Chel Hun Choi

Altered MicroRNA Expression in Cervical Carcinomas

Purpose: MicroRNAs (miRNA) are small noncoding RNAs that are 18 to 25 nucleotides in length; they regulate the stability or translational efficiency of target mRNAs. Emerging evidence suggests that miRNAs might be involved in the pathogenesis of a variety of human cancers. Experimental Design: In this study, we profiled miRNA expression in 10 early stage invasive squamous cell carcinomas (ISCC) and 10 normal cervical squamous epithelial specimens using TaqMan real-time quantitative PCR array methods. In order to evaluate the role of miR-199a, one of the most significantly overexpressed in ISCCs, we transfected cervical cancer cells (SiHa and ME-180) with anti–miR-199a oligonucleotides and assessed the cell viability. Results: We found 70 genes (68 up-regulated, 2 down-regulated) with significantly different expression in the ISCCs compared with normal samples (P < 0.05). When we analyzed the expression of the 10 most significant miRNAs in 31 ISCCs, increased miR-127 expression was significantly associated with lymph node metastasis (P = 0.006). Transfection of anti–miR-199a oligonucleotides to cervical cancer cells suppressed cell growth in vitro, which was potentiated with the anticancer agent cisplatin. Conclusions: Our results show that miRNA deregulation may play an important role in the malignant transformation of cervical squamous cells. In addition, they may offer new candidate targets to be exploited for both prognostic and therapeutic strategies in patients with cervical cancer.

Single-Port Access Laparoscopic-Assisted Vaginal Hysterectomy: A Novel Method with a Wound Retractor and a Glove

STUDY OBJECTIVE To present our initial experience with single port-access laparoscopic-assisted vaginal hysterectomy (SPA-LAVH) by use of a wound retractor and a glove. DESIGN Continuing, prospective study (Canadian Task Force classification II-3). SETTING University teaching, research hospital, and a tertiary care center. PATIENTS We performed the SPA-LAVH in 24 patients from May 6, 2008, through October 8, 2008. INTERVENTIONS All cases of SPA-LAVH were performed by a single surgeon (T. J. K.). MEASUREMENTS AND MAIN RESULTS We analyzed the data to determine the outcome of SPA-LAVH and compared the initial 10 cases (group A) and the latter 14 cases (group B) to consider the learning curve. Median and range are used to describe non-normal data. A total of 24 consecutive patients have undergone SPA-LAVH, for benign gynecologic conditions, including 16 uterine myomas and 8 cases of adenomyosis, regardless of body mass index or previous abdominal or pelvic surgery. All cases but 3 were performed exclusively through a single port. The median operative time, weight of the uterus, and estimated blood loss were 119 minutes (range 90 to 255 minutes), 347 g (range 225 to 732 g), and 400 mL (range 100 to 1000 mL), respectively. The decline in hemoglobin from before surgery to postoperative day 1 was from 0.7 to 4.3 g/dL, with a median of 2.05 g/dL. The median hospital stay (postoperative day) was 3 days (range 3 to 7). When we compared the operative outcomes between the 2 groups, there was a tendency toward a decreased operative time in group B, although the difference was not significant. However, there was a significant decrease in the estimated blood loss and hospital stay in group B (p = .00, = .04, respectively). CONCLUSION The SPA-LAVH was safe and effective, and the procedure could be learned over a short period of time. Additional experience and continued investigation are warranted.

Single Port Access Laparoscopic Adnexal Surgery

STUDY OBJECTIVE To estimate the feasibility, safety, and operative outcomes for the management of adnexal masses by single port access (SPA) laparoscopy with a wound retractor and a surgical glove. DESIGN A prospective single-center study (Canadian Task Force classification III). SETTING University hospital. PATIENTS Twenty-four well selected patients with adnexal masses on imaging scans recruited from June 2008 through January 2009. INTERVENTIONS Single port access laparoscopic adnexal surgery. MEASUREMENTS AND MAIN RESULTS Single port access laparoscopic adnexal surgery was successfully completed in 22 of 24 patients. The median age of the patients was 45 years (range 23-63 years), and the median body mass index was 22 (range 18-29). The median tumor size was 5 cm (range 3-12 cm). The median operative time was 70 minutes (range 40-128 minutes). The estimated blood loss was minimal (range 10-100mL). The postoperative course was uneventful in all patients. The median postoperative hospital stay was 1 day (range 1-3 days). No postoperative complications were observed at follow-up. The 2 failed cases were as follow: 1 required an additional trocar for adequate adhesiolysis, and the other a staging laparotomy because of the finding of a borderline ovarian malignancy on frozen section pathologic study. CONCLUSION The single port access laparoscopic adnexal surgery was safe and feasible and provided almost no visual scar.

