Hua-Hsi Wu

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.

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.

Impact of ovarian preservation in women with endometrial cancer.

Background: Bilateral salpingo‐oophorectomy (BSO) is standardly performed in the treatment of endometrial cancer. The purpose of this study was to evaluate the impact of ovarian preservation on the outcome of patients with endometrial cancer. Methods: A retrospective cohort study was performed using the 2000–2010 database of endometrial cancer patients who were treated at Taipei Veterans General Hospital. Information regarding patient age, pathologic reports, and follow‐up results was abstracted from medical records. Results: Five hundred and twenty‐nine patients were reviewed in this study. Mean age and follow‐up duration were 55.7 ± 11.4 years and 37.5 ± 30.1 months, respectively. The median disease‐free survival was 31.2 months (range 0.2–126.9 months). There were no significant differences in disease‐free survival between stage I patients with ovarian preservation versus those with oophorectomy (p = 0.473). In a multivariate Cox model, ovarian preservation had no effect on disease‐free survival [hazard ratio (HR) = 2.72; 95% confidence interval (CI), 0.48–15.59]; however, it was not significantly related to stage and para‐aortic lymph node involvement. Conclusion: Ovarian preservation may be considered in premenopausal women with early‐stage low‐risk endometrial cancer.

The Role of Secondary Cytoreductive Surgery in Patients with Recurrent Epithelial Ovarian, Tubal, and Peritoneal Cancers: A Comparative Effectiveness Analysis

Background. All published reports concerning secondary cytoreductive surgery for relapsed ovarian cancer have essentially been observational studies. However, the validity of observational studies is usually threatened from confounding by indication. We sought to address this issue by using comparative effectiveness methods to adjust for confounding. Methods. Using a prospectively collected administrative health care database in a single institution, we identified 1,124 patients diagnosed with recurrent epithelial, tubal, and peritoneal cancers between 1990 and 2009. Effectiveness of secondary cytoreductive surgery using the conventional Cox proportional hazard model, propensity score, and instrumental variable were compared. Sensitivity analyses for residual confounding were explored using an array approach. Results. Secondary cytoreductive surgery prolonged overall survival with a hazard ratio (95% confidence interval) of 0.76 (range 0.66-0.87), using the Cox proportional hazard model. Propensity score methods produced comparable results: 0.75 (range 0.64-0.86) by nearest matching, 0.73 (0.65-0.82) by quintile stratification, 0.71 (0.65-0.77) by weighting, and 0.72 (0.63-0.83) by covariate adjustment. The instrumental variable method also produced a comparable estimate: 0.75 (range 0.65-0.86). Sensitivity analyses revealed that the true treatment effects may approach the null hypothesis if the association between unmeasured confounders and disease outcome is high. Conclusions. This comparative effectiveness study provides supportive evidence for previous reports that secondary cytoreductive surgery may increase overall survival for patients with recurrent epithelial, tubal, and peritoneal cancers.

A tumor necrosis factor-α inhibitor reduces the embryotoxic effects of endometriotic peritoneal fluid

OBJECTIVE To determine whether a tumor necrosis factor-α (TNF-α) inhibitor can reduce the embryotoxicity of the peritoneal fluid (PF) of women with endometriosis. DESIGN Experimental clinical study. SETTING University hospital. PATIENT(S) Twelve women with chocolate cysts and 12 control women without endometriosis. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) We collected the PF from patients with chocolate cysts (CH-PF) and patients without endometriosis (N-PF) during laparoscopic surgery. For the in vitro studies, development and apoptosis were evaluated in two-cell stage mouse embryos after incubation with CH-PF and N-PF, with or without a TNF-α inhibitor. RESULT(S) We found that CH-PF significantly decreased the rate of blastocyst development and increased the percentage of apoptotic cells in the embryos. Cytokine assays showed that the concentrations of several cytokines, including TNF-α, were higher in embryos incubated with CH-PF than in those incubated with N-PF. Furthermore, the treatment of embryos with TNF-α retarded development and induced apoptosis. Important, adalimumab, a TNF-α inhibitor, effectively abrogated the embryotoxicity that was induced by CH-PF. CONCLUSION(S) These data collectively highlight the crucial role of TNF-α in CH-PF-induced embryotoxicity and suggest that TNF-α inhibitors may be potential therapeutic agents for treating endometriosis-induced infertility.

