Nitration of protein phosphatase 2A increases via Epac1/PLCε/CaMKII/HDAC5/iNOS cascade in human endometrial stromal cell decidualization.

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.

Comparison of vaginal hysterectomy and laparoscopic hysterectomy: a systematic review and meta-analysis.

BACKGROUND: There are various surgical approaches of hysterectomy for benign indications. This study aimed to compare vaginal hysterectomy (VH) and laparoscopic hysterectomy (LH) with respect to their complications and operative outcomes. METHODS: We selected randomised controlled trials that compared VH with LH for benign gynaecological indications. We included studies published after January 2000 in the following databases: Medline, EMBASE, and CENTRAL (The Cochrane Library). The primary outcome was comparison of the complication rate. The secondary outcomes were comparisons of operating time, blood loss, intraoperative conversion, postoperative pain, length of hospital stay and duration of recuperation. We used Review Manager 5.3 software to perform the meta-analysis. RESULTS: Eighteen studies of 1618 patients met the inclusion criteria. The meta-analysis showed no differences in overall complications, intraoperative conversion, postoperative pain on the day of surgery and at 48 h, length of hospital stay and recuperation time between VH and LH. VH was associated with a shorter operating time and lower postoperative pain at 24 h than LH. CONCLUSIONS: When both surgical approaches are feasible, VH should remain the surgery of choice for benign hysterectomy.

Coexisting ovarian and tubal pregnancies on opposite sides after intrauterine insemination: a case report.

BACKGROUND: Ovarian pregnancy is very rare, and contralateral tubal pregnancy coexisting with ovarian pregnancy must be even rarer. CASE PRESENTATION: A 33-year-old Korean nulliparous woman was referred to our hospital because she suffered lower abdominal pain and had missed her periods after controlled ovarian hyperstimulation and intrauterine insemination. We could not identify any normal gestational sac in the endometrium, or specific ectopic pregnancies, on an initial ultrasound scan. However, there was a large hematoma in the cul-de-sac and free fluid in the right paracolic gutter. We decided to perform emergent laparoscopic surgery. We found contralateral tubal and ovarian ectopic pregnancies. CONCLUSION: To the best of our knowledge, this is the first report of a case in which a patient underwent laparoscopic right salpingectomy and left ovarian ectopic mass excision due to contralateral tubal and ovarian ectopic pregnancies after assisted reproductive technology.

Encountering the Accessory Polar Renal Artery during Laparoscopic Para-Aortic Lymphadenectomy.

A 60-year-old Korean woman underwent laparoscopic bilateral salpingo-oophorectomy and was confirmed to have high-grade serous carcinoma of both ovaries with a huge omental cake, extensive agglutinated intra-abdominal metastatic masses, extensive serosa invasion of the intestines, and mesenterial deposits. She underwent 3 cycles of neoadjuvant chemotherapy followed by laparoscopic interval debulking surgery, including hysterectomy, pelvic and para-aortic lymphadenectomy, appendectomy, partial peritonectomy, and omentectomy. We encountered the right accessory polar renal artery (APRA) during the surgery and carefully preserved the right APRA from the abdominal aorta to the right kidney (Fig. 1). Postoperative computed tomography angiography showed an intact right APRA and normal-appearing kidney (Fig. 2). The patient had adjuvant chemotherapy and is alive without disease recurrence. Because APRA is a functional end artery, it is important to preserve it during surgery to prevent ischemic damage and renal failure [1]. It is very important for the gynecologic-oncologist to have knowledge of the retroperitoneal vascular anatomy, experience in laparoscopic surgery, and an accurate surgical technique to avoid vascular injury during laparoscopic para-aortic lymphadenectomy.

Prospective comparison of single port versus conventional laparoscopic surgery for ectopic pregnancy.

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.

A prospective matched case-control study of laparoendoscopic single-site vs conventional laparoscopic myomectomy.

