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The general consensus is that immune cells are exposed to physiological hypoxia in vivo (PhyO2, 2-5% P(O2)). However, functional studies of B cells in hypoxic conditions are sparse. Recently, we reported the expression in mouse B cells of TASK-2, a member of pH-sensitive two-pore domain K(+) channels with background activity. In this study, we investigated the response of K(+) channels to sustained PhyO2 (sustained hypoxia [SH], 3% P(O2) for 24 h) in WEHI-231 mouse B cells. SH induced voltage-independent background K(+) conductance (SH-K(bg)) and hyperpolarized the membrane potential. The pH sensitivity and the single-channel conductance of SH-K(bg) were consistent with those of TASK-2. Immunoblotting assay results showed that SH significantly increased plasma membrane expressions of TASK-2. Conversely, SH failed to induce any current following small interfering (si)TASK-2 transfection. Similar hypoxic upregulation of TASK-2 was also observed in splenic primary B cells. Mechanistically, upregulation of TASK-2 by SH was prevented by si hypoxia-inducible factor-1α (HIF-1α) transfection or by YC-1, a pharmacological HIF-1α inhibitor. In addition, TASK-2 current was increased in WEHI-231 cells overexpressed with O2-resistant HIF-1α. Importantly, [Ca(2+)]c increment in response to BCR stimulation was significantly higher in SH-exposed B cells, which was abolished by high K(+)-induced depolarization or by siTASK-2 transfection. The data demonstrate that TASK-2 is upregulated under hypoxia via HIF-1α-dependent manner in B cells. This is functionally important in maintaining the negative membrane potential and providing electrical driving force to control Ca(2+) influx.

Microglia are immune effector cells in the central nervous system that participate in tissue repair, inflammatory responses, and neuronal degeneration. The most important signaling factor in the differentiation of immune-active cells after stimulation is the sustained high calcium concentration in the cytosol, which is called store-operated calcium entry (SOCE). Recently, the molecular identity of the store-operated channel (SOC) has revealed that Orai1, Orai2, Orai3, Stim1, and Stim2 constitute the most of SOC. In this study, we demonstrate that Orai1- and Stim1-mediated SOC regulated the phagocytic activity and cytokine release of primary isolated murine microglia. RT-PCR analysis revealed that primary cultured microglia from neonatal ICR mouse brains had Orai1, Orai2, Orai3, and Stim1. To elucidate the role of SOCE in the immune functions of microglia, pharmacological inhibitors or knockdown with Orai1 or Stim1 siRNA was applied, and UDP-induced phagocytic activity and LPS-induced cytokine secretion activity were compared. The pharmacological inhibition and siRNA effect was verified by measuring thapsigargin (TG)-, ATP-, or UDP-activated SOCE Ca2+ influx and proper siRNA-mediated knockdown was verified by western blot analysis. UDP-induced phagocytic activity was inhibited by pharmacological inhibitors of SOCE, such as SKF96365 or 2-APB, and knockdown of Orai1 and Stim1. Cytokine secretion of TNF-α and IL-6 by LPS treatment was also inhibited by SKF96365 and knockdown of Orai1 and Stim1. Meanwhile, LPS stimulation-induced NF-κB activation was not altered, but NFAT1 activity was attenuated with Stim1 knockdown. These results indicate that SOCE, which was composed of Orais and Stim1, regulates UDP-induced phagocytosis and LPS-stimulated cytokine secretion in microglia.

The aim of this study was to evaluate the reliability of using tumour grade and cell type on preoperative endometrial biopsy for the selection of patients for conservative hormone treatment. We retrospectively reviewed results of 643 patients with endometrial carcinoma for tumour grade and 817 for tumour cell type who underwent endometrial biopsy followed by surgery. Of the 357 patients with a grade 1 tumour on preoperative endometrial biopsy, 58 (16.2%) were upgraded based on a final pathology report from hysterectomy specimens. For grade 1, the preoperative endometrial biopsy showed a sensitivity of 80.4%, a specificity of 78.6%, a positive predictive value (PPV) of 83.8% and a negative predictive value (NPV) of 74.5%. Of the 672 patients with the endometrioid cell type on preoperative biopsy, 46 (5.6%) showed a different cell type on final pathology. For the endometrioid cell type, preoperative endometrial biopsy had a sensitivity of 91.3%, a specificity of 64.9%, a PPV of 93.2% and an NPV of 58.6%. This weak predictive value should be considered when selecting patients for conservative hormone treatment.

Objective To compare outcomes after radical hysterectomy in patients with stage IB1 adenocarcinoma (AdCa) and adenosquamous carcinoma (AdSCCa) of the uterine cervix. Methods We performed a retrospective analysis of 265 patients with AdCa and 72 patients with AdSCCa. Demographic, clinicopathologic, surgical, and follow-up data were compared. Results There were no differences in demographic and clinicopathologic characteristics between the two histologic types (AdCa vs. AdSCCa). Only mean size of tumor and lymphovascular space invasion was larger and more frequent in AdSCCa (2.7cm vs 2.3cm, P=0.019 & 29.2% vs 14.7%, P=0.008). After a median follow-up time of 68months, 39 (14.7%) and 13 (18.1%) AdCa and AdSCCa patients, respectively, had recurrent disease (P=0.467), and 33 (12.5%) and 11 (15.3%) patients, respectively, died of their disease (P=0.555). 5-year RFS rates were 89% and 85% (P=0.582), respectively, and 5-year OS rates were 93% and 89% (P=0.787). Histologic type had no clinical impact on RFS and OS in multivariate analysis adjusting for significant prognostic factors. There were no differences in pattern of recurrence and time to recurrence between the two histologic types. When patients were stratified into three risk groups according to the criteria of GOG protocols 92 and 109, histologic type had no clinical impact on RFS and OS in any of the risk groups. Conclusion There are no differences in clinicopathologic factors, patterns of recurrence, time to recurrence, RFS and OS between patients with AdCa and AdSCCa.

Anoctamin 6 (ANO6) is a member of the recently identified TMEM16/anoctamin protein family comprising Ca(2+)-activated Cl(-) channels that generate outward-rectifying ionic currents in response to intracellular Ca(2+) increase. ANO6 is also essential for Ca(2+)-dependent phospholipid scrambling required for blood coagulation. Selective serotonin reuptake inhibitors (SSRIs)--fluoxetine, sertraline, and paroxetine-that are used for the treatment of major depressive disorders can increase the risk of upper gastrointestinal bleeding after chronic treatment. However, at the earlier stage of intake, which is 1-7 days after the treatment, the possibility of blood coagulation might also increase, but transiently. Therefore, in this study, we investigated whether therapeutic SSRI concentrations affected the Cl(-) current or phospholipid scrambling activity of ANO6 by assessing ANO6 currents (I ANO6), phosphatidylserine (PS) exposure, and platelet aggregation. In the whole-cell patch mode, SSRIs facilitated Ca(2+)-dependent activation of IANO6 in ANO6-transfected cells, as evidenced by a significant decrease in the delay of IANO6 generation. On the other hand, in the inside-out patch clamp configuration, SSRIs showed an inhibitory effect on ANO6 currents, suggesting that SSRIs activate ANO6 via an indirect mechanism in intact cells. SSRIs also facilitated Ca(2+)-dependent PS exposure and α-thrombin-induced platelet aggregation. These results indicate that SSRIs at clinically relevant concentrations promote Ca(2+)-dependent activation of ANO6, which may have potential clinical implications such as the underlying mechanism of SSRI-induced adverse drug reactions.

