Kuan-Chong Chao

Single-port compared with conventional laparoscopic-assisted vaginal hysterectomy: a randomized controlled trial.

OBJECTIVE: To compare the immediate results of patients undergoing either two-channel single-port laparoscopic-assisted vaginal hysterectomy or conventional multiport laparoscopic-assisted vaginal hysterectomy. METHODS: Patients were randomly assigned to undergo laparoscopic-assisted vaginal hysterectomy using the single-port (n=50) or conventional (n=50) approach. The outcome measures included blood loss, operative time, intraoperative and immediate postoperative complications, time to flatus passage after operation, and postoperative pain (assessed by the visual analog scale score and postoperative analgesics use). RESULTS: The general characteristics of the patients were similar in both groups. There were no statistically significant differences in operative time, estimated blood loss, time to first flatus, intraoperative and immediate postoperative complications, shoulder tip pain, or length of hospital stay between the two groups. However, postoperative pain was significantly less in the single-port group compared with the conventional group, as evidenced by lower mean scores on the visual analog scale (3.64±2.75 compared with 5.08±2.76 at 24 hours, P=.011 and 1.94±2.31 compared with 2.84±2.07 at 48 hours, P=.043) and less mean accumulated dose of postoperative analgesics (74.40±24.25 mg compared with 104.80±57.08 mg of meperidine, P=.001; 16±13.40 mg compared with 33.6±28.7 mg of tenoxicam, P<.001). CONCLUSION: Transumbilical two-channel single-port laparoscopic-assisted vaginal hysterectomy significantly decreases postoperative pain and analgesic use. Clinical Trial Registration: Clinical Trials.gov, www.clinicaltrials.gov, NCT01048931. LEVEL OF EVIDENCE: I

Oestrogen‐induced epithelial–mesenchymal transition of endometrial epithelial cells contributes to the development of adenomyosis

Adenomyosis is an oestrogen‐dependent disease caused by a downward extension of the endometrium into the uterine myometrium. Epithelial–mesenchymal transition (EMT) endows cells with migratory and invasive properties and can be induced by oestrogen. We hypothesized that oestrogen‐induced EMT is critical in the pathogenesis of adenomyosis. We first investigated whether EMT occurred in adenomyotic lesions and whether it correlated with serum 17β‐oestradiol (E2) levels. Immunohistochemistry was performed on adenomyotic lesions and corresponding eutopic endometrium samples from women with adenomyosis. Endometria from women without endometrial disorders were used as a control. In the epithelial component of adenomyotic lesions, vimentin expression was up‐regulated and E‐cadherin expression was down‐regulated compared to the eutopic endometrium, suggesting that EMT occurs in adenomyosis. In adenomyosis, the serum E2 level was negatively correlated with E‐cadherin expression in the epithelial components of the eutopic endometrium and adenomyotic lesions, suggesting the involvement of oestrogen‐induced EMT in endometrial cells. In oestrogen receptor‐positive Ishikawa endometrial epithelial cells, oestrogen induced a morphological change to a fibroblast‐like phenotype, a shift from epithelial marker expression to mesenchymal marker expression, increased migration and invasion, and up‐regulation of the EMT regulator Slug. Raloxifene, a selective oestrogen receptor modulator, abrogated these effects. To determine the role of oestrogen‐induced EMT in the implantation of ectopic endometrium, we xenotransplanted eutopic endometrium or adenomyotic lesions from adenomyosis patients into ovariectomized SCID mice. The implantation of endometrium was oestrogen‐dependent and was suppressed by raloxifene. Collectively, these data highlight the crucial role of oestrogen‐induced EMT in the development of adenomyosis and suggest that raloxifene may be a potential therapeutic agent for adenomyosis patients. Copyright

Enhancement of wound healing by human multipotent stromal cell conditioned medium: the paracrine factors and p38 MAPK activation.

Wound healing can be improved by transplanting mesenchymal stem cells (MSCs). In this study, we have demonstrated the benefits of the conditioned medium derived from human MSCs (CM-MSC) in wound healing using an excisional wound model. CM-MSC accelerated wound closure with increased reepithelialization, cell infiltration, granulation formation, and angiogenesis. Notably, CM-MSC enhanced epithelial and endothelial cell migration, suggesting the contribution of increased cell migration to wound healing enhanced by CM-MSC. Cytokine array, ELISA analysis, and quantitative RT-PCR revealed high levels of IL-6 in CM-MSC. Moreover, IL-6 added to the preconditioned medium enhanced both cell migration and wound healing, and antibodies against IL-6 blocked the increase in cell motility and wound closure by CM-MSC. The IL-6 secretory pathway of MSCs was inhibited by SB203580, an inhibitor of p38 MAPK or siRNA against p38 MAPK, suggesting IL-6 secretion by MSCs is mediated through the activation of p38 MAPK. Inactivation of p38 MAPK also reduced the expression and production of IL-8 and CXCL1 by MSCs, both of which were also demonstrated to enhance cell migration and wound closure. Thus, our data suggest MSCs promote wound healing through releasing a repertoire of paracrine factors via activation of p38 MAPK, and the CM-MSC may be applied to enhance wound healing.

