Tze-Ho Chen

A recurrent ITGA9 missense mutation in human fetuses with severe chylothorax: possible correlation with poor response to fetal therapy

To assess the possible correlations between the reported candidate genes (VEGFR3, FOXC2, ITGA9 and ITGB1) and the clinical response in fetuses with severe congenital chylothorax (CC) treated by prenatal OK‐432 pleurodesis.

Comparison of Immunohistochemical and Fluorescence In Situ Hybridization Assessment for HER-2/neu Status in Taiwanese Breast Cancer Patients

OBJECTIVE Accurate diagnostic assessment of human epidermal growth factor receptor-2 (HER-2) is essential and a prerequisite for appropriate application of the humanized anti-HER-2 monoclonal antibody trastuzumab (Herceptin) to the treatment of patients with breast cancer. Immunohistochemistry (IHC) is the most widely applicable diagnostic modality in studying HER-2 status. Fluorescence in situ hybridization (FISH) is also recognized as a modality in cases with an equivocal IHC status (score, 2+). Some authors claimed that FISH alone is sufficient. The aim of this study was to correlate the test results of IHC and FISH for HER-2 gene amplification in breast cancer patients. FISH for topoisomerase IIalpha (TOP2A) was also studied to see if deletion or amplification of TOP2A has any supplementary role to HER-2, FISH and IHC. MATERIALS AND METHODS Assessment of HER-2 gene amplification and TOP2A gene amplification/deletion was made by FISH analysis using the LSI TOP2A/HER-2/CEP 17 multicolor probe or the LSI HER-2/CEP dual color probe (Vysis, Downers Grove, IL, USA) in formalin-fixed and paraffin-embedded tissue sections of 54 breast cancer patients who were grouped into stages 1+, 2+ or 3+ based on IHC (HercepTest; DakoCytomation, Carpinteria, CA, USA) observations. RESULTS None of IHC 1+ breast tumors was HER-2 FISH positive, but three of 18 (17%) IHC 3+ tumors were HER-2 FISH negative. Overall, 53% of the IHC 2+ and 83% of the IHC 3+ cases were HER-2 FISH positive. Only one case with IHC 3+ tumor that was HER-2 FISH positive was found to have TOP2A amplification (>2.0) and no IHC 2+ cases were found to have TOP2A amplification. There were no cases with TOP2A deletion (<0.8) in our whole series. There were also no cases of HER-2 FISH negative tumors, but IHC scored as 2+ or 3+ (0 of 10), to be found with TOP2A amplification. The discordance rates by IHC were high (46.7% in IHC 2+, 16.7% in IHC 3+, 30.3% overall in IHC 2+ or 3+). On the contrary, the discordance rates were zero if by FISH. CONCLUSION The current algorithm to use HER-2 FISH as a supplementary role to IHC HercepTest 2+ may need some modifications according to the local setting. TOP2A FISH adds little value to HER-2 FISH and IHC staining in our study.

Ruptured Corpus Luteum with Hemoperitoneum: Case Characteristics and Demographic Changes Over Time

OBJECTIVE Women of reproductive age are at risk of ruptured corpus luteum with hemoperitoneum. We identified the clinical and demographic features of patients recently treated in our institution and compared the findings with those from an earlier series, to detect any changes in disease identity that have occurred over the past 20 years. MATERIALS AND METHODS Charts of patients treated between January 2001 and December 2003 at Changhua Christian Hospital were reviewed. Clinical parameters were compared with those from our previous study in the 1980s. RESULTS A total of 91 women were diagnosed with ruptured corpus luteum and hemoperitoneum (mean age, 26 years; range, 15-42 years). Most ruptures (60.4%) occurred during the secretory phase and most women (57.1%) reported recent sexual intercourse prior to the onset of pain. Most patients (81.3%) required laparoscopic intervention to achieve hemostasis. No obvious differences were found between the results of this study and those from the 1985 series, except that our patients were younger, were more often unmarried, chose laparoscopic interventions rather than laparotomy, and that there was an emerging trend towards conservative treatment. CONCLUSION The manifestations of corpus luteum hemorrhage in this study were similar to those observed in the 1980s at the same medical center. However, the demographic parameters (age, marital status) and the modalities of treatment (conservative treatment, mode of surgical interventions) had changed in line with the evolution of society, culture, and the progress of medical science over the past 20 years.

