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1.  The relationship between cisplatin resistance and histone deacetylase isoform overexpression in epithelial ovarian cancer cell lines 
Journal of Gynecologic Oncology  2012;23(3):182-189.
Objective
To investigate the relationship between cisplatin resistance and histone deacetylase (HDAC) isoform overexpression in ovarian cancer cell lines.
Methods
Expression of four HDAC isoforms (HDAC 1, 2, 3, and 4) in two ovarian cancer cell lines, SKOV3 and OVCAR3, exposed to various concentrations of cisplatin was examined by western blot analyses. Cells were transfected with plasmid DNA of each HDAC. The overexpression of protein and mRNA of each HDAC was confirmed by western blot and reverse transcriptase-polymerase chain reaction analyses, respectively. The cell viability of the SKOV3 and OVCAR3 cells transfected with HDAC plasmid DNA was measured using the cell counting kit-8 assay after treatment with cisplatin.
Results
The 50% inhibitory concentration of the SKOV3 and OVCAR3 cells can be determined 15-24 hours after treatment with 15 µg/mL cisplatin. The expression level of acetylated histone 3 protein in SKOV3 cells increased after exposure to cisplatin. Compared with control cells at 24 hours after cisplatin exposure, the viability of SKOV3 cells overexpressing HDAC 1 and 3 increased by 15% and 13% (p<0.05), respectively. On the other hand, OVCAR3 cells that overexpressed HDAC 2 and 4 exhibited increased cell viability by 23% and 20% (p<0.05), respectively, compared with control cells 24 hours after exposure to cisplatin.
Conclusion
In SKOV3 and OVCAR3 epithelial ovarian cancer cell lines, the correlation between HDAC overexpression and cisplatin resistance was confirmed. However, the specific HDAC isoform associated with resistance to cisplatin varied depending on the ovarian cancer cell line. These results may suggest that each HDAC isoform conveys cisplatin resistance via different mechanisms.
doi:10.3802/jgo.2012.23.3.182
PMCID: PMC3395014  PMID: 22808361
Cisplatin resistance; Epithelial ovarian cancer cell lines; Histone deacetylase
2.  Efficacy of taxane and platinum-based chemotherapy guided by extreme drug resistance assay in patients with epithelial ovarian cancer 
Journal of Gynecologic Oncology  2009;20(2):96-100.
Objective
To evaluate the efficacy of taxane and platinum-based chemotherapy guided by extreme drug resistance assay (EDRA) in patients with epithelial ovarian cancer.
Methods
Thirty-nine patients were enrolled, who were diagnosed as epithelial ovarian cancer, tubal cancer or primary peritoneal carcinoma and received both debulking surgery and EDRA in Asan Medical Center between August 2004 and August 2006. Another thirty-nine patients were enrolled, who did not receive EDRA as control. Paclitaxel 175 mg/m2 and carboplatin AUC 5 were administered as primary combination chemotherapy to both EDRA group and the control group. In the EDRA group, paclitaxel was replaced by docetaxel 75 mg/m2 if a patient showed extreme drug resistance (EDR) to paclitaxel and not to docetaxel. Carboplatin was replaced by cisplatin 75 mg/m2 if a patient showed EDR to carboplatin and not to cisplatin. If only one drug showed low drug resistance (LDR), it was allowed to add another drug which showed LDR such as gemcitabine 1,000 mg/m2. CT scan was performed every three cycles and CA-125 was checked at each cycle.
Results
There was no significant difference in overall response rate between EDRA group and the control group (84.5% vs. 71.8%, p=0.107). However, 93.8% of patients in EDRA group did not show EDR to at least one drug and its response rate was significantly higher than that of the control group (93.3% vs. 71.8%, p=0.023).
Conclusion
we could choose a combination of taxane and platinum which did not show EDR and could obtain a good response in the patients with ovarian cancer.
doi:10.3802/jgo.2009.20.2.96
PMCID: PMC2705007  PMID: 19590720
Ovarian neoplasms; Antineoplastic combined chemotherapy protocol; Drug resistance; neoplasm; Biologic assay
3.  Toothpick impaction with sigmoid colon pseudodiverticulum formation successfully treated with colonoscopy 
Foreign bodies in the colon are encountered with increasing frequency, but only sporadic reports concerning their management have appeared in the literature. While most ingested foreign bodies usually pass through the gastrointestinal tract uneventfully, sharp foreign bodies such as toothpicks infrequently cause intestinal perforation and may even result in death. We report our experience with a patient with a sigmoid colon pseudodiverticulum formation, a complication of accidental ingestion of a toothpick that was diagnosed and successfully managed colonoscopically.
doi:10.3748/wjg.14.948
PMCID: PMC2687067  PMID: 18240357
Toothpick; Colon; Colonoscopy; Pseudo-diverticulum
4.  Gallbladder lymphangioma: A case report and review of the literature 
Lymphangiomas are rare, benign tumors of the lymphatic system, usually present in children aged 5 years and younger. Because they are asymptomatic until the mass enlarges to cause symptoms, most lymphangiomas are diagnosed at adulthood incidentally. We experienced a case of a 60-year-old man diagnosed with a cystic lymphangioma of the gallbladder, which was successfully resected without any complication. Magnetic resonance imaging and magnetic resonance cholangiopancreatography were very helpful for the diagnosis of the cystic lesion around the gallbladder as were ultrasonography and computed tomography scan. These showed a multi-lobulated cystic mass with intact cystic duct and bile duct in the gallbladder fossa. The patient underwent an open cholecystectomy and the histological findings were consistent with a cystic lymphangioma of the gallbladder. We here report the case of cystic lymphangioma of the gallbladder with a review of the literature.
doi:10.3748/wjg.v13.i2.320
PMCID: PMC4065967  PMID: 17226918
Lymphangioma; Gallbladder; Cholecystectomy
5.  Analysis and Comparison of Somatic Mutations in Paired Primary and Recurrent Epithelial Ovarian Cancer Samples 
PLoS ONE  2014;9(6):e99451.
