Nae-Fang Twu

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

Induction of Insulin-Producing Cells Derived from Endometrial Mesenchymal Stem-like Cells

Studies have demonstrated that mesenchymal stem-like cells can be isolated from endometrium. However, the potential of endometrial-derived stem cells to differentiate into insulin-positive cells and functionally secrete insulin remains undetermined. We isolated endometrial mesenchymal stem-like cells (EMSCs) from human endometrial tissue from six donors. The insulin-secreting function of EMSCs was further analyzed in vitro and in transplanted grafts in vivo. We successfully isolated EMSCs from human endometrium, and our results showed that EMSCs expressed high levels of stemness genes (Nanog, Oct-4, Nestin). Under specific induction conditions for 2 weeks, EMSCs formed three-dimensional spheroid bodies (SBs) and secreted C-peptide. The high insulin content of SB-EMSCs was confirmed by enzyme-linked immunosorbent assay, and glucose responsiveness was demonstrated by measuring glucose-dependent insulin secretion. Using cDNA microarrays, we found that the expression profiles of SB-EMSCs are related to those of islet tissues. Insulin and C-peptide production in response to glucose was significantly higher in SB-EMSCs than in undifferentiated EMSC controls. Furthermore, upon differentiation, SB-EMSCs displayed increased mRNA expression levels of NKx2.2, Glut2, insulin, glucagon, and somatostatin. Our results also showed that SB-EMSCs were more resistant to oxidative damage and oxidative damage-induced apoptosis than fibroblasts from the same patient. It is noteworthy that SB-EMSCs xenotransplanted into immunocompromised mice with streptozotocin-induced diabetes restored blood insulin levels to control values and greatly prolonged the survival of graft cells. These data suggest that EMSCs not only play a novel role in the differentiation of pancreatic progenitors, but also can functionally enhance insulin production to restore the regulation of blood glucose levels in an in vivo transplantation model.

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.

Overexpression of Aurora B is associated with poor prognosis in epithelial ovarian cancer patients

Recent studies have indicated that Aurora B expression is related to cell proliferation and prognosis in many cancers, but its association with epithelial ovarian carcinoma is not fully understood. Therefore, we examined the Aurora B kinase expression in epithelial ovarian cancer patients. Using immunohistochemistry, the expression levels of Aurora B and phosphohistone H3 (Ser10) (mitosis-specific marker) were measured in 156 patients with epithelial ovarian cancer. The expression levels of Aurora B at the protein and messenger RNA levels were examined using Western blotting and reverse transcriptase polymerase chain reaction. In total, 53 tumorous ovarian samples (34.0%) showed Aurora B overexpression, which was significantly higher than that found in the 15 normal ovarian tissue samples (0%, p = 0.006). The overexpression of Aurora B was also significantly higher in cases showing phosphohistone H3 (Ser10) overexpression (44.3% vs. 27.4%, p = 0.03). In addition, the expression of Aurora B in poorly and moderately differentiated carcinomas of the ovary was significantly higher than in well-differentiated carcinomas (53.6% vs. 28.2% vs.10.0%, respectively, p = 0.02). The overexpression of Aurora B was significantly higher in cases with lymph node metastasis (p = 0.01) and a positive ascites cytology (p = 0.008). Overall, the Aurora B overexpression group demonstrated a significantly shorter progression-free survival (p = 0.001) and overall survival (p = 0.023) than the Aurora B low expression group using univariate analysis (log-rank statistic). Aurora B is an effective predictor of aggressive epithelial ovarian carcinoma in terms of differentiation, metastasis, and prognosis.

Periostin in tumor microenvironment is associated with poor prognosis and platinum resistance in epithelial ovarian carcinoma

The interplay between tumor microenvironment and cancer that causes chemoresistance remains unclear. By analyzing public available microarray datasets, we identified that periostin (POSTN) was overexpressed in cancer stroma in epithelial ovarian cancer (EOC) patients. Immunohistochemistry analysis showed overexpression of stromal POSTN is a powerful independent poor prognostic predictor for EOC patients. Furthermore, patients with high levels of stromal POSTN tend to have higher percentage of cisplatin resistance compared to those with low levels of stromal POSTN. Moreover, we found POSTN treatment can induce cisplatin resistant and activate AKT pathway in A2780 cells in vitro. Inhibition of AKT activity by AKT inhibitor MK-2206 abolished POSTN-induced AKT activation and cisplatin resistance in vitro. Taken together, we found high POSTN expression in cancer microenvironment is correlated with poor prognosis in EOC patients and associated with platinum resistance. The effect of POSTN in cancer stroma cells may activate AKT pathway in tumor and AKT inhibitor can be beneficial to augment the efficacy of existing cancer therapeutics.

