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Ebstein’s anomaly is frequently detected before birth, with prenatal detection accounting for the majority of cases in the current population. This study aimed to identify the outcome variables among these infants. The medical records of 59 patients with neonatal Ebstein’s anomaly managed at the Asan Medical Center between January, 2001 and June, 2012 were investigated retrospectively. In 46 cases, the diagnosis was made prenatally. Surgical/interventional procedures were performed for 27 of the analyzed patients. Biventricular repair was successful for 12 patients but not for 9 patients with pulmonary atresia. The median follow-up period was 1.96 years (range 0.0–10.4 years). The overall mortality rate was 23.7 % (14/59). Of the 14 deaths, 5 occurred within several hours after birth. The 1- and 5-year survival rates were 78.6 and 76.3 %, respectively. Univariate analysis identified several variables related to the time to death: fetal distress (p = 0.002), prematurity (p = 0.036), low birth weight (p = 0.003), diameter of the atrial septal defect (p = 0.022), and pulmonary stenosis/atresia (p = 0.001). Neither the Carpentier classification (p = 0.175) nor the Celermajer index (p = 0.958) was a significant variable. According to the multivariate analysis, fetal distress (p = 0.004) and pulmonary atresia/stenosis (p < 0.001) were significant determinants of outcome. In conclusion, fetal distress and pulmonary atresia/stenosis are significant predictors of mortality in the current population of patients with neonatal Ebstein’s anomaly. A close cooperation of associated clinicians is required for an improvement in outcome. To establish a better surgical strategy for patients with Ebstein’s anomaly and pulmonary atresia, studies of larger populations are required.

Fetal DNA is present in the plasma of pregnant women. Massively parallel sequencing of maternal plasma DNA has been used to detect fetal trisomies 21, 18, 13 and selected sex chromosomal aneuploidies noninvasively. Case reports describing the detection of fetal microdeletions from maternal plasma using massively parallel sequencing have been reported. However, these previous reports were either polymorphism-dependent or used statistical analyses which were confined to one or a small number of selected parts of the genome. In this report, we reported a procedure for performing noninvasive prenatal karyotyping at 3 Mb resolution across the whole genome through the massively parallel sequencing of maternal plasma DNA. This method has been used to analyze the plasma obtained from 6 cases. In three cases, fetal microdeletions have been detected successfully from maternal plasma. In two cases, fetal microduplications have been detected successfully from maternal plasma. In the remaining case, the plasma DNA sequencing result was consistent with the pregnant mother being a carrier of a microduplication. Simulation analyses were performed for determining the number of plasma DNA molecules that would need to be sequenced and aligned for enhancing the diagnostic resolution of noninvasive prenatal karyotyping to 2 Mb and 1 Mb. In conclusion, noninvasive prenatal molecular karyotyping from maternal plasma by massively parallel sequencing is feasible and would enhance the diagnostic spectrum of noninvasive prenatal testing.

Background: To better understand the mechanisms of the SDC1 expression in invasive ductal carcinoma, we studied the correlations between SDC1 expression and related gene expressions (RSPO1, WNT1, WT1, and P16). Methods: Using 100 cases of invasive ductal carcinoma tissue, we screened expressions of RSPO1, WNT1, WT1, P16, and SDC1 using immunohistochemistry. We analyzed the association between the immunoreactivities and clinicopathological parameters. Results: WT1 expression was associated with tumor grade. RSPO1 expression was associated with progesterone receptor expression. Expressions of RSPO1, WT1, and P16 were significantly associated with disease-free survival. RSPO1 and P16 showed statistically significant hazard ratios. SDC1 ectodomain expression was significantly associated only with P16 expression. Immunoreactivity of SDC1 cytoplasmic domain was associated with WT1 and WNT1. However, WNT1 expression failed to show a significant association with disease-free survival. Conclusions: RSPO1 and P16 immunoreactivity was found to be an independent prognostic indicator in invasive ductal cancer. Cytoplasmic expression of SDC1 is positively correlated with tumor-prone proteins (WT1 and WNT1) and membranous expression of SDC1 is positively correlated with the tumor suppressor (P16).

Background/Aim.Bax-interacting factor-1 (Bif-1) plays a crucial role in apoptosis and autophagy. The aim of this study was to evaluate Bif-1 protein expression and its prognostic significance in colorectal cancer (CRC).Methods.We analyzed Bif-1 protein expression in 251 resected specimens from patients with CRC by immunohistochemistry using tissue microarray.Results.Low Bif-1 expression was observed in 131 patients (52.2%) and high Bif-1 expression in 120 patients (47.8%). No significant differences were observed in clinicopathological parameters between patients with high and low Bif-1 expression. Kaplan-Meier survival analysis showed no difference in survival between patients with high and low Bif-1 expression. Stratified analysis of Bif-1 according to TNM stage demonstrated that low Bif-1 expression was significantly associated with a poor outcome in patients with stages I and II (P=0.034). Stratified multivariate analysis demonstrated that low Bif-1 expression was an independent indicator of poor prognosis (hazard ratio, 0.459; 95% confidence interval, 0.285–0.739;P=0.001).Conclusion.Patients with low levels of Bif-1 expression have shortened survival rates in CRC of stages I and II. This suggests that Bif-1 protein expression may be a useful prognostic marker in early-stage CRC.