Comparison of single-incision mini-slings (Ajust) and standard transobturator midurethral slings (Align) in the management of female stress urinary incontinence: A 1-year follow-up.

OBJECTIVE To investigate the effectiveness and safety of a new single-incision mini-sling (SIMS)-Ajust-compared with the standard transobturator midurethral sling (SMUS)-Align-for the treatment of female stress urinary incontinence (SUI). MATERIALS AND METHODS A retrospective cohort study was conducted between January 1, 2010 and August 31, 2012. Women with SUI who underwent either SMUS-Align or SIMS-Ajust were recruited. The primary outcomes included operation time, estimated operative blood loss, postoperative pain, and complications. The secondary outcomes included subjective and objective success, defined as an International Consultation on Incontinence Questionnaire (ICIQ) score of 0 or improvement as felt by the patient and a long-term complication, such as dyspareunia and mesh erosion after 6 months and 12 months of follow-up. RESULTS A total of 136 patients were enrolled, including 76 receiving SMUS-Align and 60 receiving SIMS-Ajust. Baseline characteristics of the patients in both groups were similar, without a statistically significant difference. Primary outcomes between both groups were similar, except that women treated with SIMS-Ajust had statistically significantly shorter operation time (p = 0.003), less intent to treat (p < 0.05), and earlier postoperative discharge (p = 0.001) than women treated with SMUS-Align. Secondary outcomes were similar without a significant difference between the two groups (93% vs. 88% success rate in each group). CONCLUSION Our results showed that SIMS-Ajust was not inferior to SMUS-Align with respect to success rate, and might have a slight advantage in early discharge. A long-term follow-up or prospective study is needed to confirm the above findings.

Neurofibroma involving obturator nerve mimicking an adnexal mass: a rare case report and PRISMA-driven systematic review

BackgroundPelvic masses are a common gynecologic problem, and majority of them are diagnosed as ovarian tumors finally. Sometimes, it is hard to distinguish the origin of these pelvic masses. The following case is a solitary neurofibroma arising from the right-side obturator nerve, which was impressed as a right-side ovarian tumor initially. We reported this case, and also performed a PRISMA-driven systematic review to summary the similar cases in the literature. This review includes image, molecular and pathological findings and outcome of neurofibroma.Case presentationA 33-year-old woman with a regular menstrual period denied any symptoms or signs. During her physical check-up, image examination revealed a right-side heterogeneous pelvic mass; it was suggestive of a complex of right-side ovarian tumor. A provisional diagnosis of retroperitoneal pelvic mass, probably a benign ovarian tumor, was made.Excision of the right-side pelvic mass was performed. We sent the specimens for frozen pathology, which indicated neurofibroma and lipomatous tumor and that the possibility of liposarcoma cannot be excluded. A segment of the obturator nerve was attached to the tumor and was severed. A right-side obturator nerve tear during tumor excision was observed, and a neurosurgeon was consulted for obturator nerve grafting and repair. The patient complained of mild weakness and paresthesia affecting the right leg, and we consulted a rehabilitation doctor for neuron injury. The patient’s recovery was uneventful, and she was discharged eight days after the drain was removed. Further rehabilitation treatment was arranged.ConclusionA neurofibroma is an uncommon pelvic retroperitoneal tumor, and it can be misdiagnosed as an adnexal mass. To our knowledge, this is a rare case of a solitary neurofibroma arising from the obturator nerve. It usually does not have any neurological deficit. We present this case to demonstrate that pelvic neurofibroma can be mistaken for an adnexal mass. This fact should be borne in mind during the diagnosis process.

Single-port laparoscopic surgery for cornual pregnancy after failure of methotrexate treatment.

a National Taiwan University Hospital, Chu-Tung Branch, Chu-Tung, Taiwan b Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei, Taiwan c Division of Gynecology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan d Department of Medical Research, China Medical University Hospital, Taichung, Taiwan e Division of Cytopathology, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan f Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan