Search

136 Background: Gastric cancer (GC) is a second leading cause of death in Korean elderly cancer patients. Palliative chemotherapy would be an option of treatment in inoperable elderly GC patients for gaining survival time. We analysed the differences between single and doublet first line palliative chemotherapy in elderly GC patients. Methods: More than 70-year-old GC patients treated in the hospitals of the Catholic university of Korea were analysed. Baseline characteristics, first-line chemotherapy regimen, treatment responses, toxicities, time to progression (TTP) and overall survival (OS) were evaluated. Results: From 2005 to 2012, 178 GC patients above 70 years had been treated with palliative chemotherapy with single or doublet regimen. The median age were 77 years (range 70-89) in single regimen group (SG, 70 patients) and 73 years (range 70-81) in doublet regimen group (DG, 108 patients). TS-1 or capecitabine was used in SG, and platinum combined with 5FU or taxane was the most common regimen in DG. The most common response in both group was stable disease. Median relative dose intensity was 92.4% (range 50~100%) in SG and 83.5% (range 43~100%) in DG. Median TTP in SG was 4.40 months (95% CI, 2.85-5.95) and 4.10 months in DG (95% CI, 2.62-5.57, P=0.295). Median OS was 6.90 months (95% CI, 4.20-9.59) in SG, 8.20 months (95% CI, 5.96-10.43, p=0.918) in DG. Hematologic (P=0.03) and non-hematologic toxicities (p=0.061) were more frequent in DG. The common causes to terminate chemotherapy were disease progression in SG and decreased performance status in DG. Conclusions: No significant differences were observed in TTP and OS in both groups, but treatment related hematologic toxicity of SG was less than DG. Single agent treatment would be considered as the option of first line palliative chemotherapy in the elderly more than 70 years.

Objective To report our experiences in the prenatal diagnosis of atrial isomerism and postnatal outcomes. Methods A total of 80 fetuses prenatally diagnosed with atrial isomerism were retrospectively analyzed between 1999 and 2011 at a single institution. Results Of 43 fetuses with prenatally diagnosed right atrial isomerism (RAI), 40 cases were analyzed. The diagnostic accuracy was 93%. The main intracardiac anomalies in RAI were atrioventricular septal defect (AVSD), abnormal pulmonary venous connection, bilateral superior vena cava (BSVC), and pulmonary atresia. Among 28 live births, three infants were lost to follow up, and the overall survival rate was 60%. Of 37 fetuses with prenatally diagnosed left atrial isomerism (LAI), 35 were evaluated. The diagnostic accuracy was 97%. The main intracardiac anomalies in LAI were ventricular septal defect, BSVC, AVSD, double outlet right ventricle, and bradyarrhythmia. Among seven patients with bradyarrhythmia, only one showed a complete atrioventricular block. All fetuses had an interrupted inferior vena cava with azygous continuation. The overall survival rate was 90%. Conclusion Our study confirms the previous findings of fetal atrial isomerism. We also demonstrates a much lower prevalence of AVSD and complete heart block in LAI and a better survival rate in RAI. Although the postnatal outcomes for RAI were worse than those for LAI, successful postnatal surgery with active management improved the survival rate.

Congenital cystic adenomatoid malformation (CCAM) is a rare condition which is easily detectable by prenatal ultrasonography. Fetuses with large CCAMs associating with hydrops are predisposed to perinatal mortality, therefore prenatal intervention is required. While macrocystic CCAM is treated prenatally by thoracentesis or thoraco-amniotic shunt, microcystic or mixed CCAM is difficult to manage in the fetus. In these latter lesions, fetal lobectomy, sclerotherapy, or laser ablation was used to treat lesions directly. We present an unusual prenatal case of mixed CCAM associating with hydrops and marked ascites, which was conservatively managed with prenatal abdomino-amniotic shunting and successfully treated by postnatal surgery.

Objective To report on our experiences with thoracoamniotic shunting and/or the injection of a sclerosing agent (OK-432) to treat fetuses diagnosed with macrocystic congenital cystic adenomatoid malformation (CCAM) of the lung. Methods A retrospective study was undertaken in six fetuses with macrocystic CCAM at our institute that had been confirmed by postnatal surgery between August 1999 and January 2012. Results Six fetuses that had been diagnosed with macrocystic CCAM were analyzed. The median gestational age at diagnosis was 23.5 weeks (range, 19.5-31.0 weeks), and at the time of primary treatment was 24.0 weeks (range, 20.5-31.0 weeks). The mean size of the largest cyst at the initial assessment was 42.5±15 mm. Four fetuses were associated with mediastinal shifting, and one also showed fetal hydrops. All fetuses underwent a shunting procedure within the cysts, one case among them was also treated with OK-432. After the completion of all procedures, the mean size of the largest cyst was all decreased (14.2±12 mm). The median gestational age at delivery was 38.0 weeks (range, 32.4-40.3 weeks). All of the newborns underwent the surgical resection at a median age of 6 days (range, 1-136 days) and are currently doing well without any complications. Conclusion We suggest that intrauterine decompression therapy to manage fetal macrocystic CCAM is recommendable treatment for good perinatal outcome.

