Seog Nyeon Bae

Incidence and risk factors of lower-extremity lymphedema after radical surgery with or without adjuvant radiotherapy in patients with FIGO stage I to stage IIA cervical cancer.

Objective This study aimed to determine the incidence and risk factors of lower-extremity lymphedema (LEL) in women who had radical surgery with or without adjuvant radiotherapy for International Federation of Gynecology and Obstetrics (FIGO) stage I to stage IIA cervical cancer. Methods The medical records were reviewed retrospectively on patients with histologically confirmed FIGO stage I to IIA cervical cancer. Lower-extremity lymphedema–related medical problems such as peripheral vascular disease, congestive heart failure, or chronic renal disease were excluded. A logistic regression analysis was used to examine the relationship between variable clinical characteristics and development of LEL. Results We evaluated 707 patients. Of the 707 patients evaluated, we excluded 92 patients who had received radiotherapy as the initial therapy and 19 patients with LEL related to medical problems. Seventy-five patients (12.6%) developed LEL. The incidence was high in patients with adjuvant radiotherapy (odds ratio, 3.47; 95% confidence interval, 2.086–5.788; P = 0.000), with 78.7% of the patients with LEL having developed the condition within 3 years after initial treatment. Conclusions Adjuvant radiotherapy was significantly associated with development of LEL in women who had undergone radical surgery with lymphadenectomy for FIGO stage I to stage IIA cervical cancer. The possibility for the occurrence of LEL must be fully explained before treatment and patients should be provided with the appropriate preventive education. Further prospective studies are needed to confirm the incidence and risk factors for LEL.

Clinical analysis of intra-operative frozen section proven borderline tumors of the ovary

OBJECTIVE We have assessed the accuracy of frozen section diagnosis and the outcomes of misdiagnosis in borderline tumors of the ovary (BTO) according to frozen section. METHODS All pathology reports with BTO in both frozen and permanent section analyses between 1994 and 2008 at Seoul St. Marys Hospital were reviewed. Frozen section diagnosis and permanent section histology reports were compared. Logistic regression models were conducted to evaluate the correlation of patient and tumor characteristics with diagnostic accuracy. The clinical outcomes of misdiagnosis were evaluated. RESULTS Agreement between frozen section diagnosis and permanent histology was observed in 63 of 101 patients (62.4%). Among the 76 patients with frozen section proven BTO, under-diagnosis and over-diagnosis occurred in 8 of 76 (10.5%) and 5 of 76 patients (6.6%), respectively. Mean diameter of under-diagnosed tumor was larger than matched BTO (21.0+/-11.4 vs. 13.7+/-7.1; p=0.021). Tumor size 20 cm was determined as the optimal cut-off for under-diagnosis (50% sensitivity, 87.3% specificity). Among 8 under-diagnosed patients, no patient relapsed. Among 5 over-diagnosed patients, 2 patients < 35 years of age had fertility-preserving surgery. CONCLUSION Although frozen section diagnosis is an important and reliable tool in the clinical management of patients with ovarian tumors, over-diagnosis and under-diagnosis are relatively frequent in frozen proven BTO. Surgical decision-making for BTO based on frozen section diagnosis should be done carefully, especially in large tumors.

Telomerase activity in complete hydatidiform mole

OBJECTIVE The purpose of this study was to evaluate the association of telomerase activity in complete hydatidiform moles with subsequent development of persistent gestational trophoblastic tumor. STUDY DESIGN By means of the standard telomerase repeat assay, we examined telomerase activity in 4 normal placentas, 31 complete hydatidiform moles (16 cases of uneventful regression, according to serum levels of beta-human chorionic gonadotropin, after evacuation and 15 cases in which persistent gestational trophoblastic disease developed after evacuation), 7 invasive moles, and 5 choriocarcinoma tissue samples. RESULTS Telomerase activity was detected in 13 of 15 (86.7%) complete hydatidiform moles in patients who eventually underwent chemotherapy for the treatment of persistent gestational trophoblastic tumors. All 9 patients with metastatic disease (International Federation of Gynecology and Obstetrics stage III) had telomerase activity in the initial molar tissue sample. In contrast, telomerase activity was evident in only 3 of 16 (12.5%) complete hydatidiform moles from patients with spontaneous remission after evacuation (P <.05). Telomerase activity was detected in all 7 invasive moles and all 5 choriocarcinoma tissue samples but was not detected in normal placentas. CONCLUSION The presence of telomerase activity in complete hydatidiform moles is associated with the development of persistent gestational trophoblastic tumors, such as invasive moles and choriocarcinoma.

Adjuvant therapy in high-risk early endometrial carcinoma: a retrospective analysis of 46 cases

OBJECTIVE We assessed the prognostic factors and the efficacy of adjuvant therapy and reviewed randomized studies carried out on patients receiving adjuvant therapy with early endometrial carcinoma. METHODS One hundred and five patients that received primary surgical treatment for stage IB, IC and II endometrial cancer were enrolled in this study. The clinical outcomes were compared among the patients with variable prognostic factors and adjuvant treatments. RESULTS One hundred and five patients fulfilled the eligibility criteria and 46 patients (43.8%) underwent adjuvant therapy. Disease recurrence occurred in nine patients within a median time of 24 months. Cervical involvement was an independent prognostic factor for the disease-free survival rates. Eight of 16 patients with FIGO stage II disease received adjuvant chemotherapy consisting of cisplatin and etoposide (or cyclophosphamide) or combined chemoradiation. The 5-year disease-free survival rate for these patients was 87.5%, a value significantly higher than for patients that received radiation therapy alone (30%). CONCLUSION Adjuvant chemotherapy or combination chemo-radiotherapy might be superior to radiation therapy alone in high-risk early endometrial cancer patients.