Recent evidence suggests that prenatal maternal distress increases the risk of allergic diseases in offspring. However, the effect of prenatal maternal depression and anxiety on atopic dermatitis (AD) risk remains poorly understood.We investigated whether prenatal maternal distress is associated with AD risk in offspring and whether the mechanism is mediated by reactive oxygen species.Two general population-based birth cohorts formed the study. One cohort (Cohort for Childhood Origin of Asthma and Allergic Diseases [COCOA]) consisted of 973 mother-baby dyads, and the other (Panel Study on Korean Children [PSKC]) consisted of 1531 mother-baby dyads. The association between prenatal distress and AD was assessed by using Cox proportional hazards and logistic regression models. In COCOA placental 11β-hydroxysteroid dehydrogenase type 2 and glutathione levels and serum IgE levels in 1-year-old children were measured.In COCOA and PSKC AD occurred in 30.6% (lifetime prevalence) and 11.6% (1 year prevalence) of offspring, respectively. Prenatal maternal distress increased the risk of AD in offspring, both in COCOA (hazard ratio for depression, 1.31 [95% CI, 1.02-1.69]; hazard ratio for anxiety, 1.41 [95% CI, 1.06-1.89]) and PSKC (odds ratio for distress, 1.85 [95% CI, 1.06-3.25]). In COCOA both prenatal maternal depression and anxiety scores were positively related to the predicted probability of AD (P .001 in both). Prenatal distress decreased placental glutathione to glutathione disulfide ratios (P = .037) and, especially in those who later had AD, decreased placental 11β-hydroxysteroid dehydrogenase type 2 levels (P = .010) and increased IgE levels at 1 year of age (P = .005).Prenatal maternal depression and anxiety promote risk of AD in offspring. Maternal distress increases the predicted probability of AD. The mechanism might involve chronic stress, abnormal steroid levels, and reactive oxygen species.

Background: Autophagy, a cellular degradation process, has complex roles in tumourigenesis and resistance to cancer treatment in humans. The aim of this study was to explore the expression levels of autophagy-related proteins in patients with rectal cancer and evaluate their clinical role in the neoadjuvant chemoradiotherapy setting. Methods: All specimens evaluated were obtained from 101 patients with colorectal cancer who had undergone neoadjuvant chemoradiotherapy and curative surgery. The primary outcomes measured were the expression levels of two autophagy-related proteins (microtubule-associated protein 1 light chain 3 beta (LC3β) and beclin-1) by immunohistochemistry and their association with clinicopathological parameters and patient survival. Results: Among the 101 patients, the frequency of high expression of beclin-1 was 31.7% (32/101) and that of LC3β was 46.5% (47/101). A pathologic complete response was inversely associated with LC3β expression (P = 0.003) and alterations in the expression of autophagy-related proteins (P = 0.046). In the multivariate analysis, however, autophagy-related protein expression did not show prognostic significance for relapse-free survival or overall survival. Conclusions: High expression of autophagy-related proteins shows a strong negative association with the efficacy of neoadjuvant chemoradiotherapy in patients with rectal cancer. Autophagy has clear implications as a therapeutic target with which to improve the efficacy of neoadjuvant chemoradiotherapy. Citation Format: Yoon Ho Ko, Soon Uk Hong, Der Sheng Sun, Hye Sung Won, Myung Ah Lee, Byoung Young Shim. Role of autophagy-related protein expression in patients with rectal cancer treated with neoadjuvant chemoradiotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3533.

Pulmonary arteriovenous malformations are rare vascular anomalies of the lung, only a few cases of which have been diagnosed prenatally. The diagnostic clue for prenatal diagnosis was cardiomegaly with a particularly enlarged left atrium. All previous cases of pulmonary arteriovenous malformations diagnosed prenatally have been reported as an isolated anomaly or in association with simple heart defects. We here describe the first case of a pulmonary arteriovenous malformation with a complex heart defect that was diagnosed prenatally at 21.0 weeks of gestation and confirmed by postmortem autopsy.

We describe a case of absent aortic and pulmonary valves, diagnosed at 16.4 weeks of gestation. Fetal echocardiography showed cardiomegaly with dilated both ventricles. No valve leaflets were observed in the aorta and pulmonary artery, and a typical to-and-fro flow pattern was noted in both great arteries on color Doppler imaging. Fetal hydrops was also detected. Follow-up ultrasonographic evaluation at 19 weeks demonstrated intrauterine fetal death. Postmortem autopsy revealed the absence of both aortic and pulmonary valve leaflets. To the best of our knowledge, this is the earliest diagnosed case of absent both aortic and pulmonary valves and only the second case to be diagnosed prenatally.

We describe a case of an intrathoracic kidney combined with right congenital diaphragmatic hernia (CDH) that was diagnosed at 32 weeks of gestation. Although it has been well established that a right CDH shows a poorer outcome than a left CDH, our present case showed a good outcome because there was no herniation of other abdominal viscera, except for the right kidney. Our findings in this case indicate that impaction of the intrathoracic kidney may act as a 'shield' against further herniation of other abdominal viscera into the thoracic cavity.