A case of restrictive dermopathy with complete chorioamniotic membrane separation caused by a novel homozygous nonsense mutation in the ZMPSTE24 gene.

A Case of Restrictive Dermopathy With Complete Chorioamniotic Membrane Separation Caused by a Novel Homozygous Nonsense Mutation in the ZMPSTE24 Gene Ming Chen, Hsiang-Hsu Kuo, Yi-Chen Huang, Yu-Yuan Ke, Shun-Ping Chang, Chih-Ping Chen, Dong-Jay Lee, Meng-Luen Lee, Mei-Hui Lee, Tze-Ho Chen, Chia-Hsiang Chen, Hui-Mei Lin, Chin-San Liu, and Gwo-Chin Ma* Department of Genomic Medicine, Changhua Christian Hospital, Changhua, Taiwan Department of Medical Research, Changhua Christian Hospital, Changhua, Taiwan Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan Department of Obstetrics and Gynecology, Puli Christian Hospital, Nantou, Taiwan Department of Pediatrics, Puli Christian Hospital, Nantou, Taiwan Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan Department of Neurology, Vascular Biology and Genomics Center, Changhua Christian Hospital, Changhua, Taiwan Institute of Biochemistry and Biotechnology, Chung-Shan Medical University, Taichung, Taiwan

Management of Oligohydramnios with Antepartum Amnioinfusion, Amniopatch and Cerclage

Summary Objective To evaluate the efficacy and safety of aggressive management of oligohydramnios. Methods Forty women with oligohydramnios ( Results Nine of the 11 patients prolonged their pregnancy for at least 3 weeks (81.8%), while all 29 patients in the control group delivered their babies within 3 weeks of diagnosis of oligohydramnios (p Conclusion Aggressive management seemed to provide prolongation of pregnancy compared with no treatment. Amniopatch salvaged the immediate amniorrhea in our patient.

Cardiac Tamponade: An Alternative Procedure for Late Feticide

OBJECTIVE Improvements in equipment and diagnostic skills mean that more abnormalities can now be detected antenatally, thus increasing the demand for pregnancy termination at later stages of gestation. Potassium chloride injected into the fetal circulation is the most frequently used procedure. In this study, we propose a new method of feticide using injection of normal saline into the fetal pericardial space to induce cardiac tamponade, resulting in late fetal reduction with minimal maternal risk. CASE REPORT A 32-year-old, gravida 6, woman was a carrier of a balanced translocation 45,XX,der(2),t(2,22), and had a poor obstetric history. Chorionic villus sampling was performed, and the results revealed the fetus to be a balanced translocation carrier, like the mother. Microcephaly was detected during the third trimester and amniocentesis was performed. The results showed a 45,XX,der(2)t(2;22)(q37,q11.2)mat,-22 karyotype. After counseling, the mother elected to undergo pregnancy termination. Feticide was performed before labor induction. However, she experienced discomfort when a minimal amount of potassium chloride (3 mEq) was injected into the fetal heart, without inducing fetal asystole. We, therefore, induced cardiac tamponade using 10 mL of normal saline instilled into the fetal pericardial space. Fetal asystole was noted. The whole procedure was performed without incident, and termination was achieved by hysterotomy after informed consent was given. CONCLUSION Many methods of feticide have been used, including injection of potassium chloride, lidocaine, digoxin or hyperosmolar urea into the fetal circulation. However, these methods all use medications or compounds with some potential for maternal toxicity or side effects. We provide a relatively safe and effective method of feticide for use in late termination of pregnancy.