To evaluate the prognostic factors of ovarian granulosa cell tumors (GCTs) and treatment outcomes in recurrent GCT cases.We retrospectively reviewed 91 patients with GCT who were treated in two tertiary Centers between 1989 and 2011.Eighty patients had stage I tumors, five had stage II, and six had stage III. There were 15 cases of recurrence with a median follow-up time of 58 (3-254) months. Multivariate analysis identified greater tumor size and postoperative residual tumor as independent risk factors for recurrence. Twelve patients underwent secondary surgery at first recurrence. At a median follow-up of 50 (4-185) months from first recurrence, the 5-year survival was 60% for patients with and 100% for those without residual tumor after secondary surgery, respectively (p=0.018, log-rank test).Complete cytoreduction is an important prognostic factor for recurrent cases as well as initial treatment of GCT.

To evaluate the long-term outcomes and risk factors for recurrence after fertility-sparing laparoscopic radical trachelectomy (LRT) in young women with early-stage cervical cancer.Eighty-eight consecutive patients from four tertiary cancer centers in Korea who had attempted fertility-sparing LRT for early-stage cervical cancer were included in this study.Seventy-nine patients completed LRT. The mean age and tumor size were 31 years (range, 20-40 years) and 1.8 cm (range, 0.4-7 cm), respectively. Twenty-nine patients had a tumor size greater than 2 cm, 22 had deep stromal invasion greater than 50%, and twelve had lymphovascular space invasion. After a median follow-up time of 44 months (range, 3-105 months), nine patients had recurrence and one had died of disease. A tumor size greater than 2 cm (P = 0.039) and a depth of stromal invasion greater than 50% (P = 0.016) were significant risk factors for recurrence.This is the largest series on fertility-sparing LRT in young women with early cervical cancer. LRT is a feasible and safe fertility-sparing alternative to radical hysterectomy in these women. A tumor size greater than 2 cm and a depth of stromal invasion greater than 50% were risk factors for recurrence.

The TP53 mutations have been proved to be predominated in ovarian cancer in a study from The Cancer Genome Atlas (TCGA). However, the molecular characteristics of recurrent ovarian cancers following initial treatment have been poorly estimated. This study was to investigate the pattern of somatic point mutations in matched paired samples of primary and recurrent epithelial ovarian cancers, using the OncoMap mutation detection protocol. We have adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. OncoMap v.4.4 was used to evaluate genomic DNA isolated from a set of 92 formalin-fixed, paraffin-embedded (FFPE) tumors, consisting of matched paired samples of initially diagnosed and recurrent tumors from 46 epithelial ovarian cancer (EOC) patients. Mutations were observed in 33.7% of the samples, with 29.3% of these samples having a single mutation and the remaining 4.3% having two or more mutations. Among the 41 genes analyzed, 35 mutations were found in four genes, namely, CDKN2A (2.2%), KRAS (6.5%), MLH1 (8.2%) and TP53 (20.7%). TP53 was the most frequently mutated gene, but there was no correlation between the presence of mutation in any gene and clinical prognosis. Furthermore, somatic mutations did not differ between primary and recurrent ovarian carcinomas. Every mutation present in recurrent samples was detected in the corresponding primary sample. In conclusion, these OncoMap data of Korean EOC samples provide that somatic mutations were found in CDKN2A, KRAS, MLH1, and TP53. No differences in mutational status between primary and recurrent samples were detected. To understand the biology of tumor recurrence in epithelial ovarian cancer, more studies are necessary, including epigenetic modifications or additional mutations in other genes.

Background/Aims: Ginseng regulates gastrointestinal (GI) motor activity but the underlying components and molecular mechanisms are unknown. We investigated the effect of gintonin, a novel ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, on the pacemaker activity of the interstitial cells of Cajal (ICC) in murine small intestine and GI motility. Materials and Methods: Enzymatic digestion was used to dissociate ICC from mouse small intestines. The whole-cell patch-clamp configuration was used to record pacemaker potentials and currents from cultured ICC in the absence or presence of gintonin. In vivo effects of gintonin on gastrointestinal (GI) motility were investigated by measuring the intestinal transit rate (ITR) of Evans blue in normal and streptozotocin (STZ)-induced diabetic mice. Results: We investigated the effects of gintonin on pacemaker potentials and currents in cultured ICC from mouse small intestine. Gintonin caused membrane depolarization in current clamp mode but this action was blocked by Ki16425, an LPA1/3 receptor antagonist, and by the addition of GDPβS, a GTP-binding protein inhibitor, into the ICC. To study the gintonin signaling pathway, we examined the effects of U-73122, an active PLC inhibitor, and chelerythrine and calphostin, which inhibit PKC. All inhibitors blocked gintonin actions on pacemaker potentials, but not completely. Gintonin-mediated depolarization was lower in Ca2+-free than in Ca2+-containing external solutions and was blocked by thapsigargin. We found that, in ICC, gintonin also activated Ca2+-activated Cl- channels (TMEM16A, ANO1), but not TRPM7 channels. In vivo, gintonin (10-100 mg/kg, p.o.) not only significantly increased the ITR in normal mice but also ameliorated STZ-induced diabetic GI motility retardation in a dose-dependent manner. Conclusions: Gintonin-mediated membrane depolarization of pacemaker activity and ANO1 activation are coupled to the stimulation of GI contractility through LPA1/3 receptor signaling pathways in cultured murine ICC. Gintonin might be a ingredient responsible for ginseng-mediated GI tract modulations, and could be a novel candidate for development as a prokinetic agent that may prevent or alleviate GI motility dysfunctions in human patients.

Fatty acid distribution was investigated in ethnically and economically homogenous Korean mothers (n = 40) and neonates. Venous blood, maternal before delivery and cord, was obtained. Choline (CPG) and ethanolamine (EPG) phosphoglycerides and sphingomyelin (SM) were assayed. Mean arachidonic acid (AA) level was higher in plasma CPG and SM (p < 0.0001), and red cell CPG (p < 0.0001), EPG (p < 0.0001) and SM (p = 0.005) of the neonates. Similarly, the neonates had higher proportions of docosahexaenoic acid (DHA) in plasma CPG (p < 0.0001) and red cell CPG (p = 0.001) and EPG (p = 0.036). In contrast, linoleic and alpha-linolenic acids were significantly higher in maternal blood. Mead acid was elevated in plasma CPG (p < 0.0001) and red cell CPG and EPG (p < 0.0001) of the neonates. Consistent with data from high-fat-intake populations, our subjects, whose traditional diet is low in fat, exhibited maternal-fetal gradient in AA and DHA in plasma and red cell phospholipids. This may be due to an imbalance between supply and maternal and fetal requirements, and/or a physiological response to pregnancy. Prenatal nutritional constraint is associated with impaired development and a risk of chronic diseases in adults. AA and DHA are vital nutrients. Hence, there is a need to investigate whether the discrepancy between maternal and neonatal AA and DHA is a manifestation of nutritional insufficiency.