Previous studies suggest that maternal characteristics may be associated with neonatal outcomes. However, the influence of maternal characteristics on birth weight (BW) has not been adequately determined in Korean populations. We investigated associations between maternal characteristics and BW in a sample of 813 Korean women living in the Seoul metropolitan area, Korea recruited using data from the prospective hospital-based COhort for Childhood Origin of Asthma and allergic diseases (COCOA) between 2007 and 2011. The mean maternal age at delivery was 32.3 ± 3.5 yr and prepregnancy maternal body mass index (BMI) was 20.7 ± 2.5 kg/m(2). The mean BW of infant was 3,196 ± 406 g. The overall prevalence of a maternal history of allergic disease was 32.9% and the overall prevalence of allergic symptoms was 65.1%. In multivariate regression models, prepregnancy maternal BMI and gestational age at delivery were positively and a maternal history of allergic disease and nulliparity were negatively associated with BW (all P < 0.05). Presence of allergic symptoms in the mother was not associated with BW. In conclusion, prepregnancy maternal BMI, gestational age at delivery, a maternal history of allergic disease, and nulliparity may be associated with BW, respectively.

To establish the reference range of intracranial translucency (IT) in the Korean population, and to evaluate whether Volume IT™ is a reliable technique for measuring IT.We retrospectively analyzed the IT of 93 singleton fetuses at 10.5 to 12.6 weeks of gestation using previously obtained three-dimensional volume data. The IT was measured manually and automatically using Volume IT™ in each fetus by one experienced and one beginner operator. We measured the IT values according to the crown-rump length and evaluated whether Volume IT™ can successfully measure the IT. Inter-observer agreement and intra-observer reproducibility were analyzed using the intraclass correlation coefficients (ICC), and the IT measurements obtained by the experienced operator using the manual and automated methods were then compared using the Bland-Altman plot and ICC.Among 93 cases, 2 were lost to follow-up after the first trimester scan and were excluded from further evaluation. Both operators identified the fourth ventricle in all 91 cases using Volume IT™. The experienced and beginner operators were able to measure the IT in 89 (98%) fetuses, with 4 and 13, respectively, requiring adjustments. The IT values increased with gestational age (correlation coefficient, r=0.491, P0.0001). Inter-operator agreement was moderate (ICC=0.580 for automated and 0.546 for manual measurements), and intra-operator reproducibility was highest for automated measurements by the experienced operator (ICC=0.944). Agreement of the IT values between the manual and automated methods was high (ICC=0.950).Our results provide the reference range of IT in the Korean population. The Volume IT™ may be a reliable technique for measuring IT.

Anemia is a common complication in dialysis patients because of their relative erythropoietin deficiency. Despite treatment with erythropoiesis-stimulating agents (ESAs), some patients experienced ESA hyporesponsiveness. We evaluated the clinical and laboratory factors that affect ESA hyporesponsiveness and investigated the relationships between hepcidin, inflammatory markers, and the iron profiles of hemodialysis patients. Sixty-eight patients receiving hemodialysis at a single institution were evaluated in a cross-sectional study. The patients were divided into tertiles based on the ESA hyporesponsiveness index (EHRI), defined as the weekly ESA dose per kilogram of body weight divided by the hemoglobin level. The mean EHRI values for each tertile were 3.3 ± 1.2 (T1), 10.2 ± 2.9 (T2), and 24.5 ± 11.6 (T3). The mean serum erythropoietin levels were significantly higher in the Q3 and Q4 groups. Thus, patients with ESA hyporesponsiveness showed relative resistance to erythropoietin therapy. In univariate and multivariate analyses, patients in the third tertile of EHRI showed significantly higher mean interleukin-6 (IL-6) levels. Serum C-reactive protein (CRP) levels showed a similar trend, but the differences were not significant. Serum hepcidin levels tended toward lower mean values in the third tertile of EHRI. No relationship was observed between hepcidin and inflammatory markers or iron status. In conclusion, IL-6, but not CRP, is a strong predictor of ESA hyporesponsiveness in hemodialysis patients who have sufficient iron. It may be difficult to use hepcidin as an independent clinical marker because of the many factors that influence it and their interactions.

Background: It is well known that Wnt/β-catenin signaling pathway is involved in hormone receptor negative breast cancer, especially triple-negative breast cancer. In the case of hormone resistant breast cancer cells, they rarely showed hormone receptor expression. So we aimed to investigate whether the β-catenin pathway becomes activated in endocrine-resistant breast cancer cells and inhibition of β-catenin pathway can overcome endocrine resistance. Methods: We have established an MCF-7-derived tamoxifen-resistant cell line (TamR) by long-term culture of MCF-7 cells with gradually increasing 4-hydroxytamoxifen concentration till 3μM. The levels of protein expression and mRNA transcripts were determined using western blot analysis and real-time quantitative PCR. The transcriptional activity of β-catenin was measured using luciferase activity assay. We used ICG-001 as inhibitor of β-catenin transcription activity. Results: The expression of estrogen receptor was significantly decreased in TamR cells. On the other hand, the expressions of HER2 and EGFR were increased in TamR cells than in control cells. The active (uncomplexed form) β-catenin level was increased in TamR cells, and also showed a significantly increased β-catenin transcriptional activity. The ICG-001, small-molecular inhibitor of Wnt/β-catenin pathway, treatment significantly reduced β-catenin transcriptional activity in TamR cells. The ICG-001 reduced cell viability fo TamR cells which showed resistance to tamoxifen by 65.3%, and also inhibited target gene cyclin D1 expression. The combination of ICG-001 and mTOR inhibitor, rapamycin reduced cell viability of TamR cells by 81.7% and there was an additive effect of two drugs as a combination index of 1.022. Conclusions: The β-catenin pathway is activated in endocrine-resistant breast cancer cells and inhibition of that pathway would be a new therapeutic strategy which overcomes endocrine resistance in breast cancer. Citation Format: Hye Sung Won, Kyoung Eun Lee, Eun Mi Nam, Yeung-Chul Mun, Chu-Myong Seong, Soon Nam Lee. Inhibition of β-catenin pathway to overcome endocrine resistance in tamoxifen-resistant breast cancer cell line. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B49.