STUDY OBJECTIVE: To compare operative and obstetric outcomes of laparoendoscopic single-site myomectomy (LESS-M) vs conventional laparoscopic myomectomy (LM). DESIGN: Prospective matched case-control study. SETTING: A university hospital and a tertiary care center. PATIENTS: Forty-five women underwent LESS-M, and 90 women underwent conventional LM. INTERVENTION: LESS-M or conventional LM. MEASUREMENTS AND MAIN RESULTS: Operative and obstetric outcomes. There were no significant differences between the 2 groups in demographic characteristics, operative time (135 vs 140 minutes), change in hemoglobin concentration (1.9 vs 1.95 g/dL), return of bowel activity (35 vs 28 hours), hospital stay (5 vs 5 days), or complication rate (11.1% vs 8.9%). Insofar as obstetric outcomes, no significant differences were observed between the 2 groups for duration of follow-up (24.4 vs 23.2 months), pregnancy rate in patients who desired pregnancy (66.7% vs 50.0%), full-term delivery rate (66.7% vs 58.3%), and time to first pregnancy after surgery (7.6 vs 10.1 months). CONCLUSION: LESS-M is feasible and safe and has comparable obstetric outcomes to conventional LM in selected women with symptomatic myomas. However, a large prospective randomized study is needed.

1p36.22 region containing PGD gene is frequently gained in human cervical cancer.

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.

Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial).

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

Surgical and obstetric outcomes of laparoscopic management for women with heterotopic pregnancy.

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.

Diagnostic Clues for Women with Acute Surgical Abdomen Associated with Ruptured Endometrioma.

(1) Background: An investigation of the preoperative diagnostic clues used to identify ruptured endometrioma by comparing the ruptured and unruptured states in patients who underwent laparoscopic operations due to endometrioma. (2) Methods: Patients with ruptured endometriomas (14 patients) and unruptured endometriomas (60 patients) were included, and clinical symptoms, laboratory findings, and radiological findings were analyzed. (3) Results: There were no significant differences in age, parity, last menstrual cycle days, or median size of endometrioma between two groups (group A: ruptured; group B: unruptured). The median serum level of CA 125 was 345.1 U/mL in group A and 49.8 U/mL in group B (p = 0.000). The median serum levels of CA 19-9 in group A and B were 46.0 U/mL and 19.1 U/mL, respectively (p = 0.005). The median serum level of CRP in group A was 1.2 g/dL, whereas it was 0.3 in group B (p = 0.000). ROC analysis showed that the optimal CA 125 cutoff value was 100.9 U/mL; the optimal CA 19-9 cutoff value was 27.7 U/mL; and the optimal CRP cutoff value was 1.0 g/dL. (4) Conclusions: Ruptured endometrioma can be diagnosed preoperatively using a combination of clinical symptoms, laboratory findings, and radiological findings. If a physician suspects a ruptured endometrioma, surgery should be performed to ensure optimal prognosis.

Pretreatment CT differential diagnosis of tuberculous peritonitis from peritoneal carcinomatosis of advanced epithelial ovarian cancer.

Delayed diagnosis of female genital tuberculosis (FGTB) can lead to inappropriate treatment and unnecessary surgical procedures rather than standard anti-TB medication. We tried to evaluate the use of computed tomography (CT) imaging to differentiate TB peritonitis from peritoneal carcinomatosis of advanced epithelial ovarian cancer (AEOC). We investigated women who underwent CT to distinguish between TB peritonitis and peritoneal carcinomatosis of AEOC. We evaluated various CT imaging features to identify differences between the two diseases. In addition, we performed univariate and multivariate logistic regression analyses to identify the independent imaging parameters associated with TB peritonitis and evaluated the diagnostic performance of the combined imaging parameters. We also performed the histopathological analysis of the available salpinx specimens of TB peritonitis. We included 25 women with TB peritonitis and 34 women with peritoneal carcinomatosis of AEOC. A multivariate analysis of the discriminant CT imaging features between the two diseases revealed that changes in fallopian tubes and peritoneal micronodules were independent parameters associated with TB peritonitis (p ≤ 0.012). Combining the two imaging parameters showed an area under the receiver operating characteristic curve of 0.855, a sensitivity of 88.0%, and a specificity of 67.7% for differentiating TB peritonitis from peritoneal carcinomatosis. Furthermore, changes in fallopian tubes were correlated with histopathological abnormalities in salpinx specimens. Pretreatment CT evaluation with useful imaging features could help differentiate TB peritonitis from peritoneal carcinomatosis of AEOC.

Comparison of survival and adverse events between women with stage IB1 and stage IB2 cervical cancer treated by laparoscopic radical vaginal hysterectomy.