Puerperal Pelvic Hematoma Successfully Treated by Primary Transcatheter Arterial Embolization

The incidence of puerperal hematomas ranges from 1 in 300 to 1 in 1,000 deliveries [1]. Episiotomy is the most common risk factor for puerperal hematomas. Other risk factors include operative vaginal deliveries, extensive birth tract lacerations, primiparity, a prolonged second stage, and coagulopathy [2]. Puerperal hematomas may be classified as vulvar, vulvovaginal or retroperitoneal. When the torn vessel lies above the pelvic diaphragm, the hematoma that develops can cause massive retroperitoneal bleeding and can be fatal without emergent treatment. Transcatheter arterial uterine artery embolization was first reported as a treatment for postpartum hemorrhage in 1979 [3]. This interventional radiologic procedure has been used in previous decades for the control of obstetric hemorrhage caused by uterine atony, birth tract injuries and placenta accrete when first-line treatment fails. A relatively high success rate with few complications has been reported, and fertility seems to be preserved [4]. Here, we report a case of life-threatening puerperal hematoma treated primarily and successfully by transcatheter arterial uterine artery embolization. A 29-year-old, gravida 2, para 1, woman at term gestation visited our delivery unit because of spontaneous active labor with 3-cm cervical dilatation at arrival. Her obstetric history included one uneventful term vaginal delivery. The course of this pregnancy was uncomplicated. She had no coagulopathy or previous surgery. The cervix proceeded to full dilation in 4 hours. She spontaneously delivered a live male infant weighing 3,400 g following midline episiotomy and second-degree perineal laceration. The placenta was delivered smoothly, and the perineal wound was repaired by layers. There was good uterine contraction, and only a small amount of lochia was noted. Two hours after the delivery, the patient complained of aggravating pelvic pain and cold sweating. Her pulse rate rose to 110–120 beats/minute, and her blood pressure dropped to 90/50 mmHg. A tense, large hematoma at the right upper vaginal wall was found via pelvic examination. A right lower abdominal tender mass was also palpable, which pushed the uterine fundus upwards and left. Aggressive fluid supplementation was given owing to suspected vaginal hematoma extending to the right retroperitoneal pelvis with hypovolemia. After consulting the radiologist, emergent angiography was carried out. Pelvic angiography via right femoral arterial puncture was performed uneventfully. Preliminary bilateral internal iliac arteriography showed contrast extravasation at the right vaginal artery territory (Figure 1A). The catheter was advanced into the right vaginal artery, and transarterial embolization was then performed by injection of large Gelfoam pieces mixed with cefazolin until stasis of vascular flow (Figure 1B). The whole procedure took about 70 minutes, and the patient tolerated it well without complications. Her vital signs became stable, and her pelvic pain was partially relieved to a tolerable level. A transfusion of 2 units of packed red blood cells was given, as her hemoglobin level dropped from 12.3 g/dL before delivery to 9.3 g/dL 2 hours after transarterial embolization. Magnetic resonance imaging was arranged 2 days later. This showed a lobulated hematoma on the right side of the pelvic region, extending from the right side of the perirectal fossa to the right paravesical space and the prevesical fossa region, about 15 × 7 × 11 cm in size (Figure 2). Further drainage of the hematoma was cancelled, because the patient remained hemodynamically stable without significant pain or fever. The postpartum course was otherwise unremarkable, and she was discharged 2 days later. Except for mild right PUERPERAL PELVIC HEMATOMA SUCCESSFULLY TREATED BY PRIMARY TRANSCATHETER ARTERIAL EMBOLIZATION

Differential expression of NUDT9 at different phases of the menstrual cycle and in different components of normal and neoplastic human endometrium.

