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Background The endometrium, the inner lining of the uterine cavity, plays essential roles in embryo implantation and its subsequent development. Although some positive results were preliminarily archived, the regeneration of damaged endometrial tissues by administrating stem cells only is very challenging due to the lack of specific microenvironments and their low attachment rates at the sites of injury. In this context, various biomaterial-based scaffolds have been used to overcome these limitations by providing simple structural support for cell attachment. However, these scaffold-based strategies also cannot properly reflect patient tissue-specific structural complexity and thus show only limited therapeutic effects. Method Therefore, in the present study, we developed a customizable Lego-like multimodular endometrial tissue architecture by assembling individually fabricated tissue blocks. Results Each tissue block was fabricated by incorporating biodegradable biomaterials and certain endometrial constituent cells. Each small tissue block was effectively fabricated by integrating conventional mold casting and 3D printing techniques. The fabricated individual tissue blocks were properly assembled into a larger customized tissue architecture. This structure not only properly mimics the patient-specific multicellular microenvironment of the endometrial tissue but also properly responds to key reproductive hormones in a manner similar to the physiological functions. Conclusion This customizable modular tissue assembly allows easy and scalable configuration of a complex patient-specific tissue microenvironment, thus accelerating various tissue regeneration procedures.

Background: In 2018, nocturia and nocturnal lower urinary tract function definitions were updated in a clinically and practically based consensus report by the International Continence Society Standardization Steering Committee. Previous research has suggested that the pathophysiology of nocturia has a multifactorial etiology, including obstructive sleep apnea, overactive bladder syndrome, diabetes mellitus, sleep disturbance, congestive heart failure, primary polydipsia, and other factors.Current Concepts: Three main mechanisms have been identified: low functional bladder capacity, nocturnal polyuria, and diurnal polyuria (24-hour polyuria). Multifactorial pathophysiology implies multiple possible targets for therapeutic intervention, and suggests that it is unlikely that one treatment modality, including drugs, will be successful in all patients. The bladder diary is the most important diagnostic tool.Discussion and Conclusion: Strong evidence supports the efficacy of desmopressin and continuous positive pressure breathing. Antimuscarinic drugs for treating nocturia display limited usefulness because of their low efficacy for nocturnal polyuria. Management of nocturia may require a multidisciplinary approach to visualization and phenotyping of patients for diagnosis and therapy.

The aim of this study was to compare the clinical characteristics of patients with tubo-ovarian abscess (TOA) who responded to medical treatment and those who underwent surgical intervention due to medical treatment failure. Electronic medical records were evaluated retrospectively to identify patients who were diagnosed with TOA. Demographic, clinical, and laboratory data including white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were compared between the medical treatment group and the surgical intervention group. Patient age, TOA diameter, WBC count, CRP, and ESR were significantly different between the groups. On multiple regression analysis, significant correlations were identified between age (

Background: Smokers directly inhale mainstream cigarette smoke, which contains numerous known and potential toxic substances, and thus, smoking is expected to have broad harmful effects that cause tissue injury and dysfunction. Interestingly, many studies have suggested that the recent decline in female fertility and increased rate of spontaneous abortion could be associated with increased smoking rates. Indeed, women that smoked for 10 years or more were reported to have a ~20% higher infertility rate than women that had never smoked. However, the reasons for the underlying harmful aspects of smoking on female fertility remain a matter of debate. Importantly, a previous study revealed that resident endometrial stem cell deficiency significantly limits the cyclic regeneration potential of endometrium, which in turn, decreases successful pregnancy outcomes. In this context, we postulated that exposure to mainstream cigarette smoke extracts might decrease female fertility by inhibiting the functions of resident endometrial stem cells.Methods: We investigated whether cigarette mainstream smoke exposure directly inhibits various tissue regeneration-associated functions of endometrial stem cells, such as self-renewal, migration, pluripotency, and differentiation capacity in vitro. Next, we determined whether SERPINB2 mediates cigarette smoke-induced suppressive effects on various tissue regeneration-associated functions by depleting SERPINB2 expression with specific shRNA targeting SERPINB2. Mice were injected intraperitoneally with low (0.5 mg/kg) or high (1 mg/kg) doses of cigarette smoke extract (10 times for two weeks), and endometrial stem cells were then isolated from mice uterine tissuesResults: We found that exposure to cigarette smoke extracts remarkably suppressed various tissue regeneration-associated functions of endometrial stem cells, such as self-renewal, migration, multilineage differentiation ability, and pluripotency in vitro and in vivo by activating the SERPINB2 gene. Indeed, cigarette smoke-induced inhibitory effects on various endometrial stem cell functions were significantly abolished by SERPINB2 knockdown. Conclusions: These findings provide valuable information on the harmful effects of cigarette smoking on resident endometrial stem cells and hopefully will facilitate the developments of promising therapeutic strategies for subfertile or infertile women that smoke cigarettes.

The major challenges of most adult stem cell-based therapies are their weak therapeutic effects caused by the loss of multilineage differentiation capacity and homing potential. Recently, many researchers have attempted to identify novel stimulating factors that can fundamentally increase the differentiation capacity and homing potential of various types of adult stem cells. Tryptophanyl-tRNA synthetase (WRS) is a highly conserved and ubiquitously expressed enzyme that catalyzes the first step of protein synthesis. In addition to this canonical function, we found for the first time that WRS is actively released from the site of injury in response to various damage signals both in vitro and in vivo and then acts as a potent nonenzymatic cytokine that promotes the self-renewal, migratory, and differentiation capacities of endometrial stem cells to facilitate the repair of damaged tissues. Furthermore, we also found that WRS, through its functional receptor cadherin-6 (CDH-6), activates major prosurvival signaling pathways, such as Akt and extracellular signal-regulated kinase (ERK)1/2 signaling. Our current study provides novel and unique insights into approaches that can significantly enhance the therapeutic effects of human endometrial stem cells in various clinical applications.