PURPOSE: The goal of this study was to evaluate the operative feasibility and survival for patients with stage IB2 cervical cancer who undergo laparoscopic radical vaginal hysterectomy (LRVH) compared with those with stage IB1 cervical cancer. METHODS: We identified 90 patients who were eligible to participate in the study through retrospective analysis of medical records from March 2003 to June 2010. Patients with stage IB1 cervical cancer were divided into two groups by a cutoff value of 2 cm for tumor size. Data regarding surgicopathologic risk factors, surgical outcomes, and survival rates were compared among three groups (two with stage IB1 and one with stage IB2). RESULTS: The tumor size was ≤2 cm in 27 patients, 2-4 cm in 30, and >4 cm in 33. The number of intermediate and high-risk factors was significantly lower in patients with stage IB1 cervical cancer (≤2 cm) than in those with stage IB2. Surgical outcomes (mean operating time, estimated blood loss, number of harvested lymph nodes, and sites of metastatic lymph nodes) did not show any significant difference among the three groups. The rates of intraoperative complications also did not differ among the three groups (P = 0.833). The estimated 5-year recurrence-free and overall survival rates were not significantly different among the three groups (P = 0.253 and 0.525, respectively). CONCLUSIONS: LRVH for stage IB2 cervical cancer can be performed with similar safety and survival rates compared to stage IB1 cervical cancer. Overall, LRVH is feasible for the treatment of stage IB2 cervical cancer.

7 Methyl indole ethyl isothiocyanate causes ROS mediated apoptosis and cell cycle arrest in endometrial cancer cells.

OBJECTIVE: Chemotherapy options for advanced endometrial cancer are limited and newer therapeutic agents are urgently needed. This study describes the therapeutic potential of 7 Methyl-indole ethyl isothiocyanate (7Me-IEITC) in endometrial cancer cell lines. METHODS: 7Me-IEITC was synthesized in our laboratory. The cell viability of 7Me-IEITC treated ECC-1 and KLE endometrial cancer cell was determined by MTS assay. Morphology and apoptosis were further confirmed by DAPI-staining and TUNEL assay. The measurement of reactive oxygen species (ROS), mitochondrial transmembrane depolarization potential (ΔΨm) and cell cycle phase was determined by FACS analysis. Expression of proteins involved in apoptosis, survival and cell-cycle progression was analyzed by Western blotting. RESULTS: 7Me-IEITC reduced the viability of the ECC-1 and KLE cancer cell-lines (IC(50)~2.5-10 µM) in a dose dependent fashion. 7Me-IEITC treatment caused mitochondrial transmembrane potential reduction, elevated the production of ROS, leading to activation of apoptosis in endometrial cancer KLE and ECC-1 cells. 7Me-IEITC treatment activated Bad, suppressed Bcl2 phosphorylation followed by PARP-1 deactivation and caspase 3 and 7 activation. 7Me-IEITC treatment arrested the progression of KLE cells in S-phase and caused CDC25 and cyclin-D1 downregulation. Pre-treatment with ascorbic acid abrogated 7Me-IEITC induced apoptosis in ECC-1 and KLE cells, suggesting that 7Me-IEITC mediated cytotoxicity is primarily through ROS production. CONCLUSION: 7Me-IEITC demonstrated promising cytotoxic effects in endometrial cancer cell line model.

Can laparoscopic radical hysterectomy be a standard surgical modality in stage IA2-IIA cervical cancer?

OBJECTIVES: To determine if laparoscopic radical hysterectomy (LRH) can be substituted for radical abdominal hysterectomy for women with International Federation of Gynecology and Obstetrics (FIGO) stage IA2-IIA cervical cancer. METHODS: We retrospectively reviewed the medical records of cervical cancer patients who underwent LRH with laparoscopic pelvic lymphadenectomy (LPL) and/or laparoscopic para-aortic lymphadenectomy (LPAL) from March 2003 to December 2011. RESULTS: Of 118 enrolled patients, six were in FIGO stage IA2, 66 were in IB1, 41 were in IB2, one was in IIA1, and four were in IIA2. The median operating time, perioperative hemoglobin change, the number of harvested pelvic and para-aortic lymph nodes were 270 min (range, 120-495), 1.7 g/dL (range, 0.1-5), 26 (range, 9-55), and 7 (range, 1-39), respectively. There was no unplanned conversion to laparotomy. Intra- and postoperative complications occurred in 16 (13.5%) and 8 (6.7%) patients, respectively. In a median follow-up of 31 months (range, 1-89), 5-year recurrence-free and overall survival rates were 90% and 89%, respectively. Univariate analysis showed that cervical stromal invasion (P=0.023) and lymph node metastasis (P=0.018) affected survival rate. Cox-proportional hazards regression analysis showed that lymph node metastasis was the only independent factor for poor prognosis (hazard ratio=7.0, P=0.022). CONCLUSIONS: LRH with LPL and/or LPAL in women with stage IA2-IIA cervical cancer is safe and feasible in terms of survival and morbidity. Our data suggest the need for larger prospective trials which could support this approach as a new standard of care for stage IA2-IIA cervical cancer.

