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

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. Mary's 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.

Epithelial ovarian cancer in patients under 20 years of age / 대한산부인과학회지

OBJECTIVE: Epithelial ovarian cancer is the most common cause of death due to gynecologic malignancies in adults, but is rare in children and adolescents. This is a report of series of such patients under 20 years of age documenting their presentation, histologic type, stage of disease, treatment, and outcome. METHODS: We collected data on 21 patients with epithelial ovarian cancer under 20 years of age between January 1990 and December 2005. Patient records and pathology were reviewed. RESULTS: Epithelial ovarian cancer under 20 years of age was 2.2% in overall ovarian cancer. Epithelial ovarian cancer was 42.0% among 50 patients under 20 years of age and the most common histologic type was germ cell tumors (54%). The median age at the time of diagnosis was 17.6 years (range, 13-20 years), and the median follow-up was 87 months (range, 4-175 months). There were seventeen (81.0%) mucinous tumors, four (19.0%) serous tumors. About thirty-eight percent were low malignant potential or borderline tumors. About Eighty-five percent (18 patients) of tumors were stage I disease and about fourteen percent (3 patients) were stage III disease at the time of diagnosis. Surgical treatment included conservative surgery in 18 patients (85.7%), total abdominal hysterectomy and bilateral salpingo- oophorectomy in 3 patients (14.3%). CONCLUSION: Epithelial ovarian cancers are rare in patients in children and adolescents. The majority of ovarian cancers in this age group are mucinous tumors, stage I at diagnosis and borderline ovarian tumor. Conservative management is feasible to achieve preservation of fertility.

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

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.

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

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.

Antiproliferative and Apoptotic Effects of Zinc-Citrate Compound (CIZAR(R)) on Human Epithelial Ovarian Cancer Cell (OVCAR3) / 대한산부인과학회지

OBJECTIVE: Human seminal plasma has diverse biological activities including cytotoxic effect. It contains high concentrations of zinc and citric acid. Zinc inhibits several carcinoma cell growths through induction of cell cycle arrest and apoptosis. We tried to investigate the effects of zinc-citrate compound (CIZAR(R)) on normal human ovarian epithelial (NOSE) cells and human epithelial ovarian cancer cells, OVCAR-3. METHODS: To investigate the potential effect of CIZAR(R) on cell growth and survival, cells were treated with different dose and exposed to different time. Mitochondrial(m)-aconitase activity was determined in cell extracts using aconitase assay. The flow cytometric assay, DNA laddering, telomerase activity and morphological analysis were done to investigate apoptosis of OVCAR-3 cells. Molecular mechanism of apoptosis was investigated by p53, Bcl-XL, Bcl-2, Bax protein, and caspase activity. RESULTS: Treatment of OVCAR-3 cells with CIZAR(R) resulted in a time- and dose-dependent decrease in cell number in comparison with NOSE cells. M-aconitase activity was significantly decreased in OVCAR-3 cells but relatively constant in NOSE cells. The flow cytometric assay, DNA laddering and morphological analysis indicated apoptosis of OVCAR-3 cells. CIZAR(R) did not affect p53 but increased the expression of p21waf1 upon the indicated times and induced reduction of telomerase activity. CIZAR(R) reduced expression of Bcl-2 and Bcl-xL proteins but induced expression of Bax protein. CIZAR(R) induced apoptosis of OVCAR-3 cells by activation of caspase-3 pathway. CONCLUSION: These results show that CIZAR(R) prevent the proliferation of OVCAR-3 cells by inactivation of m-aconitase activity and induce apoptosis by induction of apoptotic genes and repression of antiapoptotic genes without adverse effect on normal ovarian epithelial cells. These results will offer new window in prevention and treatment of epithelial ovarian cancer.

A case of spontaneous uterine perforation result from acute gangrenous myometritis in an old woman with IUD for 40 yrs / 대한산부인과학회지

Intrauterine devices (IUDs) are highly effective, long-term methods of contraception. Although evidences of direct association between IUD use and pelvic inflammatory disease are rare, the frequency of inflammatory complications associated with the use of IUDs ranges from 2% to 8%. Gynecological surgeries on the account of purulent, inflammatory disease associated with IUD are 4-7%. We report one case with spontaneous perforation of uterus due to acute gangrenous myometritis in an old woman with IUD for 40 yrs in pelvic cavity, followed by a review of the literature.