Single port access laparoscopic adnexal surgery versus conventional laparoscopic adnexal surgery: a comparison of peri-operative outcomes

OBJECTIVE The objective of the study was to compare the peri-operative outcomes of single port access (SPA) laparoscopic adnexal surgery and conventional laparoscopic adnexal surgery. STUDY DESIGN This is a retrospective case-control study matched by body mass index (BMI; kg/m(2)). A single surgeon (T-JK) performed 17 SPA laparoscopic adnexal surgeries (cases) consecutively between December 2008 and March 2009; 34 conventional laparoscopic adnexal surgeries (controls) were performed by another surgeon who had similar surgical skill at our hospital during the same time period. Data on the SPA laparoscopic adnexal surgery cases were collected prospectively into our data registry after Institutional Review Board (IRB) approval and we reviewed the data on the controls from the electronic medical records with IRB approval. RESULTS In both groups all procedures were performed without failure. Among preoperative baseline characteristics there was no difference between the two groups including preoperative size of ovarian tumor and bilaterality. The pathology findings were similar; a mature cystic teratoma was the most common pathological feature in both groups. The two groups were comparable with regard to operative outcomes according the surgery type. There were no differences between SPA and conventional groups in median operation time (64 min vs. 57.5 min, p=0.252), the number of patients that requested additional parenteral non-steroidal anti-inflammatory drugs (7 patients vs. 19 patients, p=0.597), and the absolute decrease (1.3mg/dl vs. 1.1mg/dl, p=0.640) from preoperative hemoglobin to postoperative day 1 measurements. No patient from either cohort required a blood transfusion. There were no complications in either group including umbilical incision complications in the SPA group. CONCLUSION Our study demonstrated that SPA laparoscopic adnexal surgery had comparable operative outcomes to conventional laparoscopic adnexal surgery. A prospective comparison is needed for confirmation and to define the role of SPA in gynecological adnexal surgery.

Increased toll-like receptor 9 expression in cervical neoplasia

Toll‐like receptors (TLRs) recognize pathogen‐associated molecular patterns (PAMPs) and enable innate immune responses. Although TLR9 has been previously considered to be expressed only in immune cells, there is now increasing evidence that TLR9 expression is present in nonimmune cells as well. In this study, we undertook to determine whether TLR9 expression was associated with disease progression in cervical neoplasia. TLR9 expression was evaluated by immunohistochemistry in 55 formalin‐fixed paraffin‐embedded cervical tissues; nine normal cervical specimens, 10 low‐grade cervical intraepithelial neoplasias (CINs), 12 high‐grade CINs, and 24 invasive squamous cell carcinomas (ISCCs). In addition, TLR9 expression was evaluated, at the RNA level, in fresh frozen cervical carcinoma tissues by real‐time quantitative RT‐PCR. Immunohistochemical staining showed that TLR9 expression was undetectable (55.6%) or weak (44.4%) in normal cervical squamous epithelial tissues, however, variable staining was observed in the basal layer of all normal endocervical glands. TLR9 expression, which was mainly observed as cytoplasmic staining, gradually increased in accordance with the histopathological grade in the following order: low‐grade CIN < high‐grade CIN < ISCC (P < 0.001), and in particular, was moderate to strong in 70% of ISCC cases. Furthermore, real‐time quantitative RT‐PCR revealed that TLR9 expression, in tumors, was significantly enhanced compared to normal cervical tissues (P = 0.012). These results suggest that TLR9 may play a significant role in tumor progression of cervical neoplasia and may represent a useful marker for malignant transformation of cervical squamous cells.