Laparoscopic lymphadenectomy for isolated lymph node recurrence in gynecologic malignancies.

STUDY OBJECTIVE: To assess the feasibility and efficacy of laparoscopic lymphadenectomy in patients with isolated lymph node recurrences (ILNR) who underwent initial surgery because of gynecologic malignancy. DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: University teaching hospital. PATIENTS: Six patients with ILNR (1 cervical, 4 ovarian, and 1 peritoneal) diagnosed between March 2003 and July 2010. INTERVENTION: Laparoscopic lymphadenectomy. MEASUREMENTS AND MAIN RESULTS: Median (range) patient age was 59.5 (24-70) years, and body mass index was 21.7 (21.0-24.6). There was no unplanned conversion to laparotomy. Operating time was 337.5 (200-400) minutes, hemoglobin change was 0.9 (0.4-2.6) g/dL, and hospital stay was 8.5 (5-19) days. The number of harvested lymph nodes was 20 (5-27), and of positive lymph nodes was 4 (1-24). One patient had common iliac vein laceration, with complete hemostasis achieved using intracorporeal suture. Postoperative lymphedema occurred in 1 patient, and was managed conservatively. All patients received adjuvant chemotherapy after laparoscopic lymphadenectomy. CONCLUSION: Laparoscopic lymphadenectomy in patients with ILNR is feasible and might be an alternative therapeutic strategy.

Is gynecological cancer a new indication for surveillance colonoscopy in Korea?

BACKGROUND/AIMS: Previous studies regarding the risk for colorectal neoplasms in women with a prior diagnosis of gynecological cancer have revealed conflicting results. Therefore, we conducted a cross-sectional study to quantify the risk for colorectal neoplasms in patients with gynecological cancers. METHODOLOGY: A total of 4613 women (including 27, 51 and 92 women with a prior diagnosis of endometrial, ovarian and cervical cancers, respectively) >20 years of age were recruited prospectively from 9 tertiary medical centers in Korea between January 2008 and February 2009. All participants underwent complete colonoscopies for vague abdominal signs or symptoms or for colorectal cancer screening. Several risk factors for colorectal neoplasms and a prior history of gynecological cancer were compared between women with and without colorectal neoplasms. RESULTS: The risk for colorectal neoplasms was only elevated among women with previous endometrial cancer, but with ovarian or cervical cancer, particularly when diagnosed at <50 years of age (adjusted OR=3.7; 95% CI=1.0-13.3, p=0.016). CONCLUSIONS: This study demonstrated a higher risk for colorectal neoplasms in women with previous endometrial cancer, particularly when diagnosed at <50 years of age. Greater emphasis on colorectal cancer screening in this population may be necessary.

Laparoscopic management of large ovarian tumors: clinical tips for overcoming common concerns.

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 ≥15cm and a low possibility of malignancy. RESULTS: The median age of patients was 35years (range 18-84), median body mass index was 22.4kg/m(2) (range 12.4-31.5) and 18 patients had previous operative history. The median tumor diameter was 17cm (range 15-40). There were no conversions to laparotomy and perioperative complications. The median operating time, estimated blood loss, and hospital stay were 80min (range 25-225), 100mL (range 50-500) and 3days (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.

Laparoscopic lymphadenectomy for gynecologic malignancies: evaluation of the surgical approach and outcomes over a seven-year experience.

