Adult granulosa cell tumor of the ovary: 35 cases in a single Korean Institute.

BACKGROUND: Adult granulosa cell tumor of the ovary is an uncommon neoplasm. The overall prognosis is favorable. The prognostic factors that are related to survival have not been well defined and are discussed in the literature amidst controversy. METHODS: Thirty-five patients diagnosed with adult granulosa cell tumor of the ovary were reviewed retrospectively. Demographic data, pathologic findings, treatments, and survival times were reviewed and analyzed for prognostic significance. RESULTS: Of the 35 cases, there were 30 cases representing stage I tumors, one case at stage II, four cases at stage III, and no cases at stage IV. The mean overall survival time of all patients was 140.3 months. The 5- and 10-year survival rates were 92.0% and 85.8% respectively. The FIGO stage was the only independent prognostic factor. CONCLUSIONS: Despite the small number of patients, the study showed that the less advanced stage is the only favorable prognostic factor of significance.

Primary peritoneal carcinoma: experience with cytoreductive surgery and combination chemotherapy.

The objective of this study was to review the clinical outcome and prognosis of patients with primary peritoneal carcinoma (PPC) treated with cytoreductive surgery and combination chemotherapy. We retrospectively reviewed the charts of 27 patients with histologically confirmed PPC, treated between March 1990 and February 2004 at Asan Medical Center, South Korea. The review included demographic data, pathologic findings, treatments, and outcomes. The mean age of the 27 patients was 57.5 +/- 7.2 years, and the rate of optimal cytoreduction was 70.4%. Seven patients had stage IIIB, 17 had stage IIIC, and 3 had stage IV; all patients received adjuvant chemotherapy. There were 4 patients with progressive disease, 5 partial responders, and 15 complete responders; the remaining 3 patients were nonevaluable. At the time of the review, 10 patients were alive without evidence of disease, 3 were alive with disease, and 14 had died from disease. The median overall survival time was 41 months, and the overall 5-year survival rate was 18.1%. Patients who had optimal cytoreduction had a longer median survival (42 months) than those who had suboptimal cytoreduction (10 months; P < 0.05). Combination chemotherapy after optimal cytoreductive surgery may be effective in the treatment of patients with PPC.

Malignant mixed müllerian tumors of the ovary: experience with cytoreductive surgery and platinum-based combination chemotherapy.

This study reviews the clinical outcome and prognosis of patients with malignant mixed müllerian tumors (MMMTs) of the ovary treated with optimal cytoreductive surgery, leaving no residual disease, and platinum-based chemotherapy. Ten patients diagnosed with MMMT of the ovary after complete surgical staging from February 1993 to February 2004 at Asan Medical Center in Korea were studied retrospectively. All ten patients were treated with optimal cytoreductive surgery, leaving no gross residual disease. Seven patients received ifosfamide/cisplatin chemotherapy, and the remaining three patients received other platinum-based combination chemotherapy. Demographic data, pathologic findings, treatments, and survival time were reviewed. Of the ten patients, two were scored at FIGO stage IIC, seven were at stage IIIC, and one was at stage IV. The median survival time of all ten patients was 46 months. The overall survival rate was 60.0% at 1 year, 40.0% at 2 years, and 20.0% at 5 years. Platinum-based combination chemotherapy after optimal cytoreductive surgery may be effective in the treatment of ovarian MMMT.

Laparoscopic-assisted vaginal hysterectomy versus abdominal hysterectomy in patients with stage I and II endometrial cancer.

