Chin-Jung Wang

Regulation of ovarian cancer progression by microRNA-187 through targeting Disabled homolog-2

MicroRNAs (miRNAs) play important roles in tumorigenesis by regulating oncogenes and tumor-suppressor genes. In this study, miR-187 and miR-200a were found to be expressed at higher levels in ovarian cancers than in benign tumors. In patients with ovarian cancer, however, higher levels of miR-187 and miR-200a expression were paradoxically associated with better OS and recurrence-free survival. Further, multivariate analysis showed that miR-187 served as an independent prognostic factor for patients with ovarian cancer (n=176). Computational prediction and microarray results indicated that miR-187 directly targeted Disabled homolog-2 (Dab2), and luciferase reporter assays confirmed that the target site of miR-187 was located at the 3′-UTR of the Dab2 gene. Generally considered as a tumor-suppressor gene, Dab2 may actually promote tumor progression in advanced cancers through epithelial-to-mesenchymal transition (EMT). Ectopic expression of miR-187 in cancer cells promoted cell proliferation, but continued overexpression of miR-187 suppressed Dab2 and inhibited migration. Suppression of miR-187 upregulated Dab2, which, by inhibiting E-cadherin levels while stimulating vimentin and phospho-FAK levels, promoted EMT. Reduced ovarian cancer Dab2 histoscores correlated with high miR-187 levels and improved outcomes of patients. Collectively, these results demonstrate distinct dual roles of Dab2 in cell proliferation and tumor progression. In the initial steps of tumorigenesis, upregulated miR-187 suppresses Dab2, promoting cell proliferation. During the later stages, however, continued increased levels of miR-187 inhibits the Dab2-dependent EMT that is associated with tumor invasiveness, which is presumed to be the reason why cancers with high miR-187 levels were associated with better survivals.

Risk analysis of torsion and malignancy for adnexal masses during pregnancy

OBJECTIVE To find the risk factors of torsion and malignancy for adnexal tumors during pregnancy. DESIGN Retrospective, historical cohort study. SETTING University hospital. PATIENT(S) Patients from 1990 to 2004 with adnexal tumors >or=4 cm during pregnancy. INTERVENTION(S) Surgery undertaken antepartum, concurrently with cesarean delivery, or postpartum. MAIN OUTCOME MEASURE(S) Tumor size, progression, pathology, incidence of malignancy, and torsion. RESULT(S) Almost all 213 managements analyzed had good surgical and obstetric outcomes. In 174 patients who were followed through pregnancy with known tumor existence, 14.84% +/- 3.05% encountered tumor torsion. Adnexal masses with sizes between 6 and 8 cm had a significantly higher risk of torsion compared with other sizes (22.41% vs. 9.48%; odds ratio 2.8, 95% confidence interval [CI], [1.1, 6.6]). Sixty percent of the torsion happened between the 10th and 17th weeks of gestation, and only 5.9% happened after 20 weeks. The incidence of malignancy was 3.4%, while that of ovarian cancer was 2.3%. Tumor diameters >or=10 cm at initial diagnosis had a higher risk of malignancy versus smaller sizes (8.77% vs. 0.85%; odds ratio 11.2, 95% CI, [1.3, 97.9]), and tumor growth rates >or=3.5 cm/week also had a significantly higher risk of malignancy versus lower rates (8.33% vs. 0.88%; odds ratio 10.2, 95% CI, [1.0, 101.2]). CONCLUSION(S) Adnexal tumors bearing higher risks for torsion and malignancy should be strongly considered for an aggressive strategy of management during pregnancy.

Stress-induced Phosphoprotein 1 as a Secreted Biomarker for Human Ovarian Cancer Promotes Cancer Cell Proliferation

Ovarian cancers are frequently not diagnosed until advanced stages, resulting in a high case fatality rate. Because of this, more tumor markers, in addition to CA125, for detecting and monitoring ovarian cancer are needed. During a systematic search for potential biomarkers of ovarian cancer, we compared the protein profiles between tumor interstitial fluid and normal interstitial fluid of ovaries, rationalizing that abnormal levels of proteins in tumor interstitial fluid may be detected in peripheral blood and thus serve as easily accessible tumor markers. Here, we show that stress-induced phosphoprotein 1 (STIP1) was secreted by ovarian cancer tissues into the peripheral blood of patients, resulting in a significant increase of serum levels of STIP1 in cancer patients compared with those in age-matched normal controls. Our results further indicated that combined use of CA125 and STIP1 may increase early detection of ovarian cancer. Functionally, recombinant STIP1 significantly induced ERK phosphorylation, promoted DNA synthesis, and increased Ki-67 immunoreactivity in ovarian cancer cells, suggesting that STIP1 in vitro promotes cell proliferation. Colocalization of STIP1 and phospho-ERK in human ovarian cancer tissues also supports an in vivo activation of ERK by STIP1. Further understanding of molecular roles of STIP1 in human ovarian cancer may shed light on its pathophysiology and development of novel therapeutic strategies.