The preventative value of progesterone in preterm labor has been recently recognized, especially when it is administered via vaginal suppository. This study was undertaken to evaluate the effect of progesterone on interleukin-6 (IL-6) production in human uterine cervical fibroblasts (UCFs) treated with lipopolysaccharides (LPS).Human uterine cervical tissue was obtained at term, prior to the onset of labor, during the scheduled cesarean section or cesarean hysterectomy. Primary UCF cultures were established and confirmed by immunohistochemistry. IL-6 mRNA and protein expressions were examined by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.Lipopolysaccharides stimulation induced a clear time- and dose-dependent increase in IL-6 mRNA and protein levels in UCFs (P0.05). Progesterone treatment significantly attenuated LPS-induced increases in IL-6 mRNA and protein expressions in UCFs (P0.05). Estrogen exposure had no effect on LPS-induced IL-6 up-regulation and did not modulate the effects of progesterone.Our preliminary results suggest that vaginal progesterone might prevent spontaneous preterm labor through a mechanism involving anti-inflammatory effects on UCFs, particularly suppression of IL-6 production.

Background A common side effect of oxaliplatin is peripheral neurotoxicity. Oxidative stress to dorsal root ganglion (DRG) may be one of important pathogenic mechanisms. Green tea contains four polyphenol catechins, which are known to be potent antioxidants. The present work is aimed to determine whether green tea extracts have neuroproective or palliative effects on neurotoxicity symptoms induced by oxaliplatin. Methods We conducted behavioral tests including sensory and thermal thresholds, an electrophysiological study, and TUNEL staining to assess neurotoxicity during the experimental period using animal models. Results A total of 14 adult rats were randomly allocated into two groups. Oxaliplatin (4 mg/kg) with or without green tea (300 mg/kg orally once daily) was administered intraperitoneally twice per week for 6 weeks. At 4 and 6 weeks after oxaliplatin administration, sensory threshold values were significantly decreased and at 6 weeks after oxaliplatin administration, thermal threshold values were significantly increased in oxaliplatin-treated rats compared with those in rat treated with oxaliplatin and green tea extracts. The electrophysiological assessment, including sensory nerve conduction and H-reflex-related sensory nerve conduction velocity, revealed no significant changes in the two groups. TUNEL staining showed no significant difference in the number of apoptotic-featured cells between the two experimental groups in the DRG or peripheral nerves, but the number of apoptotic-featured cells in DRG was higher than that in sciatic nerves within each group. Conclusions Green tea extracts may be a useful adjuvant to alleviate sensory symptoms after oxaliplatin administration, such as allodynia, but did not prevent morphometric or electrophysiological alterations induced by oxaliplatin.

Bevacizumab (Avastin(Ⓡ)) is a monoclonal antibody against the vascular endothelial growth factor (VEGF) receptor that increases the overall survival rate when added to standard chemotherapy regimens in patients with metastatic colorectal cancer. The known toxicities of bevacizumab are hypertension, proteinuria, wound healing complications, arterial thrombosis, bleeding, and gastrointestinal complications. Especially ischemic colitis can rapidly develop into bowel perforation, so an emergency operation often is needed. Recently, a 65-year-old male patient developed ischemic pancolitis after FOLFOX (85 mg/m(2) Oxaliplatin, d1; 200 mg/m(2) Leucovorin, d1; 400 mg/m(2) 5-FU iv bolus, d1-2; and 600 mg/m(2) 5-FU, d1-2, every two wk) and Bevacizumab combination chemotherapy was administered. However, he recovered after early conservative care without surgery. We report this case with a review of literature.

Background/Aims The purpose of this study was to investigate the malignant potential of aberrant crypt foci (ACF) by measuring the multiplicity of crypts and lectin expression in the early and late stages of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Methods Six-week-old Wistar rats were injected subcutaneously with DMH for 27 weeks. We classified ACF according to the number of crypts per ACF as a few crypts (≤3 crypts, FC ACF) or numerous crypts (≥4 crypts, NC ACF). Immunohistochemistry was used to evaluate lectin expression. Results In the early stage, FC ACF (590/1,902, 31.0%) occurred more frequently than NC ACF (35/449, 7.8%); whereas in the late stage, NC ACF (176/449, 39.2%) occurred more frequently than FC ACF (324/1,902, 17.0%). The number of ACF peaked at 15 to 20 weeks. The ratio of NC/FC ACF increased gradually during carcinogenesis. The expression of both UEA1 and PNA was higher in NC ACF than FC ACF. Lectin expression increased in the late stage compared with the early stage. Conclusions The expression of lectin was higher in NC ACF and ACF in the late stage. Therefore, ACF with higher multiplicities in the late stage may have more malignant potential in DMH-induced colon carcinogenesis.