To estimate the feasibility and conversion rate of laparoscopic radical hysterectomy (LRH) in early-stage cervical cancer. Data were collected from the medical records of 260 consecutive patients with stage IA2 to IIA2 cervical cancer who had undergone LRH, regardless of age, body mass index, prior abdominal surgery, uterus size, or tumor size. The median patient age was 48 years (range, 26–78 years), 11.9 % of whom were elderly (≥65 years), 11.2 % were obese (≥30 kg/m2), 15.4 % had undergone previous abdominal surgery, and 13.1 % had a tumor larger than 4 cm. Negative-margin resection was feasible in all patients except one. The median operative time and estimated blood loss were 253 min (range, 111–438 min) and 300 mL (range, 80–2000 mL), respectively. Intraoperative and postoperative complications occurred in seven (2.7 %) and 10 patients (3.8 %), respectively. Four patients (1.5 %) required intraoperative conversion to laparotomy, three of which were due to conglomerated metastatic lymph nodes surrounding the aorta (n = 2), the left external iliac vein (n = 1) or the left ureter (n = 1). LRH was still completed in the four conversion patients, and a laparotomy was required for the removal of the conglomerated metastatic lymph nodes and the repair of the injured vessels. The conversion rate to laparotomy among patients undergoing LRH for early-stage cervical cancer was 1.5 % when performed exclusively in consecutive patients. LRH showed comparable feasibility and effectiveness to open radical hysterectomy in the treatment of early-stage cervical cancer.

We describe a case of mediastinal lymphangioma that suddenly progressed in utero. The initial sonographic impression was one of pericardial effusion while the follow-up examination revealed a mediastinal cystic mass. At 35 weeks of gestation preterm labor occurred. An ultrasound examination performed at this time demonstrated the mediastinal cyst with internal hemorrhage and fetal hydrops. The cystic mass was resected 5 days after birth. The diagnosis of lymphangioma was made from histological examination. The infant was followed up for 18 months and remained well. We recommend frequent prenatal sonographic follow-up when a localized fluid collection is shown in the mediastinum. Copyright © 2000 International Society of Ultrasound in Obstetrics and Gynecology

Objectives: The purpose of the present study is to evaluate the relationship between endometrial concentrations of estrogen receptor (ER) and progesterone receptor (PR), and sonographic endometrial findings in the preovulatory phase of menstrual cycle. Study Design: In 45 cycles of 45 infertile women with tubal factor only, transvaginal sonographic assessments and biopsy for immunohistochemical staining of the endometrium were made in the preovulatory phase of unstimulated, normal menstrual cycle. Immunohistochemical localization of ER and PR was scored according to intensity of staining and proportion of cells specifically stained in glandular epithelium and stroma, and the results were analysed according to the sonographic endometrial thickness ( 10 mm) and patterns. Endometrial patterns were classified as A, centrally hyperechogenic triple-line pattern or non-A, not triple-line. Results: There were no significant differences in the endometrial thickness, serum estradiol level and serum progesterone level between A and non-A groups. The receptor scores of epithelial and stromal ER and epithelial PR were comparable in A and non-A groups. However, the receptor score of stromal PR was significantly higher in A group, with 4.8 ± 1.4 compared with 2.7 + 1.7 in non-A group (p < 0.001). There were no differences in the receptor scores of epithelial ER, epithelial PR, stromal ER and stromal PR among the 3 groups according to the endometrial thickness. Conclusions: This study suggests that high PR expression in endometrial stroma could be related to the sonographic triple-line or multilayered pattern of endometrium in the preovulatory period.

Plasma triacylglycerol (TG) fatty acid composition of healthy non-pregnant and non-lactating women, expectant mothers and their term neonates from Seoul, South Korea was investigated. They were ethnically homogenous and the women had comparable age and parity. Blood samples were obtained at recruitment, third trimester and birth from the non-pregnant women, expectant mothers and neonates respectively. Percent levels of linoleic and arachidonic acids and n-6 metabolites and total n-6 were significantly lower in the pregnant women than in the non-pregnants (p < 0.0001). Similarly, there were lower levels of alpha-linolenic (p = 0.033), eicosapentaenoic and docosahexaenoic acids and n-3 metabolites and total n-3 (p < 0.0001) in the expectant mothers. Compared with their mothers, the neonates had higher proportions of dihomo-gamma-linolenic, arachidonic, docosatetraenoic and docosapentaenoic acids and n-6 metabolites (p < 0.0001) and lower linoleic acid (p < 0.0001). Of the n-3 series, alpha-linolenic acid was lower (p < 0.0001) and eicosapentaenoic, docosapentaenoic and docosahexaenoic acids and n-3 metabolites and total n-3 higher (p < 0.0001) in the neonates compared with their mothers. The study reveals that pregnancy is associated with a reduction in the relative levels of plasma triacylglycerol arachidonic and docosahexaenoic acids. Moreover, it indicates that the decline is a manifestation of selective transfer of these fatty acids to the developing fetus.

Objective Little is known regarding cervical cancer survivors' employment status, which represents social integration of cancer survivors as a pivotal domain of long-term quality of life. The goal of this study was to assess the correlates of unemployment and evaluate the impact on the comprehensive quality of life in cervical cancer survivors. Methods We enrolled 858 cervical cancer survivors from the gynecologic oncology departments of multi-centers in Korea. Factors associated with unemployment were identified using multivariate logistic regression analyses. We assessed different health-related quality of life domains with multivariate-adjusted least-square means between cervical cancer survivors who currently work and do not. Results After diagnosis and treatment, the percentage of unemployed survivors increased from 50.6% to 72.8%. Lower income (adjusted odds ratio [aOR], 1.97; 95% confidence interval [CI], 1.38 to 2.81), medical aid (aOR, 1.58; 95% CI, 1.05 to 2.38), two or more comorbidities (aOR, 1.80; 95% CI, 1.12 to 2.90), current alcohol drinkers (aOR, 2.33; 95% CI, 1.54 to 3.52), and employed at the time of diagnosis (aOR, 10.72; 95% CI, 7.10 to 16.16) were significantly associated with unemployment. Non-working groups showed significant differences with respect to physical functioning, role functioning, depression, and existential well-being. Conclusion The proportion of unemployed cervical cancer survivors seems to increase, with low-income status and the presence of medical aid negatively being associated with employment, in addition to other comorbidities and previous working status. Effort should be made to secure the financial status of cervical cancer survivors.

