Kuo-Chang Wen

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.

Small supernumerary marker chromosome originating from chromosome 10 associated with an apparently normal phenotype

Small supernumerary marker chromosomes (sSMC) originating from chromosome 10 are rare. Only seven cases have been documented, and among those three cases were diagnosed prenatally. We reported on another prenatal diagnosis of a de novo mosaic sSMC in an apparently normal female fetus whose mother had conceived with assisted reproductive technology (ART) procedures. G‐banding analysis of amniotic cells was performed. Spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) studies with chromosome 10‐specific alphoid satellite DNA probe were used to identify the chromosome 10 origin of the sSMC. Further FISH study with telomeric sequence probes showed that the sSMC lacked a hybridization signal, suggesting that the marker could be a ring chromosome. FISH studies using BAC clone probes specific for the regions within 10p11.2, 10q11.1, and 10q11.2 showed that the short arm breakpoint was located between 29.8 and 30.7 Mb from the 10p telomere, and that the long arm breakpoint was located less than 43.6 Mb from the 10p telomere. The karyotype of the fetus was 47,XX,+mar. ish der(10)(SKY+ CEP 10+, CTD‐2130I7+, RP11‐89J23−)/46,XX. Oligonucleotide microarray‐based copy number variations (CNV) analysis was also performed and showed a 6.7 Mb duplication from 10p11.2 to 10q11.2 (36.2–42.9 Mb) with Affymetrix SNP‐array 6.0 genotype: arr cgh. 10p11.2q11.2(CN_519687 → CN_541524) X 3. At the 1‐year follow‐up, the baby did not have any findings of the trisomy 10p syndrome. This observation provided further credence to the concept that additional chromosome material of proximal 10p11.2 may not contribute to the trisomy 10p syndrome phenotype.

Challenges in the management of recurrent endometrial cancer.

It is generally believed that the outcomes of women with endometrial cancer are better than those used to be. Based on the fact that most patients with endometrial cancer have their disease detected and managed in the early stage, and pathologic cell types were less invasive (e.g., Grades 1 and 2, as well as Type Idendometrioid cell type), the majority of patients with a diagnosis of endometrial cancer can be successfully managed by standard staging surgeries, including cytology, total hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic lymph node dissection, and para-aortic lymph node dissection; most patients can be cured and/or controlled adequately. In addition, some patients with, for example, younger age, and International Federation of Gynecology and Obstetrics (FIGO) Stage IA, Grade 1, endometrioid-type carcinoma can be treated with more conservative therapy, including fertility preservation and/or ovary preservation. However, recurrenceand disease-related death will occur in a certain percentage of patients with endometrial cancer after primary treatment. Therefore, some risk factors have been reported; for patients having these risk factors, various kinds of postoperative adjuvant therapies, including chemotherapy (CT), radiation therapy (RT), tumor excision, and others not specified, have been suggested. All efforts are applied to minimize the risk of recurrence and therapeutic failure, because it is very difficult to medically manage women with recurrent endometrial cancer. Although many strategies can be applied for women with recurrent endometrial cancers, the resulting therapeutic effects are uncertain. Conventionally, recurrent tumors can briefly be separated into local recurrence and distant metastasis, or can be synchronous at both sites. By definition, local recurrence is limited to pelvic recurrence, especially recurrence on the vaginal cuff. Management of local recurrence may be much easier, although greatly varied, because these patients can undergo tumor excision, RT, CT, or a combination of any of these. By contrast, distant metastasis is occurrence of the tumor outside of the pelvic cavity and is often considered a systemic disease. In theory, it is nearly impossible to totally eradicate the tumors without a systemic therapy strategy. Under these circumstances, only CT and/or hormone therapy can achieve this goal; however, endometrial cancer is relatively resistant to CT and often unresponsive to hormone

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.

Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and serous ovarian cancer in Taiwan

OBJECTIVE To compare the prognosis of patients with advanced-stage primary peritoneal serous papillary carcinoma (PSPC) or papillary serous ovarian cancer (PSOC). MATERIALS AND METHODS This was a retrospective case-control study and included two study groups: one with stage III/IV PSPC (n = 38) patients and the other with PSOC (n = 53) patients. Patients were matched for histologic subtype (serous tumor), tumor stage, tumor grade, residual disease at the end of debulking surgery (primary or interval), and age (±5 years). RESULTS Mean age was significantly greater for patients with PSPC (63.03 ± 11.88 years) than for patients with PSOC (55.92 ± 12.56 years, p = 0.008). Optimal debulking surgery was performed initially in 71.9% of PSPC patients and 66.0% of PSOC patients. In addition, 93.9% of PSPC patients and 92.3% of PSOC patients were treated with platinum-paclitaxel chemotherapy. The frequency of high-grade tumors was significantly higher in the PSPC (100%) than in the PSOC group (68.3%; p < 0.001). Progression-free survival (PFS) was similar in the PSPC [median 12 months, 95% confidence interval (CI) 7.3-16.7] and PSOC groups (median 16.7 months, 95% CI 12.9-20.4; p = 0.470). Overall survival was shorter in the PSPC (median 62 months, 95% CI 19.6-104.4) than in the PSOC group (median 77.5 months, 95% CI 69.7-85.2; p = 0.006, log-rank statistic). CONCLUSION PFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ.

α2,3-sialyltransferase type I regulates migration and peritoneal dissemination of ovarian cancer cells

Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecologic cancers due to advanced stage presentation, peritoneal dissemination, and refractory ascites at diagnosis. We investigated the role of α2,3-sialyltransferase type I (ST3GalI) by analyzing human ovarian cancer datasets and human EOC tissue arrays. We found that high expression of ST3GalI was associated with advanced stage EOC. Transwell migration and cell invasion assays showed that high ST3GalI expression enhanced migration of EOC cells. We also observed that there was a linear relation between ST3GalI expression and epidermal growth factor receptor (EGFR) signaling in EOC patients, and that high ST3GalI expression blocked the effect of EGFR inhibitors. Co-Immunoprecipitation experiments demonstrated that ST3GalI and EGFR were present in the same protein complex. Inhibition of ST3GalI using a competitive inhibitor, Soyasaponin I (SsaI), inhibited tumor cell migration and dissemination in the in vivo mouse model with transplanted MOSEC cells. Further, SsaI synergistically enhanced the anti-tumor effects of EGFR inhibitor on EOC cells. Our study demonstrates that ST3GalI regulates ovarian cancer cell migration and peritoneal dissemination via EGFR signaling. This suggests α2,3-linked sialylation inhibitors in combination with EGFR inhibitors could be effective agents for the treatment of EOC.

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.

Advanced endocervical adenocarcinoma metastatic to the ovary presenting as primary ovarian cancer

Dear Editor,Cervical squamous cell carcinoma (SCC) and adenocarcinomamay involve the ovary. Although it is not difficult to diagnose inmost cases, on very rare occasions the presentation may showsymptoms related to an ovarian mass, with the cervical cancerbeing undetected, especially endocervical adenocarcinoma [1,2].This is important because the challenge of diagnosing primaryendocervical adenocarcinoma occurs especially in women whoshow no symptoms, and have a grossly normal cervix and anegative Pap smear [3]. The spread of cervical malignancy (bothSCC and adenocarcinoma) is often through lymphatic drainage ordirect invasion [4]; except some reports show that endocervicaladenocarcinoma carries a higher risk of ovarian metastases thanSCC of the cervix [5]. There is an apparent difference in the treat-ment strategy for advanced cervical cancers and ovarian cancers[6,7]. Therefore, making an accurate diagnosis before planningtherapy is of paramount importance. The following is a case reportof advanced cervical adenocarcinoma metastatic to the ovarymimicking primary ovarian cancer.A 54-year-old menopausal woman (G3P3) visited the emer-gency room due to acute sudden onset of abdominal pain afterseveral weeks of abdominal fullness. Her past medical history wasunremarkable. She did not have any Pap smears since the birth ofherlastchild(28yearspreviously).Physicalexaminationrevealedaprotuberant and tense abdomen, but the cervix was essentiallynormal. Transvaginal ultrasound revealed a 15 cm complex cysticmass lesion located at the right adnexal area accompanied withmassive ascites, but the uterus and the left ovary seemed to benormal.Computedtomographyidentifiedandconfirmed theabovefinding (Fig. 1). Serum tumor markers, including CA 125, CA 199,and CEA were 286.0 U/mL, 209.0 U/mL, and 226.0 ng/mL, respec-tively. Other investigations, including hematological andbiochemical tests, a chest X-ray, and upper and lower gastrointes-tinal (GI) tract evaluations were within normal limits.Under the diagnosis of ovarian malignancy, the patient under-went a laparotomy. During surgery, a right ovarian cystic complexmass with a mucinous component (Fig. 2) accompanied withmassive ascites (7000 mL) and peritoneal carcinomatosis wasfound. The immediate frozen pathology report favored a diagnosisof adenocarcinoma-mucinous type. Therefore, the patient under-went an optimal debulking surgery, including total hysterectomy(Fig. 3), bilateral salpingo-oophorectomy, infracolic omentectomyand retroperitoneal lymph node sampling, and multiple biopsies.However, the final pathologic report was primary uterine endo-cervical adenocarcinoma.Pathologic features included hyperchromatic dysplasia of themucinous glandular cells of the uterine endocervix; the mucinoustumor occupied the whole layer of the endocervix and extended tothe lower segment of the uterine body. Other sections of the rightovary, appendix, omentum, abdominal wall, and mesentery allshowed tumor metastases with floating mucinous tumor cellswithin an extensive mucin pool.The patient was treated with adjuvant systemic chemotherapy(8 cycles of topotecan [Hycamtin Injection, GlaxoSmithKline, San