The value of sentinel node HPV status for prediction of lymphnode metastasis and recurrence in cervical cancer patients / 부인종양

OBJECTIVE: The "sentinel node" is defined as the first lymph node encountered by lymphatic vessels draining a tumor. We tried to examine whether pathologic status of sentinel nodes of cervical cancer patients represent metastatic status of pelvic and paraaortic lymph nodes and to investigate the correlation between sentinel node HPV status and lymph node metastasis and recurrence of cervical cancer patients. METHODS: From August 2001 to December 2003, 57 patients affected by stage IB-IIA cervical cancer had sentinel node biopsies performed during radical hysterectomy and pelvic and paraaortic lymphadenectomy. We performed sentinel lymph node pathologic examination by frozen section and HPV typing by oligonucleotide microarray. After two years of follow up, we analyzed the prognosis of patients. RESULTS: Sentinel nodes were identified in all of our patients. A total of 79 nodes were detected as sentinel nodes. Metastasis in the sentinel nodes were found in 10 patients by frozen section and 11 patients by permanent pathologic examination. The results of sentinel lymph node frozen biopsy were statistically significant for predicting the metastatic status of the pelvic lymph nodes (p<0.05), but showed one false negative case. HPV DNA was detected in the cervices of 55 patients (96.5%), 44 (80.0%) of whom were found to have HPV DNA in the sentinel nodes. HPV DNA was detected in sentinel nodes of 10 patients among 11 patients with lymph node metastases. After mean follow up of 31.7 months (range; 1-48), disease recurred in five patients and all of these patients showed HPV in sentinel nodes. Combination of sentinel node frozen biopsy and HPV typing showed negative predictive value of 100% in predicting lymph node metastasis and recurrence. CONCLUSION: Our result suggests the possibility that sentinel node HPV typing would play a supportive role to reduce false negative rate of sentinel node biopsy. Additional study will be needed to confirm the clinical application of sentinel lymph procedure and to reveal correlation between HPV status of sentinel nodes and lymph node metastasis and recurrence of cervical cancer patients.

A case of treatment of cervical adenocarcinoma associated with pregnancy by zinc-citrate compound (SeLava(R)) / 대한산부인과학회지

Cervical carcinoma is the second leading cause of death from cancer in women worldwide. It is well known that human papillomaviruses (HPVs) is the etiologic agent of cervical neoplasia and cervical cancer. Zinc has been shown to inhibit the growth of malignant cell lines by inducing apoptosis and cell cycle arrest. Recently it was reported that zinc-citrate compound (CIZAR(R)) has a cytotoxic effect on choriocarcinoma cell line and ovarian adenocarcinoma cell line and suppresses its proliferation inducing apoptosis. CIZAR(R) prevents the proliferation by inactivation of m-aconitase activity and induces apoptosis by increasing Bax expression and reducing Bcl-2 expression and inactivation of telomerase. We report one patient of cervical adenocarcinoma with HPV infection, who desires to continue pregnancy, treated by daily topical application of SeLava(R) which contains zinc-citrate compound (CIZAR(R)). We followed up the cytologic, pathologic and coloposcopic changes of healing process.

A case of Fitz-Hugh-Curtis syndrome diagnosed by pelvic CT imaging prior to diagnostic laparoscopy / 대한산부인과학회지

Fitz-Hugh-Curtis syndrome is an extrapelvic manifestation of PID. It is associated with right upper quadrant pain that likely results from the inflammation of liver capsule and diaphragm. The liver capsule becomes involved with inflammatory exudates that later forms violin string adhesion between two liver capsule and adjacent diaphragm or peritoneum. Previously, Neisseria gonorrhea was thought to be the only etiological agent, but recent studies have reported cases of Fitz-Hugh-Curtis syndrome due to Chlamydia trachomatis infection. 15 to 30 percents of women with PID develop symptom of Fitz-Hugh-Curtis syndrome. It is often mistakenly diagnosed as either pneumonia or acute cholecystitis. Laparoscopy may be the definitive method in diagnosis of Fitz-Hugh-Curtis syndrome. However, we have experienced one cases of Fitz-Hugh-Curtis syndrome, which was diagnosed preoperative by pelvic CT imaging and report with the brief review of the literatures.