Objective The aim of this study was to elucidate the significance of tumor volume as a risk factor for predicting lymph node metastasis. Methods We applied the tumor volume index to the data that were collected for 327 Korean patients with endometrial cancer who underwent preoperative assessment including magnetic resonance imaging (MRI) and subsequent surgery including systematic lymphadenectomy. The volume index, which we previously reported in the literature, was defined as the product of maximum longitudinal diameter along the uterine axis, maximum anteroposterior diameter in a sagittal section image, and maximum horizontal diameter in a horizontal section image according to MRI data, from 425 Japanese women with endometrial cancer. Relationships between lymph node metastasis and results of preoperative examinations including volume index were analyzed by logistic regression analysis. Results The prevalence of affected lymph nodes was 14.2%. Multivariate analysis showed that high-grade histology assessed by endometrial biopsy [odds ratio (OR); 2.9, 95% confidence interval (CI): 1.4–6.4], volume index (OR; 2.4, 95% CI: 1.1–5.3), node enlargement assessed by MRI (OR; 4.2, 95% CI: 1.4–13.2), and high serum cancer antigen (CA)125 level (OR; 3.6, 95% CI: 1.6–8.1) were significantly and independently related to lymph node metastasis. When volume index was excluded from the analysis, myoinvasion assessed by MRI was an independent risk factor for lymph node metastasis as well as high-grade histology, node enlargement, and high serum CA125 level. Conclusion Volume index is compatible with myometrial invasion as a factor for predicting lymph node metastasis in endometrial cancer.

Vorinostat (VOR) has been reported to enhance the cytotoxic effects of doxorubicin (DOX) with fewer side effects because of the lower DOX dosage in breast cancer cells. In this study, we investigated the novel mechanism underlying the synergistic cytotoxic effects of VOR and DOX co-treatment in cervical cancer cells HeLa, CaSki and SiHa cells. Co-treatment with VOR and DOX at marginal doses led to the induction of apoptosis through caspase-3 activation, poly (ADP-ribose) polymerase cleavage and DNA micronuclei. Notably, the synergistic growth inhibition induced by the co-treatment was attributed to the upregulation of the pro-apoptotic protein Bad, as the silencing of Bad expression using small interfering RNA (siRNA) abolished the phenomenon. As siRNA against p53 did not result in an increase in acetylated p53 and the consequent upregulation of Bad, the observed Bad upregulation was mediated by acetylated p53. Moreover, a chromatin immunoprecipitation analysis showed that the co-treatment of HeLa cells with VOR and DOX increased the recruitment of acetylated p53 to the bad promoter, with consequent bad transactivation. Conversely, C33A cervical cancer cells containing mutant p53 co-treated with VOR and DOX did not exhibit Bad upregulation, acetylated p53 induction or consequent synergistic growth inhibition. Together, the synergistic growth inhibition of cervical cancer cell lines induced by co-treatment with VOR and DOX can be attributed to the upregulation of Bad, which is induced by acetylated p53. These results show for the first time that the acetylation of p53, rather than histones, is a mechanism for the synergistic growth inhibition induced by VOR and DOX co-treatments.

Objectives We aimed to develop a risk model to predict a risk of suboptimal cytoreduction in primary surgery of ovarian cancer. Methods The clinical records and computed tomography (CT) data of 358 patients with stages II–IV epithelial ovarian cancer were reviewed. Tumor spread patterns identified by principal component analysis, CA-125, and a newly developed surgical skill index were integrated into a logistic model along with other variables. Internal validation was performed using bootstrapped re-sampling and calibration was assessed by goodness-of-fit test. Results Among the 358 patients, optimal cytoreduction, which was defined as no residual tumor, was achieved in 145 patients (40.5%). The surgical capacity of an individual institution was estimated by a surgical skill index, which was the frequency of complex surgeries in patients with advanced disease. In a multivariate model, two distinctive CT patterns of tumor spread (diffuse spread pattern and upper abdominal extension pattern), a surgical skill index, and serum CA-125 independently predicted a risk of suboptimal cytoreduction (P=0.006, P=0.013, P=0.031, and P=0.001, respectively). The model showed a C-statistic of .73 (95% confidence interval .67 to .79), which was significantly higher than tumor stage or ascites. Rigorous internal validation by bootstrapped re-sampling successfully confirmed the model. Conclusions We identified two distinct tumor spread patterns of ovarian cancer, which can be integrated to improve a prediction model. Our model may be useful in patient referral or clinical trials for patient stratification.

This study aimed to prospectively correlate clinical outcomes of advanced epithelial ovarian cancer (AEOC), with the results of in vitro chemosensitivity testing of taxol and carboplatin using the in vitro histoculture drug response assay (HDRA). A total of 104 patients with AEOC were treated with combination chemotherapy of taxol and carboplatin after primary cytoreductive surgery between 2007 and 2012 at the Asan Medical Center, Seoul, Korea. To compare chemosensitivity in the HDRA with clinical response, all patients were first categorized into two groups as either sensitive to both taxol and carboplatin (SS), or not sensitive to one or both drugs (R) based on HDRA results. The recurrence rate was much lower in the SS group compared to the R group; 29.2% vs 69.8%, respectively (p=0.02). The SS group had a significantly longer progression-free survival compared to the R group, 34.0 months vs 16.0 months, respectively (p=0.025). These results demonstrate that the HDRA prospectively correlates to clinical outcome from chemotherapy and that treatment regimens can be individualized based on the HDRA.

Purpose To develop a nomogram predicting the risks of distant metastasis following postoperative adjuvant radiation therapy for early stage cervical cancer. Materials and methods We reviewed the medical records of 1069 patients from ten participating institutions. Patients were divided into two cohorts: a training set ( n =748) and a validation set ( n =321). The demographic, clinical, and pathological variables were included in the univariate Cox proportional hazards analysis. Clinically established and statistically significant prognostic variables were utilized to develop a nomogram. Results The model was constructed using four variables: histologic type, pelvic lymph node involvement, depth of stromal invasion, and parametrial invasion. This model demonstrated good calibration and discrimination, with an internally validated concordance index of 0.71 and an externally validated c-index of 0.65. Compared to FIGO staging, which showed a broad range in terms of distant metastasis, the developed nomogram can accurately predict individualized risks based on individual risk factors. Conclusions The devised model offers a significantly accurate level of prediction and discrimination. In clinical practice it could be useful for counseling patients and selecting the patient group who could benefit from more intensive/further chemotherapy, once validated in a prospective patient cohort.