Maneuvers to Decrease Laparoscopy-Induced Shoulder and Upper Abdominal Pain: A Randomized Controlled Study

OBJECTIVE To evaluate the effectiveness of the pulmonary recruitment maneuver (PRM) and intraperitoneal normal saline infusion (INSI) in removing postlaparoscopic carbon dioxide from the abdominal cavity to decrease laparoscopy-induced abdominal or shoulder pain after surgery. DESIGN, SETTING, AND PATIENTS A prospective, randomized, controlled trial was conducted at Taipei Veterans General Hospital, Taipei, Taiwan, from August 1, 2009, through June 30, 2010. One hundred fifty-eight women undergoing laparoscopic surgery for benign gynecologic lesions were randomly assigned to 3 groups: the PRM group (n = 53), the INSI group (n = 54), and the control group (n = 51). INTERVENTIONS Postoperative maneuvers included PRM and INSI. MAIN OUTCOME MEASURES Evaluation of pain, including abdominal pain and shoulder pain, was performed at 12, 24, and 48 hours postoperatively. RESULTS The frequency of postoperative shoulder pain at 24 and 48 hours was significantly decreased in the INSI group compared with that of either the PRM or control group (40.7% and 24.1% in the INSI group vs 66.0% and 50.9% in the PRM group [P = .009 and .004, respectively] or vs 72.5% and 54.9% in the control group [both P < .001]). Both methods significantly reduced the frequency of upper abdominal pain compared with the control condition (73.6% in the PRM group at 24 hours [P = .03] or 72.2% at 24 hours [P .02] and 44.4% at 48 hours [P = .01] in the INSI group vs 90.2% at 24 hours and 68.6% at 48 hours in the control group). CONCLUSIONS Both PRM and INSI could effectively reduce pain after laparoscopic surgery, but INSI might be better for both upper abdominal and shoulder pain.

Is the surgical approach beneficial to subfertile women with symptomatic extensive adenomyosis

Aim:  Our aim was to assess the role of surgical intervention for symptom control and reproductive performance improvement in the management of subfertile women with symptomatic extensive uterine adenomyosis.

Global distribution pattern of histological subtypes of epithelial ovarian cancer: A database analysis and systematic review

BACKGROUND Epithelial ovarian cancer is basically a heterogeneous disease with different chemosensitivity and distinct molecular alternations for each histological subtype. In order to assess whether the results of clinical trials can be extrapolated to a new country, it is critical to first examine whether the relative frequencies is homogenous across countries. METHODS Cancer registry database from a single institution in Taiwan combined with systematic review of the global literature on the relative frequencies of histological subtypes between 2003 and 2012 was provided. RESULTS Of 175 titles identified, 41 studies met inclusion/exclusion criteria. Globally, for each subtype, the median value of relative frequencies for serous subtype was 45.0%, with the Philippines (16.0%), Indonesia (22.7%), and Brazil (30.1%) as the three lowest countries and South Africa (68.0%), Greece (71.5%), and India (86.7%) as the three highest countries; for mucinous subtype, 11.4%, Italy (3.0%), Australia (3.4%), and Japan (5.4%) were the three lowest countries, while Indonesia (29.1%), Singapore (30.3%), and South Korea (38.6%) were the three highest countries; for endometrioid subtype, 12.6%, India (1.6%), Greece (5.7%), and Portugal (7.6%) were the three lowest countries, while Taiwan (24.8%), Egypt (25.0%), and Austria (25.5%) were the three highest countries; and for clear cell subtype, 5.3%, Pakistan (1.0%), Iran (2.0%), and Brazil (2.1%) were the three lowest countries while Thailand (16.0%), Taiwan (16.8%), and Spain (18.8%) were the three highest countries. CONCLUSIONS Relative frequencies of subtypes were not homogenous across countries. This diversity may reflect the geographical and ethnic variations. Globally, epithelial ovarian cancer is a heterogeneous disease with a heterogeneous distribution pattern.

Oestrogen‐induced angiogenesis promotes adenomyosis by activating the Slug‐VEGF axis in endometrial epithelial cells

Adenomyosis is an oestrogen‐dependent disease characterized by the invasion of endometrial epithelial cells into the myometrium of uterus, and angiogenesis is thought to be required for the implantation of endometrial glandular tissues during the adenomyotic pathogenesis. In this study, we demonstrate that compared with eutopic endometria, adenomyotic lesions exhibited increased vascularity as detected by sonography. Microscopically, the lesions also exhibited an oestrogen‐associated elevation of microvascular density and VEGF expression in endometrial epithelial cells. We previously reported that oestrogen‐induced Slug expression was critical for endometrial epithelial–mesenchymal transition and development of adenomyosis. Our present studies demonstrated that estradiol (E2) elicited a Slug‐VEGF axis in endometrial epithelial cells, and also induced pro‐angiogenic activity in vascular endothelial cells. The antagonizing agents against E2 or VEGF suppressed endothelial cells migration and tubal formation. Animal experiments furthermore confirmed that blockage of E2 or VEGF was efficient to attenuate the implantation of adenomyotic lesions. These results highlight the importance of oestrogen‐induced angiogenesis in adenomyosis development and provide a potential strategy for treating adenomyosis through intercepting the E2‐Slug‐VEGF pathway.