Urotensin-II (UTS-II) may be associated with preeclampsia. We therefore assessed whether the UTS-II 143 G/A polymorphism is associated with preeclampsia in Korean women.This prospective case-control study enrolled 109 patients with preeclampsia and 144 healthy pregnant controls, all of whom were genotyped for the UTS-II 143 G/A polymorphism using the real-time TaqMan SNP Genotyping Assay.There was no significant difference in the distribution of the 143 G/A polymorphism or the frequency of the 143 A allele between women with preeclampsia and controls. In a dominant model, carriers of the A allele were not significantly more prevalent in the preeclamptic (53.2%) than in the control (60.4%) group. In addition, subgroup analysis showed no significant difference in genotype distribution or allelic frequency of the 143 G/A polymorphism between women with mild or severe preeclampsia and controls.In Korean women, the common UTS-II 143 G/A polymorphism is unlikely to have an association with the risk of preeclampsia.

Introduction Smooth muscle tumors of uncertain malignant potential represent a histologically heterogeneous group of uterine smooth muscle tumors that cannot be diagnosed as either benign or malignant. Smooth muscle tumors of uncertain malignant potential are usually clinically benign, but should be considered tumors of low malignant potential because they can occasionally recur or metastasize to distant sites. Case presentation We report the case of a 62-year-old Mongol woman diagnosed with a retroperitoneal smooth muscle tumor of uncertain malignant potential and lung metastasis, with a history of prior hysterectomy. The case was initially misdiagnosed as retroperitoneal sarcoma, and our patient received chemotherapy. However, no interval change in the size of the retroperitoneal mass and metastatic lung nodules was seen over a period of at least five years. She underwent partial resection of the retroperitoneal mass for the purposes of debulking and establishing a histopathological diagnosis. The diagnosis of the retroperitoneal mass was then confirmed as a smooth muscle tumor of uncertain malignant potential. Conclusion Smooth muscle tumors of uncertain malignant potential have an unpredictable clinical course, and relapses generally appear to occur after a long disease-free interval of up to several years. Therefore, patients diagnosed with smooth muscle tumors of uncertain malignant potential should receive long-term follow-up.

Congenital left ventricular aneurysm (CVA) is a rare cardiac malformation. The prognosis is variable, depending on such factors as the size in comparison to the ventricular cavity, signs of heart failure, arrhythmia and so on. Most infants and young children with large aneurysm showed poor clinical outcomes. Here, we report the case of patient who was prenatally diagnosed with a large CVA, who had severe left ventricular dysfunction at 21 weeks' gestation for which she successfully underwent a modified Damus-Kaye-Stansel/Dor procedure.

Background Biliary tract cancers have limitations in information about different location-related pathogenesis and clinico-pathological characteristics. The goal of this study was to investigate anatomical site-related similarities and differences in biliary tract cancers and to assess the expression and clinical significance of functional proteins such as p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1. Methods One hundred and sixty-one patients with biliary tract adenocarcinomas, who underwent curative or palliative surgery in a single institution between October 1994 and December 2003 were evaluated, retrospectively. The level of protein expression of p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1 was assessed by immunohistochemistry. Results With respect to clinico-pathological characteristics, gallbladder cancer was more frequent in women, and bile duct cancer was more common in men. Perineural invasion was more common in bile duct cancer. Recurrence as a distant metastasis was more common in gallbladder cancer. Immunohistochemical analysis revealed that thymidine phosphorylase expression was significantly higher in gallbladder cancer than in bile duct cancer. Positive thymidine phosphorylase and p53 staining were associated with an advanced stage. Differentiation, vascular invasion, perineural invasion, lymphatic invasion, lymph node metastasis, and TNM stage independently predicted poor prognosis in biliary tract cancer. These correlations were seen more clearly in gallbladder cancer. The immunohistochemical staining patterns of p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1 showed no prognostic significance in biliary tract cancers. Conclusions We concluded that gallbladder and bile duct cancers are considered to be separate diseases with different clinico-pathological characteristics and prognostic factors. In addition, we hypothesize that high expression of thymidine phosphorylase by gallbladder cancer results in a higher response rate to capecitabine by gallbladder cancer than bile duct cancer.

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m(2) in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m(2) and 5-fluorouracil (5-FU) 400 mg/m(2) as a bolus followed by 600 mg/m(2) as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.

Aim: Primary adenocarcinoma of the appendix is a rare malignancy. This study assessed prognostic factors affecting the clinical outcome in patients with appendiceal neoplasms. Methods: We performed a retrospective analysis of patients who had appendectomies between 1991 and 2007 at five centers in South Korea. Results: Overall 55 patients (19 men, 36 women, median age 61 years) were identified. Of these, 37 (67.3%) were mucinous adenocarcinomas, 14 (25.5%) were intestinal-type adenocarcinomas, and four (7.3%) were signet ring cell carcinomas. The distribution of stages was: 26 (47.3%) with localized disease, five (9.1%) with regional disease, and 24 (43.6%) with distant metastatic disease. The overall 3- and 5-year survival rates among all patients were 72.2% and 64.0%, respectively, with 20 deaths during the follow-up period. In a multivariate analysis, high histological grade (hazard ratio [HR]vs low grade 15.7; P = 0.001) and pathological stage (distant vs loco-regional, HR 6.2; P = 0.021) were independent predictors of overall survival. Of the 34 patients who underwent curative resections of primary appendiceal carcinomas, the 3- and 5-year disease-free survival rates were 66.4% and 53.3%, respectively. The recurrence rate was higher in patients with regional lymph node metastasis (HR vs node negative disease 23.4; P = 0.005) and high-grade tumors (HR vs low grade 6.3; P = 0.029). Additionally, a right hemicolectomy reduced the risk of recurrence (HR vs lesser procedures 0.05; P = 0.005). Conclusion: High tumor grade and advanced stage were significantly predictive of poor survival outcome in patients with primary appendiceal carcinomas.