The TP53 mutations have been proved to be predominated in ovarian cancer in a study from The Cancer Genome Atlas (TCGA). However, the molecular characteristics of recurrent ovarian cancers following initial treatment have been poorly estimated. This study was to investigate the pattern of somatic point mutations in matched paired samples of primary and recurrent epithelial ovarian cancers, using the OncoMap mutation detection protocol. We have adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. OncoMap v.4.4 was used to evaluate genomic DNA isolated from a set of 92 formalin-fixed, paraffin-embedded (FFPE) tumors, consisting of matched paired samples of initially diagnosed and recurrent tumors from 46 epithelial ovarian cancer (EOC) patients. Mutations were observed in 33.7% of the samples, with 29.3% of these samples having a single mutation and the remaining 4.3% having two or more mutations. Among the 41 genes analyzed, 35 mutations were found in four genes, namely, CDKN2A (2.2%), KRAS (6.5%), MLH1 (8.2%) and TP53 (20.7%). TP53 was the most frequently mutated gene, but there was no correlation between the presence of mutation in any gene and clinical prognosis. Furthermore, somatic mutations did not differ between primary and recurrent ovarian carcinomas. Every mutation present in recurrent samples was detected in the corresponding primary sample. In conclusion, these OncoMap data of Korean EOC samples provide that somatic mutations were found in CDKN2A, KRAS, MLH1, and TP53. No differences in mutational status between primary and recurrent samples were detected. To understand the biology of tumor recurrence in epithelial ovarian cancer, more studies are necessary, including epigenetic modifications or additional mutations in other genes.
doi:10.1371/journal.pone.0099451
PMCID: PMC4060993  PMID: 24936796
6.  Impact of body mass index on the prognosis of Korean women with endometrioid adenocarcinoma of the uterus: A cohort study 
Obstetrics & Gynecology Science  2014;57(2):115-120.
Objective
To analyze how pretreatment body mass index relates to known endometrial cancer prognostic factors and how it impacts the disease-free survival and cause-specific survival of Korean women with endometrial cancer.
Methods
The patients were divided into the non-obese (<25 kg/m2) and obese groups (≥25 kg/m2) according to their pretreatment body mass index. The 25 kg/m2 body mass index cut-off was based on the World Health Organization criteria for Asian people. The two groups were compared in terms of their clinicopathological characteristics and survival outcomes.
Results
A total of 213 consecutive patients with endometrioid adenocarcinoma of the uterus met the eligibility criteria of this study and were included in the analysis. Of these patients, 105 patients had a body mass index less than 25 kg/m2 (non-obese group) and 108 patients had a body mass index equal to or more than 25 kg/m2 (obese group). The two groups did not differ in terms of age, menopause, parity, height, FIGO (International Federation of Obstetrics and Gynecology) stage, tumor grade, tumor size, myometrial invasion, lymphovascular space invasion, cytology, and lymph node metastasis. Body mass index was not a significant factor for disease-free and cause-specific survival in univariate analysis, and after adjusting for all prognostic factors that were significant in univariate analysis, it did not associate significantly with disease-free and cause-specific survival.
Conclusion
In Korean women with endometrioid adenocarcinoma of the uterus, a high pretreatment body mass index did not associate with other prognostic factors and had little impact on the disease-free survival and cause-specific survival of these women.
doi:10.5468/ogs.2014.57.2.115
PMCID: PMC3965694  PMID: 24678484
Body mass index; Endometrial neoplasms; Obesity; Prognosis
7.  Transactivation of bad by vorinostat-induced acetylated p53 enhances doxorubicin-induced cytotoxicity in cervical cancer cells 
Vorinostat (VOR) has been reported to enhance the cytotoxic effects of doxorubicin (DOX) with fewer side effects because of the lower DOX dosage in breast cancer cells. In this study, we investigated the novel mechanism underlying the synergistic cytotoxic effects of VOR and DOX co-treatment in cervical cancer cells HeLa, CaSki and SiHa cells. Co-treatment with VOR and DOX at marginal doses led to the induction of apoptosis through caspase-3 activation, poly (ADP-ribose) polymerase cleavage and DNA micronuclei. Notably, the synergistic growth inhibition induced by the co-treatment was attributed to the upregulation of the pro-apoptotic protein Bad, as the silencing of Bad expression using small interfering RNA (siRNA) abolished the phenomenon. As siRNA against p53 did not result in an increase in acetylated p53 and the consequent upregulation of Bad, the observed Bad upregulation was mediated by acetylated p53. Moreover, a chromatin immunoprecipitation analysis showed that the co-treatment of HeLa cells with VOR and DOX increased the recruitment of acetylated p53 to the bad promoter, with consequent bad transactivation. Conversely, C33A cervical cancer cells containing mutant p53 co-treated with VOR and DOX did not exhibit Bad upregulation, acetylated p53 induction or consequent synergistic growth inhibition. Together, the synergistic growth inhibition of cervical cancer cell lines induced by co-treatment with VOR and DOX can be attributed to the upregulation of Bad, which is induced by acetylated p53. These results show for the first time that the acetylation of p53, rather than histones, is a mechanism for the synergistic growth inhibition induced by VOR and DOX co-treatments.
