Sang Wun Kim

MicroRNA Expression Profiles in Serous Ovarian Carcinoma

Purpose: Although microRNAs have recently been recognized as riboregulators of gene expression, little is known about microRNA expression profiles in serous ovarian carcinoma. We assessed the expression of microRNA and the association between microRNA expression and the prognosis of serous ovarian carcinoma. Experimental Design: Twenty patients diagnosed with serous ovarian carcinoma and eight patients treated for benign uterine disease between December 2000 and September 2003 were enrolled in this study. The microRNA expression profiles were examined using DNA microarray and Northern blot analyses. Results: Several microRNAs were differentially expressed in serous ovarian carcinoma compared with normal ovarian tissues, including miR-21, miR-125a, miR-125b, miR-100, miR-145, miR-16, and miR-99a, which were each differentially expressed in >16 patients. In addition, the expression levels of some microRNAs were correlated with the survival in patients with serous ovarian carcinoma. Higher expression of miR-200, miR-141, miR-18a, miR-93, and miR-429, and lower expression of let-7b, and miR-199a were significantly correlated with a poor prognosis (P < 0.05). Conclusion: Our results indicate that dysregulation of microRNAs is involved in ovarian carcinogenesis and associated with the prognosis of serous ovarian carcinoma.

Transumbilical single-port access versus conventional total laparoscopic hysterectomy: surgical outcomes

OBJECTIVE The objective of the study was to compare surgical outcomes and postoperative pain between transumbilical single-port access total laparoscopic hysterectomy (SPA-TLH) and conventional 4-port total laparoscopic hysterectomy (TLH). STUDY DESIGN We retrospectively reviewed 157 patients who underwent SPA-TLH (n = 52) or conventional TLH (n = 105). A single-port access system consisted of a wound retractor, surgical glove, 2 5 mm trocars, and 1 10/11 mm trocar. RESULTS The SPA-TLH group had less intraoperative blood loss (P < .001), shorter hospital stay (P = .001), and earlier diet intake (P < .001) compared with the conventional TLH group. There was no difference in perioperative complications. Immediate postoperative pain score was lower in the SPA-TLH group (P < .001). Postoperative pain after 6 and 24 hours was lower in SPA-TLH with marginal statistical significance. CONCLUSION SPA-TLH is a feasible method for hysterectomy with lower immediate postoperative pain and better surgical outcomes with respect to recovery time compared with conventional TLH.

Diagnosis and staging of primary ovarian cancer: Correlation between PET/CT, Doppler US, and CT or MRI

PURPOSE To compare the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT), pelvic Doppler ultrasonography (US), abdomino-pelvic computed tomography (CT), and pelvic magnetic resonance imaging (MRI) for detection of ovarian cancer and to assess the role of PET/CT in evaluating the dissemination of ovarian cancer. PATIENTS AND METHODS One hundred thirty-three women suspected to have ovarian cancer were enrolled in a prospective study before surgery between March 2005 and August 2007. The accuracy of each modality in detection of malignancy was estimated by computing the relevant areas under a receiver operating characteristics curve. Histopathologic results served as the reference standard. RESULTS Histopathology showed benign tumors in 25 patients, borderline tumors in 13 patients, and malignant tumors in 95 patients. In distinguishing malignant/borderline from benign ovarian tumors, the accuracy of PET/CT (0.921) was higher than that of pelvis US (0.830) and abdomino-pelvic CT or pelvis MRI (0.749; P=0.013). Radiologic staging by PET/CT was concordant with surgical staging in 78% of patient and PET/CT revealed 15 (15.8%) unpredicted extra-abdominal lymph node metastasis in 95 patients with ovarian cancer. In addition, PET/CT detected new, unexpected co-existing malignant tumors in five (3.8%) cases including two thyroid tumors, two breast tumors, and one pancreatic neuroendocrine cancer. CONCLUSION PET/CT is superior to pelvis US, abdomino-pelvic CT, and pelvic MRI for diagnosis of malignant ovarian tumors and is useful in revealing metastatic ovarian cancer and co-existing malignant tumors. Therefore, we suggest that PET/CT could be used during pre-operative evaluation of patients suspected to have ovarian cancer.

Long non-coding RNA HOTAIR is associated with human cervical cancer progression.