The purpose of this study was to evaluate and compare the outcomes of laparoscopic surgery with those of conventional abdominal surgery in patients with early endometrial cancer. From 1997 to 2003, 79 patients underwent laparoscopic-assisted vaginal hysterectomy with or without lymphadenectomy. Laparoscopy was performed on patients deemed clinical stage I in preoperative studies. Of the 79 patients, 74 found to be surgical stage I or II were enrolled in the comparative study. As a control group, we selected 168 laparotomy cases at the same disease stage as the laparoscopy group. Operation time, amount of blood transfusion, and hemoglobin changes were similar for both groups. In the laparoscopy group, the number of lymph nodes obtained was significantly higher, and the number of postoperative complications was lower compared to the laparotomy group. The hospital stay was significantly shorter for laparoscopy group. Three-year recurrence-free survival rates were similar, being 97.5% for the laparoscopy group and 98.6% for the laparotomy group. We conclude that laparoscopic surgery for treatment of early endometrial cancer is a safe and effective alternative to laparotomy in terms of perioperative complications. Three-year recurrence-free survival did not differ significantly between the groups. However, long-term survival and risk of recurrence have yet to be determined.

Nonradical treatment is as effective as radical surgery in the management of cervical cancer stage IA1.

This study was designed to evaluate a series of patients who underwent surgical management due to cervical cancer stage IA1 fitting the 1995 FIGO definition. A total of 149 patients were followed from 3 years to 11.7 years with a median follow-up interval of 5 years. The cases with invasions of < or = 1 mm and > 1 mm but < or = 3 mm were noted in 89 (59.7%) and 60 (41.3%) patients, respectively. Lymphvascular space invasion was identified in five patients. In 49 patients, conization or nonradical hysterectomy was performed without pelvic lymph node dissection (PLND) and pelvic recurrence developed in one patient who had an extended hysterectomy. PLND was performed in 100 patients and the average number of lymph nodes examined per case was 26.5 +/- 10.1. None of the 100 patients had metastasis to the pelvic lymph node and recurrence. None of the 149 patients has died from recurrent disease. In conclusion, this study suggests that patients with cervical cancer stage IA1 have an extremely low risk of pelvic lymph node metastasis, very rarely recur, and present an excellent prognosis, so nonradical management that excludes PLND could be as effective as radical surgery in these patients.

The effect of epidermal growth factor on the preimplantation development, implantation and its receptor expression in mouse embryos.

OBJECTIVE: To investigate the influence of epidermal growth factor (EGF) on preimplantation development, implantation, and expression of epidermal growth factor receptor (EGFR) itself in mouse embryos. MATERIALS AND METHOD: Eight-cell stage mouse embryos were cultured for 48 hours with EGF at concentrations of 0.1, 1.0, 10 and 100 ng/ml. Embryos not treated with EGF were served as control. The percentages of embryos which developed to the expanded, hatched blastocyst stage and in vitro implantation at 48 hours were determined. Reverse transcription-polymerase chain reaction (RT-PCR) has been used to examine the expression of EGFR in developed hatched blastocysts. Following reverse transcription, strategically designed nested primers, optimized for specificity, were used for amplification from the cDNA equivalent of a single embryo. The products were then verified by restriction enzyme digestion and sequence analysis. Results were analyzed with chi 2 test and Student's t-test as appropriate, and statistical significance was defined as p < 0.05. RESULTS: The percentages of fully expanded blastocysts at 48 hours in all the EGF treated group were not significantly different from the control. The percentages of hatched blastocysts were significantly higher in the EGF treatment group at 0.1 ng/ml (90.5 +/- 9.8%) compared to the control (82.1 +/- 7.2%), 1.0 ng/ml (82.2 +/- 12.7%), and 100 mg/ml (81.9 +/- 11.8%) (p < 0.05, p < 0.05, p < 0.05, respectively). The percentages of hatched blastocysts were significantly higher in the EGF treatment group at 10 ng/ml (89.4 +/- 7.5%) compared to the control, and 100 ng/ml (p < 0.05, p < 0.05, respectively). The percentages of attached blastocysts in vitro were significantly higher following incubation with EGF at concentrations of 0.1 ng/ml (37.0 +/- 17.0%), 1.0 ng/ml (32.0 +/- 14.3%), 10 ng/ml (21.3 +/- 7.2%) compared to the control (9.5 +/- 7.7%) (p < 0.05, p < 0.05, p < 0.05, respectively). The attachment rates in 0.1 ng/ml and 1.0 ng/ml EGF treatment groups were also significantly higher than those in other EGF treatment groups. Embryo development and attachment were not significantly inhibited or enhanced in cultures supplemented with 100 ng/ml EGF compared to the control. The mRNA concentration of EGFR in embryos treated with 0.1 ng/ml of EGF was significantly higher than those of the control and other EGF treatment groups. CONCLUSION: EGF may have a stimulatory role in later stage embryonic development, implantation and expression of EGFR in hatched blastocyst itself at the specific concentration.