The risk factors of residual disease after conization / 대한산부인과학회잡지

OBJECTIVE: Conization is used for diagnosis and treatment of cervical neoplasia. Our purpose of this investigation is to determine the efficacy of loop conization for the treatment of cervical dysplasia and the significance of the clinical and histological factors used to predict residual dysplasia after loop conization. METHODS: We reviewed the charts of patients who were received conization and subsequently total hysterectomy at Kangnam St Mary Hospital during 1989 and 2000. Logistic regression and Chi-square test were used for analysis. RESULTS: Total 257 patients were included. The mean age of the patients was 44.7 years. Of these patients, 87 (33.8%) had residual disease in the hysterectomy specimens. Age, the involvement of cut surface of endocervix and exocervix, severity and extent of the lesion, and scattering lesion were associated with the residual disease. But preoperative HPV infection, which is known as the cause of cervical neoplasia was not associated with the residual disease. CONCLUSION: When the high risk factors are present, the validity of conservative treatment should be considered and more careful follow up with pap smear, HPV test and colposcopy is necessary. Because about one thirds of patient has residual disease after conization, LEEP conization should be used for diagnosis of cervical neoplasia rather than treatment.

Sentinel Node Biopsy as an Indicator for Pelvic Nodes Dissection in Early Stage Cervical Cancer

The purpose of this study was to investigate the feasibility of sentinel node frozen biopsy to minimize the extensive pelvic lymph nodes dissection in early stage cervical cancer patients on the basis that the risk of skip metastasis to the paraaortic area is negligible. Twenty-six patients with early stage cervical cancer were enrolled in this study. Technetium-99m colloid albumin (Tc(99m)) was injected intradermally around the tumor for allowing preoperative lymphoscintigraphy and intraoperative hand-held gama probe detection of seninel nodes. For visual detection, isosulfan blue dye was injected into the peritumoral sites before peritoneal opening. Postoperative morbidity and negative predictive value were the endpoints of this study. The 26 patients, ranging in age from 32 to 71 yr, underwent intraoperative sentinel nodes mapping. All the patients underwent complete pelvic lymph nodes dissection including para-aortic nodes. There was one case with positive non-sentinel nodes despite the negative sentinel node by frozen biopsy (negative predictive value, 95.2%). This new technique of sentinel node mapping is safe and simple to perform. Further clinical trials using the combination of Tc(99m) and isosulfan blue dye are warranted and this technique will make a true advance for less aggressive management of patients with early stage cervical cancer.

The Influence of Human Chorionic Gonadotropin and Human Placental Lactogen on Growth and Differentiation of Placental Trophoblast / 대한산부인과학회잡지

BACKGROUND: There are many factors that influence the differentiation and growth of trophoblasts. During differentiation of trophoblasts, two major hormones are secreted ; human chorionic gonadotropin (hCG) and human placental lactogen (hPL). These two hormones are secreted in a peculiar pattern during pregnancy and function of these hormones is not yet fully understood. Also, it is not known whether these hormones directly influence the differentiation and growth of trophoblasts. On the other hand, it is known that choriocarcinoma cells are undifferentiated, so they are unable to form syncytiotrophblasts. And many factors may be associated with this inhibitory potential. OBJECTIVE: The purpose of this study was to observe whether the hCG and hPL are associated with differentiation and growth of early placental trophoblasts and becoming malignant. METHOD: The hCG, hPL, IL-6 and insulin were added to cytotrophoblasts isolated from normal 8 to 10 gestational weeks' placental tissues by a degree of concentration, and observed the secreted hPL concentration and morphological change to syncytiotrophoblasts daily. And it was performed in Bewo cells in same manner. RESULT: The increased hPL secretion was noted in hCG, hPL, IL-6 and insulin were added normal trophoblasts and this may result from differentiation of cytotrophoblasts to syncytiotrophoblasts. Also, morphological changes to syncytiotrohoblasts was observed at the same time. But, Increased hPL secretion and syncytiotrophoblasts formation was not detected in Bewo cells. CONCLUSION: In this study, it seems that hCG, hPL, IL-6 and insulin had an influence on differentiation and growth of normal trophoblasts. On the other hand, no changes in hPL secretion and morphology at the choriocarcinoma cell line tells us that defects of differentiation in choriocarcinoma is due to abnormalities of the receptors on hCG and hPL or a differentiation associated gene, not a defect of these hormones themselves.