We describe a rare conjoined twinning at 9 weeks of gestation. We compared the results of two- and three-dimensional sonography with autopsy findings after the termination of pregnancy. These results showed a thoracoomphalopagus with a shared heart and visceral organs. Three-dimensional sonog- raphy showed anencephaly in one of the embryos. Early and accurate prenatal diagnosis of this type of conjoined twins using three-dimensional sonography is critical for both parental counseling and minimizing maternal morbidity. V C 2010 Wiley Periodicals, Inc. J Clin Ultrasound 39:279-282, 2011; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jcu.20774

Background: Congenital heart disease (CHD) is the most common developmental malformation and the leading cause of neonatal mortality and morbidity. The introduction of fetal echocardiography has made prenatal diagnosis of CHD possible. Objective: This study was conducted to investigate the impact of fetal echocardiography on the changing disease patterns and outcomes of CHD. Methods: A retrospective analysis of data from infants with CHD admitted to the neonatal intensive care unit (NICU) of the Asan Medical Center during the time periods was performed. Period I (1994–1996) was considered representative of a period before the introduction of fetal echocardiography, while period II (2004–2006) represented a period of more extensive application of fetal echocardiography. Results: A total of 164 patients were admitted to the NICU during period I and 320 during period II. The number of infants prenatally diagnosed with CHD was 5 of 164 (3.0%) in period I and 219 of 320 (68.4%) in period II (p < 0.05). The overall accuracy of fetal diagnosis was approximately 92%. Of the 3 CHD categories, there was a greater proportion of infants with ‘significant’ heart disease in period II than I (47 vs. 32%; p < 0.05). In contrast, there was a smaller proportion of infants with ‘simple’ heart defects in period II than I (22 vs. 40%; p < 0.05). The proportion of infants with ‘complex’ heart disease was similar in both periods (28% in period I and 31% in period II). The 1-year survival rate of patients with CHD has improved remarkably with time (70.1% in period I to 88.8% in period II). Multivariate analysis showed prenatal diagnosis and planned delivery in a tertiary NICU are factors affecting CHD outcomes, especially when defects are ‘complex’ (p < 0.01). Conclusion: Fetal echocardiography has resulted in an increased frequency of prenatal CHD diagnosis, has altered the disease patterns observed in the NICU, and has resulted in better 1-year outcomes.

Primary adenocarcinoma of the appendix is a rare malignancy that constitutes < 0.5% of all gastrointestinal neoplasms. Moreover, primary signet ring cell carcinoma of the appendix is an exceedingly rare entity. We have encountered 15 cases of primary appendiceal cancer among 3389 patients who underwent appendectomy over the past 18 years. In the present report, we describe a rare case of primary signet ring cell carcinoma of the appendix with ovarian metastases and unresectable peritoneal dissemination occurring in a 67-year-old female patient. She underwent appendectomy and bilateral salpingo-oophorectomy with a laparoscopy procedure. She then received palliative systemic chemotherapy with 12 cycles of oxaliplatin, 5-flurorouracil, and leucovorin (FOLFOX-4). The patient currently is well without progression of disease 12 mo after beginning chemotherapy.

Background Meconium peritonitis is a sterile chemical peritonitis resulting from intrauterine bowel perforation. With the development of neonatal care, the prognosis of meconium peritonitis improved much. We report our clinical experience. Methods The medical records of patients with meconium peritonitis admitted to the Asan Medical Center from June 1989 to July 2006 were retrospectively reviewed. Results Of 41 patients (17 males, 24 females), 38 (92.7%) were suspected to suffer from meconium peritonitis prenatally, at a median gestational age of 32 weeks (range, 21-40 weeks). The most common prenatal sonographic finding was fetal ascites followed by dilated bowel. Ten patients were managed conservatively, but 31 patients underwent operations including resection and anastomosis (22), drainage procedure (4), ileostomy (3) and primary repair (2). The operative 31 cases comprised generalized (16), fibroadhesive (10), and cystic types (5). The main causes were intestinal atresia and idiopathic bowel perforation. The mortality rate was 2.4%, and the morbidity rate was 34.1%. Conclusions Good survival rate was achieved. But there was rather high morbidity. More gentle and delicate approach should be done to lower the morbidity.