The aim of this study was to compare gasless single-port access (SPA) laparoscopy using a J-shaped retractor and conventional SPA laparoscopy in patients undergoing adnexal surgery. Study design The medical records of 80 patients who underwent laparoscopic adnexal surgery between May 2017 and April 2019 were reviewed. Of the 80 patients, 40 patients underwent gasless SPA laparoscopy using a J-shaped retractor and 40 underwent conventional SPA laparoscopy. All surgeries were performed by one laparoscopic surgeon. Surgical outcomes were compared between the two groups. There are no significant differences in age, body mass index, parity, previous abdominal surgery, tumor marker, and tumor diameter between the gasless and conventional groups. The median retraction setup time from skin incision was 7 min (range 5–12 min) in gasless SPA laparoscopic adnexal surgery. The median total operation times were 55.5 min (range 30–155 min) in the gasless group and 55 min (range 30–165 min) in the conventional group without a significant difference. Additionally, there were no differences in operation type, conversion rate of laparotomy, use of an additional trocar, and pathological outcomes between the two groups. No major complications, such as urologic, bowel, and vessel injuries, were found in both groups. Gasless SPA laparoscopy using a J-shaped retractor appears to offer a better alternative to conventional SPA laparoscopy that avoids the potential negative effects of carbon dioxide gas in selected cases.

Local endometrial stem cells play an important role in regulating endometrial thickness, which is an essential factor for successful embryo implantation and pregnancy outcomes. Importantly, defects in endometrial stem cell function can be responsible for thin endometrium and subsequent recurrent pregnancy losses. Therefore, many researchers have directed their efforts toward finding a novel stimulatory factor that can enhance the regenerative capacity of endometrial stem cells. Sonic hedgehog (SHH) is a morphogen that plays a key role in regulating pattern formation throughout embryonic limb development. In addition to this canonical function, we identified for the first time that SHH is actively secreted as a stem cell-activating factor in response to tissue injury and subsequently stimulates tissue regeneration by promoting various beneficial functions of endometrial stem cells. Our results also showed that SHH exerts stimulatory effects on endometrial stem cells via the FAK/ERK1/2 and/or phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. More importantly, we also observed that endometrial stem cells stimulated with SHH showed markedly enhanced differentiation and migratory capacities and subsequent in vivo therapeutic effects in an endometrial ablation animal model.

Objective This study aimed to evaluate the current surgical techniques for anterior and posterior vaginal wall prolapse repair in South Korea.Methods A web-based questionnaire survey was sent to 780 members of the Korean Society of Obstetrics and Gynecology. The items assessed in the questionnaire were the demographic characteristics and current surgical techniques used for the correction of anterior and posterior vaginal wall prolapse.Results The response rate was 16%. There were variations in the suture materials and methods used for anterior and posterior colporrhaphy. Most respondents used only rapid absorbable suture materials to plicate the fibromuscular layer and close the mucosal layer of the anterior and posterior vaginal wall. Simple interrupted sutures are the most popular suture method for both the fibromuscular and mucosal layers. Thirty-one and eleven percent of the respondents used mesh for surgical correction of anterior and posterior vaginal wall prolapse, respectively. Concomitant perineorrhaphy was routinely performed with posterior vaginal wall repair by 42% of the respondents, whereas 58% performed perineorrhaphy only in cases with perineal defects.Conclusion There is considerable diversity in the current surgical techniques for anterior and posterior vaginal wall prolapse repair in Korea. Further research is required to standardize the surgical techniques.

Luteinizing hormone (LH) stimulates the synthesis and secretion of the key steroid hormone estrogen, which subsequently promotes ovarian follicular growth and development. Therefore, the administration of exogenous LH to achieve superovulation (multiple ovulations) and an LH surge is commonly used as the most effective therapeutic option in a majority of in vitro fertilization (IVF) clinics. However, a relatively low pregnancy rate (between 20% and 35%) is one of the most challenging aspects of LH-based infertility treatment. Furthermore, the major cause of this low pregnancy rate in LH-based infertility treatment remains unidentified. Recent studies have shown that endometrial stem cell loss or deficiency can significantly decrease tissue regeneration ability during the menstrual cycle and reduce endometrial receptivity. In this context, we postulated that the low pregnancy rates following LH-based ovarian hyperactivation may be the result of the adverse effects of consecutive exogenous LH administration on endometrial stem cells. To the best of our knowledge, this study revealed for the first time that in addition to its previously reported roles in stimulating ovarian functions through the pituitary-gonadal axis, LH brings about the extragonadal suppression of various tissue regeneration-associated functions in endometrial stem cells, such as self-renewal, migration ability, multilineage differentiation potential, and pluripotency/stemness, by inhibiting pro-survival Akt and ERK1/2 signaling pathways in vitro and in vivo, and as a consequence, it decreases the endometrial receptivity.

We explored the relationship between asthma and early menarche in a representative sample of Korean adolescents.Web-based self-reported data collected from 2006 to 2015 by the Korean Youth Risk Behavior Web-based Survey were used. Menarche status was divided into "early" (12 years of age, n = 69,520) and "not early" (≥12 years of age, n = 234,065).Adolescent girls with early menarche exhibited a higher incidence of asthma (8.1% vs 7.4%, P .001), more frequent school absences because of asthma (10.8% vs 8.7%), and more frequent ≤4-day stretches of school absence (4.6% vs 2.4%) compared with girls with "not early" menarche (all P .001). Multivariate analysis performed after adjusting for multiple confounders revealed a 1.04-fold (95% confidence interval [CI] 1.00-1.07) greater likelihood of asthma in the early menarche than not early menarche group. In addition, the odds ratios for missing school due to asthma for 1 to 3 and ≥4 days per year in the early menarche group were 1.00 (95% CI 1.00-1.02) and 1.21 (95% CI 1.01-1.46), respectively.Adolescents with early menarche exhibited increased incidences of asthma and severe asthma.