doi:10.1038/emm.2013.149
PMCID: PMC3944441  PMID: 24525822
bad; cervical cancer cell; doxorubicin; p53 acetylation; vorinostat
8.  Reproductive outcomes after laparoscopic radical trachelectomy for early-stage cervical cancer 
Objective
The objective of this study was to estimate the reproductive outcome of young women with early-stage cervical cancer who underwent fertility-sparing laparoscopic radical trachelectomy (LRT).
Methods
We performed a retrospective review of the medical records of patients with early-stage cervical cancer who underwent LRT. Clinicopathological data were obtained from patient medical records, and reproductive outcome data were obtained from patient medical records and telephone interviews.
Results
Fifty-five patients who underwent successful LRT were included in this study. The median age of patients was 32 years (range, 22 to 40 years), and the median follow-up time after LRT was 37 months (range, 3 to 105 months). Menstruation resumed in all patients after LRT, with fifty patients (90.9%) and five patients (9.1%) reporting regular and irregular menstruation, respectively. Six patients (10.9%) presented with cervical stenosis, which was manifested by regular but decreased menstrual flow and newly-developed dysmenorrhea. These patients underwent cervical cannulation and dilatation. Eighteen patients (32.7%) attempted to conceive, with six out of 18 patients receiving fertility treatments. Fourteen pregnancies (i.e., four missed abortions, six preterm births and four full-term births) occurred in 10 patients after LRT. Nine out of 10 patients gave birth to 10 healthy babies. The pregnancy rate after LRT was 55.6% (10/18). The spontaneous abortion rate and live birth rate were 28.6% (4/14) and 71.4% (10/14), respectively. The preterm birth rate was 60% (6/10).
Conclusion
Pregnancy and live birth rates after LRT were promising; however, the preterm birth rate was relatively high. Cervical stenosis also occurred in a small percentage of patients.
doi:10.3802/jgo.2014.25.1.9
PMCID: PMC3893680  PMID: 24459575
Cervical cancer; Fertility; Laparoscopic radical trachelectomy; Pregnancy outcome; Reproductive outcome
9.  Endoscopic submucosal dissection as a treatment for gastric subepithelial tumors that originate from the muscularis propria layer: a preliminary analysis of appropriate indications 
Surgical Endoscopy  2013;27:3271-3279.
Background
Endoscopic submucosal dissection (ESD) is a well-established method for the treatment of gastrointestinal epithelial tumors. However, the treatment of gastric subepithelial tumors (SETs) that originate from the muscularis propria layer still depends primarily on surgical techniques. We evaluated the appropriate indications for ESD in the treatment of SETs that originate from the muscularis propria layer.
Methods
Thirty-five patients with gastric SETs that originate from the muscularis propria layer who underwent ESD were enrolled, and the charts were retrospectively reviewed to investigate the parameters predictive complete resection and complications.
Results
The mean age of the patients was 54.15 ± 9.3 years, and the male/female ratio was 2:3. Twenty-eight of the 35 SETs (85.7 %) were movable, and 15 (45.7 %) had a positive rolling sign. The most frequent location of the SETs was high body (n = 14). The most common pathological diagnoses were leiomyoma (60 %) and gastrointestinal stromal tumor (28.6 %). The complete resection rate was 74.3 %. A positive rolling sign (p = 0.022) and small tumor size (≤20 mm; p = 0.038) were significantly associated with complete resection. Two patients (6.1 %) developed perforations that required surgical treatment; their SMTs were neurogenic tumors with fixed lesion. Tumor mobility was significantly associated with perforation (p = 0.017).
Conclusions
The ESD method appears to be relatively safe for use in the complete resection of SETs that originate from the muscularis propria layer. Small tumor size (≤20 mm) and a positive rolling sign are appropriate indications for ESD.
doi:10.1007/s00464-013-2904-9
PMCID: PMC3751271  PMID: 23519491
Subepithelial tumor; Muscularis propria; Endoscopic submucosal dissection
10.  Comparison of outcomes between radical hysterectomy followed by tailored adjuvant therapy versus primary chemoradiation therapy in IB2 and IIA2 cervical cancer 
Journal of Gynecologic Oncology  2012;23(4):226-234.
Objective
To compare survival outcomes and treatment-related morbidities between radical hysterectomy (RH) and primary chemoradiation therapy (CRT) in patients with bulky early-stage cervical cancer.
Methods
We selected 215 patients with stage IB2 and IIA2 cervical cancer (tumor diameter > 4 cm on magnetic resonance imaging) who underwent RH followed by tailored adjuvant therapy (n=147) or primary CRT (n=68) at two tertiary referral centers between 2001 and 2010.