The aim of this study was to assess the relationship between prenatally diagnosed nonrefluxing hydronephrosis and urinary tract infection.We reviewed patients who were born at our institution between March 1989 and February 2006. Those who were diagnosed with fetal hydronephrosis confirmed on postnatal sonography were enrolled in the study. Hydronephrosis was graded according to the Society for Fetal Urology classification. Obstructive uropathy was diagnosed with (99m)technetium mercaptoacetyltriglycine renal scan and clinical courses. Voiding cystourethrography was done to exclude patients with vesicoureteral reflux. The prevalence of urinary tract infection was checked at 1-year followup.A total of 430 patients without reflux were enrolled in the study. Male-to-female ratio was 351:79. Urinary tract infection developed in 83 patients (19%), with first infection occurring at age 4.1 +/- 2.7 months overall and before age 6 months in 70 patients (84% of subgroup). Frequency of urinary tract infection was 1.4 +/- 0.7 (range 1 to 4) episodes during the first year. Urinary tract infection developed in 50 of 128 patients with obstructive uropathy (39%), compared to 33 of 302 patients without obstructive uropathy (11%, p0.001). High grade hydronephrosis was associated with an increased incidence of urinary tract infection-38 of 96 patients (40%) with grade IV hydronephrosis had urinary tract infection, compared to 26 of 79 (33%) with grade III, 13 of 94 (14%) with grade II and 6 of 161 (4%) with grade I disease (p0.001). Urinary tract infection occurred more frequently in patients with vs without hydroureter (37 of 78, or 47%, vs 46 of 352, or 13%; p0.001).Neonates with obstructive uropathy, severe hydronephrosis or hydroureteronephrosis have increased risk of urinary tract infection even without reflux, and antibiotic prophylaxis may be recommended.

Objective To evaluate the clinical implication of isolated right dominant heart (RDH) in fetal echocardiography. Study design We reviewed the medical records of pregnant women diagnosed with fetal RDH at Asan Medical Center from December 1999 to December 2005. The criteria of RDH were the ratio of right-to-left atrial and ventricular width and the ratio of the diameter of pulmonary artery-to-aorta were greater than 1.5. Fetuses with congenital heart disease, including coarctation of the aorta (CoA), noncardiac anomalies or chromosomal abnormalities were excluded. Results RDH was identified in 44 fetuses. Twenty-nine (66%) were confirmed to have normal heart and 15 (34%) had cardiac anomalies by postnatal echocardiogrphy; 11 CoA, 1 interruption of aortic arch, 1 patent ductus arteriosus, and 2 ventricular septal defect. Mean gestational age at presentation with RDH was later in normal fetuses as compared to fetuses with CoA (p < 0.005). Only 26% (4/15) of fetuses presenting with RDH during the second-trimester were found to have normal heart postnatally, compared with 86% (25/29) of those diagnosed in the third-trimester. Conclusion RDH in the fetus is a risk factor for postnatal CoA particularly when diagnosed in the second-trimester, and should be an indication for neonatal echocardiography. Copyright © 2007 John Wiley & Sons, Ltd.

Despite the good survival rate of fetuses with gastroschisis, the length and cost of hospitalization for surgically repaired gastroschisis are high. In gastroschisis, prolonged exposure of the intestine to amniotic fluid (AF) containing intestinal waste products results in intestinal damage, including intestinal wall thickening and fibrous peel formation. The deleterious effects of AF on gastroschisis can be prevented by lowering the concentration of intestinal waste products. We describe the treatment of a case of fetal gastroschisis by repeated AF exchange and infusion. Following repeated, successful transabdominal AF exchange and infusion, the concentrations of various intestinal waste products were decreased. AF exchange and infusion may prevent intestinal damage and improve postnatal outcome in gastroschisis by diluting the AF, probably by lowering the concentrations of intestinal waste products.

Meconium peritonitis (MP) is a chemical peritonitis, and little is known about its natural history. Below we report MP in both fetuses from a twin pregnancy, with identical clinical ultrasonographic findings but a delay in presentation.A 31-year-old woman with a twin pregnancy was referred to our institution due to fetal bowel dilatation and ascites. Serial ultrasonography demonstrated gradual but dynamic changes. Both infants were delivered at 29 weeks'gestation. The larger infant had type II MP and experienced more postoperative complications and longer ventilatory care, parenteral nutrition and hospital stay than the smaller one, who had type III MP.The type of MP at birth may be more important than birth weight in terms of neonatal morbidity. This case increases our understanding of the natural history and prognosis of MP.

OBJECTIVE: The purpose of this study was to evaluate potential associations between vascular endothelial growth factor (VEGF) gene polymorphisms and preeclampsia. STUDY DESIGN: One hundred ten patients with preeclampsia and 209 healthy pregnant control subjects were enrolled in the study. After peripheral blood was obtained from all women and the genomic DNA was isolated, we genotyped 936C/T polymorphisms in the 3=-untranslated region of the VEGF gene, using polymerase chain reaction and restriction fragment length polymorphism techniques. RESULTS: The distribution of genotypes of the 936C/T polymorphism was significantly different between women with preeclampsia and the control group (P .001). Carriage of the 936T allele was significantly more frequent in preeclamptic patients than in control subjects (odds ratio, 2.06; 95% CI,1.38-3.08). Logistic regression analysis on VEGF genotype and clinical parameters such as age, educational status, body mass index, and neonatal gender showed carriage of the 936T allele to be significantly more frequent in preeclamptic patients than in control subjects (adjusted odds ratio, 2.23; 95% CI, 1.46‐3.42). CONCLUSION: Carriage of the 936T allele of the VEGF gene may be associated with increased susceptibility to the development of preeclampsia and may be an independent risk factor for preeclampsia.

e11530 Background: It is well known that Wnt/β-catenin signaling pathway is involved in hormone receptor negative breast cancer, especially triple-negative breast cancer. In the case of hormone res...

