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Almendro V.,Dana-Farber Cancer Institute | Almendro V.,Brigham and Women's Hospital | Almendro V.,Harvard University | Kim H.J.,Dana-Farber Cancer Institute | And 17 more authors.
Cancer Research | Year: 2014

Metastatic disease is the main cause of cancer-related mortality due to almost universal therapeutic resistance. Despite its high clinical relevance, our knowledge of how cancer cell populations change during metastatic progression is limited. Here, we investigated intratumor genetic and phenotypic heterogeneity during metastatic progression of breast cancer.Weanalyzed cellular genotypes and phenotypes at the single cell level by performing immunoFISH in intact tissue sections of distant metastatic tumors from rapid autopsy cases and from primary tumors and matched lymph node metastases collected before systemic therapy.Wecalculated the Shannon index of intratumor diversity in all cancer cells and within phenotypically distinct cell populations. We found that the extent of intratumor genetic diversity was similar regardless of the chromosomal region analyzed, implying that it may reflect an inherent property of the tumors. We observed that genetic diversity was highest in distant metastases and was generally concordant across lesions within the same patient, whereas treatment-nave primary tumors and matched lymph node metastases were frequently genetically more divergent. In contrast, cellular phenotypes were more discordant between distant metastases than primary tumors and matched lymph node metastases. Diversity for 8q24 was consistently higher in HER2+ tumors compared with other subtypes and in metastases of triple-negative tumors relative to primary sites. We conclude that our integrative method that couples ecologic models with experimental data in human tissue samples could be used for the improved prognostication of patients with cancer and for the design of more effective therapies for progressive disease. © 2013 American Association for Cancer Research.


Kim K.,CHA Medical University | Shin D.G.,Seoul Medical Center | Park M.K.,TCM Epigenetics and Genomics Laboratory | Baik S.H.,Yonsei University | And 3 more authors.
Annals of Surgical Treatment and Research | Year: 2014

Purpose: The aim of this study is to determine whether levels of circulating free DNA (cfDNA) increase according to cancer progression, whether they are restored after surgical resection, and to evaluate cfDNA in gastric cancer patients as a useful biomarker. Methods: A case-control study design was used. Thirty gastric cancer patients and 34 healthy subjects were enrolled from two hospitals in South Korea. The plasma cfDNA of patients with gastric cancer were obtained before surgery and 24 hours after surgery, and then analyzed by a quantitative, real-time polymerase chain reaction. Plasma samples were also obtained from the control group. Results: The mean levels of cfDNA in the healthy control group, patients with early gastric cancer, and with advanced gastric cancer were 79.78 ± 8.12 ng/mL, 106.88 ± 12.40 ng/mL, and 120.23 ± 10.08 ng/mL, respectively (P < 0.01). Sensitivity was 96.67% and specificity was 94.11% when the cutoff value was 90 ng/mL. Variables representing the tumor burden such as tumor size, T stage, TNM stage, and curative resection are also associated with the levels of cfDNA. The levels of cfDNA in the 24-hour-after-surgery group decreased significantly (112.17 ± 13.42 ng/mL vs. 77.93 ± 5.94 ng/mL, P < 0.001) compared to the levels of cfDNA in the preoperation group. Conclusion: The changes in the levels of cfDNA can act as reliable biomarkers to detect cancer early, to predict tumor burden, estimate curative resection and even prognosis. Copyright © 2014, the Korean Surgical Society.


Bae I.K.,Silla University | Suh B.,MizMedi Hospital | Jeong S.H.,Yonsei University | Wang K.-K.,Yonsei University | And 3 more authors.
Diagnostic Microbiology and Infectious Disease | Year: 2014

This study was performed to investigate the prevalence and molecular epidemiology of Pseudomonas aeruginosa isolates from Korea that produce enzymes with extended-spectrum (ES) activity to β-lactams. A total of 205 non-duplicate P. aeruginosa clinical isolates were collected from 18 university hospitals in Korea. PCR and sequencing experiments were performed to identify genes encoding β-lactamases. PCR mapping and sequencing of the regions surrounding the β-lactamase genes were performed. Multilocus sequence typing experiments were performed. The most common sequence type (ST) was ST235 (n = 96), and 2 single-locus variants of ST235, ST1015 (n = 1) and ST1162 (n = 1), were also identified. These 3 STs were grouped as a clonal complex (CC), CC235. The remaining 107 isolates were identified as 59 different STs. Isolates belonging to CC235 showed higher rates of non-susceptibility to imipenem (85.4% versus 47.7%) and meropenem (92.7% versus 52.3%) compared to non-CC235 isolates. All the metallo-β-lactamase (MBL)-producing isolates were identified as CC235, except for 1 ST591. Genes encoding OXA-17 and OXA-142 were detected in 1 isolate and 4 isolates of CC235, respectively; while the blaSHV-12 gene was detected in 4 non-CC235 isolates. Class A and D β-lactamases with ES activity play a role in acquiring ceftazidime resistance in P. aeruginosa in Korea. Production of IMP-6 and VIM-2 MBLs is the main mechanisms in acquiring resistance to ceftazidime and carbapenems in P. aeruginosa isolates in Korea. Clonal spread of P. aeruginosa CC235 may be an important conduit for the dissemination of MBL genes in Korea. © 2014 Elsevier Inc.