PURPOSE: The purpose of this study was to evaluate the feasibility and efficacy of laparoscopic lymphadenectomy in patients with gynecologic malignancies and improve upon the existing published data regarding laparoscopic lymphadenectomy. METHODS: We conducted a retrospective chart review of 225 patients with various gynecologic malignancies who had undergone laparoscopic pelvic lymphadenectomy (LPL) and/or laparoscopic para-aortic lymphadenectomy (LPAL) at Kangbuk Samsung Hospital between November 2003 and October 2010. RESULTS: One hundred and seventy-two patients underwent both LPL and LPAL, 47 patients underwent LPL alone, and six patients underwent a repeat laparoscopic lymphadenectomy. The median age and body mass index of the patients were 49.4 years (range 23-79 years) and 24.2 kg/m(2) (range 17.5-37.2 kg/m(2)). The median numbers of harvested pelvic and para-aortic lymph nodes were 25.9 (range 3-63) and 10.6 (range 1-34), respectively. The median operating times for the LPL and LPAL were 72.3 min (range 40-120 min) and 40 min (range 20-70 min), respectively. There were seven cases of major vessel injuries, two lymphocytes, two lymphedemas, and two chylous ascites. There was no unplanned conversion to laparotomy. CONCLUSIONS: Laparoscopic lymphadenectomy can be considered a technically feasible and safe procedure and has become the alternative modality in the field of gynecologic oncology surgery. And our results could reinforce the existing published data regarding laparoscopic lymphadenectomy.

Laparoscopic systemic restaging surgery for women with unexpected uterine malignancy.

OBJECTIVE: We investigated the feasibility of laparoscopic restaging surgery in patients with unexpected uterine cancer. METHODS: This retrospective study included eight patients who underwent laparoscopic restaging surgery for Iran University uterine cancer after a prior hysterectomy or myomectomy. RESULTS: The median age of the patients and their body mass index were 55 years (range, 44-78) and 23.8 kg/m2 (range, 20.75- 31.89), respectively. The median interval between the prior hysterectomy and the restaging surgery was 21 days (range, 10-35). The median operating time and time for the return of bowel activity were 325 minutes (range, 200-475) and 35 hours (range, 18-50), respectively. The median numbers of harvested pelvic and para-aortic lymph nodes were 17.5 (range, 14-29) and 20.5 (range, 7-36), respectively. In seven of the eight patients, uterine extraction was performed with vaginal or electronic morcellation. The final International Federation of Gynecology and Obstetrics stage was IA in all patients. Intraoperative and postoperative complications did not occur in any of the patients, except for the need for transfusion. Patient 4 had synchronous primary cancer (stage IA) of the endometrium and left ovary. Two of the eight patients with clear cell carcinoma received chemotherapy, and none received radiotherapy. All patients survived without disease recurrence. CONCLUSION: Restaging surgery might be necessary for highly selective patients with unexpected uterine malignancies. This would be an alternative surgical modality for complete staging and planning tailored adjuvant treatments. However, lymphadenectomy might not be performed in patients with early uterine cancer.

Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem cells to acquire the physical and functional characteristics of tumor-supporting myofibroblasts.

OBJECTIVE: Most tumor tissue is composed of parenchymal tumor cells and tumor stroma. Mesenchymal stem cells (MSCs) can function as precursors for tumor stromal cells, including myofibroblasts, which provide a favorable environment for tumor progression. A close relationship between tumor cells and MSCs in a tumor microenvironment has been described. Exosomes are small membrane vesicles that are enriched with a discrete set of cellular proteins, and are therefore expected to exert diverse biological functions according to cell origin. METHODS: In the current study, we determined the biological effect of exosomes from two ovarian cancer cell lines (SK-OV-3 and OVCAR-3) on adipose tissue-derived MSCs (ADSCs). RESULTS: Exosome treatment induced ADSCs to exhibit the typical characteristics of tumor-associated myofibroblasts, with increased expression of α-SMA, and also increased expression of tumor-promoting factors (SDF-1 and TGF-ß). This phenomenon was correlated with an increased expression of TGF-ß receptors I and II. Analysis of TGF-ß receptor-mediated downstream signaling pathways revealed that each exosome activated different signaling pathways, showing that exosomes from SK-OV-3 cells increased the phosphorylated form of SMAD2, which is essential in the SMAD-dependent pathway, whereas exosomes from OVCAR-3 cells increased the phosphorylated form of AKT, a representative SMAD-independent pathway. Taken together, exosomes from ovarian cancer cells induced the myofibroblastic phenotype and functionality in ADSCs by activating an intracellular signaling pathway, although the activated pathway could differ from exosome-to-exosome. CONCLUSION: The current study suggested that ovarian cancer-derived exosomes contribute to the generation of tumor-associated myofibroblasts from MSCs in tumor stroma.