above, respectively. In conclusion, we established a stable IFN-responsible HeLa-Mx2 cell line, which has advantages with regard to simplicity, selectivity, and reliability over conventional cytopathic effect reduction assays used to quantify IFN-alpha activity.

Elevated CA 19-9 levels in mature cystic teratoma of the ovary.

The purpose of this study was to evaluate the clinical value of serum tumor markers in patients with ovarian mature cystic teratoma (MCT). We retrospectively evaluated 163 women who underwent surgery for MCT of the ovary between March 2003 and August 2007 and who provided preoperative blood samples for the measurement of CA 19-9 and CA 125. The rates of elevated serum CA 19-9 and CA 125 levels were 31.9% (52/163) and 13.5% (22/163), respectively. The rate of ovarian torsion was 12.9% (21/163). There were significant differences between the elevated CA 19-9 group and the normal CA 19-9 group in the diameters of the tumors and the rates of ovarian torsion. Elevated serum CA 19-9 levels correlated with larger tumor diameters and higher torsion rates. CA 19-9 may be a useful tool for the diagnosis of ovarian MCT. Elevated CA 19-9 levels appear to correlate with larger tumor diameters and higher rates of ovarian torsion.

Influence of tumor necrosis factor-alpha on estradiol, progesterone, insulin-like growth factor-II, and insulin-like growth factor binding protein-1, 2, and 3 in cultured human luteinized granulosa cells.

OBJECTIVE: The objective was to investigate the influence of tumor necrosis factor (TNF)-alpha on estradiol, progesterone, insulin-like growth factor (IGF)-II, and insulin-like growth factor binding protein (IGFBP)-1, 2, and 3 in cultured human luteinized granulosa cells. STUDY DESIGN: Human luteinized granulosa cells were obtained from follicular fluid by transvaginal oocyte aspiration from infertile patients undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). The cells were cultured for 72 h with TNF-alpha at concentrations of 1.0, 10.0, and 100.0 ng/ml. The cells not treated with TNF-alpha served as controls. Radioimmunoassay (RIA) and reverse transcription-polymerase chain reaction (RT-PCR) were used to examine the influence of TNF-alpha on estradiol, progesterone, IGF-II, and IGFBP-1, 2, and 3. Results were analyzed using the Kolmogorov-Smirnov test and analysis of variance (ANOVA). Statistical significance was defined as p<0.05. RESULTS: The concentrations of progesterone seemed to decrease as the concentrations of TNF-alpha increased and the concentration of progesterone in the 100.0 ng/ml TNF-alpha group was significantly lower than that in the control and other TNF-alpha groups. The expressions of IGF-II mRNA in the 10.0 and 100.0 ng/ml TNF-alpha groups were significantly lower than that in the control group. The expressions of IGFBP-2 mRNA seemed to be decreased in the 10.0 and 100.0 ng/ml TNF-alpha groups compared with that in the control group, but there were no statistical significances. CONCLUSION: TNF-alpha may play a role as a regulator of human ovarian physiology by modulating the IGF systems in luteinized granulosa cells.

Study of gelatin-containing artificial skin V: fabrication of gelatin scaffolds using a salt-leaching method.

Porous gelatin scaffolds were prepared using a salt-leaching method and these were compared to scaffolds fabricated using a freeze-drying method. The salt-leached gelatin scaffolds were easily formed into desired shapes with a uniformly distributed and interconnected pore structure with an average pore size of around 350 microm. The mechanical strength and the biodegradation rate of the scaffolds increased with the porosity, and were easily modulated by the addition of salt. After 1 week of in vitro culturing, the fibroblasts in salt-leached scaffolds were mainly attached on the surface of the pores in the scaffold, whereas cells seeded on freeze-dried scaffolds were widely distributed and aggregated on the top and the bottom of the scaffold. After 14 d of culturing, the fibroblasts showed a good affinity to, and proliferation on, the gelatin scaffolds without showing any signs of biodegradation. An in vivo study of cultured artificial dermal substitutes showed that an artificial dermis containing the fibroblasts enhanced the re-epithelialization of a full-thickness skin defect when compared to an acellular scaffold after 1 week.