Follicle-stimulating hormone (FSH) promotes the production and secretion of estrogen, which in turn stimulates the growth and maturation of ovarian follicles. Therefore, consecutive FSH treatment to induce ovarian hyperstimulation (superovulation) is still considered the most cost-effective option for the majority of assisted reproductive technologies (ARTs). However, a relatively high cancellation rate and subsequent low pregnancy outcomes (approximately 15%) are the most challenging aspects of this FSH-based ART. Currently, the main cause for this low implantation rate of FSH-based ART has not yet been revealed. Therefore, we hypothesized that these high cancellation rates with FSH-based superovulation protocols might be associated with the harmful effects of consecutive FSH treatment. Importantly, several recent studies have revealed that tissue-resident stem cell deficiency can significantly reduce cyclic endometrial regeneration and subsequently decrease the pregnancy outcome. In this context, we investigated whether FSH treatment could directly inhibit endometrial stem cell functions and consequently suppress endometrial regeneration. Consistent with our hypothesis, our results revealed for the first time that FSH could inhibit various regeneration-associated functions of endometrial stem cells, such as self-renewal, migration, and multilineage differentiation capacities, via the PI3K/Akt and ERK1/2 signaling pathways both in vitro and in vivo.

Chronic stress has a negative impact on many fertility-related functions; thus, the recent decline in female fertility seems to be at least partially associated with increased stress. The secretion of glucocorticoids is a typical endocrine response to chronic stress and indirectly reduces uterine receptivity through the hypothalamus-pituitary-gonadal (HPG) axis. However, in addition to its well-known canonical role, the direct effects of chronic stress-induced glucocorticoids on various uterine functions and their underlying molecular mechanisms are complex and have not yet been revealed. Recent studies have found that resident stem cell deficiency is responsible for the limited regenerative potential of the endometrium (the innermost lining of the uterine cavity) during each menstrual cycle, which subsequently increases infertility rates. In this context, we hypothesized that stress-induced glucocorticoids directly damage endometrial stem cells and consequently negatively affect endometrial reconstruction, which is important for uterine receptivity. In addition to its well-known canonical roles, we identified for the first time that cortisol, the most abundant and potent glucocorticoid in humans, directly suppresses the multiple beneficial functions (self-renewal, transdifferentiation, and migratory potential) of human endometrial stem cells through its functional receptor, glucocorticoid receptor (GR). Glucocorticoids inhibit well-known survival signals, such as the PI3K/Akt and FAK/ERK1/2 pathways. More importantly, we also found that immobilization of stress-induced glucocorticoids suppresses the various beneficial functions of tissue resident stem cells in vivo. To the best of our knowledge, this is the first study to investigate the direct effects of glucocorticoids on the regenerative capacity of endometrial stem cells, and the findings will facilitate the development of more promising therapeutic approaches to increase female fertility.

Endometrial stem cells are located in the basal layer of the endometrium, and they are responsible for the cyclic regeneration of the uterus during the menstrual cycle. Recent studies have revealed that recurrent pregnancy loss is associated with an age-related stem cell deficiency in the endometrium. Therefore, intensive study of endometrial stem cell aging may provide new insights for preventing recurrent pregnancy loss. Sonic hedgehog (SHH) signaling has been identified as a morphogen during the embryonic development processes. In addition to this canonical function, we found that the age-associated decline in regenerative potential in the endometrium may be due to decreased SHH-signaling integrity in local stem cells with aging. Importantly, the current study also showed that SHH activity clearly declines with aging both in vitro and in vivo, and exogenous SHH treatment significantly alleviates various aging-associated declines in multiple endometrial stem cell functions, suggesting that SHH may act as an endogenous anti-aging factor in human endometrial stem cells. Moreover, we found that stem cell senescence may enhance SERPINB2 expression, which in turn mediates the effect of SHH on alleviating senescence-induced endometrial stem cell dysfunctions, suggesting that SERPINB2 is a master regulator of SHH signaling during the aging process.

Cancer stem cells (CSCs) have been identified in a multiple of cancer types and resistant to traditional cancer therapies such as chemotherapeutic agents and radiotherapy, which may destroy bulk tumor cells but not all CSCs, contributing to reformation tumor masses and subsequent relapse. Moreover, it is very difficult to effectively identify and eliminate CSCs because they share some common phenotypic and functional characteristics of normal stem cells. Therefore, finding better therapeutic strategies to selectively target CSCs might be helpful to reduce subsequent malignancies. In the present study, we found that caffeic acid effectively suppresses self-renewal capacity, stem-like characteristics, and migratory capacity of CD44+ and CD133+ colorectal CSCs in vitro and in vivo. In addition, we also revealed that PI3K/Akt signaling may be linked to multiple colorectal CSC-associated characteristics, such as radio-resistance, stem-like property, and tumorigenic potential. To the best of our knowledge, this is the first study demonstrating that caffeic acid effectively targets colorectal CSC populations by inhibiting the growth and/or self-renewal capacity of colorectal CSCs through PI3K/Akt signaling in vitro and in vivo.

IntroductionThe anterior vaginal wall is the segment most commonly affected by prolapse. Traditionally, anterior vaginal wall prolapse is repaired via anterior colporrhaphy, which is known to have a high recurrence rate. Several factors might affect the outcome of anterior colporrhaphy, and the use of absorbable sutures might also be associated with the high recurrence rate because the sutures might not be able to retain adequate strength until the plicated pubocervical fascia remodels and regains maximum tensile strength. Nonetheless, no comparative data exist about the relative efficacy and safety of anterior colporrhaphy using non-absorbable versus absorbable sutures. The objective of this study is to compare the surgical outcomes of anterior colporrhaphy using non-absorbable sutures with those of anterior colporrhaphy using absorbable sutures.Methods and analysisThis is a randomised, multicentre, superiority trial. Anterior colporrhaphy will be performed in a traditional manner with midline plication of the fibromuscular layer using either non-absorbable or absorbable sutures. The primary outcome is composite surgical success 1 year after surgery defined as the absence of all of the following: (1) anterior vaginal descent beyond the hymen, (2) the presence of vaginal bulge symptoms and (3) retreatment for recurrent anterior vaginal wall prolapse with either surgery or pessary. The secondary outcomes include the individual components of the composite primary end point, anatomical outcomes, condition-specific quality of life and adverse events related to anterior colporrhaphy. The planned number of participants is 192.Ethics and disseminationThis study was approved by the Institutional Review Board of Seoul National University Hospital (H-1810-037-977). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings.Trial registration numberNCT03736811