An Ebstein anomaly is a rare congenital heart defect defined by an inferior displacement of the septal and posterior leaflets of the tricuspid valve from the tricuspid annulus. This anomaly shows various ultrasonographic manifestations, thus making the prenatal diagnosis sometimes difficult. We here report a rare case of an Ebstein anomaly which was prenatally suspected as the absence of the tricuspid valve with functional pulmonary atresia because of non-visible tricuspid leaflets on an echocardiograph at 24 weeks of gestation. An emergency cesarean section was performed at 35 weeks of gestation as fetal hydrops were seen on a follow-up scan. Postnatal surgery confirmed Ebstein anomaly type-D which demonstrates an almost complete atrialization of the right ventricle with the exception of a small and infundibular component. Because of its rarity, prenatal findings of a type-D Ebstein anomaly have not been reported previously. We suggest from this first such case report that this anomaly should be considered as a possible diagnosis when the tricuspid leaflets are not well visualized.

Thanatophoric dysplasia (TD) is caused by mutation of the gene that encodes fibroblast growth factor 3 (FGFR3). Owing to the poor prognosis for TD, prenatal diagnosis is critical to optimal perinatal management. We report here a case of TD in twin pregnancy, which was prenatally diagnosed by DNA analysis following amniocentesis at 15 weeks, and was managed by selective fetal termination. Prenatal ultrasonography and molecular analysis to detect TD-specific mutations enable accurate diagnosis of FGFR3-related TD in utero and appropriate obstetrical management at early gestation during twin pregnancy.

We describe two cases of fetal atrial flutter associated with severe fetal hydrops which were unresponsive to digoxin but were successfully treated with flecainide acetate. Two cases of fetal atrial flutter were identified in fetuses with severe fetal hydrops on 3rd trimester ultrasonogram(28 weeks' gestation and 30 weeks' gestation). Following failed digoxin monotherapy, flecainide acetate was added to digoxin. On the 7th day and 13th day after combined therapy, fetal heart rate converted to normal sinus rhythm without recurrence. Our cases showed that the combined therapy of digoxin and flecainide acetate can effectively treat fetal atrial flutter associated with fetal hydrops unresponsive to digoxin monotherapy.

Background: Both smoking and human papillomavirus (HPV) infection play an significant role in the development and progression of oropharyngeal squamous cell carcinoma (OSCC). MicroRNAs are short noncoding RNAs that regulate multiple mRNAs and are frequently dysregulated in cancer. The miR-21 microRNA is overexpressed in a wide variety of cancers and has been causally related to cellular proliferation and apoptosis. In this study, we investigated the association between the expression of miR-21 and the clinicopathologic features by stratified analysis based on HPV infection status. Patients and Methods: The expression of miR-21 in the OSCC tissues of 137 patients was evaluated by in situ hybridization method. In addition, PDCD4 and PTEN were also examined by immunohistochemistry using tissue microarray. The clinicopathological implications of these molecules were analyzed statistically. Results: The up-regulation of miR-21 expression was 22.7% for HPV negative group and 42.1% for HPV positive group (P = 0.081), and significantly correlated with advanced lymph node metastasis and extracapsular extension (P = 0.005 and P = 0.014, respectively). There was a significant association between miR-21 and cytoplasmic PDCD4 overexpression (P = 0.027). Kaplan-Meier analysis showed that up-regulation of miR-21 was significantly related with shorter overall survival (OS; 77.0 v 193.0 months; P =0.05) in HPV-negative OSCC, but not in HPV-positive OSCC (P =0.95). At HPV-stratified multivariate analysis, up-regulation of miR-21 was independent prognostic factor for both relapse-free survival (RFS; HR, 2.681; 95% CI, 1.090 to 6.591; P = 0.032) and OS (HR, 6.286; 95% CI, 2.047 to 19.302; P = 0.001). Conclusion: Up-regulation of miR-21 expression is closely associated with poor prognosis in HPV-negative OSCC, but not in HPV-positive OSCC, suggesting that miR-21 may have a different role according to the HPV infection status. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B224. Citation Format: Yoon Ho Ko, Ho Jung An, Der Sheng Sun, Hye Sung Won, Jin Hyoung Kang, Chan-Kwon Jung. HPV-stratified analysis of prognostic role of miR-21 in oropharyngeal squamous cell carcinoma. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B224.