Kim J.Y.,Sungkyunkwan University | Kim K.H.,Sungkyunkwan University | Choi J.S.,Hanyang University | Lee J.H.,MizMedi Hospital
Journal of Minimally Invasive Gynecology | Year: 2014

Study Objective: To compare operative and obstetric outcomes of laparoendoscopic single-site myomectomy (LESS-M) vs conventional laparoscopic myomectomy (LM). Design: Prospective matched case-control study. Setting: A university hospital and a tertiary care center. Patients: Forty-five women underwent LESS-M, and 90 women underwent conventional LM. Intervention: LESS-M or conventional LM. Measurements and Main Results: Operative and obstetric outcomes. There were no significant differences between the 2 groups in demographic characteristics, operative time (135 vs 140minutes), change in hemoglobin concentration (1.9 vs 1.95g/dL), return of bowel activity (35 vs 28hours), hospital stay (5 vs 5days), or complication rate (11.1% vs 8.9%). Insofar as obstetric outcomes, no significant differences were observed between the 2 groups for duration of follow-up (24.4 vs 23.2months), pregnancy rate in patients who desired pregnancy (66.7% vs 50.0%), full-term delivery rate (66.7% vs 58.3%), and time to first pregnancy after surgery (7.6 vs 10.1months). Conclusion: LESS-M is feasible and safe and has comparable obstetric outcomes to conventional LM in selected women with symptomatic myomas. However, a large prospective randomized study is needed. © 2014 AAGL.


Seo W.S.,MizMedi Hospital | Jee B.C.,Seoul National University | Moon S.Y.,Seoul National University
Fertility and Sterility | Year: 2011

Endometrial biopsies were performed during the luteal phase just before an IVF cycle in 104 infertile women, and immunohistochemical staining was performed to investigate expression patterns of hCG-LH receptor, leukemia-inhibitory factor, macrophage colony-stimulating factor, HOXA-10, vascular endothelial growth factor A, and their relation to subsequent IVF pregnancy. Only glandular expression of vascular endothelial growth factor A in early luteal endometrium was significantly higher in the pregnant group compared with the nonpregnant group (6.0 ± 3.9 vs. 2.9 ± 3.4) and thus could be a predicting marker for subsequent IVF pregnancy. © 2011 by American Society for Reproductive Medicine.


Yuk J.-S.,MizMedi Hospital | Kim Y.J.,Korea University | Hur J.-Y.,Korea University | Shin J.-H.,Korea University
International Journal of Gynecology and Obstetrics | Year: 2013

Objective To estimate the ectopic pregnancy rate in the Republic of Korea and to identify whether socioeconomic factors contribute to the incidence of ectopic pregnancy. Methods Korean National Health Insurance data from January to December 2009 were analyzed to calculate the rate of ectopic pregnancy. Results Among the patient sample (n = 599 186), 59 261 had diagnosis codes for ectopic pregnancies, abortions, or deliveries, and 1102 ectopic pregnancies were identified. The frequency of ectopic pregnancy treated by either surgery or methotrexate was 16.60 per 1000 pregnancies. Low socioeconomic status was a risk factor for ectopic pregnancy (odds ratio [OR], 1.718; 95% confidence interval [CI], 1.065-2.772; P = 0.03), as was older age (OR, 1.016; 95% CI, 0.998-1.033, P = 0.07), although the association was not significant. Among women aged 25-44 years, low socioeconomic status and age were associated with a high incidence of ectopic pregnancy (OR, 1.863; 95% CI, 1.074-3.233, P = 0.03; and OR, 1.061; 95% CI, 1.041-1.081, P < 0.01, respectively). Surgical and methotrexate treatment rates were 90.7% and 9.3%, respectively. The methotrexate failure rate was 30.7%. The recorded ectopic pregnancy sites were tubal or ovarian (90.2%), cornual (6.0%), cervical (2.8%), and abdominal (1.0%). Conclusion Older age and low socioeconomic status were risk factors for ectopic pregnancy. © 2013 International Federation of Gynecology and Obstetrics.


Yuk J.-S.,MizMedi Hospital | Kim Y.-J.,Korea University | Hur J.-Y.,Korea University | Shin J.-H.,Korea University
International Journal of Gynecology and Obstetrics | Year: 2013

Objective To estimate the incidence of Bartholin duct cysts and abscesses in the Republic of Korea during 2009. Methods A national patient sample (n = 599 186) was obtained from Korean Health Insurance Review and Assessment Service data and analyzed to estimate the incidence of Bartholin duct cysts and abscesses among Korean women in 2009. Results There were 587 Bartholin duct cysts and 757 Bartholin duct abscesses during 2009. The total incidence of Bartholin duct cysts and abscesses was 0.55 per 1000 person-years and 0.95 per 1000 person-years, respectively. In women aged 35-50 years, the incidence was 1.21 per 1000 person-years and 1.87 per 1000 person-years, respectively. In multivariate logistic regression analysis, the incidence of Bartholin duct cysts and abscesses was associated with age (P < 0.01), but not with season or socioeconomic status, among women aged 15-50 years. The main operation performed was marsupialization (45.2%) for Bartholin duct cysts and incision (71.5%) for Bartholin duct abscesses. Conclusion The incidence of Bartholin duct cysts and abscesses increased with age until menopause, decreasing thereafter. © 2013 Published by Elsevier Ireland Ltd. on behalf of International Federation of Gynecology and Obstetrics.


