Jae Yun Song

Detection of Microrna as Novel Biomarkers of Epithelial Ovarian Cancer From the Serum of Ovarian Cancer Patient

Objective MicroRNA (miRNA) is an abundant class of small noncoding RNAs that act as gene regulators. Recent studies have suggested that miRNA deregulation is associated with the initiation and progression of human cancer. However, information about cancer-related miRNA is mostly limited to tissue miRNA. The aim of this study was to find specific profiles of serum-derived miRNAs of ovarian cancer based on a comparative study using a miRNA microarray of serum, tissue, and ascites. Methods From 2 ovarian cancer patients and a healthy control, total RNA was isolated from their serum, tissue, and ascites, respectively, and analyzed by a microarray. Under the comparative study of each miRNA microarray, we sorted out several miRNAs showing a consistent regulation tendency throughout all 3 specimens and the greatest range of alteration in serum as potential biomarkers. The availability of biomarkers was confirmed by qRT-PCR of 18 patients and 12 controls. Results Out of 2222 kinds of total miRNAs that were identified in the microarray analysis, 95 miRNAs were down-regulated and 88 miRNAs were up-regulated, in the serum, tissue, and ascites of cancer patients. Among the miRNAs that showed a consistent regulation tendency through all specimens and showed more than a 2-fold difference in serum, 5 miRNAs (miR-132, miR-26a, let-7b, miR-145, and miR-143) were determined as the 5 most markedly down-regulated miRNAs in the serum from ovarian cancer patients with respect to those of controls. Four miRNAs (miR-132, miR-26a, let-7b, and miR-145) out of 5 selected miRNAs were significantly underexpressed in the serum of ovarian cancer patients in qRT-PCR. Conclusions Serum miR-132, miR-26a, let-7b, and miR-145 could be considered as potential candidates as novel biomarkers in serous ovarian cancer. Also, serum miRNAs is a promising and useful tool for discriminating between controls and patients with serous ovarian cancer.

Clinicopathologic characteristics of granulosa cell tumors of the ovary: a multicenter retrospective study

Objective To evaluate the clinicopathologic characteristics and prognostic factors of ovarian granulosa cell tumors. Methods Medical records of 113 patients presenting between January 1995 and December 2007 were retrospectively reviewed. Results One-hundred two patients had adult type disease, with a mean age of 46.2 years (range, 18 to 83 years) and a mean follow-up period of 54.7 months (range, 1 to 155 months). The distribution of FIGO stages was 86 patients at stage I, 11 at stage II, and 5 at stage III. During follow-up, ten patients recurred at a mean time of 48 months (range, 4 to 109 months). Among them, three patients died after a mean of 57 months (range, 25 to 103 months). In recurrence analysis, advanced stage (p=0.032) and presence of residual disease (p=0.012) were statistically significant, and age<40 years, premenopause and positive washing cytology were marginally significant (p<0.1). In multivariate analysis, stage was the only factor associated with recurrence; adjuvant chemotherapy and fertility-sparing surgery were not statistically significant. Among 36 patients with fertility-sparing operations, eight patients had nine pregnancies and delivered seven babies. Eleven patients had juvenile type tumors; the mean age was 20.0 years (range, 8 to 45 years) and the mean follow-up period was 69.8 months (range, 20 to 156 months). The distribution of FIGO stage was nine patients at stage I and two at stage III. There were no recurrences or deaths reported. Four patients had seven pregnancies and delivered six babies. Conclusion Stage is the only factor associated with disease-free survival, and fertility-sparing surgery may be a treatment option for women with early-stage disease who want to retain fertility.

Obesity and epithelial ovarian cancer survival: a systematic review and meta-analysis

