Seung-Su Han

Evaluation of preoperative criteria used to predict lymph node metastasis in endometrial cancer

Objective. To evaluate whether we could accurately predict lymph node (LN) metastasis with preoperative tests in endometrial cancer. Design. Retrospective study. Setting. Seoul National University Hospital, South Korea. Population. Three hundred patients with endometrial cancer who underwent surgical staging including lymphadenectomy between January 1999 and July 2007. Methods. We reviewed the medical records of 300 patients with endometrial cancer. The preoperative factors used to predict LN metastasis were as follows: old age (≥55 years), serum CA‐125 level [level ≥ 20 U/mL (if age < 50 years), level ≥ 28 U/mL (if age ≥ 50 years)], non‐endometrioid histologic type and Grade 3, metastatic LN assessed by pelvic MRI or CT, and deep myometrial invasion assessed by pelvic MRI only. Logistic regression analysis was used to determine the significant predictive factors. Main outcome measures. Sensitivity/specificity and false positive/negative rates. Results. Thirty patients had LN metastasis. Although LN evaluation by pelvic MRI or CT and high CA‐125 level were the significant independent predictors for LN metastasis, the sensitivity/specificity and false positive/negative rates for LN metastasis by these two combined preoperative tests were 86.7%/71.4% and 68.7%/2.7%, respectively. However, the sensitivity/specificity and false positive/negative rates for LN metastasis by six combined preoperative tests were 100%/28.9% and 84.6%/0%, respectively. Conclusions. The six combined preoperative tests are useful in selecting patients without LN metastasis in endometrial cancer. Lymphadenectomy could be avoided in about 29% of patients with endometrial cancer who have no LN metastasis by using six combined preoperative tests.

Underuse of ovarian transposition in reproductive‐aged cancer patients treated by primary or adjuvant pelvic irradiation

Aim:  To investigate the application status of ovarian transposition (OT) in reproductive‐aged cancer patients undergoing radiation therapy.

Expression of Vascular Endothelial Growth Factor and Hypoxia Inducible Factor-1α in Cervical Neoplasia

Altered angiogenesis is an important phenotype of high‐grade cervical lesions and invasive cervical carcinomas. Many researchers, including us, have shown that oncoproteins of human papillomavirus could enhance the vascular endothelial growth factor (VEGF) expression. We investigated the change in VEGF and hypoxia‐inducible factor‐1α (HIF‐1α) expression patterns that occur during the carcinogenesis and progression of cervical cancer. Expressions of HIF‐1α and VEGF were evaluated by immunohistochemistry using paraffin‐embedded specimens obtained from 41 patients with a normal cervix, 39 patients with cervical intraepithelial neoplasia (CIN 1, 10; CIN 2/3, 29), and 36 patients with cervical cancer. The VEGF and HIF‐1α expressions were higher in CIN and invasive cancer than in normal cervix (P= 0.021, P < 0.001, respectively). It is interesting to note that there was no significant difference in VEGF and HIF‐1α overexpressions between CIN 2/3 and cervical cancer and between nonmetastatic and metastatic cancers. In addition, there was a significant correlation between the immunohistochemical score of HIF‐1α and that of VEGF expression (Spearmans correlation coefficient 0.275, P= 0.003, n= 116). Taken together, the results of our study suggest that expressions of VEGF and HIF‐1α could be involved in cervical carcinogenesis. In addition, the weak correlation between VEGF and HIF‐1α expressions suggests that regulatory mechanisms other than HIF‐1α may be involved in the expression of VEGF during cervical carcinogenesis.

Predictive Value of Individualized Tumor Response Testing by ATP-Based Chemotherapy Response Assay in Ovarian Cancer

The aim of this study is to investigate the correlation between ATP-based chemotherapy response assay (ATP-CRA) results and clinical outcomes in ovarian cancer. Twenty-nine fresh tumor specimens were collected. Tumor cells were isolated and cultured for 48 hrs in medium containing anticancer drugs. The median age of patients was 56 years. The sensitivity, positive predictive value, and accuracy of ATP-CRA were respectively 94.1%, 94.1%, and 90.0%. There was a significant relationship between ATP-CRA results and clinical responses (p = 0.046). This study suggests that ATP-CRA has high sensitivity, positive predictive value, and accuracy for predicting response to chemotherapy in ovarian cancer.

