Ari Kim

Identification of biomarkers for preterm delivery in mid-trimester amniotic fluid.

OBJECTIVE We investigated whether the level of vascular endothelial growth factor (VEGF) and inflammatory markers in mid-trimester amniotic fluid have predictive value for spontaneous preterm birth in singleton pregnancy. METHOD Our subjects were 72 pregnant women who were undertaken with amniocentesis from 16 to 19 weeks of gestation. 36 cases were women with preterm delivery, and other 36 cases were matched women with full-term delivery. Stored amniotic fluid was investigated after the delivery. The levels of matrix metalloproteinases-8 (MMP-8), interleukin-6 (IL-6), C-reactive protein (CRP), and VEGF were measured by enzyme-linked immunosorbent assay (ELISA) and Western blot. RESULTS The levels of MMP-8 and IL-6 in preterm group were significantly higher than control group (5.76 ± 1.53 ng/ml vs 4.89 ± 1.77 ng/ml and 170.54 ± 55.69 pg/ml vs 141.92 ± 57.21 pg/ml, respectively) (p < 0.05). In terms of VEGF, the levels were elevated in preterm group (30.76 ± 4.06 pg/ml vs 22.36 ± 7.03 pg/ml) (p < 0.05). CONCLUSION This study suggests that elevated levels of IL-6 and MMP-8 in amniotic fluid at mid-trimester are predictive of preterm delivery, and that VEGF which is representative of angiogenesis can be a new and useful predictor of preterm delivery.

Detection of endometrial and subendometrial vasculature on the day of embryo transfer and prediction of pregnancy during fresh in vitro fertilization cycles

OBJECTIVES Successful implantation depends on interaction between a blastocyst and a receptive endometrium. Endometrial vasculature is important in the early endometrial response to blastocyst implantation, and vascular changes can affect uterine receptivity. This study aims to investigate whether vascular parameters measured using three-dimensional power Doppler ultrasound (3D PD-US) could predict pregnancy following fresh in vitro fertilization and embryo transfer (IVF-ET) using a gonadotropin releasing hormone (GnRH) agonist long protocol. MATERIALS AND METHODS This prospective observational study enrolled 236 nulliparous women who underwent a first IVF-ET using a GnRH long protocol with stimulation by recombinant FSH (rFSH) from May 2009 to April 2012. After excluding two cases of tubal pregnancy, 234 women were in either a pregnant group (n = 113) or a nonpregnant group (n = 121). Color Doppler ultrasound and 3D PD-US examinations were performed on the day of embryo transfer. Main outcomes were pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (S/D) of the uterine artery, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) of the endometrium and subendometrial region. Measurements were analyzed relative to IVF-ET outcome (pregnant vs. nonpregnant). RESULTS No significant differences were observed in patient age, infertility duration, body mass index (BMI), basal FSH levels, number of retrieved oocytes or good quality embryos, or endometrial thickness or volume between the two groups. The pregnant group had higher endometrial VI, FI, and VFI scores than the nonpregnant group (p = 0.001, p = 0.000, p = 0.021, respectively). By contrast, neither subendometrial region VI, FI, and VFI scores (p = 0.770, p = 0.252, p = 0.451), nor uterine artery PI, RI, or S/D scores (p = 0.256, p = 0.527, p = 0.365) differed between groups. Cut-off values of endometrial VI, FI, and VFI scores were 0.95, 12.94, and 0.15 for pregnancy achievement. CONCLUSION Three dimensional PD-US was a useful and effective method for assessing endometrial blood flow in IVF cycles. Good endometrial blood flow on the day of embryo transfer might be associated with high pregnancy success with a GnRH long protocol, because this is indicative of endometrial receptivity in fresh IVF cycles.

Absolute monocyte and lymphocyte count prognostic score for patients with gastric cancer

AIM To measure the prognostic significance of absolute monocyte count/absolute lymphocyte count prognostic score (AMLPS) in patients with gastric cancer. METHODS We retrospectively examined the combination of absolute monocyte count (AMC) and absolute lymphocyte count (ALC) as prognostic variables in a cohort of 299 gastric cancer patients who underwent surgical resection between 2006 and 2013 and were followed at a single institution. Both AMC and ALC were dichotomized into two groups using cut-off points determined by receiving operator characteristic curve analysis. An AMLPS was generated, which stratified patients into three risk groups: low risk (both low AMC and high ALC), intermediate risk (either high AMC or low ALC), and high risk (both high AMC and low ALC). The primary objective of the study was to validate the impact of AMLPS on both disease-free survival (DFS) and overall survival (OS), and the second objective was to assess the AMLPS as an independent prognostic factor for survival in comparison with known prognostic factors. RESULTS Using data from the entire cohort, the most discriminative cut-off values of AMC and ALC selected on the receiver operating characteristic curve were 672.4/μL and 1734/μL for DFS and OS. AMLPS risk groups included 158 (52.8%) patients in the low-risk, 128 (42.8%) in the intermediate-risk, and 13 (4.3%) in the high-risk group. With a median follow-up of 37.2 mo (range: 1.7-91.4 mo), five-year DFS rates in the low-, intermediate-, and high-risk groups were 83.4%, 78.7%, and 19.8%, respectively. And five-year OS rates in the low-, intermediate-, and high-risk groups were 89.3%, 81.1%, and 14.4%, respectively. On multivariate analysis performed with patient- and tumor-related factors, we identified AMLPS, age, and pathologic tumor-node-metastasis stage as the most valuable prognostic factors impacting DFS and OS. CONCLUSION AMLPS identified patients with a poor DFS and OS, and it was independent of age, pathologic stage, and various inflammatory markers.