Poor Prognosis of Intraoperative Rupture of Mature Cystic Teratoma with Malignant Transformation

OBJECTIVE To present the phenomenon of the postoperative rapid progression of mature cystic teratoma (MCT) with malignant transformation (MT) when intraoperative spillage occurs during operation. CASE REPORTS Two patients with MCT were treated, one with total hysterectomy plus bilateral salpingo-oophorectomy in an exploratory laparotomy, and the other with cystectomy with laparoscopy, respectively. Tumor spillage occurred during both operations. The postoperative pathology showed MCT with MT (squamous cell carcinoma type). Both patients were referred to our hospital and underwent treatment (3 months and 8 days, respectively, after the initial operation). At the secondary laparotomy for staging surgery, tumor dissemination was observed in both patients. CONCLUSION Whether or not tumor dissemination is correlated with tumor rupture during operation, we emphasize that any patient with a preoperative diagnosis of MCT should have it removed intact to avoid the possibly catastrophic event of tumor dissemination.

Expression of Aurora kinase A and B in normal and malignant cervical tissue: High Aurora A kinase expression in squamous cervical cancer ☆

OBJECTIVE Aurora kinases such as Aurora A and B are key regulators of mitosis and tumorigenesis and have been reported to be overexpressed in various malignancies. However, the expression of Aurora kinases in normal and neoplastic cervical tissues remains undetermined. STUDY DESIGN Immunohistochemical expression of Aurora A and B kinase was examined in 20 normal cervix, 35 cervical intraepithelial neoplasm 3 (CIN 3) and 95 cervical cancers, including squamous cell carcinoma (SCC) (n=76) and adenocarcinoma (AC) (n=19). Expression of Aurora A and B kinase was confirmed by Western blot. The correlation between Aurora A and B kinases expression and the clinico-pathological parameters was analyzed by statistical analysis. RESULTS The Aurora A and B expression was significantly increased in carcinoma and CIN 3, compared with normal cervix. However, expression of Aurora A and B showed no significant correlation between CIN 3 and cervical cancer. The nuclear expression of Aurora A showed a significantly positive correlation with the expression of Aurora B (P=0.018). The percentage of Aurora A overexpression between SCCs and ACs showed a significant difference (50% vs. 21.1%, P=0.023). However, there was no correlation of Aurora A and B expression with patient survival. CONCLUSION According to our study, Aurora A and B overexpression is a relatively early phenomenon in the genesis of malignant epithelial neoplasm tumorigenesis. Based on the results of this study, it would be interesting to know whether Aurora kinases play a role in pathogenesis of cervical dysplasia and SCC patients.

Robotic-assisted laparoscopic complex myomectomy: A single medical center's experience

OBJECTIVE Conventional laparoscopic myomectomy (LM) has inherent limitations due to its rigid structure. The robotic system is a newly developed technology equipped with a flexible EndoWrist that offers good performance in delicate motions. Our objective was to share our clinical experience in the management of complex myomectomy using this robotic system. MATERIALS AND METHODS From October 2010 to March 2012, 21 patients with symptomatic complex uterine myomas were evaluated. Complex myomectomy was defined as surgery involving more than two fibroids, large fibroids, or preexisting pelvic adhesions. We recorded and analyzed the preoperative characteristics of the patients and the fibroids, the detailed surgical time, and several postoperative outcomes to evaluate the feasibility and efficacy of robotic-assisted LM (RALM) for complex fibroids. RESULTS A total of 21 patients were enrolled in this study. The mean age of the patients was 40.1 ± 4.5 years and the mean size of the largest fibroid was 7.3 ± 3.5 cm. RALM achieved satisfactory results, including a short postoperative hospital stay (3.1 ± 0.9 days), a low conversion rate (none of our patients required conversion to either a minilaparotomy or conventional open surgery), and a low complication rate (1 case in 21 patients, 4.8%). The average estimated blood loss was 235.7 ± 283.3 mL. CONCLUSION Our study results demonstrated that RALM is a safe and effective method for handling complex fibroids.

Unilateral salpingo-oophorectomy as fertility-sparing surgery for borderline ovarian tumors

Background: To investigate recurrence rates and fertility outcomes of patients with borderline ovarian tumors (BOTs) treated with fertility‐sparing surgery. Methods: This was a retrospective study. All women with BOTs from 2000 to 2006 were evaluated. Clinical outcomes were compared among groups that underwent radical, unilateral salpingo‐oophorectomy, or ovarian cystectomy. The effects of clinical characteristics on recurrence were analyzed by independent t test, chi‐square test, and Cox proportional hazard model. Results: After a mean follow‐up period of 56.5 months, all 61 patients were alive. Seven (11.5%) had developed disease recurrence, and all were in the fertility‐sparing group. Of these, five were in the cystectomy‐only group and two in the unilateral salpingo‐oophorectomy group. There was significant difference in tumor recurrence rates between the two groups (hazard ratio: 0.26, 95% confidence interval: 0.11–0.61). Nine pregnancies were achieved in six women, resulting in five deliveries Conclusion: Fertility‐sparing surgery is an acceptable and safe option for women with BOTs who wish to preserve fertility. Unilateral salpingo‐oophorectomy must be considered as the first choice.