In 1988 we published three papers describing immunoassay results for urine beta-core fragment as a marker of gynecological cancers. Many other papers have been published since, and three commercial immunoassays have been established. beta-Core fragment is called beta-core, UGF, or UGP by different commercial vendors. To avoid confusion we call it beta-core/UGF/UGP here. In this 7-year report, we compare the three commercial assays, establish cutoff limits, and use the Ciba-Corning kit for two large studies. The first was a retrospective study, measuring beta-core/UGF/UGP in gynecological cancer and control urines accumulated in our freezers (n = 486). The second is a first prospective study, testing over a 16-month period beta-core/UGF/UGP levels in urines of all new patients attending the Gynecology Oncology Clinic (n = 548). In the retrospective study, elevated beta-core/UGF/UGP levels (1.9 ng/ml) were detected in 11% of urines from healthy individuals (n = 132), in 11% from women with benign gynecological disease (n = 196), in 44% from cervical cancer (n = 68), 56% from ovarian cancer (n = 54), and 47% from endometrial cancer (n = 38). Altogether, beta-core/UGF/UGP levels were elevated in 50% of 170 samples from gynecological cancers. Overall, sensitivity increased with advancing stage of malignancy. Sensitivity was 28% for stage I, 50% for stage II, 47% for stage III, and 68% for stage IV malignancies. In the prospective study very similar results were recorded. Elevated beta-core/UGF/UGP levels (1.9 ng/ml) were detected in 11% of urines from healthy individuals (n = 99), 11% from individuals with benign gynecological disease (n = 196), 7% from women with carcinoma in situ (n = 28), in 42% of samples from cervical cancer (n = 69), 56% from ovarian cancer (n = 59), and 52% from endometrial cancer. Altogether, beta-core/UGF/UGP levels were elevated in 48% of 225 gynecological cancer samples. Overall, sensitivity increased with advancing stage of malignancy. Sensitivity was 29% for stage I, 66% for stage II, 60% for stage III, and 77% for stage IV malignancies. In both studies sensitivity for beta-core/UGF/UGP increased with advancing stage of disease. Sensitivity for cervical and endometrial cancers was slightly lower than that for ovarian malignancies. This difference may be due to the preponderance of advanced-stage-disease patients in the ovarian cancer group. beta-Core/UGF/UGP may be a general stage-dependent marker for all gynecological cancers. The same false-positive results and very similar sensitivity values were found in a retrospective and a prospective study. They confirm each other, and suggest a definitive false-positive rate and sensitivity of this tumor marker for gynecological cancers.

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.

OBJECTIVE: To analyze pregnancy outcomes in young women with stage IA, grade 1 endometrioid adenocarcinoma of the uterus after successful fertility-sparing management using progestin. METHODS: We reviewed the medical records of 141 women with stage IA, grade 1 endometrioid adenocarcinoma of the uterus who had complete remission after progestin treatment. Statistical analysis was performed using Student's t test or Mann-Whitney U test for continuous variables, using χ or Fisher's exact test for categorical variables, and using log-rank test for survival comparison. RESULTS: Fifty-four (38.3%) women in the study cohort had a history of infertility. Seventy (49.6%) of the 141 patients tried to conceive with 44 (62.9%) receiving fertility drugs. The median interval to attempted pregnancy after treatment was 5 months (range 1-31 months). The median age at the time of the pregnancy trial was 32.4 years (range 23-40 years). Fifty-one (73%) of 70 women who tried to conceive were successful and 46 (66%) gave birth to 58 live neonates. The spontaneous abortion rate, ectopic pregnancy rate, and preterm delivery rates in our cohort were 24%, 2.8%, and 11.5%, respectively. The 5-year disease-free survival was similar between patients who received fertility drugs (n=44) or who did not (n=97) (73% compared with 62%, P=.335), and this rate was significantly higher in patients who achieved at least one pregnancy (n=51) than those who did not (n=90) (76% compared with 62%, P=.028). CONCLUSIONS: Although the proportion of patients with a history of subfertility or infertility was high in our cohort, the pregnancy outcomes were very promising using assisted reproductive technology. The use of fertility drugs was not associated with a higher incidence of cancer recurrence after successful fertility-sparing management in this study population. LEVEL OF EVIDENCE: II.

ObjectiveTo investigate potential therapeutic targets and prognostic markers for low-grade endometrial stromal sarcoma (LGESS).Materials and MethodsThirty-nine patients with LGESS were included in this study. Using tissue microarrays, the immunohistochemical expression levels of 5 therapeutic targets (epidermal growth factor receptor, human epidermal growth factor 2, vascular endothelial growth factor receptor, platelet-derived growth factor receptor [PDGFR], and c-kit) and 3 proteins involved in cell proliferation (p16, p53, and ki67) were investigated. The associations between these targets, markers, other clinicopathological factors, disease-free survival (DFS), and overall survival (OS) were analyzed.ResultsEpidermal growth factor receptor and human epidermal growth factor 2 were not expressed in these 39 patients. Vascular endothelial growth factor receptor, PDGFR, c-kit, p16, p53, and ki67 were expressed in 10 (25.6%), 28 (71.8%), 32 (82.1%), 18 (46.2%), 4 (10.3%), and 21 (53.8%) patients, respectively. The expression of each marker was not significantly associated with other clinicopathological factors. On multivariate analysis, p53 and ki67 were associated with significantly poorer DFS and OS. The 5-year DFS rates were 88%, 46%, and 0% for the p53(−)/ki67(−) group (n = 18), p53(−)/ki67(+) group (n = 17), and p53(+)/ki67(+) group (n = 4) (P = 0.002), respectively; the 5-year OS rates were 100%, 71%, and 0%, respectively (P < 0.001). The time to recurrence was longer (P = 0.123), and more patients had distant recurrence in the p53(+)/ki67(+) group (P = 0.063).ConclusionsIn patients with LGESS, c-kit and PDGFR were expressed in higher portions of patients, suggesting that imatinib mesylate should be investigated as a potential targeting agent. Both p53 and ki67 demonstrated strong prognostic implications, suggesting that further evaluation using these markers is required.

The Korean Gynecologic Oncology Group (KGOG) recently proposed new pre-operative criteria to identify a low-risk group for lymph node metastasis in endometrial cancer. The aim of this study was to test whether the good performance of the criteria can be reproducible in diverse clinical settings.From two Japanese hospitals, 319 patients with endometrial cancer who underwent systemic lymphadenectomy were retrospectively reviewed. In one hospital, para-aortic lymphadenectomy was routinely performed, but it was selectively performed in the other hospital. The performance of the criteria was determined by adjusting the false-negative rate (FNR) at the given prevalence of nodal metastasis of 10% using Bayes' theorem.Nodal metastasis rate of the study population was 12.9%. The KGOG low-risk criteria identified 181 of 319 patients as a low-risk group (51%), and three false-negative cases were found (1.9%). Despite a significant difference in the nodal metastasis rate (18.2% and 8.8%, P=.012) and the surgical policy for para-aortic lymphadenectomy (100% and 48.9%, P.001) between the two hospitals, KGOG criteria consistently showed a very low adjusted FNR at the prevalence of 10% in both hospitals (1.8% vs. 1.1%, respectively). Among the entire study population, the adjusted FNR was 1.4% (95% confidence interval, .5% to 4.3%), which was similar to the FNR of 1.3% in our previous study.The KGOG low-risk criteria accurately identified a low-risk group for lymph node metastasis with acceptable false negativity regardless of diverse clinical settings.