Large cell neuroendocrine carcinoma of the ovary: a case report and a brief review of the literature

Large cell neuroendocrine carcinoma (LCNC) of the ovary, or ovarian undifferentiated non-small cell carcinoma of neuroendocrine type, is a rare entity that is frequently associated with ovarian surface epithelial tumors. Few cases have been reported in the literature. LCNC is an aggressive tumor with tendency to present at advanced stages and to cause death after a short postoperative duration. We report three cases of LCNC diagnosed histopathologically. Immunohistochemically, the tumor cells were positive for chromogranin A, NSE, CD56, and pancytokeratin. The patients were treated postoperatively with combination chemotherapy. Due to the rarity of LCNC, the general consensus on standard therapy is not established. Although most patients are at stage I, the biological aggressiveness and poor prognosis of the tumors have been reported in previous reports despite extensive surgery and chemotherapy.

Zinc induces apoptosis on cervical carcinoma cells by p53-dependent and -independent pathway

OBJECTIVE There is evidence that the mineral zinc is involved in the apoptotic cell death of various carcinoma cells. In this study, we aim to determine whether zinc in the form of CIZAR induces apoptosis in cervical carcinoma cells by increasing intracellular zinc concentration. STUDY DESIGN CaSki and HeLa cervical carcinoma cells and HPV-16 DNA-transformed keratinocyte (CRL2404) were treated with different concentrations of CIZAR. The cell viability test was carried out, the intracellular level of zinc was determined, and apoptosis was confirmed by flow cytometry after propidium iodide (PI) staining and fluorescence microscopy under DAPI staining. The expression of cell-cycle regulators was analyzed by Western blot, including the knock down of p53 and expression of HPV E6 and E7 genes by RT-PCR. RESULTS Intracellular zinc accumulation induced the down-regulation of E6/E7 proteins through targeting of the specific transcriptional factors in the upstream regulatory region. p53 was induced after CIZAR treatment and p53-dependent apoptosis did not occur after knock down by p53 siRNA. In cervical carcinoma cells, regardless of HPV-infection, CIZAR induces apoptosis by the activation of the p53-independent pathways through the up-regulation of p21waf1, the down-regulation of c-Myc, and by decreasing the Bcl-2/Bax ratio. CONCLUSIONS CIZAR induces apoptosis not only through the restoration of p53/Rb-dependent pathways in HPV-positive cells, but also through the activation of p53/Rb-independent pathways and the mitochondrial death-signal pathway in cervical carcinoma cells regardless of HPV-infection.

Conservative Chemotherapy in Gestational Trophoblastic Disease: Experience With Etoposide, Methotrexate, and Dactinomycin Chemotherapy.

Objective The goal of this study was to evaluate the efficacy, toxicity, and survival of patients in our institution treated by EMA (etoposide, methotrexate [MTX], and dactinomycin) chemotherapy for 3 groups of patients: ones that had low-risk gestational trophoblastic disease (GTD) that was resistant to MTX (group A), those with high-risk GTD (group B), and the group having low-risk GTD but the cancer being metastatic (group C). Methods The medical records of 58 patients who received EMA chemotherapy in groups A, B, and C in the 2000 to 2012 period at St Mary’s Hospital were examined. Clinical characteristics, chemotherapy responses, causes of treatment failure, and cases of drug toxicity were analyzed retrospectively. Results Treatment with the EMA regimen resulted in primary remission in 52 (96%) of 54 patients and resistance in 2 of the patients (3%). In the resistance group, one belonged to group B and was treated with etoposide, MTX, and actinomycin D with cyclophosphamide and vincristine (EMA-EP) and the other belonged to group A and died of refractory disease. World Health Organization (WHO) grade 4 leukocytopenia and thrombocytopenia with the EMA regimen occurred in 6% and 0.4% of the cycles, respectively; the other toxic effects were acceptable and manageable. Median cycles of EMA chemotherapy during the treatment were 7, 8, and 8 in groups A, B, and C, respectively. There was some reduction in total chemo cycle and toxicity, as compared with a previously reported study using the alternative cyclophosphamide and vincristine regimen. Among the EMA treated patients, 1 patient with a second malignancy of breast cancer was documented. In addition, 5 child births for the treated patients were recorded during the follow-up period of mostly 10 years. Conclusions The EMA chemotherapy seemed to reduce treatment duration and the relapse rate without increasing the adverse effects in patients with MTX resistance and low-risk GTD, but having confirmed metastatic lesions. Although this study had some limitations regarding the high-risk GTD, our findings will provide a basis for the use of EMA chemotherapy when cyclophosphamide and vincristine is contraindicated due to toxicity.