The prognostic significance of the SUVmax (maximum standardized uptake value for F-18 fluorodeoxyglucose) of the cervical tumor in PET imaging for early cervical cancer: Preliminary results

OBJECTIVE The objective of this study was to evaluate the prognostic significance of the cervical tumor uptake of fluorine-18-labeled FDG (fluorodeoxyglucose) measured as the SUVmax (maximum standardized uptake value) by PET (Positron Emission Tomography) in patients with early cervical cancer treated with surgery+/-adjuvant therapy. METHODS Forty-four patients (FIGO clinical stage IB to IIA) with biopsy-proven cervical cancer underwent PET before surgery. The SUVmax of the primary cervical tumor mass was obtained and compared with pathological prognostic factors after the initial treatment. In addition, we investigated the recurrence pattern according to the SUVmax and analyzed independent risk factors associated with the recurrence of disease. RESULTS According to the tumor stage, the mean SUVmax significantly differed among groups (P=0.013). The SUVmax was significantly higher in patients with deep stromal invasion (>or=1 cm, P=0.0208), LVSI (lymph-vascular space invasion) (P=0.0429) and a pathologically confirmed large tumor size of more than 4 cm (P=0.0074) when compared to controls. Patients with a high SUVmax (>or=13.4) had a significantly reduced disease-free survival rate compared to patients with a low SUVmax (P=0.021). In addition, the SUVmax (>or=13.4) was a significant independent predictor of recurrence of cervical cancer after treatment with surgery (+/-adjuvant therapy) (P=0.0207). CONCLUSION Patients with early cervical cancer showing a high SUVmax (>or=13.4) of the cervical tumor should be considered at increased risk for disease recurrence after surgery and may need more aggressive multimodal treatment.

Volumetric MR-guided High-Intensity Focused Ultrasound Ablation with a One-Layer Strategy to Treat Large Uterine Fibroids: Initial Clinical Outcomes

PURPOSE To evaluate initial clinical outcomes of volumetric magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) ablation by using a one-layer strategy to treat large (>10 cm in diameter) uterine fibroids, with investigation of the correlation between effectiveness of the one-layer strategy and dynamic contrast material-enhanced (DCE) MR parameters. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. Twenty-seven women (mean age, 44.5 years) with 27 large uterine fibroids (mean diameter, 11.3 cm ± 1.4 [standard deviation] [range, 10.1-16.0 cm]; fibroid volume, 502.5 mL ± 214.3 [range, 253.8-1184.0 mL]) underwent volumetric MR-guided HIFU ablation with a one-layer strategy. (All treatment cells were placed in one coronal plane at a depth of half to anterior two-thirds of the anteroposterior dimension of fibroids.) Treatment time, immediate nonperfused volume (NPV), and effectiveness of a one-layer strategy (ratio of immediate NPV to total volume of treatment cells planned) correlating with baseline DCE MR parameters (volume transfer constant [K(trans)], fractional extravascular extracellular space, and fractional blood plasma volume [Pearson correlation test]), complications, 3-month follow-up volumes, and symptom severity score (SSS) changes (paired t test) were assessed retrospectively. RESULTS All treatments showed technical success in one session (mean treatment time, 166.2 minutes ± 38.9). NPV was 301.3 mL ± 119.1, which was 64.2% ± 19.9 (<50%, n = 4; ≥ 50%, n = 23) of fibroid volume. Ratio of immediate NPV to total volume of treatment cells (1.79 ± 0.61) negatively correlated with DCE MR imaging K(trans) values (r = -0.426, P = .017). Minor complications occurred in five patients (18.5% [thermal injury of abdominal wall, n = 3; 30-day leg numbness, n = 1; cystitis, n = 1]). At 3-month follow-up (n = 18), mean SSS had decreased from 37.4 at baseline to 24.0 (P < .001), and volume reduction ratio was 0.64 ± 0.15 (P < .001). CONCLUSION Volumetric MR-guided HIFU ablation with a one-layer strategy is safe and effective for treatment of large uterine fibroids. Effectiveness of this strategy showed a significant negative correlation with K(trans) values at baseline DCE MR imaging.

Prognosis of ovarian clear cell carcinoma compared to other histological subtypes: A meta-analysis

OBJECTIVE To compare the survival outcome between clear cell carcinoma (CCC) and other histological subtypes in epithelial ovarian carcinoma (EOC). METHODS From January 1974 to February 2011, we identified a total of 31,800 (CCC; 2152, non-CCC; 29648) patients from 12 studies meeting the inclusion criteria. RESULTS Heterogeneity tests demonstrated significant between-study variation (I(2)=92.1%) with no significant difference in hazard ratio (HR) for death between CCC and non-CCC (HR; 1.16, 95% CI; 0.85-1.57, random-effects model). Comparing the HR based on stage I+II, and stage III+IV, between CCC and non-CCC, showed that CCC patients had a higher hazard rate for death than those with non-CCC of the ovary (stage I+II; HR; 1.17, 95% CI; 1.01-1.36, stage III+IV; HR; 1.65, 95% CI; 1.52-1.79). In a comparison of CCC and serous EOC, advanced stage (III and IV) CCC only showed a poorer hazard rate for death than serous EOC (HR; 1.71, 95% CI; 1.57-1.86). CONCLUSION This analysis suggests that ovarian CCC patients had poorer prognosis than those with other histological subtypes of EOC, especially in advanced EOC stages. Different treatment strategies may be needed for patients with ovarian CCC.

Single-port access (SPA) laparoscopic surgery in gynecology: a surgeon's experience with an initial 200 cases

OBJECTIVE To report our initial two hundred single-port access (SPA) gynecologic surgeries and present the perioperative outcomes. STUDY DESIGN This is a prospective single-center study (Canadian Task Force classification II-2). Two hundred selected patients with gynecological disease were recruited for the study from May 2008 through December 2009 at Samsung Medical Center. RESULTS Two hundred patients underwent SPA gynecological surgery (105 a total hysterectomy; 11 a subtotal hysterectomy; 43 an oophorectomy; 31 an ovarian cystectomy; 5 a salpingectomy; 2 a myomectomy; 3 adhesiolysis only). The median age and body mass index were 45.5 and 22.9 kg/m(2), respectively. SPA surgery was successfully completed in 187 patients, without the need for ancillary ports (93.5%). Two cases required a conventional multiport, and nine cases needed one additional port. Two patients were converted to a laparotomy. One intra- and five post-operative complications occurred. The complication rate was 3.2% (6/187). The median operative time was 120 min (54-250) for a total hysterectomy, 180 (150-345) for a subtotal hysterectomy, 60 (27-245) for an oophorectomy, 105 (50-185) for a cystectomy, and 60 (30-115) for a salpingectomy. CONCLUSION Single-port surgery was safe and feasible for gynecological indications. Further study of single-port surgery is required to determine whether it has significant benefits compared to conventional techniques.

Galectin 1 expression is associated with tumor invasion and metastasis in stage IB to IIA cervical cancer

Galectin 1 is a 14-kd laminin-binding lectin involved in important biologic mechanisms of tumors, including neoplastic transformation, cell survival, angiogenesis, cell proliferation, and metastasis. In this study, we investigated the role of galectin 1 in cell survival and metastasis in cervical cancer. The expression of galectin 1 was determined in 73 formalin-fixed, paraffin-embedded cervical cancer tissues using an immunohistochemical method and compared with clinicopathologic risk factors for recurrence after surgery. To evaluate the role of galectin 1 in cell proliferation and invasion, we performed proliferation and invasion assays with galectin 1 small interfering RNA (siRNA) using cervical cancer cell lines, including HeLa and SiHa cells. Immunohistochemical analysis revealed that galectin 1 expression was found in most peritumoral stroma samples (72/73; 98.6%). Galectin 1 expression was significantly correlated with the depth of invasion in the cervix (P=.015) and lymph node metastasis (P=.045) on univariate analysis. When progression-free survival of all of the patients studied was analyzed based upon galectin 1 expression, galectin 1 expression was not correlated with progression-free survival (P=.32). Down-regulation of galectin 1 using small interfering RNA resulted in the inhibition of cell growth and proliferation of HeLa and SiHa cells. Moreover, the ability of cells to invade was significantly reduced by galectin 1 small interfering RNA. Our results revealed that high galectin 1 expression in peritumoral stroma was significantly correlated with depth of invasion in cervical lesions and lymph node metastasis of cervical cancer and that galectin 1 may be functionally involved in cell proliferation and invasion.