Results
About twenty nine percent of patients were cured by RH alone and these patients experienced the best survival outcomes with the lowest morbidity rates. After the median follow-up times of 40 months, 27 RH (18.4%) and 20 CRT (29.4%) patients had recurrence (p=0.068) and 23 (15.6%) and 17 (25%) patients died of disease (p=0.101). The 5-year progression-free survival were 77% and 66% (p=0.047), and the 5-year overall survival were 78% and 67% (p=0.048) after RH and primary CRT, respectively. In multivariate analysis, patients who received primary CRT was at higher risk for tumor recurrence (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.24 to 4.14; p=0.008) and death (OR, 3.02; 95% CI, 1.53 to 5.98; p=0.001) than those who received RH. Grade 3-4, early (17% vs. 30.9%, p=0.021) and late (1.4% vs. 8.8%, p=0.007) complications were significantly less frequent after RH than primary CRT.
Conclusion
Thirty percent of patients were cured by RH alone. A treatment outcome was better in this retrospective study in terms of morbidity and survival. Randomized trials are needed to confirm this result.
doi:10.3802/jgo.2012.23.4.226
PMCID: PMC3469857  PMID: 23094125
Bulky early-stage cervical cancer; Chemoradiation therapy; Radical hysterectomy; Stage IB2; Stage IIA2
11.  Safety and Efficacy of Deep Sedation with Propofol Alone or Combined with Midazolam Administrated by Nonanesthesiologist for Gastric Endoscopic Submucosal Dissection 
Gut and Liver  2012;6(4):464-470.
Background/Aims
Endoscopic submucosal dissection (ESD) is accepted as a treatment for gastric neoplasms and usually requires deep sedation. The aim of this study was to evaluate the safety and efficacy profiles of deep sedation induced by continuous propofol infusion with or without midazolam during ESD.
Methods
A total of 135 patients scheduled for ESDs between December 2008 and June 2010 were included in this prospective study and were randomly assigned to one of two groups: the propofol group or the combination group (propofol plus midazolam).
Results
The propofol group reported only one case of severe hypoxemia with no need of mask ventilation or intubation. Additionally, 18 cases of mild hypotension were observed in the propofol group, and 11 cases were observed in the combination group. The combination group had a lower mean total propofol dose (378 mg vs 466 mg, p<0.012), a longer mean recovery time (10.5 minutes vs 7.9 minutes, p=0.027), and a lower frequency of overall adverse events (32.8% vs 17.6%, p=0.042).
Conclusions
Deep sedation induced by continuous propofol infusion was shown to be safe during ESD. The combination of continuous propofol infusion and intermittent midazolam injection can decrease the total dose and infusion rate of propofol and the overall occurrence of adverse events.
doi:10.5009/gnl.2012.6.4.464
PMCID: PMC3493727  PMID: 23170151
Deep sedation; Propofol; Midazolam; Endoscopy; Gastrointestinal
12.  Management of endoscopic retrograde cholangiopancreatography-related perforations 
Purpose
The purpose of this study is to analyze the treatment strategies of patients with endoscopic retrograde cholangiopancreatography (ERCP)-related perforations. This is a retrospective study.
Methods
We experienced 13 perforations associated with ERCP. We reviewed the medical recordsand classified ERCP-related perforations according to mechanism of injury in terms of perforating device. Injury by endoscopic tip or insertion tube was classified as type I, injury by cannulation catheter or sphincterotomy knife as type II, and injury by guidewire as type III.
Results
Of four type I injuries, one case was managed by conservative management after primary closure with a hemoclip during ERCP. The other three patients underwent surgical treatments such as primary closure orpancreatico-duodenectomy. Of five type II injuries, two patients underwent conservative management and the other three cases were managed by surgical treatment such as duodenojejunostomy, duodenal diverticulization and pancreatico-duodenectomy. Of four type III injuries, three patients were managed conservatively and the remaining patient was managed by T-tube choledochostomy.
Conclusion
Type I injuries require immediate surgical management after EPCP or immediate endoscopic closure during ERCP whenever possible. Type II injuries require surgical or conservative treatment according to intra- and retro-peritoneal dirty fluid collection findings following radiologic evaluation. Type III injuries almost always improve after conservative treatment with endoscopic nasobilliary drainage.
doi:10.4174/jkss.2011.81.3.195
PMCID: PMC3204541  PMID: 22066121
Endoscopic retrograde cholangiopancreatography; Perforation; Surgery
13.  The effect of combined treatment with cisplatin and histone deacetylase inhibitors on HeLa cells 
Journal of Gynecologic Oncology  2010;21(4):262-268.
Objective
To investigate the combined effects of cisplatin and the histone deacetylase (HDAC) inhibitors suberoylanilide hydroxamic acid (SAHA) or sirtinol on HeLa cells and assess the mechanism underlying HDAC inhibitor-cisplatin synergy.
Methods
The antineoplastic actions of cisplatin, SAHA and sirtinol, alone and in combination, were evaluated using the tetrazolium dye-based MTT cell proliferation assay, DAPI nuclear staining and cytotoxicity analysis.
Results
Exposure to cisplatin, SAHA or sirtinol alone induced a dose-dependent reduction in HeLa cell viability. Combined treatment with cisplatin and SAHA or sirtinol was significantly more cytotoxic than cisplatin alone. Individually, cisplatin, SAHA and sirtinol activated caspase-3 and induced apoptosis, but the effects of combined treatment were greater. Importantly, both HDAC inhibitors dose-dependently inhibited the expression of the antiapoptotic proteins Bcl-2 and x-linked inhibitor of apoptosis protein (XIAP).