Prognostic nomogram for overall survival in stage IIB-IVA cervical cancer patients treated with concurrent chemoradiotherapy.

OBJECTIVE On the basis of outcome data from concurrent chemoradiotherapy (CCRT) for locally advanced cervical squamous cell carcinoma, the authors developed a nomogram for predicting survival outcome. STUDY DESIGN Two hundred fifty-one eligible patients with International Federation of Gynecology and Obstetrics stage IIB-IVA squamous cell carcinoma of the uterine cervix who underwent CCRT were included for the construction of the nomogram. Predictor variables included age, serum squamous cell carcinoma antigen, tumor size, parametrium invasion, hydronephrosis, bladder/rectum invasion, and lymph node metastases. Internal validation of the nomogram was performed. RESULTS A nomogram for predicting the 5 year overall survival for these patients was constructed on the basis of a Cox regression model from 7 parameters. The concordance index was 0.69. CONCLUSION This nomogram is a predictive tool, upon external validation, that can be used to counsel patients in predicting outcomes. The discriminatory ability of the nomogram indicates that this population should not be considered homogeneous with respect to risk of death.

An overview of a 30-year experience with amniocentesis in a single tertiary medical center in Taiwan.

OBJECTIVE Amniocentesis is a popular and effective prenatal diagnostic tool for chromosomal disorders. It is well-established that the risk of chromosomal abnormalities increases with maternal age; however, other related indications are seldom reported. Herein, we report our 30-year experience with amniocentesis from a single medical center, focusing on the indications and rates of abnormality. MATERIAL AND METHODS A retrospective review of 16,749 pregnant women in the mid-trimester between January 1981 and December 2010 was conducted. The medical records were analyzed. RESULTS The indications for amniocentesis were advanced maternal age (≥ 34 years old) (n=10,970, 65.5%), increasing-risk maternal triple-marker Downs screening test (≥ 1/270) (n=2090, 12.5%), history of abnormal offspring birth (n=792, 4.7%), abnormal ultrasound findings (n=484, 2.9%), parent with abnormal karyotype (n=252, 1.5%), family history of chromosomal abnormality (n=183, 1.1%), drug and radiation exposure (n=165), abnormal chorionic villus sampling (CVS) results (n=25), intrauterine fetal death (n=50), and other non-specific causes (n=1662, 9.9%). The rate of abnormality for each indication was 16% in the abnormal CVS group, 12% in the intrauterine fetal death group, 11.5% for parental chromosomal abnormality, 8.7% in the abnormal ultrasound finding group, 3.0% in the increasing-risk maternal triple-marker Downs screening test group, 2.5% in the advanced maternal age group, 1.5% for other non-specific causes, 1.4% for history of abnormal offspring birth, and 1.1% for family history of chromosomal abnormality. CONCLUSIONS Both parents with abnormal karyotype and abnormal ultrasound findings are indications for which consideration of further amniocentesis is highly recommended.

USE OF A GONADOTROPIN-RELEASING HORMONE AGONIST TO MANAGE PERIMENOPAUSAL WOMEN WITH SYMPTOMATIC UTERINE MYOMAS

OBJECTIVE To determine the acceptability and effectiveness of a gonadotropin-releasing hormone (GnRH) agonist for the treatment of perimenopausal women with symptomatic uterine myomas. MATERIALS AND METHODS The participants included 43 women with symptomatic myomas who wished to retain their uteri. All the women were older than 45 years old, agreed to use the GnRH agonist for menopause induction, and were without any underlying malignancy. They were treated with six courses of GnRH agonist between 2004 and 2005. The definition of re-intervention included: (1) surgical intervention, such as hysterectomy, myomectomy or laparoscopic uterine vessel occlusion, or (2) modification of GnRH agonist use. Modification of GnRH agonist use included either failure to complete a 6-month GnRH agonist treatment course, or re-use of GnRH agonist with/without interruption of continuity. Failure was defined as women who underwent surgical intervention or failed to complete the 6-month GnRH agonist treatment. Evaluations were performed every 6 months, for up to 2 years. RESULTS Re-intervention rates were 14.0% (n = 6), 23.3% (n = 10) and 32.6% (n = 14), and failure rates were 7.0% (n = 3), 11.6% (n = 5) and 16.3% (n = 7), at the end of the 6-, 12- and 24-month follow-up periods, respectively. Three patients failed to complete the 6-month GnRH agonist treatment, and four received surgical interventions. CONCLUSION More than 80% of women in this study benefited from the use of GnRH agonist to produce menopause, suggesting that this can be an alternative choice for managing perimenopausal women with symptomatic uterine myomas.