The functions of many long non-coding RNAs (lncRNAs) in human cancers remain to be clarified. The lncRNA Hox transcript antisense intergenic RNA (HOTAIR) has been reported to reprogram chromatin organization and promote breast and colorectal cancer metastasis, the involvement of lncRNAs in cervical cancer is just beginning to be studied. In the present study, we examined the expression and the functional role of HOTAIR in cervical cancer. HOTAIR expression was determined in cervical cancer tissues (n=111) and corresponding normal tissues (n=40) by using real-time polymerase chain reaction, and its correlation with clinical parameters and prognosis were analyzed. To determine the effect of HOTAIR knockdown and overexpression in cervical cancer cell lines, we used the CCK-8 assay, wound healing migration and Matrigel invasion assay. The expression level of HOTAIR in cervical cancer tissues was higher than that in corresponding non-cancerous tissues. High HOTAIR expression correlated with lymph node metastasis, and reduced overall survival. A multivariate analysis showed that HOTAIR was a prognostic factor for predicting cervical cancer recurrence. Knockdown of HOTAIR reduced cell proliferation, migration, and invasion in cervical cancer cell lines. Moreover, HOTAIR regulated the expression of vascular endothelial growth factor, matrix metalloproteinase-9 and epithelial-to-mesenchymal transition (EMT)-related genes, which are important for cell motility and metastasis. Therefore, HOTAIR may promote tumor aggressiveness through the upregulation of VEGF and MMP-9 and EMT-related genes. These findings indicate that HOTAIR may represent a novel biomarker for predicting recurrence and prognosis and serve as a promising therapeutic target in cervical cancer.

Analysis of chromosomal changes in serous ovarian carcinoma using high-resolution array comparative genomic hybridization: Potential predictive markers of chemoresistant disease

The mechanism of drug resistance in cancer is multifactorial, and the accumulation of multiple genetic changes may lead to drug‐resistant phenotypes. This study sought to determine characteristic genetic changes in chemoresistant serous ovarian carcinomas using high‐resolution array comparative genomic hybridization (aCGH), and identified genomic aberrations that could be used as predictive markers of chemoresistant disease. Seventeen primary ovarian tumors from optimally debulked stage IIIc serous ovarian carcinoma patients were analyzed using aCGH. Ten patients had chemoresistant disease (progression within 12 months of initial chemotherapy), whereas seven patients had chemosensitive disease (no recurrence for more than 36 months). Receiver operating characteristics curve analysis was used to select chromosomal aberrations that could help distinguish chemoresistant disease from chemosensitive disease. In 17 tumors, frequent increases in DNA copy number were seen on 1p36.33, 3q26.2, 8q24.3, 10q26.3, 12p11.21, 20q13.33, and 21q22.3, and frequent losses were observed on 4p12, 5q13.2, 7q11.21, 8p23.1, 14q32.33, Xq13.3, and Xq21.31. The gains on 5p15.33 and 14q11.2, and losses on 4q34.2, 4q35.2, 5q15, 8p21.1, 8p21.2, 11p15.5, 13q14.13, 13q14.2, 13q32.1, 13q34, 16q22.2, 17p11.2, 17p12, and 22q12.3 were more frequent in chemoresistant disease. The losses on 13q32.1 and 8p21.1 had the largest areas under the curve (AUC 0.90 and 0.85, respectively). The most reliable combination of chromosomal aberrations for detecting chemoresistant disease was the loss on 13q32.1 and 8p21.1 (AUC 0.950). Our findings suggest that these chromosomal aberrations are potential predictive markers of chemoresistant disease in patients with serous ovarian carcinomas.

Learning curve and surgical outcome for single-port access total laparoscopic hysterectomy in 100 consecutive cases.

Aims: To define the learning curve for single-port access (SPA) total laparoscopic hysterectomy (TLH) and evaluate the surgical outcomes. Methods: Patient demographics and segmental operating times of all 100 patients who underwent SPA-TLH by a single surgeon were analyzed. Patients were arranged in order based on surgery date. Results: 100 patients underwent SPA-TLH. There was no conversion to conventional laparoscopy or laparotomy. The median time until the removal of a specimen (TR) was 45 min and the median time for closure of the vaginal cuff (TC) was 18 min. The median total operating time from skin opening to closure (TO) was 80 min. TR, TC, and TO decreased significantly over the study period. The TC decreased significantly from the first 20 cases to the next 20 (p = 0.028) and the TO from the second 20 cases to the next 20 (p = 0.029). Conclusions: Proficiency for SPA-TLH was achieved after 40 cases. Operating time and postoperative hemoglobin drop decreased with experience, without increasing complication.