IntroductionTransvaginal reconstructive surgery is the mainstay of treatment for symptomatic pelvic organ prolapse. Although adequate support for the vaginal apex is considered essential for durable surgical repair, the optimal management of anterior and posterior vaginal wall prolapse in women undergoing transvaginal apical suspension remains unclear. The objective of this trial is to compare surgical outcomes of pelvic organ prolapse quantification (POPQ)-based surgery with outcomes of simulated apical support-based surgery for anterior or posterior vaginal wall prolapse at the time of transvaginal apical suspension.Methods and analysisThis is a randomised, multicentre, non-inferiority trial. While women who are assigned to the POPQ-based surgery group will undergo anterior or posterior colporrhaphy for all stage 2 or greater anterior or posterior vaginal prolapse, those assigned to simulated apical support-based surgery will receive anterior or posterior colporrhaphy only for the prolapse unresolved under simulated apical support. The primary outcome measure is the composite surgical success, defined as the absence of anatomical (anterior or posterior vaginal descent beyond the hymen or descent of the vaginal apex beyond the half-way point of vagina) or symptomatic (the presence of vaginal bulge symptoms) recurrence or retreatment for prolapse by either surgery or pessary, at 2 years after surgery. Secondary outcomes include the rates of anterior or posterior colporrhaphy, the changes in anatomical outcomes, condition-specific quality of life and sexual function, perioperative outcomes and adverse events.Ethics and disseminationThis study was approved by the institutional review board of each participating centre (Seoul National University College of Medicine/Seoul National University Hospital, Chonnam National University Hospital, Seoul St. Mary’s Hospital, International St. Mary’s Hospital). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings.Trial registration numberNCT03187054

Thin endometrium lining or severe endometrial injury which may occur during artificial abortion can cause defective endometrial receptivity and subsequent infertility. Therefore, much effort has been devoted toward regenerating thin or damaged endometrial lining by applying multiple types of stem cells. Even though there are some positive preliminary outcomes, repairing the injured endometrium with stem cells is considerably challenging, due to the lack of an adequate microenvironment for the administrated stem cells within the tissues and subsequent poor therapeutic efficiency. In this context, as an alternative, we fabricated a 3D stem cell-laden artificial endometrium by incorporating several biodegradable biomaterials (collagen and hyaluronic acid) and multiple cellular components of endometrium (endometrial stem cells, stromal cells, and vessel cells) to properly recapitulate the multicellular microenvironment and multilayered structure. Agarose was used as an inert filler substrate to enhance the mechanical integrity of the three-layered artificial endometrium. Various mechanical characteristics, such as morphology, compression properties, swelling, and viscosity, have been evaluated. Various biological features, such as steroid hormone responsiveness, specific endometrial cell-surface marker expressions, and the secretion of multiple growth factors and steroid hormones, as well as the viability of encapsulated endometrial cells are relatively well maintained within the artificial endometrium. More importantly, severe tissue injuries were significantly relieved by transplanting our 3D artificial endometrium into endometrial ablation mice. Remarkably, artificial endometrium transplantation resulted in a successful pregnancy with subsequent live birth without any morphological or chromosomal abnormalities.

Objective This study aimed to compare the risks of intraoperative and postoperative urologic complications after robotic radical hysterectomy (RRH) compared with laparoscopic radical hysterectomy (LRH). Data Sources We searched Pubmed, EMBASE, and the Cochrane Library for studies published up to March 2019. Related articles and relevant bibliographies of published studies were also checked. Methods of Study Selection Two researchers independently performed data extraction. We selected comparative studies that reported perioperative urologic complications. Tabulation, Integration, and Results Twenty-three eligible clinical trials were included in this analysis. When all studies were pooled, the odds ratio for the risk of any urologic complication after RRH compared with LRH was .91 (95% confidence interval [CI], .64–1.28; p = .585). The odds ratios for intraoperative and postoperative complications after RRH versus LRH were .86 (95% CI, .48–1.55; p = .637) and .94 (95% CI, .64–1.38; p = .767), respectively. In a secondary analysis study quality, study location, and the publication year were not associated with intraoperative or postoperative urologic complications. Conclusion Current evidence suggests that RRH is not superior to LRH in terms of perioperative urologic complications.

Conventional 2D or even 3D in vitro culture models for human reproductive organs cannot properly recapitulate the bidirectional endocrine crosstalk between the uterine endometrium and the ovary. This crosstalk is essential for maintaining the various physiological features and functions of each tissue. Moreover, most in vitro models for the female reproductive tract also fail to mimic its multicellular structure. We therefore developed a novel ‘dual reproductive organ on a chip’ that reflects the bidirectional endocrine cross-talk and the complex multicellular structures by integrating various cellular components of both the human uterine endometrium and the ovary with several biodegradable natural polymers. Indeed, the bidirectional endocrine crosstalk between these two tissues is achieved through media sharing between channels, and it can markedly improve the viability of loaded cells within each chamber of the chip platform. In addition, we also identified a reliable reproductive toxicity marker, SERPINB2, which is significantly increased in response to various toxic exposures in both endometrial and ovarian follicular cells. Based on these findings, we next established a SERPINB2 luciferase reporter system that was specifically designed for detecting and quantifying the toxicity of certain substances. By introducing this SERPINB2 luciferase reporter system into the loaded cells within the chip platform, we ultimately developed an effective ‘dual reproductive organ-on-chip’ that was successfully used to predict the reproductive toxicity of various hazardous materials.

Background and objectives Gasless laparoscopy is an alternative method to reduce the number of carbon dioxide (CO2)-insufflated, pneumoperitoneum-related problems including shoulder pain, postoperative nausea/vomiting, and decreased cardiopulmonary function. In this study, we investigated the feasibility of gasless total laparoscopic hysterectomy (TLH) with a newly developed abdominal-wall retraction system. Methods Abdominal-wall retraction for gasless laparoscopy was performed using the newly developed J-shape retractor and the Thompson surgical retractor. Surgical outcomes between gasless TLH and conventional CO2-based TLH were compared for each of 40 patients for the period from January 2017 to October 2019. Results Between gasless TLH and conventional CO2-based TLH, no significant differences were observed for age, body mass index, parity, or surgical indications. The mean retraction setup time from skin incision was 7.4 min (range: 4-12 min) with gasless TLH. The mean total operation times were 87.9 min (range: 65-170) with gasless TLH and 90 min (range: 45-180) with conventional TLH, which showed no significant difference. Estimated blood loss and uterus weight also showed no significant intergroup difference. No major complications related to the ureter, bladder, or bowel were encountered. Conclusion Our new abdominal-wall retraction system for gasless TLH allowed for easy setup and a proper operation field in the performance of laparoscopic hysterectomy.

OBJECTIVE We compared the outcomes of the midurethral sling (MUS) with and without concomitant prolapse repair. METHODS We retrospectively reviewed the outcomes of 203 women who underwent MUS at Severance Hospital from January 2009 to April 2012 with and without concomitant prolapse repair. Patients completed the urogenital distress inventory questionnaire preoperatively and postoperatively. The outcomes were assessed by using validated questionnaires and reviewing medical records. McNemar's test, t-test, and multiple logistic regression were used for analysis. RESULTS We noted that women who underwent MUS alone were more likely to experience urinary frequency (12% vs. 25%, P = 0.045), urgency (6% vs. 24%, P < 0.001), and bladder emptying difficulty (2% vs. 10%, P = 0.029) compared to those who underwent concomitant repair. Women who only MUS were more likely to experience discomfort in the lower abdominal or genital region compared to those who than those who underwent concomitant repair; however, the difference was not significant (5% vs. 11%, P = 0.181). In the MUS only group, maximal cystometric capacity (MCC) was a significant parameter of preoperative and postoperative urinary frequency (P = 0.042; odds ratio, 0.994; P = 0.020; odds ratio, 0.993), whereas the Valsalva leak point pressure (VLPP) was a significant factor of postoperative bladder emptying difficulty (P = 0.047; odds ratio, 0.970). CONCLUSION The outcomes did not differ between patients who underwent MUS alone and those with concomitant repair. In the MUS only group, MCC and VLPP were significant urodynamics study parameters related to urinary outcome.

Breast cancer is the leading cause of deaths from cancer in women. Cancer recurrence is the most common cause of mortality in breast cancer patients. The cancer stem cell (CSC) hypothesis proposes that CSCs are the center of cancer development and recurrence. Targeting CSCs, in combination with standard chemotherapy, may prevent cancer recurrence and improve long-term survival. Stem cells can be enriched in non-adherent sphere cultures. To identify molecular targets in breast CSCs, we evaluated the transcription levels of stem cell-related genes in 4T1 mouse mammary cancer cells grown as spheres or in a monolayer culture. The most differentially expressed gene was found to be wingless-type MMTV integration site family member 1 (Wnt1) in the 4T1 sphere culture. Functionally, knockdown of Wnt1 in breast cancer cell lines suppressed the in vitro properties of the stem-like cells, including their sphere-forming ability and ALDH activity, whereas the addition of recombinant Wnt1 to breast cancer cell lines enhanced the in vitro properties of these stem-like cells. In addition, knockdown of Wnt1 in 4T1 cells affected the properties of the stem-like cells in vivo, including their tumorigenic potential and tumor initiation ability. Collectively, these results suggest that Wnt1 expression may give rise to the properties of CSCs in breast tumors. Therefore, targeting Wnt1-associated signaling proteins may provide an effective therapeutic approach for the treatment of advanced breast cancer.

Aberrant DNA methylation plays an important role in the development of cancer. It has been reported recently that DNA hypermethylation is involved in the maintenance of cancer stem cells. The present study was designed to test the hypothesis that the demethylating agent, 5-aza-2`-deoxycytidine (AZA), can inhibit the potential for maintenance of cancer stem cells. To validate this hypothesis, we used 4T1 syngeneic mouse models of breast cancer. The AZA pre-treated 4T1 cells showed a dramatic inhibition of tumorsphere formation, compared to their counterparts in vitro. In addition, the AZA treatment significantly suppressed the expression of stem regulator genes, such as oct-4, nanog and sox2, compared to counterparts in vivo. Therefore, selective inhibition of DNA methylation may be useful for stem-specific cancer therapy.

Alzheimer’s disease (AD) is characterized by neuronal loss in several regions of the brain. Recent studies have suggested that stem cell transplantation could serve as a potential therapeutic strategy to halt or ameliorate the inexorable disease progression. However, the optimal stage of the disease for stem cell transplantation to have a therapeutic effect has yet to be determined. Here, we demonstrated that transplantation of neural stem cells into 12-month-old Tg2576 brains markedly improved both cognitive impairments and neuropathological features by reducing β-amyloid processing and upregulating clearance of β-amyloid, secretion of anti-inflammatory cytokines, endogenous neurogenesis, as well as synapse formation. In contrast, the stem cell transplantation did not recover cognitive dysfunction and β-amyloid neuropathology in Tg2576 mice aged 15 months when the memory loss is manifest. Overall, this study underscores that stem cell therapy at optimal time frame is crucial to obtain maximal therapeutic effects that can restore functional deficits or stop the progression of AD.