Placenta percreta is an extremely rare and the most severe form of placental invasion, that is associated with severe maternal morbidity and mortality. We report a case of nulliparous woman who underwent 10 cycles of in vitro fertilization (IVF) without any known risk factors. We conserved her uterus by spontaneous vaginal delivery, leaving the placenta in situ, pelvic arterial embolization, and primary resection of the remaining placental tissues. This case demonstrates that repetitive IVF is a possible risk factor for placental invasion, and that conservation of the uterus can be achieved in such cases using a multidisciplinary approach.

Introduction Autophagy is a critical intracellular pathway for removal of aggregated proteins and damaged organelles. The aim of this study was to explore the contribution of autophagy-related proteins on clinical outcomes of patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods The expression of five autophagy-related proteins in the PDAC tissues of 73 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of autophagy-related proteins. Results Of the 73 patients, autophagy-related proteins expression frequencies were 49.3% (36/73) for ATG 5, 63.9% (46/72) for ambra 1, 47.9% (35/73) for beclin-1, 83.3% (60/72) for LC3B, and 69.9% (51/73) for bif-1. The correlation between the expressions of autophagy-related proteins was statistically significant in all protein pairs. Advanced T stage was marginally associated with a higher number of protein changes (P=0.059). Multivariate analysis revealed that beclin 1 overexpression or increases in alteration of autophagy-related proteins wereindependently associated with poor prognosis (hazard ratio 5.365, P=0.001 and hazard ratio 5.270, P=0.022, respectively). Conclusion The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDAC. The awareness and inhibition of autophagy offer a potential therapeutic target for PDAC.

e14634 Background: Autophagy is a critical intracellular pathway for removal of aggregated proteins and damaged organelles. The aim of this study was to explore the contribution of autophagy-related proteins on clinical outcomes of patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods: The expression of five autophagy-related proteins in the PDCA tissues of 73 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of autophagy-related proteins. Results: Of the 73 patients, autophagy-related proteins expression frequencies were 49.3% (36/73) for ATG5, 63.9% (46/72) for Ambra 1, 47.9% (35/73) for Beclin-1, 83.3% (60/72) for LC3B, and 69.9% (51/73) for Bif-1. The correlation between the expressions of autophagy-related proteins was statistically significant in all protein pairs. Advanced T stage was marginally associated with a higher number of protein changes (p = 0.059). Multivariate analysis revealed that Beclin 1 overexpression or increases in alteration of autophagy-related proteins were independently associated with poor prognosis (hazard ratio 5.365, p=0.001 and hazard ratio 5.270, p=0.022, respectively). Conclusions: The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDCA. The awareness and inhibition of autophagy offer a potential therapeutic target for PDCA.

Background High-risk type of human papillomavirus (HPV) has recently been found to be etiologically associated with 20 to 25% of SCCHN, particularly common in or pharyngeal tumors. We investigated the protein expression of PTEN/PI3K/AKT/mTOR signal pathway on HPV 16 +/− tonsillar squamous cell carcinomas. And, we analyzed microRNA expression profile in tongue cancer cell line transfected with HPV 16 E6/E7 oncogene. Method Tonsil cancer patients who had been treated at Seoul St. Mary's Hospital between 2000 and 2009 were reviewed. Tissue microarrays were prepared from formalin-fixed, paraffin-embedded tumor tissues of 65 surgical specimens, and stained with antibodies against PTEN, PIK3CA, phosphorylated AktSer473, and phosphorylated mTORSer2448. High-risk HPV infection status was determined by in situ hybridization. The protein expression of EGFR, PIK3CA, pAkt, mTOR, and PTEN was assessed by immunohistochemistry. MicroRNA expression was studied using microarrays (PANArray™ miRNA expression profiling kit) in two tongue cancer cell lines (YD8 and YD10B) transfected with HPV 16 E6/E7 oncogene. Results Of the 65 pts, 26 (40%) pts were HPV positive. Overall survival and relapse-free survival were significantly different between two groups (P = 0.05 and P = 0.036, respectively). PTEN expression was significantly higher in HPV-positive- than in HPV-negative patients (P = 0.02). PIK3CA, phosphorylated AktSer473, and phosphorylated mTORSer2448 expression was negatively correlated with HPV status, yet not significantly. HPV status (P = 0.03) and nodal stage (P = 0.05) were found to significantly affect overall survival, as determined by multivariate analysis. The expression profile of miRNAs was different in HPV 16 E6/E7 transformed cells compared with vector alone cells. In the final round, 8 of 158 miRNAs were selected to be most differently expressed miRNAs; let-7b, miR-1, miR-107, miR-122, miR-127-5p, miR-95, miR-23b and miR-370 (>1.2-fold). Conclusion We observed the higher expression of PTEN in HPV 16 positive tonsil tumor than HPV 16 negative tumor. Our data suggest that some microRNAs induced by E6/E7 oncogene might directly affect PTEN expression level independent of p53. We are underway on the experiments confirming that PTEN is regulated by which among these miRNAs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 185. doi:1538-7445.AM2012-185