5560Background: The efficacy and safety of laparoscopic surgery in the treatment of apparently early stage epithelial ovarian cancer is controversial. The aim of this study was to evaluate the long...

Difference in prognosis between grade 3 endometrioid carcinoma (G3EC) of the endometrium and uterine serous carcinoma (USC) is controversial. In this study, we further evaluated the difference in prognosis, if any, between G3EC (n = 61) and USC (n = 47) on a total of 565 patients with endometrial cancer. In addition, meta-analysis was performed using data from seven previous publications (n = 8,637) and from the Asan Medical Center (n = 108). Regarding the cases from our institution, USC tended to occur in older patients (≥65 years) than G3EC (P = 0.011). Deep myometrial invasion (more than or equal to half) was more frequently identified in G3EC (36/61, 59.0 %) than in USC (17/47, 36.2 %) (P = 0.021). Between patients with early stage G3EC and USC (stages I and II), there were no significant differences in any clinicopathological parameter, but there was a significant difference in overall survival (P = 0.017) that was not found in advanced stage (P = 0.588). USC was an independent prognostic factor for poor overall survival (hazard ratio, 6.125; P = 0.030) in early stage patients. In the meta-analysis on 5-year survival in patients with early stage cancers, which also included our study results, a higher relative risk (1.92, 95 % CI 1.62–2.27) was demonstrated in USC than in G3EC (P

Objective To develop a nomogram for predicting the probability of 5year survival after definitive concurrent chemoradiotherapy (CCRT) in locally advanced cervical cancer (LACC). Methods Between 1998 and 2008, 209 patients with LACC were treated with definitive CCRT. Multivariate analysis using Cox proportional hazards regression model was performed. A nomogram based on this Cox model was developed and internally validated by bootstrapping. Its performance was assessed by using the concordance index and a calibration curve. Results The median age was 55years (range, 26–78). Of the patients, 9, 16, 129, 3, 42 and 10 had FIGO stage IB2, IIA, IIB, IIIA, IIIB, and IVA disease, respectively. Histology revealed that 190, 13, 4, and 2 patients had squamous, adenocarcinoma, adenosquamous, and small cell cervical cancer, respectively. In 91 patients, PET/CT was performed before CCRT. The median follow-up period was 51months (range, 6–151) and there were 50 (23.9%) disease-related deaths. Multivariate regression analysis revealed that histology, tumor size, and paraaortic lymph node metastasis (defined by MRI), but not PET/CT before CCRT, were independent predictors of overall survival. A nomogram for predicting the 5year survival incorporating these three significant variables was constructed. The concordance index was 0.69. The predictive ability of the nomogram proved to be superior to that of the FIGO staging system ( p Conclusions The nomogram was a better predictive model for overall survival than the FIGO staging system. If externally validated, it could be used to counsel patients with LACC who must choose additional treatment modalities after definitive CCRT.

Objective To analyse the long-term oncologic outcomes of a fertility-sparing management using oral progestin in young women with endometrial cancer. Methods We analysed 148 patients (age⩽40years) with stage IA, grade 1, endometrioid adenocarcinoma of the uterus who underwent fertility-sparing management using daily oral medroxyprogesterone acetate (MPA) or megestrol acetate (MA). Results 115 (77.7%) showed complete response (CR) to progestin treatment, and 35 (30.4%) of them experienced recurrence after median follow-up time of 66months. The 5-year recurrence-free survival was 68% (95% confidence interval [CI], 58.5–76.9%). However, 33 patients (22.3%) who failed to achieve CR underwent definitive surgical management, and no one had recurrence after median follow-up time of 41months. During progestin treatment and at the time of recurrence, no patient showed clinical progression of disease over stage IA. Body mass index (BMI) ⩾25kg/m 2 was the only significant factor associated with a failure to achieve CR (odds ratio [OR], 3.00; 95% CI, 1.35–6.66; P =0.007). Upon multivariate analysis, BMI⩾25kg/m 2 (OR, 2.14; 95% CI, 1.06–4.31; P =0.033) was significantly associated with a higher risk of recurrence and the use of MPA (compared to MA) (OR, 0.44; 95% CI, 0.22–0.88; P =0.021), maintenance treatment (OR, 0.22; 95% CI, 0.05–0.94; P =0.042) and pregnancy (OR, 0.25; 95% CI, 0.11–0.56; P =0.001) were significantly associated with a lower risk of recurrence. Conclusion Fertility-sparing management was highly effective and safe. BMI 2 , MPA (compared to MA), maintenance treatment and pregnancy were associated with higher possibility of long-term success.

To compare survival and surgical outcomes of laparoscopic (LRH) and open radical hysterectomy (ORH) in patients with stage IB2 and IIA2 cervical cancer.A retrospective analysis was performed on 303 patients with stage IB2 and IIA2 cervical cancer who underwent LRH (n = 115) or ORH (n = 188).Two patients (1.7%) in the LRH group required conversion to laparotomy. There was no difference with respect to operating time, perioperative change in hemoglobin level, and need for transfusion. However, in the LRH group, estimated blood loss (P = 0.003) was significantly lower, time to recovery of bowel movement (P0.001) and length of postoperative hospital stay (P0.001) were significantly shorter, and postoperative complications were significantly less frequent (P = 0.036). The 5-year disease-free survival was 78% in the LRH group and 77% in the ORH group (P = 0.718), and 5-year overall survival was 83% in both groups (P = 0.746). There were no differences in pattern of recurrence (P = 0.225) and median time to recurrence (12 vs. 13 months; P = 0.240).LRH has similar therapeutic efficacy to ORH in patients with bulky early-stage cervical cancer. However, LRH has more favorable surgical outcomes. Therefore, LRH is not only a reasonable alternative to ORH but also the preferred surgical procedure for these patients.

article i nfo Objective. The purpose of this study was to evaluate the performance of human epididymis protein 4 (HE4) and the Risk of Ovarian Malignancy Algorithm (ROMA) for distinguishing between benign and malig- nant pelvis masses in Asian women. Methods. This was a prospective, multicenter (n=6) study with patients from six Asian countries. Pa- tients had a pelvic mass on imaging and were scheduled to undergo surgery. Serum CA125 and HE4 were measured on preoperative samples. CA125, HE4, and ROMA were evaluated for sensitivity, specificity, posi- tive predictive value (PPV) and negative predictive value (NPV). Results. A total of 414 women with an adnexal mass were evaluated, of which 65 had epithelial ovarian (EOC) cancer, 16 had borderline tumors and 11 had other malignant diseases. Compared to CA125, HE4 had lower sensitivity (56.9% vs 90.8%) and NPV (91.8% vs 97.3%), but improved specificity (96.9% vs 67.1%) and PPV (78.7% vs 35.8%) for differentiating between benign pelvic mass and EOC. ROMA had similar sensi- tivity (89.2% vs 90.8%) and NPV (97.6% vs 97.3%) as CA125, but showed improved specificity (87.3% vs 67.1%) and PPV (58.6% vs 35.8%). ROMA accurately predicted 87.3% of benign cases as low risk, and 82.6% of stage I/II EOC and 89.2% of all EOC as high risk. Conclusion. ROMA showed similar sensitivity as CA125 but improved specificity and PPV, especially in premenopausal women. Using ROMA may help predict if a pelvic mass is benign or malignant and facilitate subsequent management planning.