Conclusion
The combination of cisplatin and SAHA or sirtinol had synergistic effect on the HeLa cell viability. This potentiation of cisplatin activity was associated with HDAC inhibitor-mediated down-regulation of Bcl-2 and XIAP. These may result from the relaxation of chromatin by these HDAC inhibitors that increase cisplatin sensitivity by enhancing the accessibility of DNA to cisplatin and transcriptional regulators.
doi:10.3802/jgo.2010.21.4.262
PMCID: PMC3026306  PMID: 21278889
Cervical cancer; Apoptosis; Cisplatin; Suberoylanilide hydroxamic acid; Sirtinol
14.  Asian society of gynecologic oncology workshop 2010 
Journal of Gynecologic Oncology  2010;21(3):137-150.
This workshop was held on July 31-August 1, 2010 and was organized to promote the academic environment and to enhance the communication among Asian countries prior to the 2nd biennial meeting of Australian Society of Gynaecologic Oncologists (ASGO), which will be held on November 3-5, 2011. We summarized the whole contents presented at the workshop. Regarding cervical cancer screening in Asia, particularly in low resource settings, and an update on human papillomavirus (HPV) vaccination was described for prevention and radical surgery overview, fertility sparing and less radical surgery, nerve sparing radical surgery and primary chemoradiotherapy in locally advanced cervical cancer, were discussed for management. As to surgical techniques, nerve sparing radical hysterectomy, optimal staging in early ovarian cancer, laparoscopic radical hysterectomy, one-port surgery and robotic surgery were introduced. After three topics of endometrial cancer, laparoscopic surgery versus open surgery, role of lymphadenectomy and fertility sparing treatment, there was a special additional time for clinical trials in Asia. Finally, chemotherapy including neo-adjuvant chemotherapy, optimal surgical management, and the basis of targeted therapy in ovarian cancer were presented.
doi:10.3802/jgo.2010.21.3.137
PMCID: PMC2948221  PMID: 20922136
ASGO; Workshop; Cervical caner; Endometrial cancer; Ovarian cancer; Clinical trials
15.  Proliferation of CD4+CD25high+Foxp3+ regulatory T lymphocytes in ex vivo expanded ascitic fluid from primary and recurrent ovarian carcinoma 
Objective
Regulatory T lymphocytes evoke the immune tolerance by suppressing and inactivating cytotoxic T lymphocytes. The objective of this study was to compare the proportion of regulatory T lymphocytes, precisely defined as CD4+CD25high+Foxp3+ T lymphocytes, in primary and recurrent ovarian carcinoma before and after ex vivo expansion of ascites with interleukin-2 (IL-2).
Methods
Ascitic fluid samples were obtained from 26 patients with ovarian carcinoma. Lymphocytes were isolated from ascites and cell markers were analyzed by flow cytometry using anti-CD3/CD4/CD8/CD16/CD56/CD25 and anti-Foxp3 antibodies. Lymphocytes were incubated for 2 to 3 weeks and expanded ex vivo by IL-2 stimulation and their phenotypes were analyzed by flow cytometry.
Results
Following ex vivo expansion, ascitic fluid lymphocytes increased by a greater extent in the recurrent group than in the primary group. The proportion of ex vivo-expanded lymphocytes changed as follows; CD4+ T lymphocytes increased, CD8+ T lymphocytes decreased, and the proportion of CD3-CD16+56+ NK cells was unchanged. The proportion of CD4+CD25high+Foxp3+ regulatory T lymphocytes in CD4+ T lymphocytes increased after ex vivo expansion in both groups, but to a greater degree in the recurrent group.
Conclusion
This study showed that regulatory T lymphocytes, neither cytotoxic T lymphocytes nor NK cells, were extensively increased after ex vivo expansion, especially in recurrent ovarian carcinoma. These results may provide information that helps to guide the future development of adoptive immunotherapy against ovarian carcinoma.
doi:10.3802/jgo.2010.21.1.38
PMCID: PMC2849947  PMID: 20379446
Regulatory T lymphocyte; Foxp3; Ex vivo expansion; Ovarian carcinoma; Ascites
16.  Hexamethylmelamine as Consolidation Treatment for Patients with Advanced Epithelial Ovarian Cancer in Complete Response after First-Line Chemotherapy 
Journal of Korean Medical Science  2009;24(4):679-683.
The aim of this study was to assess the efficacy of consolidation therapy with hexamethylmelamine (HMM) in patients with advanced epithelial ovarian cancer (EOC). Patients treated at our hospital between January 1997 and November 2006 and in documented clinical complete response from advanced ovarian cancer following front-line platinum-based therapy were retrospectively analyzed. The patients treated with HMM were compared to the patients of matched counterpart without consolidation therapy. Of 102 patients enrolled, 49 were treated with HMM and 53 received no consolidation treatment. For patients with HMM and observed patients, the mean age were 54.6 and 55.6 yr; the distribution of stage was similar (P=0.977); the optimal surgery was performed in 36 (73.5%) and 44 (83%) (P=0.336); the recurrence rate were 27 (55.1%) and 33 (62.3%) (P=0.463); and the median progression-free survival were 38 months and 21 months for patients with HMM and observed patients (P=0.235). No treatment-related adverse events were reported during the follow-up period. Although this study failed to show the significant survival benefit of consolidation therapy with HMM in patients with advanced EOC, we consider that our study can contribute data to investigate the effectiveness of consolidation therapy in epithelial ovarian cancer.
doi:10.3346/jkms.2009.24.4.679
PMCID: PMC2719200  PMID: 19654952
Altretamine; Consolidation Therapy; Advanced Epithelial Ovarian Cancer
17.  Surgical practice patterns in endometrial cancer: results of the Korean Gynecologic Oncology Group survey 
Journal of Gynecologic Oncology  2009;20(2):107-112.
