Ju-Won Roh

Low Initial Human Papilloma Viral Load Implicates Worse Prognosis in Patients With Uterine Cervical Cancer Treated With Radiotherapy

PURPOSE To evaluate whether human papillomavirus (HPV) viral load measured in cervical smear and HPV type 18 are associated with radiotherapy outcomes in uterine cervical cancer. PATIENTS AND METHODS HPV DNA: was semiquantitatively measured in the cervical smears of 169 radiotherapy patients. HPV viral load was classified as low or high according to median HPV DNA titer and examined for its prognostic value. The multivariable Cox proportional hazards model was used to adjust for covariates. A relapse-predicting model was constructed to classify three risk groups for disease-free survival (DFS), which were used for internal validation. RESULTS Patients with lower HPV viral load showed worse DFS in univariate analysis. HPV type 18, younger patient age, stage group, nodal status, histologic grade, and histologic type were other prognostic factors for poor DFS. Among these factors, all except stage group were associated with HPV viral load. Multivariate analysis showed the strong influence of HPV viral load for poor DFS. The prognostic model developed using our outcome data performed well in predicting the risk of relapse. CONCLUSION Our data suggest that HPV viral load is a strong independent prognostic factor for DFS. HPV type 18 showed a significant relationship with poor radiotherapy outcome in univariate analysis, but not in multivariate analysis.

Tumor carbonic anhydrase 9 expression is associated with the presence of lymph node metastases in uterine cervical cancer

Tumor hypoxia has a pronounced effect on malignant progression and metastatic spread of human tumors. As carbonic anhydrases (CA) 9 and 12 are induced by the low‐oxygen environment within tumors, we investigated the relationship between the expression of these two CA and the presence of metastatic lymph nodes (LN) in uterine cervical cancer. CA9/CA12 expression was evaluated histochemically in primary cervical cancer tissues of 73 patients who underwent laparoscopic LN staging and two patients with clinical staging before definitive radiotherapy at the National Cancer Center, Korea. We also evaluated CA9 expression in 33 patients with pathologically confirmed metastatic LN. CA9 expression in the primary tumors was significantly associated with LN metastasis (P = 0.03) and poorer disease‐free survival (relative risk, 6.1; 95% confidence interval, 1.3–28.3, P = 0.02, multivariate analysis), whereas CA12 expression did not show such a relationship. In addition, 21 of 24 metastatic LN revealed similar CA9 expression (P = 0.001), suggesting that CA9‐expressing tumor cells had a higher metastatic potential. CA9 was expressed in 45 of 75 (60%) primary tumors, with positive tumor cells observed predominantly in the area away from the blood vessels. In contrast, CA12 expression was observed in only 29 of 74 primary tumors (39%), without a specific pattern. These findings indicate that expression of CA9, but not CA12, in tumors is associated with the presence of LN metastases and poorer prognosis. Selective application of new treatment modalities based on CA9 expression to prevent LN metastases may improve overall treatment outcome in patients with uterine cervical cancer. (Cancer Sci 2007; 98: 329–333)

Efficacy and oncologic safety of nerve-sparing radical hysterectomy for cervical cancer: a randomized controlled trial

Objective A prospective, randomized controlled trial was conducted to evaluate the efficacy of nerve-sparing radical hysterectomy (NSRH) in preserving bladder function and its oncologic safety in the treatment of cervical cancer. Methods From March 2003 to November 2005, 92 patients with cervical cancer stage IA2 to IIA were randomly assigned for surgical treatment with conventional radical hysterectomy (CRH) or NSRH, and 86 patients finally included in the analysis. Adequacy of nerve sparing, radicality, bladder function, and oncologic safety were assessed by quantifying the nerve fibers in the paracervix, measuring the extent of paracervix and harvested lymph nodes (LNs), urodynamic study (UDS) with International Prostate Symptom Score (IPSS), and 10-year disease-free survival (DFS), respectively. Results There were no differences in clinicopathologic characteristics between two groups. The median number of nerve fiber was 12 (range, 6 to 21) and 30 (range, 17 to 45) in the NSRH and CRH, respectively (p<0.001). The extent of resected paracervix and number of LNs were not different between the two groups. Volume of residual urine and bladder compliance were significantly deteriorated at 12 months after CRH. On the contrary, all parameters of UDS were recovered no later than 3 months after NSRH. Evaluation of the IPSS showed that the frequency of long-term urinary symptom was higher in CRH than in the NSRH group. The median duration before the postvoid residual urine volume became less than 50 mL was 11 days (range, 7 to 26 days) in NSRH group and was 18 days (range, 10 to 85 days) in CRH group (p<0.001). No significant difference was observed in the 10-year DFS between two groups. Conclusion NSRH appears to be effective in preserving bladder function without sacrificing oncologic safety.

Biologic Effects of Platelet-Derived Growth Factor Receptor α Blockade in Uterine Cancer

Purpose: Platelet-derived growth factor receptor α (PDGFRα) expression is frequently observed in many kinds of cancer and is a candidate for therapeutic targeting. This preclinical study evaluated the biologic significance of PDGFRα and PDGFRα blockade (using a fully humanized monoclonal antibody, 3G3) in uterine cancer. Experimental Design: Expression of PDGFRα was examined in uterine cancer clinical samples and cell lines, and biologic effects of PDGFRα inhibition were evaluated using in vitro (cell viability, apoptosis, and invasion) and in vivo (orthotopic) models of uterine cancer. Results: PDGFRα was highly expressed and activated in uterine cancer samples and cell lines. Treatment with 3G3 resulted in substantial inhibition of PDGFRα phosphorylation and of downstream signaling molecules AKT and mitogen-activated protein kinase (MAPK). Cell viability and invasive potential of uterine cancer cells were also inhibited by 3G3 treatment. In orthotopic mouse models of uterine cancer, 3G3 monotherapy had significant antitumor effects in the PDGFRα-positive models (Hec-1A, Ishikawa, Spec-2) but not in the PDGFRα-negative model (OVCA432). Greater therapeutic effects were observed for 3G3 in combination with chemotherapy than for either drug alone in the PDGFRα-positive models. The antitumor effects of therapy were related to increased apoptosis and decreased proliferation and angiogenesis. Conclusions: These findings identify PDGFRα as an attractive target for therapeutic development in uterine cancer. Clin Cancer Res; 20(10); 2740–50. ©2014 AACR.

Surgical manual of the Korean Gynecologic Oncology Group: classification of hysterectomy and lymphadenectomy

The Surgery Treatment Modality Committee of the Korean Gynecologic Oncologic Group (KGOG) has determined to develop a surgical manual to facilitate clinical trials and to improve communication between investigators by standardizing and precisely describing operating procedures. The literature on anatomic terminology, identification of surgical components, and surgical techniques were reviewed and discussed in depth to develop a surgical manual for gynecologic oncology. The surgical procedures provided here represent the minimum requirements for participating in a clinical trial. These procedures should be described in the operation record form, and the pathologic findings obtained from the procedures should be recorded in the pathologic report form. Here, we focused on radical hysterectomy and lymphadenectomy, and we developed a KGOG classification for those conditions.

Diastolic forward flow in the fetal main pulmonary artery and its implication for fetal cardiac cycle evaluation

Abstract Objectives: To examine if the fetal main pulmonary artery diastolic forward flows (MPADFs) are detected consistently, if the waves from fetal MPADFs coincide with those from atrial contractions, and the reproducibility of the cardiac cycle measurements using this technique. Methods: Two examiners performed a fetal pulsed Doppler echocardiography of the four chamber (4CV), ductal arch (DA) and short axis (SA) views on 44 women with singleton pregnancies. Time intervals between atrial contraction peaks and those between MPADF peaks were compared. Atrioventricular (AV) and ventriculoatrial (VA) intervals were measured from MPADF waves in DA and SA views and compared between observers. Intraclass correlation coefficients (ICCs) were calculated as a measure of inter-observer reproducibility. Results: In all observations, MPADFs were demonstrated. The mean time intervals between atrial contraction peaks from 4CV and those between MPADF peaks from DA and SA views were not significantly different. The mean AV and VA intervals were not significantly different between observers. Comparison of measurements of two observers had substantial agreements. Conclusions: Our data show that MPADFs can be found consistently and coincide with atrial contractions. As cardiac cycle measurements can be done with considerable reproducibility, this technique may be useful in assessing fetal cardiac cycle.

Estrogen-induced acute pancreatitis: A case report and literature review

Estrogens are commonly used in gynecologic area, such as oral contraception, hormone replacement therapy, and in vitro fertilization-embryo transfer. Although estrogen is a common cause of acute drug-induced pancreatitis, there has been paucity of report in Korea. Clinical course of estrogen-induced acute pancreatitis is usually mild to moderate, but fetal case can occur. In addition, there can be a latency from the first administration to the symptom. Therefore, physicians should consider the possibility of the disease when a woman taking estrogen or previous history of taking estrogen presents with acute abdominal pain. Here, we report a case of estrogen-induced acute pancreatitis that occurred during the preparation for embryo transfer.