Purpose The aim of this study was to evaluate the effect of surgical repair of pelvic organ prolapse on female sexual function and to assess correlations between the two using two current standardized questionnaires. Materials and Methods From October 2009 to September 2010, 143 patients with posterior compartment or combined vaginal prolapse were included. We assessed surgical outcomes according to anatomical change in the vagina and results of the Female Sexual Function Index (FSFI) and Pelvic Organ Prolapse/Urinary Incontinence Sexual Function questionnaire (PISQ-12) both pre- and postoperatively. Results Among the 143 preoperative patients, 99 and 84 patients responded to the PISQ-12 and FSFI, respectively. The mean PISQ-12 score increased after surgery (p

Objective To demonstrate the significance of bladder outlet obstruction (BOO) in preoperative urodynamic studies (UDS) in women who have been diagnosed with pelvic floor dysfunction including pelvic organ prolapsed (POP) and stress urinary incontinence (SUI). Methods The medical records of 150 patients with pelvic floor dysfunction who underwent preoperative UDS at Yonsei University Health System from 2006 to 2012 were reviewed. Under the criteria of BOO, as a maximal flow rate in free-flow study (Qmax) less than 12 mL/sec and a detrusor pressure at Qmax in pressure-flow study (PdetQmax) higher than 20 cmH2O in UDS, they were divided into two groups: a group of 50 patients with BOO and a group of 100 patients without BOO. Comparisons were made between the patients with and without BOO in preoperative UDS. Results In the POP-with-SUI group, 25 patients with BOO had lower mean Qmax (10.0 vs. 25.4 mL/sec, P < 0.001), higher PdetQmax (49.6 vs. 21.5 cmH2O, P < 0.001), lower maximum cystometric capacity (422.7 vs. 454.0 mL, P = 0.007), and higher postvoidal residual volume (44.3 vs. 21.1 mL, P = 0.021) than the patients without BOO. In the SUI-only group, the mean Qmax was significantly lower in the 25 patients with BOO (9.4 vs. 25.4 mL/sec, P < 0.001). The mean PdetQmax was significantly higher with BOO (39.6 vs. 25.4 cmH2O, P = 0.004). In the univariate analyses, menopause, maximum cystometric capacity, and cystoscopic bladder trabeculation were associated with BOO. Conclusion In the univariate analysis, menopause, MCC and cystoscopic bladder trabeculation were associated with BOO. In the multivariate model, however, no significant association with BOO was found.

High aldehyde dehydrogenase (ALDH) activity has been recognized as a marker of cancer stem cells (CSCs) in breast cancer. In this study, we examined whether inhibition of ALDH activity suppresses stem-like cell properties in a 4T1 syngeneic mouse model of breast cancer. We found that ALDH-positive 4T1 cells showed stem cell-like properties in vitro and in vivo. Blockade of ALDH activity reduced the growth of CSCs in breast cancer cell lines. Treatment of mice with the ALDH inhibitor diethylaminobenzaldehyde (DEAB) significantly suppressed 4T1 cell metastasis to the lung. Recent evidence suggests that ALDH affects the response of stem cells to hypoxia; therefore, we examined a possible link between ALDH and hypoxia signaling in breast cancer. Hypoxia-inducible factor-2α (HIF-2α) was highly dysregulated in ALDH-positive 4T1 cells. We observed that ALDH was highly correlated with the HIF-2α expression in breast cancer cell lines and tissues. DEAB treatment of breast cancer cells reduced the expression of HIF-2α in vitro. In addition, reduction of HIF-2α expression suppressed in vitro self-renewal ability and in vivo tumor initiation in ALDH-positive 4T1 cells. Therefore, our findings may provide the evidence necessary for exploring a new strategy in the treatment of breast cancer.

Despite the high sensitivity of screening colonoscopy, polyps and cancers can still go undetected. With the polyp-to-cancer transformation cycle averaging 7-10 years, present guidelines recommend repeat colonoscopy within 10 years after negative screening. However, not all colorectal malignancies follow this decade-long progression. This study evaluates the incidence and pathology of colorectal cancers following a previous negative screening colonoscopy.Records of patients who underwent a colectomy at our institution, from 1998 to 2009, were reviewed retrospectively. A total of 1,784 patient records were screened using exclusion criteria for inclusion in this study. The patients were divided as follows: Group 1 included patients with a negative colonoscopy within the previous 5 years; Group 2 included patients without a previous colonoscopy or with a previous colonoscopy more than 5 years prior. Group 1 patients were evaluated by colonoscopy for anemia, diverticulitis, signs of obstruction, and bleeding. Age, tumor location, operation performed, and pathology findings were recorded. The χ(2) test and paired t test were used for statistical analysis.A total of 233 patients were included in this study. Group 1 contained 43 patients with a mean age of 73 years (range = 35-94, median = 75). Group 2 had 190 patients with a mean age of 68 years (range = 19-91, median = 70). Group 1 consisted of 18 male and 25 female patients, and Group 2 included 94 male and 96 female patients. Both groups were further classified into the following age categories:50 years, 50-80 years, and80 years. Eighteen percent of the total study population had newly discovered colorectal cancer within a 5-year colonoscopy screening period. There were no significant differences in the distribution of the T and N stages between the two groups and no statistically significant differences when the rate of lymphovascular invasion (19 vs. 17 %; p = 0.39) and perineural invasion (7 vs. 11 %; p = 0.58) were compared.Within 5 years, 18 % of our study population developed colorectal cancer. Most of these malignancies were found within the 50-80-year age group and located predominantly in the right colon and distally in the sigmoid and rectum. While distal cancers may be visualized by flexible sigmoidoscopy, those located more proximally may be missed, necessitating the need for a full colonoscopy. Although staging was similar between the two groups, Group 1 tumors were less aggressive despite having appeared within 5 years. As a result of our incidence of colorectal cancer within a 5-year interval, a shorter period for routine colonoscopy may be considered.