Expression of MMP‐2, MMP‐9, and Urokinase‐Type Plasminogen Activator in Cervical Intraepithelial Neoplasia

Matrix metalloproteinase‐2 (MMP‐2), MMP‐9, and urokinase‐type plasminogen activator (uPA) are important factors for cancer invasion and metastasis, degrading the extracellular matrix. They are also associated with angiogenesis. Angiogenic phenotype is another feature of high‐grade cervical intraepithelial neoplasia (CIN). However, their associations with the progression of low‐grade CIN to high‐grade CIN are unexplored. We investigated whether these proteolytic enzyme expressions correlate with the progression of CIN. A total of 39 paraffin‐embedded specimens from 10 patients with CIN grade 1, nine with CIN grade 2, and 20 with CIN grade 3 were assessed immunohistochemically by specific antibodies against MMP‐2, MMP‐9, and uPA. MMP‐9 expression was higher in CIN 3 lesions (47.4%) than in CIN 1 (22.2%) and CIN 2 (20.2%) lesions, although the difference failed to reach statistical significance. The expression level of uPA and MMP‐2 was not associated with the grade of CIN lesions. Interestingly, we found a significant association between expressions of uPA and MMP‐2 (P= 0.028). Our results suggest that MMP‐9 might play a role in the progression of CIN.

Value of pelvic examination and imaging modality for the evaluation of tumor size in cervical cancer

OBJECTIVE The purpose of this study was to compare the accuracy of pelvic examination versus imaging modality such as computed tomography (CT) or magnetic resonance imaging (MRI) in the measurement of the tumor size of invasive cervical carcinoma based on pathologic findings. METHODS Patients with stage Ib-II cervical cancer who underwent primary surgical treatment between January 2003 and December 2005 were evaluated retrospectively. One hundred three consecutive patients aged 24 to 81 years (mean age, 50.6 years), who had not received any treatment previously were included in this study. Accuracy of preoperative CT or MRI versus pelvic examination in the measurement of tumor size was compared based on pathologic findings. All patients were examined and staged clinically by the gynecologic oncologist. Surgery was performed within 2 weeks after imaging studies. The data were analyzed using descriptive statistics. RESULTS The largest diameter of the tumor measured by pathologic findings was 2.76+/-1.76 cm. Based on pathologic findings, accuracy was estimated by the degree of agreement with a difference of <0.5 or 1.0 cm between the measurements of tumor size obtained by pelvic examination and imaging modality. Pelvic examination and imaging modality had an accuracy of 46.6% and 39.8%, respectively, with a difference of <0.5 cm, and an accuracy of 72.8% and 55.3%, respectively, with a difference of <1.0 cm. Correlation with pathologic findings was higher for pelvic examination (r(s)=0.680) than for imaging modality (r(s)=0.410). In determining the size of tumor mass differentiating >4.0 cm from </=4.0 cm, imaging modality showed higher accuracy than pelvic examination. CONCLUSION For the patients with stage Ib to II cervical cancer, pelvic examination is superior to imaging modality with regard to evaluation of the tumor size. However, imaging modality may be accurate for evaluating bulky tumors of cervical cancer.

Phase I/IIa Study of Combination Chemotherapy with CKD‐602 and Cisplatin in Patients with Recurrent Epithelial Ovarian Cancer