Factors Affecting Unused Remaining Volume of Intravenous Patient-controlled Analgesia in Patients Following Laparoscopic Gynecologic Surgery

PURPOSE This study was undertaken to evaluate the factors affecting the unused remaining volume of intravenous patient-controlled analgesia (IV PCA) in patients who had undergone laparoscopic gynecologic surgery. METHODS We retrospectively collected patient records from pre-existing PCA log sheets from 98 patients. Surgical factors and IV PCA-related data including remaining volume, administration duration, early discontinuation (yes or no), and adverse reactions were recorded. Chi-square test, one-way analysis of variance, and multiple linear regression were applied for data analysis. RESULTS The average age of the 98 patients was 40.0 ± 8.24 years. The incidence of postoperative nausea and vomiting (PONV) and early discontinuation were not statistically significant among the different surgical groups (p = .540 and p = .338, respectively). Twenty-eight patients wanted discontinuation of IV PCA and the remaining volume was 33.6 ± 7.8 mL (range 20-55 mL). The significant determinants of remaining volume were whether IV PCA was discontinued due to PONV and duration of surgery (p < .001). The surgical duration was inversely correlated with the remaining volume. CONCLUSION Early discontinuation of IV PCA due to PONV is a major contributing factor to wastage of medicine. Prevention and treatment of PONV is needed to encourage patients to maintain PCA use for pain control.

Persistent chemical peritonitis resulting from spontaneous rupture of an ovarian mature cystic teratoma

726 PERSISTENT CHEMICAL PERITONITIS RESULTING FROM SPONTANEOUS RUPTURE OF AN OVARIAN MATURE CYSTIC TERATOMA Hyun Sung Yang, MD, Tae Hun Song, MD, Hyun Chul Bang, MD, Jun-Ho Park, MD, Chae Hyeong Lee, MD, Ju-Won Roh, MD, PhD, Eo-Jin Kim, MD, PhD, Yong Seok Lee, MD, PhD, Seung-Su Han, MD Departments of Obstetrics and Gynecology, Pathology, Radiology, Dongguk University College of Medicine; Department of Obstetrics and Gynecology, Chung-Ang University College of Medicine, Seoul, Korea

Abstract 406: Mechanisms of stress-buffering effects of dopamine on tumor vasculature

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Chronic stress is known to promote tumor growth by activating the sympathetic nervous system (SNS) with resultant increases in norepinephrine (NE) and epinephrine (E). In contrast to NE and E, dopamine (DA) levels are low under chronic stress conditions. We have recently demonstrated that dopamine replacement in mice exposed to daily restraint stress can reverse the stimulatory effects of NE and E on ovarian cancer growth. Ovarian tumor tissues from stressed mice treated with dopamine showed significant increases in pericyte coverage of tumor microvessels. The focus of the current study was to examine the mechanisms by which dopamine treatment affected pericyte coverage of tumor endothelial cells under stress conditions. Female nude mice were subjected to chronic stress using the restraint-stress procedure. Tumor formation was induced by injecting the SKOV3 ip1 or HeyA8 ovarian cancer cells into the peritoneal cavity. Stressed and non-stressed mice were divided into four treatment groups: Control (PBS), DA, DA plus butaclamol (DR1 antagonist) and DA plus eticlopride (DR2 antagonist). Following therapy, harvested tumors were examined for microvessel density (MVD), vascular maturation (pericyte coverage) and proliferating cell nuclear antigen (PCNA). Expression of DA receptors (DR1-DR5) was analyzed by RT-PCR and Western blotting. Mice exposed to daily restraint stress showed 2-fold increased SKOV3ip1-tumor growth compared to non-stressed mice; treatment with DA alone resulted in 78% (p<0.01) decrease in tumor growth and 68% (p<0.01) decrease in MVD compared to control stressed mice. Similarly, DA/butaclamol combined treatment led to 71% (p<0.01) reduction in tumor growth and a 65% (p<0.01) decrease in MVD. Eticlopride in combination with DA reversed the inhibitory effects of DA on tumor growth. Furthermore, in stressed mice, daily dopamine treatment resulted in significant increase in pericyte coverage (51.4%; p<0.001) compared to controls. This effect was abrogated by butaclamol (44%; p<0.01), but not by eticlopride treatment. Similar results were obtained in stressed mice bearing HeyA8-tumors. In T10.5-pericyte like cells, treatment with DA, DA plus NE, DA agonist: [SKF38393][1] or PDGFBB increased significantly cell migration. No significant changes were noted with NE alone or DA plus butaclamol treatments. In MOEC, no significant changes in cell migration were observed under these experimental conditions. Collectively, our data indicate that DA, acting through DR1, could stimulate recruitment of pericytes to tumor endothelial cells, and promote vascular maturation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 406. doi:10.1158/1538-7445.AM2011-406 [1]: /lookup/external-ref?link_type=GENPEPT&access_num=SKF38393&atom=%2Fcanres%2F71%2F8_Supplement%2F406.atom