Two cases of atrial flutter with fetal hydrops: successful fetal drug therapy.

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.

The immunotherapy during in vitro fertilization and embryo transfer cycles in infertile patients with endometriosis.

OBJECTIVE: To investigate if the immunotherapy with corticosteroids would improve the pregnancy rate in infertile patients with endometriosis who undergo in vitro fertilization and embryo transfer (IVF-ET). METHODS: Forty-two infertile patients with endometriosis plus tubal factor and 87 pure tubal infertility patients who underwent IVF-ET in our unit were allocated randomly to the corticosteroid treatment group and the control group. RESULTS: The prevalence of autoantibodies (antinuclear antibody, lupus anticoagulant, anticardiolipin antibody, rheumatoid factor) was elevated significantly in patients with endometriosis plus tubal factor compared with pure tubal infertility patients (38.1% vs 2.3%). Twenty-one patients with endometriosis plus tubal factor underwent 54 cycles of IVF-ET, receiving corticosteroids. Forty-three patients with pure tubal factor underwent 81 cycles of IVF-ET, receiving corticosteroids. Twenty-one patients with endometriosis plus tubal factor who underwent 57 cycles of IVF-ET and 44 patients with pure tubal factor who underwent 84 cycles of IVF-ET served as controls, not receiving corticosteroids. In patients with endometriosis plus tubal factor, there was a significantly higher clinical pregnancy rate per cycle in the treatment group, with 42.6% (23/54) compared with 22.8% (13/57) in the control group but no differences between 2 groups in spontaneous abortion rate (21.7% vs 15.4%) and multiple pregnancy rate (17.4% vs 15.4%). In patients with pure tubal infertility, there were no significant differences between the treatment group and control group in clinical pregnancy rate (40.7% vs 34.5%), spontaneous abortion rate (12.1% vs 10.3%) or multiple pregnancy rate (18.2% vs 10.3%). In the endometriosis plus tubal infertility group with autoantibodies, the clinical pregnancy rate per cycle was significantly higher in the treatment group at 40.9% compared with 14.8% in the control group. In endometriosis plus tubal infertility group without autoantibodies, there was no significant difference between 2 groups with respect to the clinical pregnancy rate per cycle (43.8% vs 30.0%). CONCLUSIONS: This study suggests that immunotherapy with corticosteroids could improve the clinical pregnancy rate in endometriosis patients undergoing IVF-ET and may be more effective in patients with positive autoantibodies.

Loss of FHIT expression in cervical carcinoma cell lines and primary tumors.