Caesarean scar pregnancy successfully treated by operative hysteroscopy and suction curettage

A 36 year old woman, gravida 5, para 2, was admitted seven weeks and three days after her last menstrual period because a transvaginal ultrasound examination showed a gestational sac with yolk sac and fetal cardiac activity located within the isthmic area of the lower anterior wall of the uterus and protruding toward the vesicouterine junctional region. This appearance raised the suspicion of a caesarean scar pregnancy (CSP). Both ovaries appeared normal and there were no adnexal masses or free fluid in the cul-de-sac. The plasma b-human chorionic gonadotrophin (b-hCG) level was 28,338 miu/mL and general physical examination was normal. Her obstetric history revealed two-term transverse lower segment caesarean sections and two uterine curettages for abortion, and her youngest child was five years old. After counseling, the patient opted for conservative treatment with diagnostic and operative hysteroscopy. Under general anaesthesia without endotracheal intubation, the patient was placed in the dorsolithotomy position. After a speculum was placed inside the vagina, a tenaculum was applied to the cervix and gentle traction was exerted to align the uterus. The cervix was dilated by Hegar dilators to 12 mm and a continuous flow 26F hysteroscopic resectoscope (Karl Stortz, Tuttlingen, Germany) with a 90j wire loop electrode was introduced under ultrasound control. Uterine distension was achieved using 10% dextrose solution propelled by simple gravity. An Aspen Excalibur (Aspen Labs, Englewood, Colorado) electrosurgical generator was used on a setting of 80 W of cutting waveform current and 100 W of coagulation current. The intervention began by an overview of the uterine cavity. The endometrial cavity was empty and the gestation sac was implanted in a niche located in anterior endocervical wall, compatible with prior caesarean section scar (Fig. 1). The sac was pushed toward the fundal direction via wire loop electrode and blood vessels in the implantation site were identified. These vessels were coagulated by loop electrode and the resectoscope was then withdrawn. A placenta forceps followed by a vacuum curette were used to remove the partial detached gestational tissue under the ultrasound guidance. Thereafter, the resectoscope attached with a rollerball was introduced again to achieve haemostasis. During the 20-minute procedure, total fluid input was 3200 mL and output was 3150 mL. Vaginal bleeding was minimal at the end of the procedure. The patient had an unremarkable post-operative course and was discharged on the next day. The plasma b-hCG level was 5211 and 593 miu/mL at post-operative days 1 and 7, respectively. The pathology report confirmed a CSP. Urine pregnancy test was negative and plasma b-hCG level was 4.6 miu/mL at the post-operative 27th day visit and normal echotecture of the uterus was noted. Menstruation resumed three days after that visit and there has been no subsequent abnormal uterine bleeding within the three months of follow up period.

Laparoscopic Radical Trachelectomy for Stage Ib1 Cervical Cancer

Radical trachelectomy by vaginal approach is an alternative for young women with early-stage cervical cancer. We modified this procedure to treat two patients with stage Ib1 cervical cancer. With 100% laparoscopic pelvic lymphadenectomy and 80% laparoscopic approach, the technique is laparoscopic radical trachelectomy (LRT). Under direct enhanced vision of the laparoscope, it is easy to identify and preserve ascending branches of the uterine arteries and to divide ligaments surrounding the cervix and vagina. Vaginal procedures require only colpotomy, amputation of cervix, dividing caudal paracolpium, and corpus-vagina anastomosis. Short-term follow-up results of our first patients are satisfactory. Thus, LRT could be a useful alternative for women with early cervical cancer who want to preserve fertility.

Recurrent cervical carcinoma after primary radical surgery

OBJECTIVE This study was undertaken to investigate prognostic factors in patients with recurrent cervical carcinoma who had undergone a primary radical hysterectomy and pelvic lymphadenectomy. STUDY DESIGN A retrospective analysis of 177 patients with recurrent cervical carcinoma after radical hysterectomy and pelvic lymphadenectomy for stage IB to II disease at a single institution was performed to evaluate clinicopathologic parameters, time to recurrence, pattern of failure, use of salvage therapy, and survival after recurrence. RESULTS The 5-year survival rate from diagnosis of recurrence in this series was 10.1%. Survival after recurrence was significantly decreased in patients with pelvic lymph node metastasis at primary surgery and adenocarcinoma-adenosquamous carcinoma histologic type. Patients with extravaginal recurrences receiving chemoradiation for recurrent cervical carcinoma had significantly better outcomes than those receiving radiation alone. Six patients who had a distant relapse at a sole site had prolonged survival after salvage therapy, which was accomplished by chemoradiation, surgery plus radiotherapy, or surgery alone. CONCLUSIONS Our results demonstrate the benefit of adding chemotherapy to radiotherapy in the treatment of recurrent cervical carcinoma. Salvage multimodality treatment should be offered to selected patients who have isolated relapse at a single distant site.