Objective
This study was undertaken to document current practice patterns for the surgical treatment of endometrial cancer in Korea.
Methods
Questionnaires were distributed to 131 Korean gynecologic oncologists, all members of the Korean Gynecologic Oncology Group. Questions addressed extent of hysterectomy procedure, pelvic (PEN) or paraaortic (PAN) lymph node dissection, ovarian preservation, and omentectomy.
Results
Completed questionnaires were returned by 64.1% (84/131) of the oncologists at 50 institutes. Extrafascial hysterectomy (EH) was used by 32% of respondents and modified radical hysterectomy (MRH) or radical hysterectomy (RH) by 17%. Hysterectomy procedures were selectively employed based on tumor-related factors by 51% of the respondents. Laparoscopic hysterectomy was routinely utilized by 49% and was more commonly used by younger surgeons with 10 years of experience or less. PEN dissection was routinely utilized by 67% and was used selectively based on tumor-related factors by 33%. PAN dissection/biopsy was used either routinely (43%) or selectively based on tumor-related factors (43%). PAN dissection/biopsy had never been employed by 12% of the respondents. Sixty-nine percent of respondents stated that grossly normal looking ovaries can be preserved during surgery in young aged patients with early stage disease, and 29% stated that bilateral oophorectomy should be performed irrespective of age or stage. Omentectomy was routinely performed by 11% of respondents, and was selectively performed when extrauterine spread was present by 41%.
Conclusion
Surgical procedures for the treatment of endometrial cancer are still not standardized among Korean gynecologic surgeons. Clinical trials to determine the benefits of the different surgical procedures should be developed.
doi:10.3802/jgo.2009.20.2.107
PMCID: PMC2704991  PMID: 19590722
Practice pattern; Endometrial cancer
18.  Mutational Analysis of KRAS, BRAF, and TP53 Genes of Ovarian Serous Carcinomas in Korean Women 
Yonsei Medical Journal  2009;50(2):266-272.
Purpose
To assess the prevalence of KRAS, BRAF, and TP53 mutations in cases of low-grade and high-grade serous carcinomas and to evaluate the clinical outcomes of these morphologically distinct carcinomas.
Materials and Methods
Patients with primary invasive serous carcinomas were classified according to the universal grading system. Grade 2 serous tumors were excluded. A total of 100 patients were included for clinical evaluation. Thirty-seven patients, including 20 with low-grade and 17 with high-grade carcinomas, were selected for mutational analysis.
Results
The low-grade carcinoma group was characterized by young age and premenopausal period compared with the high-grade carcinoma group, but there were no statistically significant differences in stage, metastasis of lymph node and residual disease. There were no statistically significant differences in survival rates, however, the low-grade carcinoma group showed a trend for improved progression-free survival compared with the high-grade carcinoma group of early stage (p = 0.064). Mutations in KRAS and BRAF were found in 6 (30%) and 2 (10%) patients in the low-grade carcinoma group, respectively, however, they were not found in the high-grade carcinoma group. KRAS and BRAF mutations were mutually exclusive, and both mutations were observed in 40% (8/20). The frequency of TP53 mutations in low-grade and high-grade carcinoma groups were found in 20% (4/20) and 70.6% (12/17), respectively (p = 0.009).
Conclusion
Low-grade serous carcinoma shows mutation pattern different from that with high-grade carcinoma. As there were no significant differences in stage distribution and survival, especially in advanced stage, we suggest that more studies are needed to segregate these patients into distinct disease entities.
doi:10.3349/ymj.2009.50.2.266
PMCID: PMC2678703  PMID: 19430562
Ovary; serous carcinoma; grade; mutation
19.  Postoperative acute renal failure in patients with gynecologic malignancies: analysis of 10 cases and review of the literature 
Objective
Postoperative acute renal failure (PO-ARF) is an important cause of mortality among surgical patients. Although there have been many reports on PO-ARF after cardiac surgery and liver transplantation, less is known about the risk of PO-ARF after gynecologic operations. We aimed to investigate the risk of PO-ARF on gynecologic malignancy operations.
Methods
1,155 patients' medical charts were reviewed who underwent therapeutic surgery for gynecologic malignancies from January 1, 2005 to December 31, 2007, at the Asan Medical Center, Seoul, Korea.
Results
Of these, 10 patients, comprising 0.89% of those who underwent radical hysterectomies and 0.86% of those who underwent debulking operations, were diagnosed with PO-ARF. Their mean age was 61.9±10.1 years. Five patients had preoperative risk factors. Mean operating time was 360.8±96.2 minutes. Five patients experienced intra-operative hypotension and all patients were given blood transfusions during surgery. Eight patients underwent hemodialysis, with two continuing on dialysis to date. Only two patients fully recovered.