To compare the surgical and oncological outcomes of laparoscopic radical hysterectomy and open radical hysterectomy in obese women with early-stage cervical cancer.The medical records of 166 patients with stage IA2-IIA2 cervical cancer and a body mass index of at least 30 who underwent laparoscopic radical hysterectomy (n=54) or open radical hysterectomy (n=112) at the Asan Medical Center between 1998 and 2011 were reviewed.None of the patients in the laparoscopic radical hysterectomy group required conversion to laparotomy. The resection margin was negative in 98.1% of the laparoscopic radical hysterectomy group and 98.2% of the open radical hysterectomy group (P=.976). No difference between the two groups was observed in terms of operating time, perioperative hemoglobin level change, transfusion requirement, or the number of retrieved lymph nodes. Compared with open radical hysterectomy, laparoscopic radical hysterectomy was associated with a significant reduction in the following: interval to return of bowel movements (2 days compared with 2.7 days, P.001); duration of postoperative hospital stay (9.3 days compared with 21 days, P.001), postoperative complications (5.6% compared with 17.9%, P=.032), and estimated blood loss (494 mL compared with 620 mL, P=.009). After a median follow-up period of 44 months, the 5-year disease-free survival rate was 88% for the laparoscopic radical hysterectomy group and 85% for the open radical hysterectomy group (P=.682). The 5-year overall survival rate was 97% for the laparoscopic radical hysterectomy group and 90% for the open radical hysterectomy group (P=.220).Laparoscopic radical hysterectomy was a preferred alternative to open radical hysterectomy in the present cohort of obese women with early-stage cervical cancer because it is associated with a more favorable surgical outcome without compromising survival outcomes.II.

Introduction The main methods of treatment of endometrial carcinoma are hysterectomy and bilateral oophorectomy with lymphadenectomy. However, another option for hormonal treatment of endometrial carcinoma, the use of progesterone in young patients to preserve childbearing capacity, has been reported, and a high remission rate has been described in well-selected stage I, grade 1 endometrial cancer. Although it is intriguing that hormonal therapy alone can treat endometrial carcinoma without surgery or cytotoxic chemotherapy, the molecular basis for the effects of progesterone on endometrial carcinoma is not clearly known. MicroRNAs (miRNAs) are a class of naturally occurring small, noncoding RNA molecules that control cellular function and are known to function as both tumor suppressors and oncogenes. Thus, in the present study, changes in the miRNA profile of endometrial carcinoma cells on progesterone treatment were studied. Method To elucidate the mechanism of hormonal treatment in endometrial carcinoma cells, we studied the changes in miRNA expression in endometrial carcinoma cells on treatment with progesterone using the Hec1A endometrial carcinoma cell line as a model system. Hec1A cells were treated with medroxyprogesterone acetate, and total RNA was extracted. The changes in the miRNA profile after progesterone treatment were determined using a microarray containing 868 miRNAs. Results Of 868 miRNAs, the expression levels of miR-625*, -21, -142-5p, and 146b-5p were increased by more than 400%, whereas the expression levels of miR-633, -29c, -29*, and -193b were decreased by 50%. To validate the array results, quantitative real-time polymerase chain reactions were performed. Conclusions MiRNA expression was modulated by progesterone treatment in endometrial carcinoma cells, implying a possible critical role of miRNAs in regulating posttranscriptional gene expression on progesterone treatment. Further studies are required to clarify the mechanism involved in the hormonal treatment of endometrial carcinoma.

Transient receptor potential melastatin 7 (TRPM7) plays a role in a number of physiological and pharmacological functions in variety of cells. The aim of this study was to clarify the role for TRPM7 channels and the effect of waixenicin A on the pacemaking activity of interstitial cells of Cajal (ICCs) and on the cell viability of the human gastric and breast adenocarcinoma cell lines, AGS and MCF-7, respectively. Waixenicin A decreased the amplitude of pacemaker potentials in cultured ICC clusters and inhibited TRPM7 currents, but had no effect on Ca(2+) -activated Cl(-) conductance (ANO1). Furthermore, waixenicin A was found to inhibit the growth and survival of AGS and MCF-7 cells. These findings indicate that TRPM7 channel modulates intestinal motility and regulates the pathophysiology of human gastric and breast adenocarcinoma cells. These findings suggest that TRPM7 channel be considered a potential target for the treatment of gut motor disorders and gastric and breast cancer.

Congenital mesoblastic nephroma is the most common neonatal kidney tumor and surgical excision is almost always curative. We report the prenatal detection of congenital mesoblastic nephroma by sonography and magnetic resonance imaging. After birth, a right nephrectomy was performed and the baby recovered well.

Aims and background Radiation therapy provides a safe and effective alternative treatment option for recurrent epithelial ovarian cancer, although it has not been a treatment of choice. We evaluated the efficacy and toxicity of radiation therapy for recurrent epithelial ovarian cancer after chemotherapy according to the disease status. Methods This was a retrospective study of 38 patients with recurrent epithelial ovarian cancer treated with radiation therapy at the Asan Medical Center, Seoul, Korea, between January 1997 and December 2007. We analyzed their clinical characteristics and the outcome of radiation therapy. Results Thirty-eight patients were treated with radiation therapy. Their median age was 51.5 years. Most patients were FIGO stage III (27/38) with serous adenocarcinoma (26/38). All patients had received at least one regimen of platinum-based chemotherapy; 24 patients were sensitive to the first chemotherapy and the others were resistant. Lymph node and abdominopelvic wall were the most common sites of radiation therapy. The response rate was 65.0% (16 complete remissions and 10 partial remissions), and the median regression rate was 78.8% (range, −66.6 to 100.0). Median progression-free survival was 7.2 months (range, 1.0–66.6). In 28 patients who had a solitary relapsed site from the radiographic finding at the time of radiation therapy, it was 10.7 months (range, 1.8–66.6). Neither hematologic nor intestinal toxicity of grade 3–4 was observed. Prognostic factors were sensitivity to platinum and the site treated with radiation therapy. Conclusions Radiation therapy is a treatment that should be considered for recurrent epithelial ovarian cancer, especially in good responders to platinum or patients with solitary relapsed lesions.