BACKGROUND: Autophagy is a catabolic process and provides metabolic support for the cell by degradation of intracellular macromolecules. Various types of stress, including hypoxia, activate autophagy. Recent studies have suggested that hypoxia has been shown to associate with resistance to chemotherapy and radiotherapy and hence poor prognosis in pancreatic cancer. This study investigated the role of autophagy in the treatment of pancreatic cancer with gemcitabine under hypoxic condition. METHODS: To evaluate the role of autophagy inhibition in hypoxia-induced chemoresistance, BxPC-3 human pancreatic cancer cell line was used under normoxic and hypoxic conditions. We evaluated the extent of LC3-II, as an autophagosome marker, by Western blotting to measure the hypoxia- or chemotherapy-induced autophagy. We then examined the effects of gemcitabine on induction of apoptosis under normoxic and hypoxic conditions. Finally, to determine the effect of 3-MA, a known inhibitor of autophagy, on overcoming hypoxia-induced chemoresistance, the MTS assay and flow cytometry were performed.RESULTS: Compared with normoxia, gemcitabine-induced cell death was significantly decreased under hypoxia, as a result of the reduced apoptosis. Western blotting analysis demonstrated that LC3-II was increased under hypoxia, compared with normoxia. However, we found that 3-MA can enhance the growth inhibition and apoptotic effect of gemcitabine, even under hypoxia. These findings mean that autophagy mediates the chemoresistance under hypoxia. Conclusions: Activated autophagy plays a role in hypoxia-induced chemoresistance of pancreatic cancer cells. These findings may have important implications for future therapeutic strategies using gemcitabine against pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4107. doi:1538-7445.AM2012-4107

Objective To report our experience of using radiofrequency ablation (RFA) to treat fetuses diagnosed with twin reversed arterial perfusion (TRAP) sequence and to evaluate the perinatal outcome of pump twins. Methods Twenty-six fetuses diagnosed with the TRAP sequence were retrospectively analyzed between July 1998 and September 2011 at Asan Medical Center. Four were lost to follow-up after diagnosis and, therefore, were excluded from further evaluation. The perinatal outcomes of pump twins were evaluated by reviewing the medical records. Results Twenty-two fetuses were diagnosed with the TRAP sequence during the study period, including 15 monochorionic-diamniotic pregnancies and four monochorionic-monoamniotic pregnancies. Three patients had triplet pregnancies. The median gestational age at diagnosis was 17.4 weeks (range, 11.0 to 27.0 weeks). Of these 22 cases, in utero RFA was performed in 11 (50%), alcohol ablation in one (4.5%) and the remaining 10 (45.5%) underwent conservative management. The median gestational age at in utero intervention was 21.0 weeks (range, 17.6 to 25.0 weeks). The overall neonatal survival rate was 77% (17 of 22). The median gestational age at delivery was 37.3 weeks (range, 30.2 to 40.1 weeks). All of the surviving infants are doing well without any complications. Conclusion For fetuses with the TRAP sequence, proper in utero treatment with RFA enables to continue the pregnancy with a good prognosis.

An obstruction of the fetal upper airway in utero due to various reasons may cause a fatal condition congenital high airway obstruction syndrome (CHAOS). The prenatal ultrasound fi ndings of CHAOS include large echogenic lungs, fl attened or inverted diaphragms, dilated airways distal to the obstruction, and fetal ascites and/or hydrops [1]. If it is associated with severe hydrops and/ or associated anomalies, its prognosis is fatal. Here we present a case of antenatally diagnosed CHAOS with associated anomalies and a literature review.