Heterotopic pregnancy after in vitro fertilization–embryo transfer

Objective: A ruptured cornual pregnancy is a rare and challenging problem. We present two cases of cornual pregnancies after in vitro fertilization and embryo transfer (IVF‐ET) treated by cornual resection, with an excellent perinatal outcome for the intrauterine pregnancy in both cases. A literature review of cornual pregnancy after IVF‐ET is also included. Case reports: Two women had undergone IVF‐ET because of tubal problems. Emergent laparotomy was performed because of internal bleeding at 12 weeks of gestation in one case and 17 weeks in the other, and in both cases, ruptured cornual pregnancies were found. Cornual resection and primary repair were performed. The women were discharged on the 6th and 7th postoperative day, respectively, and they underwent an elective cesarean delivery at 37 weeks of pregnancy. They were delivered of healthy babies, one weighing 2700 g and the other 2310 g. Conclusion: These cases illustrate that good perinatal outcomes can be achieved by surgical intervention in heterotopic pregnancies, even in the event of a ruptured cornu.

A New Portal for Gynecologic Laparoscopy

We used the middle upper abdomen as a primary port insertion as an alternative portal for laparoscopy and multiport operative pelviscopy in 188 women who were at high risk for subumbilical adhesions because of previous abdominal surgeries or history of gynecologic cancer. Primary cannula insertion was in the middle upper abdomen between xyphoid process and umbilicus (Lee-Huang point). This was the single entry site for the Veress needle and primary laparoscopy port. In 184 (98.4%) of 188 women surgery was performed without complications. No procedure was converted to laparotomy due to visceral or vascular injuries. Two omentum injuries from primary port insertion were repaired with bipolar electrocoagulation; a colon injury was repaired with laparoscopic sutures. In our experience, this laparoscopic port is effective in women who have had abdominal surgery or gynecologic malignancy. (J Am Assoc Gynecol Laparosc 8(1):147-150, 2001)

Laparoscopic ovarian cystectomy of endometriomas: surgeons’ experience may affect ovarian reserve and live-born rate in infertile patients with in vitro fertilization-intracytoplasmic sperm injection

OBJECTIVE To assess whether the laparoscopists experience can affect ovarian reserve and pregnancy outcome in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) patients who previously underwent laparoscopic conservative treatment for ovarian endometriomas. STUDY DESIGN One hundred and forty-nine IVF-ICSI cycles with infertile patients who previously underwent laparoscopic conservative treatment for ovarian endometriomas were enrolled. There were 76 cycles with an inexperienced surgeon and 73 cycles with an experienced surgeon. RESULTS The number of antral follicle count (7.5±3.8 vs. 9.6±6.6; p=0.011), and live-born rate per cycle (9.3% vs. 32.9%; p<0.001) were significantly lower in the inexperienced group comparing with the experienced group. However, the mean number of oocytes, fertilization rate, mean number of embryos transferred, rate of good-quality embryos transferred, implantation rate and clinical pregnancy were similar between both groups. CONCLUSIONS The experience of the laparoscopist may affect ovarian reserve and live-born rate after treating ovarian endometrioma in infertile women with IVF-ICSI.

Laparoscopic-Assisted Vaginal Myomectomy

STUDY OBJECTIVE To evaluate the safety and efficacy of combined laparoscopic and vaginal approach in dealing with uterine myomas. DESIGN Retrospective case study (Canadian Task Force classification II-2). SETTING Tertiary care major teaching hospital. PATIENTS Thirty-one women with symptomatic fundal and/or posterior wall uterine myomas. INTERVENTION Laparoscopic-assisted vaginal myomectomy performed by one of the authors from July 1996 to December 1998. MEASUREMENTS AND MAIN RESULTS Mean +/- SD operating time, blood loss, and length of hospital stay were 79.19+/-18.31 minutes, 150.00+/- 103.28 ml, and 3.10+/-0.75 days, respectively. No patients developed serious complications, and only two minor complications occurred. CONCLUSION After laparoscopic inspection and location of uterine myomas, dealing with posterior and fundal uterine myomas by the vaginal route makes hemostasis and uterine repair easier than by purely laparoscopic approach.