Expression Patterns of Thymosin β4 and Cancer Stem Cell Marker CD133 in Ovarian Cancers

Thymosin β4 (Tβ4), a small acidic actin binding peptide, is overexpressed in a side population of cancer stem cells and CD133-positive colorectal cancer stem cells. In order to understand the relationship between Tβ4 and CD133, we studied the expression patterns of Tβ4 and CD133 in ovarian cancers. The expression patterns of Tβ4 and CD133 were studied in normal ovaries, primary ovarian cancers, metastatic ovarian cancers, primary stomach cancers, and normal stomachs by Western blot and immunohistochemistry. Expression patterns and co-localization of Tβ4 and CD133 were examined by immunofluorescence and confocal laser-scanning microscopy. Tβ4 is overexpressed in primary ovarian cancers, but not in primary stomach cancers, when compared with normal controls. However, Tβ4 levels in metastatic stomach cancers to the ovary are significantly upregulated compared with levels in normal stomachs and primary stomach cancers. These results suggest that Tβ4 levels are related to tumorigenesis in ovarian cancers and metastasis in stomach cancers. The expression of Tβ4 in normal ovaries and normal stomachs was weak, but was co-localized with CD133 expression. Tβ4 expression was also co-localized with CD133 expression in primary ovarian carcinomas, metastatic ovarian cancers from stomach cancers and primary stomach cancers. These data suggest that Tβ4 expression is strongly related to CD133 expression and is a characteristic of stem cells or cancer stem cells.

Expression of Interactive Genes Associated with Apoptosis and Their Prognostic Value for Ovarian Serous Adenocarcinoma

BACKGROUND Malignant ovarian tumor is one of the leading causes of worldwide cancer death. It is usually characterized by insidious onset and late diagnosis because of the absence of symptoms, allowing ovarian cancer cases to progress rapidly and become unresectable. The tumor suppressor, p53, plays an important role in regulating cell cycles and apoptosis. p53 is regulated by several molecules, and it interacts with other apoptotic proteins. OBJECTIVES To compare the prognosis of ovarian serous carcinoma and evaluate the expression of DNA-PKcs, Akt3, GSK-3β, and p53 in cancerous cells. MATERIAL AND METHODS DNA-PKcs, Akt3, GSK-3β, and p53 expression levels were scored using immunohistochemistry staining of tissue samples from 132 women with ovarian serous adenocarcinoma. Expression was confirmed by real-time RT-PCR. Analyses were stratified by age, tumor grades, cancer stages and serum CA 125 levels. RESULTS Significant differences in DNA-PKcs, Akt3, and p53 expression were observed between participants with different stages and tumor grades of ovarian serous adenocarcinoma. DNA-PKcs and p53 expression increased along with increasing tumor grade. Meanwhile, DNA-PKcs, Akt3, and p53 expression increased along with increasing cancer stage, and with a decrease in 5-year overall survival rate. CONCLUSIONS This study shows that elevated expression of DNA-PKcs, Akt3, and p53 in ovarian serous adenocarcinoma tissues are an indication of more advanced disease and worse prognosis.

Accuracy of three dimensional ultrasound and treatment outcomes of intrauterine adhesion in infertile women