Allelic deletions involving the short arm of chromosome 3 (3p13-21.1) have been observed frequently in cervical carcinomas. Recently, a candidate tumor suppressor gene, FHIT (Fragile Histidine Triad), was cloned and mapped to this chromosomal region (3p14.2). Abnormal FHIT transcripts have been identified previously in a variety of tumor cell lines and primary carcinomas, although their significance and the molecular mechanisms underlying their origin remain incompletely defined. In addition, integration of human papillomavirus DNA has been identified at a fragile site (FRA3B) within the FHIT locus in cervical cancer. These observations motivated us to evaluate FHIT mRNA and protein expression in cervical cancer cell lines, primary cervical carcinomas, and normal tissues. Transcripts of the expected size and sequence were the predominant species identified by reverse transcription (RT)-PCR in cultured keratinocytes and all normal tissues evaluated. In contrast, aberrant FHIT transcripts were readily demonstrated in 6 of 7 cervical carcinoma cell lines and 17 of 25 (68%) primary cervical carcinomas. Northern blot analyses demonstrated reduced or absent FHIT expression in the cervical carcinoma cell lines, particularly those with aberrant RT-PCR products. Immunohistochemical analysis of Fhit expression in cervical tissues revealed strong immunoreactivity in nonneoplastic squamous and glandular cervical epithelium and marked reduction or loss of Fhit protein in 25 of 33 (76%) primary cervical carcinomas. In those cervical cancer cell lines and primary tumors with exclusively aberrant or absent FHIT transcripts by RT-PCR, Fhit protein expression was always markedly reduced or absent. The frequent alterations in FHIT expression in many cervical carcinomas, but not in normal tissues, suggest that FHIT gene alterations may play an important role in cervical tumorigenesis.

Effect of population density on the early post-implantation mouse embryo growth in vitro.

OBJECTIVES: To investigate the relationship between embryo population density and embryo development in vitro. METHODS: Swiss Webster albino mice were used and blastocysts were flushed from the uterine horns. Various numbers of blastocysts were randomly assigned to separate 35 mm dishes and cultured for 9 days. RESULTS: The effect of duration of culture to the mean success rates was different as the number of embryos in the dish was changed. In early egg cylinder (EEC) stage, the mean success rate was a flat function of the number of embryos. But the mean success rate was a decreasing function in late egg cylinder (LEC) stage and the decreasing rate was faster in early somite (ES) stage. Interestingly, the mean success rate to ES stage was nearly constant when more than 10 embryos were cultured in one dish. CONCLUSION: The success rate to each developmental stage in vitro decreased as the number of embryos in the dish and the duration of cultured increased.

Tumor implantation along abdominal trocar site after pelviscopic removal of malignant ovarian tumor--a case report.

The application of pelviscopic surgery for the management of ovarian tumors has increased dramatically in the last few years. Of particular concern is the pelviscopic excision of malignant ovarian tumors. One of the important potential problems with this approach is disseminating malignant cells to peritoneal surface. The aim of this report is to draw attention to the possibility of the occurrence of a tumor implantation at the pelviscopic port site in patients with malignant ovarian tumors. A case is presented here in which a localized tumor implant occurred in the abdominal trocar site after pelviscopic removal of ovarian mass subsequently found to be squamous cell carcinoma arising in mature cystic teratoma with brief review of literatures.

Lamellar body count in amniotic fluid as a rapid screening test for fetal lung maturity.

We conducted a 2-year prospective clinical outcome study to evaluate the usefulness of amniotic fluid lamellar body count (LBC) as a screening test for fetal lung maturity. During the interval under study, outcomes of 170 neonates were used to evaluate the test; 14 neonates had respiratory distress syndrome (RDS). Both LBC and lecithin-sphingomyelin ratio (L/S ratio) test results were available in 129 cases. All the cases of RDS had LBC of 50,000/microliter or less and L/S ratio of 2.8 or less; 72.7% of cases with no RDS had LBC greater than 50,000/microliter, and 80.4% of normal cases had L/S ratio higher than 2.8. LBC test results showed good correlation with L/S ratio test results between 26 weeks and 33 weeks of gestation (r = 0.78, p < 0.0001). With the cutoff value of 50,000/microliter for LBC, the diagnostic sensitivity and specificity were 100% and 80%, respectively. Determining LBC by cell counter is justified as a useful rapid initial screening test for the assessment of fetal lung maturity.

Simplified ultralong protocol of gonadotrophin-releasing hormone agonist for ovulation induction with intrauterine insemination in patients with endometriosis.