Kim K.-C.,Mizmedi Hospital | Kim K.-C.,Yonsei University | Shin D.-H.,Mizmedi Hospital | Lee S.-Y.,Mizmedi Hospital | And 2 more authors.
Yonsei Medical Journal | Year: 2010

Purpose: The traditional belief that obesity is protective against osteoporosis has been questioned. Recent epidemiologic studies show that body fat itself may be a risk factor for osteoporosis and bone fractures. Accumulating evidence suggests that metabolic syndrome and the individual components of metabolic syndrome such as hypertension, increased triglycerides, and reduced high-density lipoprotein cholesterol are also risk factors for low bone mineral density. Using a cross sectional study design, we evaluated the associations between obesity or metabolic syndrome and bone mineral density (BMD) or vertebral fracture. Materials and Methods: A total of 907 postmenopausal healthy female subjects, aged 60-79 years, were recruited from woman hospitals in Seoul, South Korea. BMD, vetebral fracture, bone markers, and body composition including body weight, body mass index (BMI), percentage body fat, and waist circumference were measured. Results: After adjusting for age, smoking status, alcohol consumption, total calcium intake, and total energy intake, waist circumference was negatively related to BMD of all sites (lumbar BMD p = 0.037, all sites of femur BMD p < 0.001) whereas body weight was still positively related to BMD of all sites (p < 0.001). Percentage body fat and waist circumference were much higher in the fracture group than the non-fracture group (p = 0.0383, 0.082 respectively). Serum glucose levels were postively correlated to lumbar BMD (p = 0.016), femoral neck BMD (p = 0.0335), and femoral trochanter BMD (p = 0.0082). Serum high density lipoprotein cholesterol (HDLC) was positively related to femoral trochanter BMD (p = 0.0366) and was lower in the control group than the fracture group (p = 0.011). Conclusion: In contrast to the effect favorable body weight on bone mineral density, high percentage body fat and waist circumference are related to low BMD and a vertebral fracture. Some components of metabolic syndrome were related to BMD and a vertebral fracture. © Yonsei University College of Medicine 2010.


Chi H.-J.,Mizmedi Hospital | Koo J.-J.,Hanna Womens Clinic | Choi S.-Y.,Mizmedi Hospital | Jeong H.-J.,Mizmedi Hospital | Roh S.-I.,Mizmedi Hospital
Fertility and Sterility | Year: 2011

Objective: To explore the association between embryo fragmentation and necrosis and apoptosis. Design: A prospective study. Setting: Mizmedi Hospital. Patient(s): None. Intervention(s): None. Main Outcome Measure(s): Staining with annexin V (a marker of apoptosis) and propidium iodide (PI, a marker of necrosis), DNA integrity and mitochondrial distribution, and a beneficial effect of fragment removal in human fragmented embryos. Result(s): Most of the mouse and human fragmented embryos were stained with PI but not with annexin V. The comet assay revealed severe DNA fragmentation of the fragmented human embryos but not of the unfragmented embryos. Fewer mitochondria were observed in the fragmented compared with the normal blastomeres, indicating a rapid depletion of ATP in the fragmented embryos. Microsurgical fragment removal from the embryos had a beneficial effect on their subsequent development. Conclusion(s): Fragments of human embryos exhibited various characteristics of necrosis, such as staining with PI, DNA fragmentation, rapid depletion of ATP, and harmful effects on neighboring blastomeres. We suggest that the fragmentation of embryos is closely associated with both necrosis and apoptosis. Whether this fragmentation is associated with primary or secondary necrosis remains to be elucidated. © 2011 by American Society for Reproductive Medicine.


Chung D.Y.,Mizmedi Hospital
Surgical Laparoscopy, Endoscopy and Percutaneous Techniques | Year: 2013

It is difficult to perform intracorporeal knot tying in a single-incision laparoscopic surgery. The instruments may not work together willingly in the limited working area. To get the proper triangulation to manipulate the instruments might be the main issue in the process of knot tying. It has been known that the knit stitch might improve knot tying in a conventional laparoscopic surgery. The modified method of knit stitch in this study was performed using a single-incision laparoscopic surgery. To use the half circle of the curved needle in the intracorporeal knot-tying procedure was effective in getting the proper angle for manipulation of rigid instruments. Spinning instrument according to the butt of the curved needle minimized the movement of working instruments. The modified method might be useful in solving the difficulty of the knot tying in a single-incision laparoscopic surgery. Copyright © 2013 Lippincott Williams & Wilkins.

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