Conclusion
Patients undergoing surgery for gynecologic malignancies may be at high risk for PO-ARF, because of old age, long operation times, and profuse bleeding. It is necessary to monitor these patients for postoperative renal function and urine output. If a postoperative oliguric state is detected, aggressive volume expansion should be started immediately, followed by hemodialysis.
doi:10.3802/jgo.2009.20.1.55
PMCID: PMC2676502  PMID: 19471672
Postoperative acute renal failure; Gynecologic malignancy
20.  Comparative study of neoadjuvant chemotherapy before radical hysterectomy and radical surgery alone in stage IB2-IIA bulky cervical cancer 
Objective
To compare the efficacy of neoadjuvant chemotherapy with paclitaxel plus platinum followed by radical hysterectomy with radical surgery alone in patients with stage IB2-IIA bulky cervical cancer.
Methods
From November 1999 to September 2007, stage IB2-IIA cervical cancers with tumor diameter >4 cm, as measured by MRI, were managed with two cycles of preoperative paclitaxel and platinum. As a control group, we selected 35 patients treated with radical surgery alone.
Results
There were no significant between group differences in age, tumor size, FIGO stage, level of SCC Ag, histopathologic type and grade. Operating time, estimated blood loss, the number of lymph nodes yielded and the rate of complications were similar in the two groups. In surgical specimens, lymph-vascular space invasion (LVSI), nodal metastasis and parametrial involvement did not differ significantly between the two groups. In the neoadjuvant group, pathologic tumor size was significantly smaller and fewer patients had deep cervical invasion. Radiotherapy, alone and in the form of concurrent chemoradiation, was administered to more patients treated with radical surgery alone (82.9% vs. 52.9%, p=0.006). No recurrence was observed in patients who could avoid adjuvant radiotherapy owing to improved risk factors after neoadjuvant chemotherapy. There were no significant differences in 5-year disease free and overall survival.
Conclusion
As neoadjuvant chemotherapy would improve pathologic prognostic factors, adjuvant radiotherapy can be avoided, without worsening the prognosis, in patients with locally advanced bulky cervical cancer. Neoadjuvant chemotherapy would be improving the quality of life after radical hysterectomy in patients with bulky cervical cancer.
doi:10.3802/jgo.2009.20.1.22
PMCID: PMC2676495  PMID: 19471665
Locally advanced cervical cancer; Neoadjuvant chemotherapy; Radical hysterectomy
21.  Acute Pancreatitis Complicating Spontaneous Acute Exacerbation of Chronic Hepatitis B Virus Infection: Case Report and Review of the Literature 
Gut and Liver  2009;3(1):64-66.
Acute pancreatitis may complicate viral hepatitis B, as well as the other causes of viral hepatitis. There have been reports of acute pancreatitis complicating acute exacerbations of chronic hepatitis B virus infection, most of which were related to immunosuppressive treatment or organ transplantation. However, acute pancreatitis complicating spontaneous acute exacerbation of chronic hepatitis B virus infection is rare. We report a case of acute pancreatitis that developed while a spontaneous acute exacerbation of chronic hepatitis B virus infection was underway in a healthy carrier.
doi:10.5009/gnl.2009.3.1.64
PMCID: PMC2871560  PMID: 20479905
Pancreatitis; Hepatitis B, Chronic
22.  Stage IIIC epithelial ovarian cancer classified solely by lymph node metastasis has a more favorable prognosis than other types of stage IIIC epithelial ovarian cancer 
Journal of Gynecologic Oncology  2008;19(4):223-228.
Objective
To verify whether it can be justified to classify patients to stage IIIC epithelial ovarian cancer based on nodal involvement only.
Methods
This study included all consecutive patients with stage IIIC epithelial ovarian cancer who underwent upfront cytoreductive surgery according to the FIGO guideline followed by platinum based chemotherapy from September 1989 to September 2006 at Asan Medical Center.
Results
During the study period, a total of 272 patients met the inclusion criteria. Optimal cytoreduction was achieved in 213 patients, and complete cytoreduction was achieved in 85 patients. Median follow-up time was 37 months (range, 6-181 months). The 5-year disease free survival (DFS) and overall survival (OS) rate of all patients were 23% and 57%, respectively. Forty-one patients were allocated to stage IIIC by positive nodes only. Patients with stage IIIC disease due to positive nodes only had significantly longer DFS and OS compared to other stage IIIC patients (p<0.001 and p<0.001). The DFS and OS of these patients was significantly better than those of other stage IIIC patients who achieved complete or optimal cytoreduction (p<0.001 and p<0.001). The outcome was even better than that of stage IIIA and IIIB patients (p<0.05 and p<0.05).
Conclusion
Patients with stage IIIC epithelial ovarian cancer due to positive nodes only had a more favorable prognosis compared to other stage IIIC patients. Therefore, reevaluation of the current FIGO staging system for stage IIIC epithelial ovarian cancer is required.
doi:10.3802/jgo.2008.19.4.223
PMCID: PMC2676474  PMID: 19471577
Epithelial ovarian cancer; Stage IIIC; Lymph node metastasis; Prognosis
23.  Expression profile of histone deacetylases 1, 2 and 3 in ovarian cancer tissues 
Journal of Gynecologic Oncology  2008;19(3):185-190.
Objective
To investigate the expression levels of histone deacetylase (HDAC) 1, 2, and 3 in ovarian cancer tissues and normal ovarian tissues.