The present study was designed to assess the usefulness of the simplified ultralong protocol of gonadotrophin-releasing hormone agonist (GnRHa) for ovulation induction with intrauterine insemination (IUI) in patients with various stages of endometriosis. A prospective randomized trial was set up to compare the simplified ultralong protocol (ULP) and the long protocol (LP) of GnRHa for ovulation induction with IUI in patients with endometriosis. There was no evidence of other factors in infertility in any patient. In the ULP group (39 patients), 4 weeks after a single injection of 3.75 mg Decapeptyl had been given, daily s.c. administration of 0.1 mg Decapeptyl was initiated and continued for at least 2 weeks prior to ovarian stimulation. In the LP group (41 patients), daily s.c. administration of 0.1 mg Decapeptyl was initiated from the mid-luteal phase of the cycle preceding the stimulation cycle. After 14 days of administration, ovarian stimulation was started if pituitary desensitization had been achieved. The amount of gonadotrophins required, number of days of gonadotrophin administration, serum oestradiol response, and the number of mature follicles were comparable in both groups. The clinical pregnancy rate per cycle was significantly higher in the ULP group at 48.7% (19/39) compared with 26.8% (11/41) in the LP group. The miscarriage rates were 21.1% (4/19) in the ULP group and 18.2% (2/11) in the LP group. In patients with stage I or II endometriosis, there was no significant difference between the two groups with respect to clinical pregnancy rate per cycle (47.4 versus 35.0%). In patients with stage III or IV endometriosis, the clinical pregnancy rate per cycle was significantly higher in the ULP group at 50.0% (10/20) compared with 19.0% (4/21) in the LP group. This study suggests that a simplified ULP of GnRHa could give better chances of achieving pregnancy in endometriosis patients undergoing assisted reproductive technologies and that this protocol may be more useful in patients with an advanced stage of endometriosis.

The efficacy of immunotherapy in patients who underwent superovulation with intrauterine insemination.

OBJECTIVE: To determine if the immunotherapy with corticosteroids would improve pregnancy rate in infertile patients with ovulatory factor and patients with unexplained infertility who undergo superovulation with IUI. DESIGN: Prospective, controlled study. SETTING: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Ulsan, Seoul, Korea. PATIENTS: Nine-one infertile patients with ovulatory factors and 78 patients with unexplained infertility who underwent superovulation with IUI. RESULTS: The prevalence of autoantibodies (antinuclear antibody, lupus anticoagulant, anticardiolipin antibody, antidouble-stranded DNA antibody) was elevated significantly in patients with unexplained infertility compared with patients with ovulatory infertility (20.5% versus 3.3%). Forty-five patients with ovulatory factor underwent 72 cycles of superovulation with IUI, receiving corticosteroids. Thirty-eight patients with unexplained infertility underwent 75 cycles of superovulation with IUI, receiving corticosteroids. Forty-six patients with ovulatory factor who underwent 66 cycles of superovulation with IUI and 40 patients with unexplained infertility who underwent 75 cycles of superovulation with IUI served as controls, not receiving corticosteroids. In patients with ovulatory factor, there were no significant differences between the corticosteroid treatment group and control group in clinical pregnancy rate (38.9% versus 33.3%) or in spontaneous abortion rate (14.3% versus 13.6%). In patients with unexplained infertility, there was a significantly higher clinical pregnancy rate per cycle in the corticosteroid treatment group, with 45.3% (34/75) compared with 29.3% (22/75) in the control group but no difference between the corticosteroid treatment and control groups in spontaneous abortion rate (17.6% versus 13.6%). There were no side effects due to the use of corticosteroids.

Endodermal sinus tumor arising from a dysgenetic gonad in a 46,XX female combined with müllerian agenesis.

The occurrence of neoplastic transformation in a dysgenetic gonad of a female with 46,XX karyotype is very rare. Moreover, to our knowledge, a case of endodermal sinus tumor arising from that setting combined with Müllerian agenesis has not been reported. This case suggests the possibility of development of cancer in a dysgenetic ovary of a female even with 46,XX or Müllerian agenesis.