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Decidualization of the endometrial stroma is an essential differentiation process for embryo implantation and maintenance of pregnancy. We previously reported that protein phosphatase 2A (PP2A) acts as a key mediator during cAMP-induced decidualization of human endometrial stromal cells (hESCs). However, the mechanism underlying its activation has remained obscure in hESCs. In the present study, we aimed to reveal the mechanism that induces the nitration of PP2A catalytic subunit (PP2Ac) during cAMP-induced decidualization of hESCs. First, cAMP-induced PP2Ac nitration was significantly repressed using L-NAME, an inhibitor of nitric oxide synthase (NOS). Among several NOS isoforms, only inducible NOS (iNOS) was highly expressed in hESCs, indicating that iNOS directly induces the nitration of PP2Ac. Second, cAMP-induced iNOS expression and PP2Ac nitration were decreased by treatment with TSA, an inhibitor of histone deacetylase 5 (HDAC5). cAMP-induced phosphorylation of CaMKII and HDAC5 was suppressed by treatment with U73122 (an inhibitor of phospholipase C) or transfection of PLCε siRNA. Finally, small G protein Rap1 and its guanine nucleotide exchange factor Epac1 were found to be involved in cAMP-induced PP2A activation. Taken together, our results suggest that PP2Ac nitration during cAMP-induced decidualization of hESCs is induced through the Epac1-Rap1-PLCε-CaMKII-HDAC5-iNOS signaling pathway.

Decidualization of human endometrial stromal cells (hESCs) is crucial for successful uterine implantation and maintaining pregnancy. We previously reported that phospholipase D1 (PLD1) is required for cAMP-induced decidualization of hESCs. However, the mechanism by which phosphatidic acid (PA), the product of PLD1 action, might regulate decidualization is not known. We confirmed that PA induced decidualization of hESCs by observing morphological changes and measuring increased levels of decidualization markers such as IGFBP1 and prolactin transcripts (P < 0.05). Treatment with PA reduced phosphorylation of Akt and consequently that of FoxO1, which led to the increased IGFBP1 and prolactin mRNA levels (P < 0.05). Conversely, PLD1 knockdown rescued Akt phosphorylation. Binding of PP2A and Akt increased in response to cAMP or PA, suggesting that their binding is directly responsible for the inactivation of Akt during decidualization. Consistent with this observation, treatment with okadaic acid, a PP2A inhibitor, also inhibited cAMP-induced decidualization by blocking Akt dephosphorylation.

Aim To investigate the feasibility and safety of single port laparoscopic surgery (SP-LS) for ectopic pregnancy, irrespective of type of ectopic pregnancy and hemodynamic stability. Methods A prospective case–control study of 106 women who underwent SP-LS or conventional LS for a suspected ectopic pregnancy was performed at a university teaching hospital from January 2009 to March 2012. Twenty-six women underwent SP-LS (SP-LS group) and 80 women underwent conventional LS (conventional LS group). Results There were no statistical differences between the groups in terms of demographic characteristics, operating time, hemoglobin change, return of bowel activity, hospital stay or complication rate. There were no cases of additional trocar use or conversion to laparotomy. Of five women with heterotopic pregnancy, one underwent SP-LS, and three underwent conventional LS for tubal pregnancy, which all resulted in vaginal delivery without obstetric complication; one woman received SP-LS for cornual pregnancy and had an ongoing pregnancy. Conclusion SP-LS for ectopic pregnancy is feasible and safe regardless of the type of ectopic pregnancy and hemodynamic stability. However, further work is needed to confirm this conclusion and to demonstrate any advantage of SP-LS for ectopic pregnancy.

Aim To identify commonly occurring DNA copy number alterations in Korean cervical cancers. Methods DNA copy number alteration was screened by whole-genome array comparative genomic hybridization (CGH) analysis. For the array CGH discovery, genomic DNA from five cervical cancers and 10 normal cervical tissues were examined. For the independent validation of the most significant chromosomal alteration (1p36.22, PGD gene), 40 formalin-fixed paraffin-embedded cervical tissue samples were collected; 10 of them were used for quantitative polymerase chain reaction and the other 30 samples were used for immunohistochemical analysis. Chromosomal segments differently distributed between cancers and normal controls were determined to be recurrently altered regions (RAR). Results A total of 13 RAR (11 RAR losses and two RAR gains) were defined in this study. Of the 13 cervical cancer-specific RAR, RAR gain in the 1p36.22 locus where the PGD gene is located was the most commonly detected in cancers (P = 0.004). In the quantitative polymerase chain reaction replication, copy number gain of the PGD gene was consistently identified in cervical cancers but not in the normal tissues (P = 0.02). In immunohistochemical analysis, PGD expression was significantly higher in cervical cancers than normal tissues (P = 0.02). Conclusion Our results will be helpful to understand cervical carcinogenesis, and the PGD gene can be a useful biomarker of cervical cancer.