The aim of this study was to determine the maximum tolerated dose (MTD) and therapeutic efficacy of a newly developed CKD‐602 topoisomerase I inhibitor and cisplatin in patients with recurrent epithelial ovarian cancer. CKD‐602 (0.30 mg/m2 daily for 5 days) and cisplatin (60 mg/m2 on day 5) were administered to patients every 3 weeks with dose adjustment of CKD‐602 by 0.05 mg/m2 daily until the MTD was reached. Dose‐limiting toxicity was defined as grade ≥ 3 neutropenia or thrombocytopenia for more than 4 days or accompanied by fever ≥ 38.5°C, infection, hemorrhage, or transfusion; grade ≥ 3 nonhematological toxicity except for alopecia, nausea, and vomiting. We enrolled 26 patients with recurrent epithelial ovarian cancer who had measurable disease (MD) estimated by computed tomography scan (n= 12) and nonmeasurable disease (NMD) evaluated by serum CA‐125 levels (n= 14). All patients received 188 cycles of CKD‐602 and cisplatin with a median number of six cycles per patient (range, 2 to 12). MTD of CKD‐602 was 0.30 mg/m2 daily. The overall response rate was 69.2% (18/26) with 58.3% (7/12) and 78.6% (11/14) in MD and NMD, respectively. Among the responsive patients, 14 were platinum sensitive (14/18, 77.7%) and four were platinum resistant (4/8, 50.0%). The most common toxicity was grade ≥ 3 neutropenia developing in 17 patients (65.4%) and 72 cycles (38.3%). Grade 3 nausea and anorexia were the most common gastrointestinal toxicities, developing in 15 cycles (8.0%) of four patients (15.4%) and 10 cycles (5.3%) of five patients (19.3%), respectively. The median disease‐free interval was 6 months (range 0–26 months). CKD‐602 at a concentration of 0.3 mg/m2 daily for 5 days and cisplatin at 60 mg/m2 on day 5 every 3 weeks showed high efficacy, with acceptable toxicity, against platinum‐sensitive/resistant recurrent epithelial ovarian cancer.

ERCC1 C19007T polymorphism and the risk and invasiveness of cervical cancer in Korean women

Aim:  Various DNA alterations by environmental or endogenous carcinogens, if not repaired, can cause genetic mutagenesis, resulting in carcinogenesis. A polymorphic variant of excision repair cross‐complementation group 1 (ERCC1) (the DNA repair gene) may be associated with carcinogenesis due to reduced DNA repair capacity. The aim of this study was to investigate whether the ERCC1 C19007T polymorphism might be associated with the increased risk and invasiveness of cervical cancer in Korean women.

Long-Term Results of Laparoscopic Colposuspension with Bilateral Round-Infundibulopelvic Ligaments after Hysterectomy for Uterovaginal Prolapse

STUDY OBJECTIVE To evaluate the long-term outcomes of laparoscopic colposuspension with bilateral round-infundibulopelvic ligaments after hysterectomy in high-grade uterovaginal prolapse. DESIGN Retrospective analysis of medical records (Canadian Task Force Classification II-3). SETTING University clinic center. PATIENTS Fifty-one patients with grade 3 (22 patients) or 4 (29 patients) uterovaginal prolapse. INTERVENTIONS We performed laparoscopic colposuspension with bilateral round-infundibulopelvic ligaments after hysterectomy in 51 patients with grade 3 or 4 uterovaginal prolapse. MEASUREMENTS AND MAIN RESULTS After a mean follow-up of 59.0 months (95% CI, 56.3-61.7), 51 patients (100.0%) had no sign or recurrence of prolapse. Postoperative transient abdominal discomfort, voiding difficulty, and vaginal spotting developed in 4 patients (7.8%), 2 patients (3.9%), and 1 patient (2.0%), respectively. CONCLUSION Laparoscopic colposuspension using bilateral round-infundibulopelvic ligaments after hysterectomy could be an effective surgical option in the treatment of high-grade uterovaginal prolapse.

A case of secondary postpartum hemorrhage with shock followed by rupture of progressive retroperitoneal hematoma through left upper vaginal wall

Puerperal genital hematomas are uncommon causes of postpartum hemorrhage but can be a cause of serious morbidity and even maternal death. When puerperal genital hematomas are clinically occult despite signifi cant blood loss or found as delayed postpartum hemorrhage, there is a high risk of shock. We report a case with shock accompanied by rupture of progressive retroperitoneal hematoma through left upper vaginal wall on 2nd postpartum day.