Recently, there is growing evidence to support that oral cavity and oropharyngeal squamous cell carcinoma are two distinct diseases with different etiology. The aim of this study was to evaluate the expression of EGFR, PI3K/Akt/mTOR pathway, and PTEN in oral cavity and oropharyngeal cancers, and to investigate their clinical significance as prognostic markers. One hundred twenty-one patients who underwent curative surgery for oral cavity or oropharyngeal squamous cell carcinoma in Seoul St. Mary's Hospital between January 1995 and September 2009 were evaluated. The level of protein expression of EGFR, PIK3CA, pAkt, mTOR, and PTEN was assessed by immunohistochemistry. In situ hybridization was used for assessment of human papillomaviruses (HPV). Nineteen of 61 patients with oropharyngeal cancer showed HPV-positive tumors, and 2 of 60 patients with oral cavity cancer showed HPV-positive tumors. EGFR and pAkt expression were significantly higher in oray cavity cancer than in oropharyngeal cancer. Loss of PTEN was significantly higher in oral cavity cancer than in oropharyngeal cancer. There were no significant differences in PIK3CA, mTOR, and p53 expressions. HPV-negative tumors overexpressed more EGFR and pAkt than HPV-positive tumors. Loss of PTEN expression was more frequent in HPV-negative tumors than in HPV-positive tumors. In multivariate cox regression analysis, pAkt expression showed a significant impact on relapse-free survival. There was a significantly negative correlation between PTEN and pAkt expression, and positive correlation between pAkt and mTOR expression. We concluded that there were differences in expression of EGFR, pAkt, and PTEN between oropharyngeal and oral cavity cancer. It was attributed to etiologic role of human papillomaviruses in oropharyngeal cancer. The expression of pAkt may be a prognostic marker for relapse-free survival in oropharyngeal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B21.

목적: 본 연구는 임신 10주 이내의 임신부를 대상으로 자궁경부 분비물내 angiogenin과 interleukin (IL)-6 농도를 측정하고, 해당 임신의 경과를 확인하여 이들 물질들의 농도와 초기임신의 예후가 관련성이 있는지 확인하고자 하였다. 연구방법: 2001년 1월부터 2001년 12월까지 전향적으로 임신 10주 이전에 연속적으로 서울아산병원 산부인과를 처음 방문한 단태임신부를 대상으로 모체 혈청 β-hCG 및 progesterone 농도의 측정하였으며, 자궁경부 분비물을 채취하여 angiogenin과 IL-6의 농도를 ELISA kit를 이용하여 측정하였다. 또한 질초음파를 시행하여, 정둔장, 융모막하출혈 유무, 태아 심박동수 등을 측정하였다. 결과: 총 121명의 임신부를 대상으로 하였으며, 이 중 임신 20주 이전에 자연유산된 임신부는 10명(8.3%)이었다. 모체 혈청 progesterone 농도,자궁경부 분비물내 angiogenin과 IL-6 농도는 임신주에 따른 유의한 변화를 보이지 않았다. 임신 20주 이후까지 임신을 유지한 임신부에 대해 최종월경일과 초음파검사를 통한 임신주수가 서로 6일 미만으로 일치하는 군과 6일 이상 차이가 나는 군으로 나누고, 임신 20주 이내에 자연유산된 군은 따로 분류하였다. 모체 혈청 progesterone 농도는 각 군 간의 유의한 차이를 보이지 않았으나, 자궁경부 분비물내 angiogenin 농도는 유의한 차이를 보였으며(P=0.041), 자궁경부 분비물내 IL-6 농도는 각 군 간에 차이를 보이는 경향을 보였다(P=0.059). 결론: Angiogenin이 초기임신 경과에 결정적 역할을 할 것이라 예상되며, 자궁경부 분비물내 angiogenin 농도는 예후 예측 표지자로서 중요한역할을 할 수 있을 것이다.

Purpose: The objectives were to identify the characteristics of neonates with hydrops fetalis, and to identify the risk factors associ- ated with mortality. Methods: A retrospective review of AMC (Asan Medical Center) dataset was performed from January 1990 to June 2009. The characteristics of 71 patients with hydrops fetalis were investigated and they were divided into two groups: the survived group and the expired group. Various perinatal and neonatal factors in two groups were compared to find out risk factors associated with mortality based on univariate analysis, followed by multiple regression analyses (SPSS version 18.0). Results: Of those 71 neonates (average gestational age: 33 weeks, birth weight: 2.6 kg), 38 survived, 33 died, resulting in over- all mortality rate of 46.5%. The most common etiology was idiopathic followed by chylothorax, cardiac anomalies, twin-to-twin transfusion, meconium peritonitis, cardiac arrythmias, and congenital infections. Factors that were associated independently with mortality in logistic regression analyses were low 5-minutes Apgar score, hyaline membrane disease and delayed in achieving 50th percentile ideal body weight for appropriate gestational age by 10 days. Conclusion: In this study, 5-minutes Apgar score, hyaline membrane disease and delayed in achieving 50th percentile ideal body weight for appropriate gestational age by 10 days were significant risk factors associated with mortality in hydrops fetalis. There- fore, the risk of death among neonates with hydrops fetalis depends on the illness immediately after birth and severity of hydrops fetalis. Informations from this study may prove useful in prediction of prognosis to neonates with hydrops fetalis.