Aim The aim of this study was to investigate the obstetric outcomes and clinical efficacy of laparoscopic surgery for women with heterotopic pregnancy. Material and Methods We conducted a retrospective study of women who had undergone laparoscopic surgery for heterotopic pregnancy. The primary outcome was the feasibility of laparoscopic surgery for the treatment of heterotopic pregnancy and the secondary outcomes were obstetric outcomes. Results Seventeen women underwent laparoscopic surgery for heterotopic pregnancy: 14 with tubal heterotopic pregnancies and three with cornual heterotopic pregnancies. There were no intraoperative or postoperative complications. Of these women, 13 delivered 14 healthy babies, whereas two failed to maintain their pregnancies; one had a missed abortion 2 weeks after the surgery and the other had a miscarriage due to preterm premature rupture of the membrane at 16 gestational weeks. The remaining two women have ongoing pregnancies. Conclusion Laparoscopic surgery performed by experienced surgeons is a feasible and beneficial surgical modality for treating heterotopic pregnancy.

Aim: This study was performed to assess the feasibility and efficacy of laparoscopic management for patients with large ovarian tumors. Material and Methods: A retrospective analysis was performed of the medical records of 52 women who underwent laparoscopic surgery for large ovarian tumors whose maximum diameter was ≥15 cm and a low possibility of malignancy. Results: The median age of patients was 35 years (range 18–84), median body mass index was 22.4 kg/m2 (range 12.4–31.5) and 18 patients had previous operative history. The median tumor diameter was 17 cm (range 15–40). There were no conversions to laparotomy and perioperative complications. The median operating time, estimated blood loss, and hospital stay were 80 min (range 25–225), 100 mL (range 50–500) and 3 days (range 2–14), respectively. The operative procedures performed were salpingo–oophorectomy (n = 26), ovarian cystectomy (n = 16), laparoscopically assisted vaginal hysterectomy with unilateral or bilateral salpingo-oophorectomy (n = 9), and laparoscopically assisted staging surgery (n = 1). The histopathological results were mucinous cystadenoma (n = 25), mature cystic teratoma (n = 9), serous cystadenoma (n = 6), endometrioma (n = 5), mucinous borderline tumor (n = 4), follicular cyst (n = 2), and clear cell carcinoma (n = 1). Conclusion: Laparoscopic management of large ovarian tumors is feasible and efficient with appropriate patient selection and experience of surgeons.

Objective. To investigate the effects of conventional and single port laparoscopically assisted vaginal hysterectomy (LAVH) on sexual function in premenopausal women. Design. A prospective case-control study. Setting. University teaching hospital. Population. A total of 95 premenopausal women having LAVH from January 2009 to December 2009. Methods. Comparison of 47 premenopausal women who had single port LAVH using trans-umbilical GelPort access (SP-LAVH group) and 48 premenopausal women who had conventional multiport LAVH (conventional LAVH group). Main outcome measures. Evaluation of sexual function was done prior to and six months after surgery using a validated tool, the female sexual function index (FSFI). Results. In terms of women’s demographic characteristics and operative results, there was no signif icant difference between the two study groups, or between pre- and postoperative individual domain scores or total female sexual function index in women who underwent either conventional or single port LAVH. Conclusions. Neither conventional nor single port LAVH affects sexual function in premenopausal women. Women can be counseled that this type of surgery is unlikely to alter sexual function.

Aim: To evaluate the feasibility, efficacy, and safety of laparoscopic surgery for benign gynecological disease in women over 70 years old. Materials and Methods: Fifty-four women over 70 years old underwent surgery for benign gynecological disease from January 2003 to December 2009. Each woman was matched with two subjects of 30–50 years old in the younger group; the matching with patients undergoing a similar surgical technique was retrospective from December 2009. We evaluated body mass index, comorbidities, number of previous abdominal surgeries, operating time, hemoglobin change, postoperative complications, hospital stay, and return of bowel activity. The χ2-test and t-test were used to compare the results of the elderly group and the younger group. Results: There were no significant differences between the elderly group (over 70 years old) and a matched younger group (aged 30–50 years old) in body mass index, number of previous abdominal surgeries, operating time, hospital stay, and postoperative complications. Conclusion: Laparoscopic surgery in elderly women for benign gynecological disease is feasible, efficient, and safe. However, a large prospective randomized study is needed to confirm the conclusion.

Aims: The aim of this study was to evaluate the feasibility and efficacy of laparoscopically-assisted staging surgery for ovarian cancer. Methods: Twenty four patients were evaluated. Among them, nineteen underwent initial laparoscopic staging surgery and five patients who were incompletely staged by other institutions underwent complete restaging surgery. The procedure included pelvic lymphadenectomy, paraaortic lymphadenectomy, multiple biopsies, washing cytology, infracolic omentectomy, and appendectomy. Laparoscopically assisted vaginal hysterectomy and bilateral salpingo-oophorectomy were performed on all patients except one. Parameters such as tumor diameter, operating time, estimated blood loss, length of hospital stay, number of harvested lymph nodes, intraoperative and postoperative complications, and recurrence were evaluated. Results: The patients’ mean age was 52.8 ± 11.3 years and the mean parity was 2.5 ± 1.6. The mean diameter of the tumors was 8.4 ± 3.3 cm, the mean operating time was 253.7 ± 65.7 minutes, and the mean blood loss was 567.0 ± 170.9 mL. The mean postoperative hospital stay was 10.6 ± 4.0 days. The mean number of harvested pelvic lymph nodes was 22.5 ± 8.9 and the mean number of harvested paraaortic lymph nodes was 11.0 ± 5.8. None of the operations were switched to laparotomy. There were no major intraoperative complications, however, port site metastasis developed postoperatively in one patient. Conclusion: Comprehensive laparoscopically-assisted staging surgery, performed by a specialized laparoscopic oncologist with sufficient laparoscopic experience and a well-trained operating team, is both feasible and effective in treating ovarian cancers.

Background: Several studies reported that pathology of the appendix is frequently detected alongside endometriosis, especially with chronic pelvic pain. Furthermore, ovarian endometriosis is a marker of more extensive pelvic and intestinal disease. Aims: To evaluate the feasibility and efficacy of incidental appendectomy in laparoscopic surgical treatment for ovarian endometrioma. Methods: One hundred and six women with ovarian endometrioma underwent laparoscopic surgery including laparoscopic appendectomy. Clinicopathological data were collected and analysed. Results: The main symptoms consisted of lower abdominal pain in 51 (48.1%) women, dysmenorrhoea in 23 (21.7%), left lower quadrant pain in 6 (5.7%), right lower quadrant pain in nine (8.5%), chronic pelvic pain in five (4.7%), and others in 12 (11.3%). Only three (3.3%) of the 106 women had abnormal findings on gross inspection during laparoscopic surgery: two women with endometriotic spots on the surface of their appendixes, and one with peri-appendiceal inflammation with severe adhesions. Of the 106 resected appendixes, 37 (34.9%) had histopathologically confirmed pathology including lymphoid hyperplasia in 12 (11.3%), endometriosis in 14 (13.2%), peri-appendicitis and serositis in five (4.7%), carcinoid tumour in three (2.8%), and others in three (2.8%). Conclusions: In all surgical treatments for ovarian endometrioma, surgeons need to preoperatively inform the patients of the fact that appendiceal pathology including endometriosis is found frequently regardless of concurrent symptoms or gross finding of the appendix. Furthermore, surgeons should take into account the possibility of appendiceal pathology during operation.

Background: Laparoscopy is becoming common for the management of complex benign gynaecological diseases, in which considerable adhesions are expected, thus making the laparoscopic surgery more difficult to perform. Aims: To evaluate the efficacy and safety of laparoscopic surgery for adnexal tumours in post-hysterectomy women. Methods: In a retrospective study, we reviewed and analysed 40 post-hysterectomy women who were treated surgically for benign ovarian tumours at Kangbuk Samsung Hospital, from May 1999 to April 2007. Twenty women received laparotomic surgery and 20 were treated by laparoscopic surgery. Operating time, haemoglobin changes, complication rates, return of bowel activity, and duration of hospital stay were evaluated. Results: Operating time, haemoglobin changes, and complication rates were similar for both groups. For the laparoscopy group, the return of bowel activity was significantly faster (33 vs 45 h; P = 0.0131) and hospital stay was significantly shorter (four vs eight days; P = 0.0005) than for the laparotomy group. Conclusions: Laparoscopic surgery for adnexal tumours in post-hysterectomy women might be an effective and safe alternative to laparotomic surgery. Surgical experience in this procedure and a thorough understanding of retroperitoneal anatomy from a laparoscopic view are mandatory to ensure low morbidity.