Hemorrhage: A strong indicator for myomectomy-related complication.

Uterine fibroid (leiomyoma or myoma) is the most common benign uterine tumor, accounting for 20e60% of cases in women of reproductive age. Three variant-subcategories include: (1) ordinary leiomyomadbenign, including nondegenerated and degenerated [cystic, hemorrhagic (carneous), fatty (lipoleiomyoma), hyaline, and myxoids]; (2) leiomyoma variantsdunclassified (mitotically active, cellular, atypical, and smooth muscle tumors of uncertain malignant potential); and (3) leiomyosarcomadmalignant. The use of a uterinepreservation strategy, including medical or surgical treatment rather than hysterectomy, to treat uterine myoma has become popular, because it not only provides adequate symptom control, but also preserves fertility. Advanced surgical instruments, including new and innovative laparoscopic techniques with and without robotics-assisted systems, have allowed a greater number of gynecologic surgeons to use laparoscopic surgery in place of conventional exploratory laparotomy in the management of various kinds of diseases, including some gynecological malignancies. Furthermore, these so-called minimally invasive surgeries claim to have many patient-focused benefits, such as a decreasing risk of postoperative adhesion, promoting rapid recovery, and cosmetic advantages. However, the malignant form (leiomyosarcoma) is difficult to differentially diagnose clearly between benign and malignant tumors, resulting in an almost impossible presurgical diagnosis and contributing to the elevated possibility of widespread malignant tumors during and after operation, especially for those surgeries using morcellation. An increasing number of surgeons are hesitant, and some are outright opposed, to this approach in the management of uterine fibroids. Therefore, conventional laparotomy has regained a measure of popularity. Moreover, as surgical techniques have continued to advance, it is now possible to shorten the incision wound (ultramini-laparotomy), enabling patients to receive benefits similar to those of traditional laparoscopic surgery. Therefore, abdominal myomectomy is still considered the best choice for women with fibroids and who need to maintain their reproductive function. The study by Çinar et al in this issue of the Journal of the Chinese Medical Association entitled, “Association of clinical outcomes and complications with obesity in patients who

Heterotopic triplet pregnancy with an intrauterine, a tubal, and a cervical gestation following in vitro fertilization and embryo transfer

Medical Research and Educational Department, Taipei Veterans General Hospital, Taipei, Taiwan Department of Obstetrics and Gynecology, Taipei Veterans General Hospital and National Yang-Ming University, School of Medicine, Taipei, Taiwan c Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan Department of Pathology, Taipei Veterans General Hospital and National Yang-Ming University, School of Medicine, Taipei, Taiwan Kempas Medical Centre, Johor Baru, Malaysia