High dysadherin expression has been recognized as a biological predictor of metastasis and poor prognosis for many different cancer types; however, the molecular mechanisms of how dysadherin affects cancer progression are still poorly understood. In this study, we examined whether AKT signaling could link dysadherin expression with downstream events that promote the metastatic potential of human breast cancer cells. Immunohistochemical analysis of breast cancer tissues showed that dysadherin expression was highly associated with elevated expression of phospho-AKT. The introduction of dysadherin cDNA into BT-474, MCF-7 and T-47D breast cancer cell lines enhanced their levels of AKT phosphorylation, while knockdown of dysadherin in MDA-MB-231 and Hs578T breast cancer cell lines suppressed AKT phosphorylation. Treatment with the AKT inhibitor triciribine suppressed dysadherin-mediated pro-metastatic effects, including epithelial–mesenchymal transition, cell motility and drug resistance. These findings suggest that dysadherin might contribute to breast cancer progression through AKT activation. (Cancer Sci 2012; 103: 1280–1289)

Background & Aims Hepatocellular carcinoma (HCC) is associated with a high potential for metastasis and disease recurrence, even after surgical resection. The cancer stem cell (CSC) hypothesis proposes that CSCs are responsible for chemo-resistance, recurrence, and metastasis. Dysadherin is a prognostic indicator of metastasis and poor survival in many different cancer types. In this study, we investigated the possible link between dysadherin and CSC in HCC. Methods We analyzed the functional implications of dysadherin on cancer stemness by modification of the dysadherin gene in HCC cell lines. Results The transfection of dysadherin cDNA into the liver cancer cell line PLC/PRF/5 enhanced the properties of CSCs, including anti-apoptosis, their sphere-forming ability, side population phenotype, and tumor initiation ability in vivo . Furthermore, knockdown of dysadherin in the liver cancer cell line SK-Hep1 suppressed its stem cell-like properties . Conclusions These results show that dysadherin give rise to properties of CSC in HCC. Therefore, these findings suggest that dysadherin may be a potential molecular prognostic marker of HCC and may aid in the development of more effective therapies.

The cancer stem cell (CSC) hypothesis proposes that CSCs are the root of cancer and cause cancer metastasis and recurrence. In this study, we examined whether Ras signaling is associated with stemness of the CSCs population characterized by the stem cell antigen (Sca-1) phenotype in a 4T1 syngeneic mouse model of breast cancer. The Sca-1(pos) putative CSCs had high levels of activated Ras and phosphorylated MEK (p-MEK), compared with counterparts. The Ras farnesylation inhibitor (FTI-277) suppressed the maintenance and expansion of CSCs. Therefore, selective inhibition of Ras activation may be useful for stem-specific cancer therapy.

Purpose: To determine whether levels of nerve growth factor (NGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) can be used to objectively assess overactive bladder syndrome (OAB) treatment outcome and to evaluate the effects of fixed-dose fesoterodine on OAB symptoms. Materials and Methods: This study included 124 participants (62 patients with OAB and 62 controls) in Severance Hospital between 2010 and 2012. In patients with OAB, 4 mg fesoterodine was administered once daily. Repeated evaluations of putative biomarker levels, urine creatinine (Cr) levels, and questionnaire responses, including the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire (OAB q), were performed from baseline to 16 weeks. Results: Urinary levels of NGF/Cr (OAB: 1.13±0.9 pg/mg; control: 0.5±0.29 pg/ mg) and HB-EGF/Cr (OAB: 8.73±6.55 pg/mg; control: 4.45±2.93 pg/mg) were significantly higher in subjects with OAB than in controls ( p

Cancer relapse is the most common cause of mortality in breast cancer patients. The cancer stem cell (CSC) hypothesis proposes that CSCs are the root of cancer. CSC-targeted therapies may prevent cancer relapse and provide more effective treatment. It has been known that stem cells can be enriched in non-adherent sphere culture. To identify molecular targets in breast CSC, we compared transcription levels of stem cell-related genes between tumorspheres established from Balb/c mice-derived 4T1 mammary carcinoma and mammospheres from the mammary glands of Balb/c mice. The most differentially expressed gene was found to be Wingless-type MMTV integration site family, member 1 (WNT1). To determine whether WNT1 has any relevance in breast carcinoma, we analyzed the expression of WNT1 in the human matched normal breast and breast cancer samples. Immunofluorescent staining showed that WNT1 expression was elevated ∼17-63-fold in cancerous tissues compared with non-cancerous tissues from the same breast cancer patients. Functionally, knockdown of WNT1 in 4T1 cells reduced the Aldefluorpos cell compartment enriched in CSCs and suppressed the properties of CSCs, including anti-apoptosis, sphere-forming ability, and tumor initiation ability in vivo. Collectively, these results show that WNT1 expression gives rise to properties of CSC in breast cancer. Therefore, the targeting of WNT1-associated signaling may provide an effective therapeutic approach in the treatment of advanced breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5201. doi:1538-7445.AM2012-5201

Results The two groups had no difference with cardiovascular disease, history of cardiovascular disease, age, obesity, smoking, alcohol, hypertension, dyslipidemia, excluding diabetes. In the univariate logistic regression analysis, diabetes was associated with prevalence of overactive bladder than stress urinary incontinence. In the multiple logistic regression analysis, there was no factor which had influence on the status of urinary incontinence.

Copyright © 2012. Korean Society of Obstetrics and Gynecology Pelvic organ prolapse (POP) is a bulge or protrusion into or through the vagina of pelvic organs and associated vaginal segments [1]. With the aging population, POP is an increasingly common condition seen in women with a lifetime prevalence of 30% to 50% [1,2]. Symptomatic urogenital prolapse has been shown to have significant negative impacts such as those relating to the lower urinary tract, fecal incontinence, back pain, pelvic pain, defecatory problems, and dyspareunia. Management options for women with symptomatic POP include observation, pelvic floor muscle training, mechanical support (pessaries), and surgery. A patient’s perception of discomfort from POP and subsequent treatment will vary in relation to the stage of the POP and her ethnicity. Currently, many surgical approaches have been introduced to correct POP. The life time risk of undergoing surgery was estimated to be between 11% and 19%. However, none of these techniques is without risks for complications [2-4]. The prevalence of reoperaORIGINAL ARTICLE