Methods
Randomly assigned each of six patients with serous, mucinous and endometrioid ovarian cancer were included. Another six patients with normal ovarian tissue were included for comparison. RT-PCR was performed to quantify the levels of HDACs1-3 mRNA in the cancer and normal tissues. Western blot analysis was performed to measure the expression levels of HDACs1-3 protein. The HDACs1-3 expression pattern was also topologically examined by immunohistochemistry.
Results
Increased mRNA expressions of HDCA1, HDAC 2 and HDAC 3 were detected in 83%, 67% and 83% of 18 cancer tissue samples, compared to normal tissue samples. The relative densities of HDAC1 mRNA and HDAC3 mRNA in the serous, mucinous and endometrioid cancer tissues, and HDAC2 mRNA in serous cancer tissues were significantly higher than those of the normal tissues, respectively (p<0.05). Overexpression of HDAC1, HDAC2 and HDAC3 proteins were detected in 94%, 72% and 83% of 18 cancer samples, respectively. The relative densities of HDAC1 protein and HDAC3 protein in serous, mucinous and endometrioid cancer, and HDAC2 protein in serous and mucinous cancer tissues were significantly higher than those of normal tissues, respectively (p<0.05). Most cancer tissues expressed moderate to strong staining of HDACs1, 2 and 3 in immunohistochemistry. Staining of HDAC2 was weak in only one endometrioid cancer tissue.
Conclusion
HDACs1-3 are over expressed in ovarian cancer tissues and probably play a significant role in ovarian carcinogenesis.
doi:10.3802/jgo.2008.19.3.185
PMCID: PMC2676472  PMID: 19471575
HDAC1; HDAC2; HDAC3; Ovarian cancer
24.  Simple Tests to Predict Hepatic Fibrosis in Nonalcoholic Chronic Liver Diseases 
Gut and Liver  2007;1(2):145-150.
Background/Aims
Several simple tests for hepatic fibrosis employ indirect markers. However, the efficacy of using direct and indirect serum markers to predict significant fibrosis in clinical practice is inconclusive. We analyzed the efficacy of a previously reported indirect marker of hepatic fibrosis - the aspartate aminotransferase to platelet ratio index (APRI) - in patients with nonalcoholic chronic liver diseases (CLDs).
Methods
A total of 134 patients who underwent a percutaneous liver biopsy with a final diagnosis of chronic hepatitis B (n=93), chronic hepatitis C (n=18), or nonalcoholic fatty liver disease (n=23) were enrolled. A single-blinded pathologist staged fibrosis from F0 to F4 according to the METAVIR system, with significant hepatic fibrosis defined as a METAVIR fibrosis score of ≥2.
Results
The mean area under the receiver operating characteristic curve (AUROC) of APRI for predicting significant fibrosis in nonalcoholic CLDs was 0.84 [95% confidence interval (CI), 0.78-0.91]. APRI yielded the highest mean AUROC in the patients with chronic hepatitis B (0.85; 95% CI, 0.771-0.926). The positive predictive value of APRI ≥1.5 for predicting significant fibrosis was 89%. The negative predictive value of APRI <0.5 for excluding significant fibrosis was 80%.
Conclusions
APRI might be a simple and noninvasive index for predicting significant fibrosis in nonalcoholic CLDs.
doi:10.5009/gnl.2007.1.2.145
PMCID: PMC2871633  PMID: 20485631
Aspartate aminotransferase; Fibrosis; Hepatitis B
25.  Gene expression changes associated with Barrett's esophagus and Barrett's-associated adenocarcinoma cell lines after acid or bile salt exposure 
BMC Gastroenterology  2007;7:24.
Background
Esophageal reflux and Barrett's esophagus represent two major risk factors for the development of esophageal adenocarcinoma. Previous studies have shown that brief exposure of the Barrett's-associated adenocarcinoma cell line, SEG-1, or primary cultures of Barrett's esophageal tissues to acid or bile results in changes consistent with cell proliferation. In this study, we determined whether similar exposure to acid or bile salts results in gene expression changes that provide insights into malignant transformation.
Methods
Using previously published methods, Barrett's-associated esophageal adenocarcinoma cell lines and primary cultures of Barrett's esophageal tissue were exposed to short pulses of acid or bile salts followed by incubation in culture media at pH 7.4. A genome-wide assessment of gene expression was then determined for the samples using cDNA microarrays. Subsequent analysis evaluated for statistical differences in gene expression with and without treatment.
Results
The SEG-1 cell line showed changes in gene expression that was dependent on the length of exposure to pH 3.5. Further analysis using the Gene Ontology, however, showed that representation by genes associated with cell proliferation is not enhanced by acid exposure. The changes in gene expression also did not involve genes known to be differentially expressed in esophageal adenocarcinoma. Similar experiments using short-term primary cultures of Barrett's esophagus also did not result in detectable changes in gene expression with either acid or bile salt exposure.
Conclusion
Short-term exposure of esophageal adenocarcinoma SEG-1 cells or primary cultures of Barrett's esophagus does not result in gene expression changes that are consistent with enhanced cell proliferation. Thus other model systems are needed that may reflect the impact of acid and bile salt exposure on the esophagus in vivo.
doi:10.1186/1471-230X-7-24
PMCID: PMC1925102  PMID: 17597535

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