OBJECTIVE To determine the accuracy and usefulness of three-dimensional transvaginal ultrasound (3D-TVUS) in diagnosing intrauterine adhesion (IUA) and to evaluate treatment outcomes associated with fertility. MATERIALS AND METHODS IUA patients (110) underwent hysteroscopy to definitively diagnose and treat adhesiolysis. Morphologic characteristics of endometrium suggesting IUA, such as marginal irregularity, thinning, defects, obliteration, fibrosis, and calcification, were identified and recorded by 3D-TVUS. The sensitivity of 3D-TVUS findings and the attainment of postoperative fertility were evaluated prospectively. The clinical records were followed up for 2 years for obstetrical outcomes and analyzed. RESULTS On comparing the findings of 3D-TVUS with those of hysteroscopy in 110 patients, 45 (88.23%) patients were confirmed as IUA by hysteroscopy among 51 (46.36%) patients, with one finding in 3D-TVUS; 42 (97.67%) patients were confirmed among 43 (39.09%) patients with two findings; and 16 (100%) patients were confirmed among 16 (14.55%) patients with over three findings. A pregnancy rate of eight out of 47 (17.02%) was achieved in patients who desired fertility. CONCLUSION 3D-TVUS assessment of the uterus provides an accurate depiction of adhesion and extent of cavity damage in patients with suspected IUA.

Bone Density in Patients with Cervical Cancer or Endometrial Cancer in comparison with Healthy Control; According to the stages.

Objective: To evaluate the bone mineral density (BMD) in the lumbar spine and femur in postmenopausal women with cervical cancer and endometrial cancer without bone metastasis in comparison with that in healthy control postmenopausal women, and to assess the loss of BMD according to the cancer stage. Materials and methods: We analyzed the BMD of the lumbar spine and femur using dual-energy X-ray absorptiometry (DXA) in 218 patients with cervical cancer, 85 patients with endometrial cancer, and 259 healthy controls. The serum levels of calcium (Ca), phosphorus (P), osteocalcin (OSC), and total alkaline phosphatase (ALP), and urine deoxypyridinoline(DPL) were measured in all participants. Results: Age, body mass index, parity, and time since menopause were not significantly different between the three groups. Serum Ca level was higher in the cervical cancer group (p = 0.000), however, urine DPL was lower in endometrial cancer group (p = 0.000). The T-scores of basal BMD at the second and fourth lumbar vertebra (L2, L4) were significantly lower in patients with cervical cancer (p = 0.038, 0.000, respectively) compared to those in the healthy control groups. Additionally, the incidence of osteoporosis and osteopenia basal status of bone mass was significantly higher in patients with cervical cancer compared to that in controls (p = 0.016). No differences in basal BMD of the lumbar spine and femur were observed between patients with cervical cancer according to their stages. Conclusion: Our results suggest that postmenopausal women with cervical cancer have a lower BMD and are at increased risk of osteoporosis in the lumbar spine before receiving anticancer treatment compared with postmenopausal women with endometrial cancer.

Changes in bone density after cancer treatment in patients with cervical and endometrial cancer.

OBJECTIVE: This study aimed to evaluate the impact of cancer treatment on bone mineral density (BMD) in the lumbar spine (LS) and femur in the postmenopausal women with cervical or endometrial cancer without bone metastasis compared to normal control postmenopausal women. METHODS: We retrospectively evaluated the BMD data in the LS, femur neck (FN) and trochanter (FT) by dual-energy X-ray absorptiometry and laboratory data of bone turnover markers at baseline and after one year in 130 patients with cervical cancer, 68 patients with endometrial cancer, and 225 healthy controls. RESULTS: There were no significant differences in the T-scores of basal BMD in LS and femur between patients with endometrial cancer and controls, and only T-score of basal BMD at the fourth lumbar vertebra (L4) was significantly lower in patients with cervical cancer compared to controls. One year later, T-scores of BMD at all LS sites and FN in patients with cervical cancer and T-scores of BMD at L3, L4, FN, and FT in those with endometrial cancer after cancer treatment were significantly lower compared to controls. Lower proportions of normal BMD at all skeletal sites except L2 in patients with endometrial cancer and those at L1, L4, and FN in patients with cervical cancer were observed compared to controls after cancer treatment. CONCLUSIONS: Our results suggest that cancer treatment increase bone loss in postmenopausal women with cervical and endometrial cancer.

Primary extraskeletal mesenchymal chondrosarcoma of the vulva

Extraskeletal chondrosarcoma is rare, making up only 1% of reported chondrosarcoma. We experienced 3 cases of extraskeletal chondrosarcoma, especially in vulva. They were suspected as lipoma of the vulva. The patients had noticed a small but growing mass on their vulva which had been palpated earlier. The masses were excised with a 2 cm resection margin. The final pathological reports confirmed extraskeletal mesenchymal chondrosarcoma (EMC) of the vulva revealing no microscopic lesions on the resection margins. After 24 months of following from the initial diagnosis, the patients remain without evidence of any recurrent. Management of EMC is not well studied due to the rare and variable nature of the disease. However, the surgery, such as we had, is the mainstay of local treatment with studies showing better survival in patients who undergo wide surgical resection. The establishment of adjuvant systemic pharmacotherapy could be expected in the future.

25-hydroxyvitamin D levels and body mass index in healthy postmenopausal women

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