목적 본 연구는 골반장기탈출증을 가진 환자들의 수술 전에 시행하는 요역동학 검사에서 수술 후 결과 및 합병증과 관련된 유용한 지표를 알아보고, 골반장기탈출증 교정술과 복압성 요실금교정술을 동시에 시행하는 경우 그 타당성을 입증하기 위한 목적으로 시행되었다. 연구방법 2006년 1월부터 2010년 12월까지 연세대학교 세브란스병원에 등록된 수술 전 요역동학 검사 및 골반장기탈출증 수술을 시행한 308명의 환자를 대상으로 후향적 코호트 연구를 시행하였다. 결과 수술 후 복압성 요실금의 유병률은 수술 전 요역동학 검사상 복압성 요실금을 진단받지 않아 골반장기탈출증 수술만 시행한 그룹 2 (3.1%, 4명)에서 복압성 요실금을 진단받아 요실금교정 수술을 동시에 시행한 그룹 1 (1.7%, 3명)보다 높게 나타났으나 통계적으로 유의한 차이는 없었다. 우리는 valsalva 유발 요누출 시 복압, 최대요도 폐쇄압, 최대요속, 최대요속 시 배뇨근압력, 최대 방광용적의 5가지 요역동학 검사 지표를 비교하였다. 수술 후 복압성 요실금에서는 최대요속 시 배뇨근압력(교차비, 1.029; 95% 신뢰구간, 1.001-1.038)이, 절박성 요실금의 경우 최대요도 폐쇄압(교차비, 0.969; 95% 신뢰구간, 0.942-0.996)이 통계적으로 유의한 지표로 나타났다. 결론 수술 후 합병증의 유병률에 중점을 두면, 동시 수술은 골반장기탈출증 수술만 하는 경우보다 더 나은 결과를 나타내며 수술 전 요역동학 검사에서도 의미 있는 지표가 있어 그 시행이 필요하다.

The cancer stem cell (CSC) hypothesis proposes that CSCs are the root of cancer and cause cancer metastasis and recurrence. High activity of aldehyde dehydrogenase (ALDH) has been recognized as a marker for normal and malignant stem cells. It has been also known that ALDH activity is important for multiple biological activities including drug resistance, cell differentiation, and oxidative metabolism. In this study, we focused on the molecular mechanism of ALDH activity in CSC dynamics. To address the underlying mechanism, we have used the 4T1 mouse model of breast cancer. We found that ALDHpos cells showed a high increase of the stem cell-like properties, such as sphere forming ability, expression of stem markers, and tumor initiation ability in vivo, when compared with the counterparts. Blockade of ALDH activity suppressed these properties of CSC. Especially, the high activity of ALDH was shown to enhance CSC properties through up-regulating Oct-4 expression that is dependent on oxygen-related transcription factor. Therefore, these findings suggest that the selective targeting of ALDH activity may be useful for stem specific cancer therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3360.

Hepatocellular carcinoma (HCC) is associated with a high potential for metastasis and disease recurrence, even after surgical resection. The cancer stem cell (CSC) hypothesis proposes that CSCs are responsible for chemo-resistance, recurrence and metastasis. Dysadherin is a prognostic indicator of metastasis and poor survival in many different cancer types. In this study, we investigated the possible link between dysadherin and CSC in HCC. The transfection of dysadherin cDNA into the liver cancer cell line PLC/PRF/5 enhanced the properties of CSC, including anti-apoptosis, sphere-forming ability, side population (SP) phenotype and tumor initiation ability in vivo. Furthermore, knockdown of dysadherin in the liver cancer cell line SK-Hep1 suppressed its stem cell-like properties. In particular, SP phenotype is mediated by the ATP-binding cassette (ABC) transporter proteins which are responsible for multidrug resistance (MDR) that is a major obstacle in cancer chemotherapy. Dysadherin was also shown to regulate ABCB1 expression. Taken together, these results show that new roles for the dysadherin in cancer progression that was in part dependent on CSC dynamics. Therefore, these findings suggest that dysadherin may be a potential molecular prognostic marker of HCC and may aid in the development of more effective therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4244.

Radical trachelectomy is an alternative method to preserve the fertility of young women with early stage cervical cancer. Abdominal radical trachelectomy has been replaced with laparoscopic radical trachelectomy in selected patients due to several advantages of laparoscopic surgery compared to laparotomy. Recently, as surgical technology has significantly advanced, robot‐ assisted procedures have been performed. However, there are only four case reports of robot‐assisted radical trachelectomy where four robotic arms were used. This report may be the first to describe robot‐assisted laparoscopic radical trachelectomy which uses only 2 robotic instruments ports and 1 assistant port while preserving the ascending branches of both uterine arteries.

Objective The aim of this study was to determine whether the presence of bacterial vaginosis (BV) is associated with cervical intraepithelial neoplasia (CIN) and human papilloma virus (HPV) infection. Methods A total of 588 women who had abnormal Pap smears and had finally undergone loop electrosurgical excision procedure (LEEP) in our institute from September 2002 to May 2006 were selected. The screening tests for BV were done in 552 of the 588, and BV was diagnosed if three of the following four findings were satisfied: presence of abnormal discharge, vaginal pH>4.5, presence of clue cells, positive amine or whiff test. Five hundred and five patients had HPV typing tests by the HPV DNA chip. Forty two patients diagnosed with invasive cancer were excluded from this study. CIN was subdivided into low-grade CIN (CIN I) and high-grade CIN (CIN II/III) groups. Results There was no statistically significant difference in patient characteristics between BV-present and BV-absent group. The incidence of CIN was significantly higher in the BV-present group (p=0.043), however, no statistical significance of BV on CIN was observed on multivariate analysis. HPV infection showed no significant relationship with BV. BV with or without HPV infection did not influence the incidence of CIN, regardless of the severity. Conclusion There was significant correlation between BV and the presence of CIN, regardless of the severity of CIN. In addition, there was no significant association between the presence of BV and HPV infection.