3583 Background: We performed a genome-wide association analyses in a cohort of curatively- resected colon cancer patients receiving fluorouracil, folinic acid and oxaliplatin (FOLFOX) adjuvant chemotherapy in order to determine association with chronic neurotoxicity and recurrence. Methods: This was a prospective study in which DNA was purified from peripheral blood of colon cancer patients starting FOLFOX adjuvant chemotherapy. Genotypic analysis was performed using the Affymetrix Genome-Wide Human SNP Array 6.0 which includes > 906,600 SNPs. Neurotoxicity was assessed in accordance with NCI CTCAE v3. Primary endpoint was the development of severe (grade ≥ 2) neuropathy. Recurrence was the secondary endpoint. Fisher's exact test was used to evaluate allelic association with the development of severe neurotoxicity as well as recurrence. Results: For the 96 registered patients, 1113 FOLFOX cycles were delivered (median 12, range 6-12). All patients received > 500 mg/m2 of oxaliplatin (median 935 mg/m2, ra...

5546 Background: HPV infection has been known to be one of the important risk factors for carcinogenesis of head and neck squamous cell carcinoma (HNSCC). The over-expression of epidermal growth fa...

5120 Background: Platinum based neoadjuvant chemotherapy (NAC) for locally advanced uterine cervix cancer has some benefits to the patients who responded to the chemotherapy, but there is no validated clinical or biologic predictor of response to the chemotherapy. Methods: We used immunohistochemical analysis to determine the expression of the excision repair cross-complementation group1 (ERCC1) protein in pretreatment uterine cervical biopsy tissue. 42 patients only stage IIB had been enrolled in the previous etoposide and cisplatin NAC phase II clinical trial, thereby allowing comparison of the effect of cisplatin based NAC on response according to ERCC1 expression. Results: Among 42 patients, ERCC1 was positive in 33 (78.6%) and negative in 9 (21.4%). Response to chemotherapy (by RECIST criteria) was observed in all patients with negative ERCC1 expression. With logistic regression analysis, ERCC1 negatively continued to be an independent predictor for responsiveness of NAC (p = 0.007). Also, regression...

Objective: To determine whether the duration and timing of prophylactic antibiotics influence maternal postoperative infectious morbidity in cesarean section performed at tertiary center. Methods: This study was a prospective, randomized trial. Pregnant women who underwent cesarean section between December 2008 and September 2009 at tertiary center were enrolled and divided into two groups: Group A, antibiotic prophylaxis was applied for 24 hours and Group B, antibiotic prophylaxis was applied for 48 hours. First generation of cephalosporin was administrated within 30 minutes prior skin incision or after cord clamping. The occurrence of postoperative infectious morbidity such as febrile morbidity, wound infection, endometritis, urinary track infection, pneumonia, sepsis and pelvic abscess and hospital stays were compared. Results: There were 413 pregnant women enrolled and then randomized into 220 for group A and 197 for group B. No demographic differences were observed between two groups. The infectious morbidity was 1.9% (8/413) and wound infection was the most common postoperative infections morbidity. No significant difference was found between the groups for infectious morbidity and hospital stays. Also timing of prophylactic antibiotics did not result in significant difference for infectious morbidity. Conclusion: Short course of prophylactic antibiotics has been shown to be as efficacious as multidose of prophylactic antibiotics for preventing infectious morbidity in cesarean section and timing did not influence on infections morbidity. Further studies focusing on duration and timing of prophylactic antibiotics for cesarean section are needed.