BackgroundStudies on the association between obesity and ovarian cancer survival have had conflicting results. We reviewed and quantitatively summarized the existing evidence, exploring potentially important sources of variability, such as the timing of body mass index (BMI) assessment, BMI cut points, references used in multivariate analysis, and ovarian cancer stage.MethodsEligible studies were searched using MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials, relevant bibliographies were manually reviewed for additional studies. Adjusted hazard ratios (HRs) from individual studies were pooled using a random effects model.Results17 cohort studies of 929 screened articles were included in the final analysis. Obesity in early adulthood and obesity 5 years before ovarian cancer diagnosis were associated with poor patient survival (early adulthood: pooled HR 1.67; 95% CI 1.29-2.16; 5 years prediagnosis: pooled HR 1.35; 95% CI 1.03-1.76). However, the results for obesity at diagnosis depended on whether BMI was analyzed as a categorical or continuous variable. Analysis of obesity with BMI as a categorical variable did not affect ovarian cancer prognosis (pooled HR 1.07; 95% CI 0.95-1.21); obesity with BMI as a continuous variable showed slightly poorer survival with each incremental increase in BMI (pooled HR 1.02; 95% CI 1.01-1.04).ConclusionsObesity 5 years before ovarian cancer diagnosis and obesity at a young age were associated with poor prognosis. The association between obesity at diagnosis and survival of ovarian cancer patients still remains equivocal. BMI at diagnosis cannot be a prognostic factor for the survival of ovarian cancer patients. Further well-designed studies are needed to elucidate the variety effect of obesity on the survival of ovarian cancer patients.

Significance of CD44v6 expression in gynecologic malignancies

Aim:  Variants of CD44 have been proposed to be important in cancer invasion and metastasis. The purpose of this study was to evaluate the diagnostic and prognostic value of CD44v6 expression in gynecologic malignancies.

Transvaginal Single-Port Natural Orifice Transluminal Endoscopic Surgery for Benign Uterine Adnexal Pathologies

Transvaginal natural orifice transluminal endoscopic surgery (NOTES) with pneumoperitoneum has been used in cholecystectomies, appendectomies, and nephrectomies, but transvaginal NOTES using a single port in gynecologic procedures has not been described despite gynecologist familiarity with the vaginal approach. We performed transvaginal single-port NOTES in 10 women with benign uterine adnexal disease: oophorectomy in 3 patients, salpingostomy and salpingectomy in 2 each, and ovarian cystectomy, paratubal cystectomy, and ovarian wedge resection in 1 each. The patients were discharged at 1 or 2 days postoperatively, and were satisfied, with minimal pain, no abdominal scar, and no complications at 2-month follow-up. We conclude that transvaginal single-port NOTES to treat benign uterine adnexal disease is a feasible and attractive option.

Practice guidelines for the early detection of cervical cancer in Korea: Korean Society of Gynecologic Oncology and the Korean Society for Cytopathology 2012 edition

The consensus guideline development committee of Korean Society of Gynecologic Oncology was reconvened in March 2012. The committee consisted of 36 experts representing 12 university hospitals and professional organizations. The objective of this committee was to develop standardized guidelines for cervical cancer screening tests for Korean women and to distribute these guidelines to every clinician, eventually improving the quality of medical care. Since the establishment of the consensus guideline development committee, evidence-based guidelines have either been developed de novo considering specific Korean situations or by adaptation of preexisting consensus guidelines from other countries. Recommendations for cervical cancer screening tests, management of atypical squamous and glandular cells, and management of low-grade and high-grade squamous intraepithelial lesions were developed. Additionally, recommendations for human papillomavirus DNA testing and recommendations for adolescent and pregnant women with abnormal cervical screening test results were also included.

Should endometrial clear cell carcinoma be classified as type II endometrial carcinoma

Endometrial clear cell carcinomas (ECCCs) are considered to be Type II endometrial carcinomas, like uterine serous adenocarcinoma (SCA), and therefore aggressive clinical management is indicated. However, according to the limited clinical, immunohistochemical, and molecular data available in the literature, ECCCs show overlapping features of SCA and endometrioid adenocarcinomas. Therefore, questions regarding their designation as the Type II carcinomas have been raised. We performed immunohistochemical staining for hepatocyte nuclear factor-1&bgr; and napsin A for the histologic confirmation of clear cell carcinoma (CCC), and analyzed immunohistochemical findings for estrogen receptor, progesterone receptor, HER2/neu, p53, p16, ARID1A, PTEN, DNA mismatch-repair proteins along with other prognostic factors. We performed DNA sequencing for the K-RAS, BRAF, PIK3CA, and PTEN genes for 16 pure CCCs. No patients with pure CCC experienced recurrent disease or died of the disease (0/16, 0%). ECCCs had SCA-like features with rare expression of estrogen receptor/progesterone receptor (18.8%/6.3%) and no K-RAS mutations, intermediate features regarding expressions of p53 (37.5%) and p16 (25%), and endometrioid adenocarcinoma-like features regarding losses of PTEN (81.3%), ARID1A (25%) and mismatch-repair protein (68.8%), expression of microsatellite instability-high (25%), HER2/neu (12.5%), and PIK3CA mutations (18.8%). Pure ECCC should not be regarded as Type II carcinoma, because it shares the immunohistochemical and molecular characteristics of Type I endometrioid adenocarcinoma and Type II SCA.