Recent advances of robotic surgery and single port laparoscopy in gynecologic oncology

Two innovative approaches in minimally invasive surgery that have been introduced recently are the da Vinci robotic platform and single port laparoscopic surgery (SPLS). Robotic surgery has many advantages such as 3-dimensional view, the wrist like motion of the robotic arm and ergonomically comfortable position for the surgeon. Numerous literatures have demonstrated the feasibility of robotic surgery in gynecologic oncology. However, further research should be performed to demonstrate the superiority of robotic surgery compared to conventional laparoscopy. Additionally, cost reduction of robotic surgery is needed to adopt robotic surgery into gynecologic oncology worldwide. SPLS has several possible benefits including reduced operative complications, reduced postoperative pain, and better cosmetic results compared to conventional laparoscopy. Although several authors have indicated that SPLS is a feasible approach for gynecologic surgery, there have been few reports demonstrating the potential advantages over conventional laparoscopy. Moreover, technical difficulties of SPLS still exist. Therefore, the advantages of a single port approach compared to conventional laparoscope should be evaluated with comparative study, and further technologic development for SPLS is also needed. These two progressive technologies take the lead in the development of MIS and further studies should be performed to evaluate the benefits of robot surgery and SPLS.

Robotic single-port transumbilical total hysterectomy: a pilot study

Objective To evaluate the feasibility of robotic single-port transumbilical total hysterectomy using a home-made surgical glove port system. Methods We retrospectively reviewed the medical records of patients who underwent robotic single-port transumbilical total hysterectomy between January 2010 and July 2010. All surgical procedures were performed through a single 3-4-cm umbilical incision, with a multi-channel system consisting of a wound retractor, a surgical glove, and two 10/12-mm and two 8 mm trocars. Results Seven patients were treated with robotic single-port transumbilical total hysterectomy. Procedures included total hysterectomy due to benign gynecological disease (n=5), extra-fascial hysterectomy due to carcinoma in situ of the cervix (n=1), and radical hysterectomy due to cervical cancer IB1 (n=1). The median total operative time was 109 minutes (range, 105 to 311 minutes), the median blood loss was 100 mL (range, 10 to 750 mL), and the median weight of the resected uteri was 200 g (range, 40 to 310 g). One benign case was converted to 3-port robotic surgery due to severe pelvic adhesions, and no post-operative complications occurred. Conclusion Robotic single-port transumbilical total hysterectomy is technically feasible in selected patients with gynecological disease. Robotics may enhance surgical skills during single-port transumbilical hysterectomy, especially in patients with gynecologic cancers.

Robot-assisted staging using three robotic arms for endometrial cancer: Comparison to laparoscopy and laparotomy at a single institution

To demonstrate the feasibility of robot‐assisted staging surgery using three arms in patients with endometrial cancer.

The long non-coding RNA HOTAIR increases tumour growth and invasion in cervical cancer by targeting the Notch pathway

Evidence suggests that the long non-coding RNA (lncRNA), HOTAIR, is involved in cervical cancer pathogenesis. We examined serum HOTAIR expression levels in cervical cancer patients and determined the relationships between HOTAIR expression and several clinicopathological factors, including survival. We also examined the functional consequences of HOTAIR overexpression both in vitro and in vivo. Compared with control patients, HOTAIR expression was significantly greater in the serum of cervical cancer patients (P < 0.001). The results indicated that this increase was significantly associated with tumour size (P = 0.030), lymphovascular space invasion (P = 0.037), and lymph node metastasis (P = 0.043). Univariate analysis revealed that disease-free survival and overall survival times were significantly shorter in cervical cancer patients with high HOTAIR expression (hazard ratio [HR] = 4.27, 4.68 and P = 0.039, 0.031, respectively). Cell proliferation and invasion in vitro increased as a result of lentiviral-mediated HOTAIR overexpression in cervical cancer cell lines. HOTAIR knockdown inhibited these properties and increased apoptosis. In vivo xenograft experiments using the HOTAIR-overexpressing SiHa cell line revealed that HOTAIR was a strong inducer of tumour growth and modulated the expression of epithelial-mesenchymal transition and Notch-Wnt signalling pathway-related genes. This result suggested that HOTAIR overexpression promoted cell proliferation and invasion. In conclusion, increased HOTAIR expression was associated with decreased patient survival times. HOTAIR may be a useful target for treatment of cervical cancer patients.