Objective: We investigated the usefulness of shortening of the fetal femur length (FL) and humeral length (HL) to predict Down syndrome at the middle gestation of pregnancy in Korean subjects. Methods: This retrospective study involved 41 fetuses with Down syndrome and 328 fetuses with normal chromosome between 14+0 and 28+6 weeks of gestation. The expected FL and HL for any biparietal diameter (BPD) was calculated based on the control group data. The odds ratios for measure to expected FL and HL in comparison between normal fetuses and Down syndrome fetuses were calculated. The sensitivities of short FL and HL to predict Down syndrome were analyzed at a fixed false positive rate of 5%. Results: The lengths of femur and humerus long bone for any BPD in Down syndrome group were significantly shorter than the lengths in control group (P < 0.001). A low ratio of measured to expected FL and HL increased the risk of fetal Down syndrome (P

P

Background : Growing tumors adapt to a hypoxic environment and increase anaerobic glycolysis. This metabolic switch is related to aggressive behavior. We investigated the relationship between glycolytic metabolism biomarkers associated with hypoxia-inducible factor (HIF)1a and prognosis. Methods : We performed immunohistochemical staining of HIF-1a, pyruvate dehydrogenase kinase (PDK) 1 and lactate dehydrogenase (LDH) 5 in 74 patients with oral squamous cell carcinoma (SCC) who had received curative radical resection. Results : High reactivity of HIF-1 a, PDK 1 and LDH 5 was observed in 29 (39.2%), 32 (43.2%) and 54 (73.0%) patients, respectively. Expression levels of the three biomarkers were significantly correlated. All three markers were highly expressed in 16 (21.6%) patients. Elevated expression of the three markers was associated with increased invasiveness (p = 0.043) and recurrence (p = 0.017) of tumors. In survival analysis, upregulation of the three markers was additionally associated with shorter disease free survival (DFS, p = 0.001) and overall survival (OS, p = 0.002). High expression of all three markers was a strong independent prognostic factor for DFS (p = 0.030) and OS (p = 0.026). Conclusions : Oral SCC with altered glycolytic metabolism exhibits a more invasive and aggressive phenotype. Our results indicate that glycolytic metabolism biomarkers related to HIF-1 a may be independent prognostic factors in patients with oral SCC.

Pseudo-Meigs’ syndrome is a syndrome that includes hydrothorax and ascites secondary to ovarian tumors other than solid benign fibroma. In this report, we present the case of a 29-years-old female who complained of abdominal distension with peripheral edema during her third trimester. Two solid masses of 15 cm dimension in the left abdomen and 7 cm dimension in the right abdomen were detected by ultrasound and chest X-ray revealed right pleural effusion. Magnetic resonance imaging (MRI) confirmed the ovarian masses and ascites. As the patient had regular uterine contractions, we decided to perform emergency cesarean section because of previous cesarean section history. A laparotomy was performed and pathologists confirmed the presence of a metastatic adenocarcinoma. Four days following the surgery, gastroduodenoscopy revealed a huge ulcerofungating mass was visible in greater curvature of stomach. The final diagnosis was metastatic adenocarcinoma from gastric cancer. Although pseudo-Meigs’ syndrome is very rare, it should be carefully considered when evaluating female complaining with ascites in ovarian tumor.

Background Use of nuchal skinfold thickness (NT) measurement as an ultrasound marker for Down syndrome has been limited due to a high false positive rate. We suggested that some variables, which influence on NT have been presented. The purpose of our study was to identify the variables that have effects on measured values of NT, and to make a regression equation based on those variables. Method The data on gestational age (GA), cephalic index (CI), presentation (Pr; vertex or breech) and the presence or absence of nuchal cord (NC) were collected prospectively on 548 normal singleton fetuses between 16 and 24 weeks' gestation. We calculated independent correlation of those variables with NT by multiple regression analysis and made a regression equation based on GA, CI, Pr, and NC. Results GA has positive correlation and CI has negative correlation with NT significantly. The nuchal skinfold was thicker among fetuses with breech presentation rather than those of vertex presentation and increased in the presence of nuchal cord. The all four variables (GA, CI, Pr, and NC) were independent factors to NT by multiple regression analysis. We calculated the expected NT through these observations; for fetuses presenting vertex, NT = 5.608 + 0.243GA − 0.066CI + NC* and for breech, NT = 2.803 + 0.392GA − 0.066CI + NC* (*if no NC, NC* equals −0.785 and zero for the other). Conclusion This is the first report, which takes GA, CI, Pr and NC for correlation factors with NT as a whole. These equations may be considered as a screening method for the detection of aneuploidies.