OBJECTIVE The human endometrium manifests different and distinct morphologies and physiologies during the different phases of the menstrual cycle. We aimed to determine which candidate genes demonstrate differential expression patterns in the endometrium during different phases of the menstrual cycle. MATERIALS AND METHODS Using differential display reverse transcription polymerase chain reaction to compare day 5 and day 18 human glandular endometrium obtained by laser capture microdissection, we identified a specific gene, NUDT9 (nucleoside diphosphate-linked moiety X motif 9). NUDT9 is known to function as a highly specific adenosine diphosphate ribose pyrophosphatase and has been mapped to chromosome 4q22.1. It gives rise to two alternatively spliced messenger RNAs, NUDT9alpha and NUDT9beta, encoding a member of the Nudix hydrolase family. In this study, we purified NUDT9 protein and produced an antibody, which we then used for immunohistochemical studies. RESULTS Using this anti-NUDT9 antibody, we successfully demonstrated that NUDT9 protein was differentially expressed in endometrial glandular cells at different phases of the menstrual cycle. NUDT9 was also found to be expressed more prominently in the epithelial glandular component than in the stromal component of human endometrial carcinomas. CONCLUSION We suggest that NUDT9 may be involved in the regulation of the menstrual cycle and may be related to the proliferation of glandular cells in the human endometrium.

Late Termination of Pregnancy: Experience From an East Asian Population and Report of a Novel Technique for Feticide

We report our experience of late feticide in Taiwan as well as a novel technique, fetal cardiac tamponade, which can be used in the late termination of pregnancy. Twenty-six patients who elected to undergo feticide were enrolled in this study (among 40 pregnancies with fetal abnormalities diagnosed late in gestation during 2005–2008 in a tertiary referral center in Taiwan). The fetal abnormalities in these patients included structural malformations and/or genetic defects. This study conformed strictly to the regulation of law and was approved by the Institutional Review Board/Ethics Committee of the Changhua Christian Hospital. Two methods were used to perform feticide: intracardiac injection of potassium chloride (6 mmol) and intracardiac injection of lidocaine (10 mL in 2% preparation). If fetal asystole was not achieved 3 minutes after initial injection, fetal cardiac tamponade was then performed by instilling normal saline into the fetal pericardium. Permanent cessation of fetal heart activity was regarded as successful feticide. The gestational age of the feticide group ranged from 24 to 38 weeks (mean, 30.85 ± 3.77 weeks). The body weight of the aborted fetuses ranged from 675 g to 2,860 g (mean, 1,618.1 ± 590.7 g). The use of lidocaine was successful in six of the seven cases (85.7% success rate). The use of potassium chloride was successful in 11 of the 19 cases (57.9% success rate). Fetal cardiac tamponade as a salvage technique was performed in nine cases, including eight cases in which pumping of the fetal heart resumed following potassium chloride administration and in one case when lidocaine alone failed to achieve permanent cessation of fetal heart activity. The success rate of fetal cardiac tamponade as a salvage technique was therefore 100%. No maternal complications were noted in our series. Fetal cardiac tamponade is a useful and safe supplementary technique in late feticide when cardiac depressing agents fail to cease fetal cardiac activity.

Antenatally Ultrasound-impressed Placenta Percreta Complicated with Massive Hemorrhage Despite a Combinational Arterial Embolization and Two-stage Surgery

Morbidly adhered placentas include the spectrum of accreta, increta, and percreta. Abnormal placentation carries a significant risk of hemorrhage when late in gestation especially at peripartum. Many measures including extirpative surgery, selective arterial embolization, and methotrexate have been proposed either as a single method or in combination in the literature. We report a woman with placenta percreta who suffered from massive hemorrhage despite being treated with two-stage surgery plus intervening prophylactic uterine artery embolization. Classical incision at cesareans followed by selective uterine artery embolization and delayed hysterectomy still resulted in a failure to control bleeding. The patient survived after prolonged surgery and hospitalization in the intensive care unit. Treatment of placenta percreta needs to be considered on an individual basis and carries a significant risk of morbidity.