Purpose Histological assessment of parametrial invasion in uterine cervical cancer is often subjective due to the parametrium being a loosely defined structure without apparent definitive landmarks. This study defines a precise and consistent histological landmark for the parametrium. Methods Based on study of cervico-parametrial junctions in 22 type III radical hysterectomy specimens from FIGO stage IB/IIA patients, three candidate histological landmarks were tested for ease in determination and reliability in 66 hysterectomy specimens with FIGO stage IIB tumors. The candidate landmarks were abrupt narrowing point of vascular branches, adipose/loose connective tissue of parametrium, and presence of a distinct smooth muscle layer in the outermost cervical wall. Results All uteri had a distinct smooth muscle layer in outermost cervical wall. The layer was compact, circumferential, and continuous with the corpus above and vagina below. It clearly distinguished parametrium from cervical wall, especially when the Masson trichrome stain was used which differentiated fibrous tissue from smooth muscle. Smooth muscle bundles are also present in the parametrium, but course perpendicularly or diagonally to the cervical wall, clearly distinguishable from the circular smooth muscle in the outer wall. With clear histological criteria, concordance rates among three pathologists rose from 55% to 98%. Conclusion Clear histological criteria together with the use of Masson trichrome stains to distinguish smooth muscle from fibrous tissue improved concordance rates in identifying parametrial invasion by tumor to near 100%.

Objective To analyze the role of surgical staging and adjuvant chemotherapy in patients with adult type granulosa cell tumor (GCT) of the ovary. Methods Patients were divided into those with early-stage (stages I–II, n=93) and advanced-stage (stages III–IV, n=13) GCT and analyzed separately in this retrospective study. Results Of the 93 patients with early-stage GCT, 30 were completely staged and 25 underwent lymph node dissection. After surgery, 17 patients received adjuvant chemotherapy with bleomycin/etoposide/cisplatin (BEP). None had lymph node metastasis. Completely staged patients had no recurrence or deaths. However, recurrences were observed in 9 of 63 patients (14.3%) who did not undergo complete staging, with four (6.3%) dying due to disease. The 5-year disease-free survival (DFS) rates of groups with and without complete staging were 100% and 84%, respectively (P=0.037). Adjuvant chemotherapy was not significantly associated with DFS (P=0.193). All patients with advanced-stage GCT underwent optimal cytoreduction and received adjuvant chemotherapy with BEP. None of the 6 patients who completed 6 cycles of BEP had recurrence, whereas 5 of the 7 patients (71.4%) who received fewer than 6 cycles of BEP had recurrences and 3 (42.9%) died due to disease. The 5-year DFS rates of these two groups were 100% and 50%, respectively (P=0.022), with cycles of chemotherapy being the only significant factor for DFS in patients with advanced-stage GCT. Conclusions Complete surgical staging is recommended, but lymph node removal is not recommended for early-stage GCT. Optimal debulking followed by six cycles of BEP chemotherapy is recommended for advanced-stage GCT.

Uterine sarcomas are rare, heterogeneous malignant tumours of several histologic types originating from mesenchymal tissues of the uterus. The most common histologic types are carcinosarcoma, leiomyosarcoma, and endometrial stromal sarcoma, accounting for 90% of uterine sarcomas. To date, no effective treatment has been found to achieve a high rate of cure or prolong survival. Although complete surgical excision of the tumour is the only curative treatment modality, the rarity of these tumours and their diversity of histologic types have precluded the development of standard surgical strategies. Surgery may also be optimal for recurrent uterine sarcomas, but indications for secondary surgical treatment have not been established. Here, we describe recent changes in, and updates of, the surgical treatment of the three most common types of malignant uterine sarcomas.

To evaluate the clinical and prognostic impact of micropapillary pattern in patients with serous borderline ovarian tumors (SBOT).We retrospectively assessed 130 consecutive patients with typical (n=97, 74.6%) or micropapillary (n=33, 25.4%) SBOT. Clinicopathologic factors and outcomes were compared between these two groups.There were no significant between-group differences in age, menopausal status, parity, body mass index, cancer antigen 125 concentration, tumor size, tumor rupture, positive cytology, ovarian surface involvement, retrieved lymph nodes, use of laparoscopy, fertility-sparing and ovary-sparing procedures, complete staging and restaging, and adjuvant chemotherapy. However, the incidences of advanced stage (II-III) tumors (10.3% vs 36.4%, P=0.001), microinvasion (2.1% vs 15.2%, P=0.012), peritoneal implants (8.3% vs 33.4%, P0.001), and lymph node involvement (0% vs 21.2%, P0.001) were significantly higher in patients with micropapillary than with typical SBOT. Five patients with typical (5.2%) and three with micropapillary (9.1%) SBOT had recurrent disease (P=0.418), and one patient (3%) in micropapillary SBOT group died due to the disease (P=0.254). The 5-year disease-free survival (DFS) rates for patients with typical and micropapillary SBOT were 96% and 86%, respectively (P=0.148). All three patients with micropapillary SBOT who had recurrence had peritoneal implants (one noninvasive and two invasive). Multivariate analysis showed that peritoneal implant was the only significant factor related to DFS (P=0.002).Because micropapillary SBOT was significantly associated with peritoneal implants, especially invasive implants, and lymph node involvement, complete staging procedures, including lymph node dissection, are recommended. However, micropapillary SBOT itself was not significantly associated with DFS. Peritoneal implant was the only factor independently associated with tumor recurrence.

Mast cells are activated by specific allergens and also by various nonspecific stimuli, which might induce physical urticaria. This study investigated the functional expression of temperature sensitive transient receptor potential vanilloid (TRPV) subfamily in the human mast cell line (HMC-1) using whole-cell patch clamp techniques. The temperature of perfusate was raised from room temperature (RT, 23~25℃ to a moderately high temperature (MHT, 37~39℃ to activate TRPV3/4, a high temperature (HT, 44~46℃ to activate TRPV1, or a very high temperature (VHT, 53~55℃ to activate TRPV2. The membrane conductance of HMC-1 was increased by MHT and HT in about 50% (21 of 40) of the tested cells, and the I/V curves showed weak outward rectification. VHT-induced current was 10-fold larger than those induced by MHT and HT. The application of the TRPV4 activator 4α-phorbol 12,13-didecanoate (4αPDD, 1µM) induced weakly outward rectifying currents similar to those induced by MHT. However, the TRPV3 agonist camphor or TRPV1 agonist capsaicin had no effect. RT-PCR analysis of HMC-1 demonstrated the expression of TRPV4 as well as potent expression of TRPV2. The [Ca(2+)](c) of HMC-1 cells was also increased by MHT or by 4αPDD. In summary, our present study indicates that HMC-1 cells express Ca(2+)-permeable TRPV4 channels in addition to the previously reported expression of TRPV2 with a higher threshold of activating temperature.