e22169 Background: Topoisomerase IIα protein(topo II) is the molecular target of topo II inhibitors such as anthracyclines and Microtubule-Associated Protein(MAP)-tau protein is associated with taxane sensitivity. Anthracyclins and taxanes are major cytotoxic agents of breast cancer in the adjuvant setting. The aim of this study was to evaluate the predictive and prognostic functions of MAP-tau and topo II in early breast cancers. Methods: Representative breast tumor sections were constructed from paraffin embedded specimens from 78 node positive breast cancer patients. MAP-tau and topo II protein were assessed by immunochemistry using antibody clone 4F1(Affinity BioReagents,USA) and clone Ki-S1 antibody(Dakocytomation,USA). MAP-tau staining of tumor cells was semiquantatively scored as 0, 1+, 2+, 3+ and cases with 0 or 1+ staining intensity were considered MAP-tau negative. Topo II protein over- expression was defined as the detection of nuclear staining in more than median value of evaluated cells. Results: Thirty- four cases (43.6%) of 78 samples showed topo II overexpression and 35 cases(44.9%) showed MAP-tau overexpression in node positive breast cancers. HER2 overexpression was noted in 28 samples (35.9%) and 56 cases (71.8%) were compatible with the luminal type. In 43 patients (55.1%), anthracyclin and taxane were used as adjuvant therapy and in this group, both MAP-tau and topo II overexpression showed lower disease-free survival (DFS) than the others, but statistically not significant. In luminal type, MAP-tau overexpression was poor prognostic factor on DFS in Cox regression.(HR 5.644, 95% CI 1.14–28.07, p=0.034) Conclusions: Topo II overexpression and MAP-tau overexpression in node positive breast cancers were not significant predictive factors for anthracyclin and taxane therapies. As several investigators reported, MAP-tau is associated endocrine therapy sensitivity in patients without chemotherapy, but higher MAP-tau in luminal type was a strong poor prognostic factor in patients who were given chemotherapy and hormonal therapy. No significant financial relationships to disclose.

6082 Background: During tumor growth, tumor adapts the hypoxic environment and increases glycolysis. This metabolic switch is related to the aggressive malignant behavior. We investigated the connection between the biomarkers related to the glycolytic metabolism (HIF-1α, PDK-1, LDH-5) and clinicopathologic characteristics in oral cavity and oropharynx squamous cell carcinoma (SCC). Methods: Eligibility criteria was the patients diagnosed oral SCC, received curative radical resection and had available tissue samples. Immunohistochemical stain of the HIF-1α, PDK-1, and LDH-5 was done. Statistical analysis was performed to compare biomarkers between patients and time point. Results: Overall 74 patients were enrolled and stage grouping of the patients was as follows: stage I, 25 (33.8%) patients; stage II 17 (23.0%); stage III 8 (10.8%); stage IV 24 (32.4%). 25 patients were relapsed and 5-year disease-free survival (DFS) rate was 61.4%. High expression of HIF-1α was related to the advanced T stage (p = 0.029), more invasive tumor (p = 0.003) and tumor recurrence (p = 0.037). High expression of PDK-1 was related to the advanced N stage (p = 0.026) and high expression of LDH-5 was related to the lymphatics invasion (p = 0.028), advanced N stage (p = 0.020) and more invasive tumor (p = 0.015). The high expression of HIF-1α, PDK-1, and LDH-5 showed a significant correlation to each other. 16 (21.6%) patients were highly expressed all three markers. High expression of all three markers correlated with more invasive tumor (p = 0.004) and tumor recurrence (p = 0.017). In survival analysis, high expression of HIF-1α and LDH-5 associated with shorter DFS in log rank test (p = 0.002 and p = 0.016, respectively). High expression of all three markers was also associated with shorter DFS (p = 0.002). In multivariate Cox regression analysis, high expression of all three markers was strong independent prognostic factor for DFS (p = 0.021). Conclusions: The oral SCC which glycolytic metabolism was changed showed a more invasive and aggressive phenotype. Taken together, biomarkers related tumor metabolism may be independent prognostic markers for the DFS in the patients with oral SCC. No significant financial relationships to disclose.

The pyrimidine antimetabolite 5-fluorouracil (5-FU) is a chemotherapeutic agent used widely for various tumors. Common side effects of 5-FU are related to its effects on the bone marrow and gastrointestinal epithelium. Neurotoxicity caused by 5-FU is uncommon, although acute and delayed forms have been reported. Wernicke's encephalopathy is an acute, neuropsychiatric syndrome resulting from thiamine deficiency, and has significant morbidity and mortality. Central nervous system neurotoxicity such as Wernicke's encephalopathy following chemotherapy with 5-FU has been reported rarely, although it has been suggested that 5-FU can produce adverse neurological effects by causing thiamine deficiency. We report a patient with Wernicke's encephalopathy, reversible with thiamine therapy, associated with 5-FU-based chemotherapy.