The prognostic significance of preoperative leukocytosis in epithelial ovarian carcinoma: a retrospective cohort study.

OBJECTIVE Preoperative leukocytosis is known to be a negative prognostic factor for several gynecologic malignancies, but its relationship with epithelial ovarian carcinoma (EOC) is unknown. We sought to evaluate the prognostic implications of preoperative leukocytosis for women with EOC. METHODS We retrospectively reviewed the medical records of patients who underwent primary debulking surgery and adjuvant platinum-based chemotherapy for EOC between January 1993 and October 2011. Associations between leukocytosis and recurrence-free survival (RFS) and overall survival (OS) were determined by univariate analyses. Multivariate Cox proportional hazards regression was used to identify independent prognostic factors for RFS and OS. RESULTS Of 155 women, 23 (14.8%) had leukocytosis and 132 (85.2%) did not have leukocytosis. RFS and OS were significantly shorter for women with leukocytosis than for women without leukocytosis (P=0.009 and P<0.0001, respectively). The mortality rate was also higher among women with leukocytosis (P<0.0001). Multivariate analysis revealed that preoperative leukocytosis (hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.55-4.41; P=0.009), advanced stage (HR: 3.12; 95% CI: 1.44-6.75; P=0.004), and optimal cytoreduction (HR: 0.38; 95% CI: 0.14-0.70; P=0.031) were independent prognostic factors for RFS. Additionally, preoperative leukocytosis was independently associated with decreased OS (HR: 7.66; 95% CI: 2.78-21.16; P<0.0001). CONCLUSIONS Among women with EOC, preoperative leukocytosis might be an independent prognostic factor for RFS and OS. A larger-scaled, prospective study is needed to verify these results.

Fertility preservation in women with cancer

Fertility preservation (FP) is an effort to retain the fertility of cancer patients, and as an emerging discipline, it plays a central role in cancer care. Because of improvement in diagnostic and therapeutic strategies, an increasingly large number of patients are surviving with cancer. FP specialists should make an effort to spread the significance of FP among reproductive women with cancer and provide appropriate education both for associated physicians and for cancer patients who wish to preserve their fertility. Physicians who take part in the initial diagnosis and management of cancer should consider the importance of early referral of young cancer patients to FP specialists and take care of those patients by providing timely information and appropriate counseling. Individualized treatment strategies should be delivered depending on the patients situation with appropriate team approach.

Evaluation of risk factors of vaginal cuff dehiscence after hysterectomy

Objective The purpose of this study was to evaluate risk factors of vaginal cuff dehiscence or evisceration according to the type of operation. Methods Medical records of 604 women who underwent hysterectomies at Korea University Anam Hospital between June 2007 and June 2011 were reviewed. They were allocated to six groups. The six types of hysterectomies included robotic hysterectomy (n = 7), robotic radical hysterectomy and node dissection (RRHND, n = 9), total laparoscopic hysterectomy (TLH, n = 274), laparoscopy assisted vaginal hysterectomy (LAVH, n = 238), laparoscopic radical hysterectomy and node dissection (n = 11), and abdominal radical hysterectomy (ARH, n = 63). The characteristics and outcomes of each groups were compared. Results There was no difference in the characteristics of patients between 6 groups. In total of 604 hysterectomies, 3 evisceration (0.49%) and 21 dehiscences (3.47%) occurred. Evisceration were found in RRHND (1/9, 11.1%), TLH (1/276, 0.36%), and ARH (1/63, 1.56%). Dehiscences occurred in TLH (15/274, 5.42%), LAVH (4/238, 1.68%), and ARH (2/63, 3.17%). In 169 cases of TLH with intra-corporeal continuous suture, 1 evisceration and 4 dehiscences occurred, whereas 11 dehiscences occurred in 105 TLH cases with vaginal continuous locking suture (2.96% vs. 10.47%, P = 0.02). Conclusion The incidence of vaginal cuff dehiscenceand eviscerationwas significantly higher in TLH than LAVH. The intra-corporeal cuff suture was superior to the vaginal suture to prevent the vaginal cuff complications in TLH.