To estimate the effect of vesicoamniotic shunting using a double-basket catheter on treating fetal bladder outlet obstruction.A retrospective study involving 8 prenatally diagnosed bladder outlet obstruction cases that underwent vesicoamniotic shunt placement using a double-basket catheter from 1998 to 2004. Patients were followed-up for prenatal and neonatal outcome analyses.Vesicoamniotic shunting was performed in 8 fetuses aged between 13.7 and 25.4 weeks' gestation (mean+/-SD, 19.7+/-3.5 weeks). Final diagnoses included 5 posterior urethral valves, 1 cloacal anomaly, 1 urethral stenosis, and 1 unknown. There were no maternal complications associated with the procedures. One woman diagnosed as having a fetus with posterior urethral valves decided to terminate her pregnancy and one fetus died in uterus spontaneously. Six women delivered live babies, and one baby required postnatal ventilatory support. Postnatal follow-up ranged from 3 to 60 months. Of the 6 newborns, 4 survived with normal renal function, 1 had renal insufficiency, and 1 died of renal failure at 3 months of age.Vesicoamniotic shunt placement using a double-basket catheter may be effective in improving perinatal and neonatal outcomes through long-term decompression of the fetal urinary tract in carefully selected cases.

This study was undertaken to describe the results of angiographic embolization for obstetrical hemorrhage and the follow-up outcome of fertility.Consecutive patients who received angiographic embolization for the management of obstetrical hemorrhage at a single tertiary center were included in this study. Medical records were reviewed to collect the clinical data and details on the procedure. Patients were interviewed by telephone to obtain the long-term outcomes for complications, menstruation, desire for conception, and subsequent pregnancies.Embolization was successful in 42 (86%) of 49 patients with obstetrical hemorrhage resulting from various causes. The main cause of hemorrhage was uterine atony (n=24). The success rate was significantly lower in cases with abnormal placentation than in other causes of hemorrhage (p0.05). The procedure took an average of 45.6 min (range, 20-120 min). There were no major complications related to the procedure. We were able to follow-up 48 patients. Among 37 patients with preserved uteri, menstruation resumed spontaneously in 36 patients. Nine patients became pregnant, of which six gave birth to healthy babies and three ended in early miscarriage.Angiographic embolization is an effective noninvasive method for the management of obstetrical hemorrhage and a useful technique for preserving fertility.

Bladder outlet obstructions are a diverse and heterogeneous group of developmental abnormalities that generally involve obstruction of the proximal urethra in the male fetus. Indications for prenatal intervention are few and are usually restricted to the male fetus because bladder outlet obstruction in female fetuses is usually caused by complex cloacal development anomalies. We report on a female fetus with an enlarged bladder and a dilated proximal urethra (known as typical keyhole sign). A vesicoamniotic shunt was performed despite non-reassuring prognostic factors, but the procedure resulted in a successful outcome. We propose that in selected cases of bladder outlet obstruction, fetal intervention should be considered even when the fetus is female.

A 33-year-old multigravida was referred to our fetaltreatment center for early oligohydramnios at 11+2weeksof gestation. The examinations were performed using anAccuvix XG (Samsung Medison Co., Ltd, Seoul, Korea) with a2 to 6MHz transabdominal probe. The fetal size was compatiblewith the gestational age (crown –rump length (CRL): 45.4mm).Ultrasound showed IT enlargement of 3mm. We could notmeasure the nuchal translucency (NT) because of the smallamniotic sac. Follow-up ultrasound at 13+0weeks of gestationrevealed that the CRL was 71.7mm, the IT was still enlarged(3.7mm), and micrognathia was suspected (Figure 1). Theamniotic sac was becoming larger, and the NT was normal(1.1mm). Two weeks later, we performed amniocentesis forkaryotyping,andwhichyieldedanormalresult(46,XY).Thepatient was lost to follow-up until 23+2weeks of gestation.Ultrasonography showed hypoplasia of the cerebellar inferiorvermis without marked enlargement of the posterior fossa(Figure 2). No other abnormality of the central nervous systemwas observed. Retrognathia rather than micrognathia wassuspected. We counseled the parents regarding the prognosisand they decided to continue the pregnancy. Follow-upultrasound at 31+2weeks of gestation demonstrated the samefindings. The male infant was delivered vaginally at 39+0weeksof gestation, and bilateral cleft palates with retrognathia werenoted. Postnatal brain magnetic resonance imaging showedmild hypoplasia of the inferior cerebellar vermis with normalposterior fossa. The baby was doing well when seen for theone-month follow-up.

Twin pregnancy consisting of complete hydatidiform mole (H-mole) and a coexisting fetus occurs with an estimated incidence of 1 per 22,000–100,000 pregnancies. The incidence of this unusual twin pregnancy with complete H-mole and a coexisting fetus after in vitro fertilization and embryo transfer (IVF–ET) is not thought to be greater than that of general population. We present an unusual twin pregnancy with complete H-mole and a coexisting fetus that occurred following IVF–ET, which was terminated at 21 weeks of gestation and developed into nonmetastatic gestational trophoblastic tumor.