CT and MR Findings of Placental Site Trophoblastic Tumor: A Report of Two Cases

Placental site trophoblastic tumor(PSTT) is a very rare form of gestational trophoblastic disease; weencountered two cases. MR imaging of the first patient revealed a solid uterine mass, slightly hyperintense tonormal myometrium on T1-weighted images and hyperintense on T2-weighted images. After intravenous gadoliniuminfusion, the mass was more enhanced than normal myometrium, and PSTT was confirmed pathologically after totalhysterectomy. In the second patient, PSTT was proven pathologically after laparoscopic left adnexectomy and wedgeresection of the right ovary. Postoperative enhanced CT scans revealed a well-enhanced right ovarian mass andextensive metastasis to the liver, pancreas, both adrenals, the stomach, lung and brain, but no mass was detectedin the uterus. Many of these metastatic lesions were infiltrating low density masses associated with highlyenhanced tubular or serpiginous structures, while some were of very high density.

Telomerase Activity in Gestational Trophoblastic Disease / 대한산부인과학회잡지

The purpose of this study was to evaluate the significance of telomerase activity in gestational trophoblastic disease and the association of telomerase activity in complete hydatidiform mole and subsequent development of persistent gestational trophoblastic tumor. By using the standard telomerase repeat assay, we examined telomerase activity in 2 normal placentas, 31 complete hydatidiform moles, 7 invasive moles, 5 choriocarcinoma tissues and choriocarcinoma cell line (JEG-3). Telomerase activity was detected in 13 of 15 (86.7%) complete hydatidiform mole patients who eventually had chemotherapy for the treatment of persistent gestational trophoblastic tumor. All of the 9 patients with metastatic disease (FIGO Stage III) had telomerase activity in their initial molar tissue. In contrast, telomerase activity was evident in only two of 16 (12.5%) complete hydatidiform mole patients with spontaneous remission. While telomerase activity was not detected in normal placentas, high level of telomerase activity was detected in all of 7 invasive moles, 5 choriocarcinoma tissues and choriocarcinoma cell line (JEG-3). The presence of telomerase activity in a complete hydatidiform mole is associated with the development of persistent gestational trophoblastic tumor, such as invasive mole and choriocarcinoma.

MR Imaging of Gestational Trophoblastic Tumor: Role of Gadolinium Enhancement

PURPOSE: To investigate the role of gadolinium enhanced MR imaging in the evaluation of gestational trophoblastic tumors (invasive mole and choriocarcinoma). MATERIALS AND METHODS: Pre-enhanced T1-and T2-weighted images and gadolinium enhanced T1-weighted images of 34 gestational trophoblastic tumors (15 choriocarcinomas, 19 invasive moles) were evaluated retrospectively. Enhanced patterns of gestational trophoblastic tumors were analyzed. Morphologic differences and structural characterstics were analyzed by the evaluation of tumor margin, patterns of hemorrhagic necroses, development of intratumoral vascularity, and molar villi. Graded scores of MR findings between pre- and gadolinium enhanced images were given in the following criteria ; 1) visualization of tumor margin 2) distinction between tumor necrosis and zone of trophoblastic proliferation, and 3) molar villi. Statistical differences between graded scores of pre-and post-enhanced images were analyzed. RESULTS: Choriocarcinoma was a well-defined mass with peripheral rim enhancement and central hemorrhagic necrosis. Invasive mole was a ill-defined mass with partial necrosis, tiny cystic areas and increased intratumoral vascularity with dense reticular enhancement. Interface between tumor necrosis and zone of trophoblastic proliferation was better visualized on the gadolinium enhanced images than on the pre-enhanced images. Tumor margin and intratumoral molar villi were clearly discrimated on the gadolinium enhanced images only in invasive mole. There was no statistical difference in the visualization of tumor margin of choriocarcinoma between the pre-and post-enhanced images. CONCLUSION: Gadolinium enhanced MR image was helpful in the visualization of tumor characterstics in gestational trophoblastic tumors, and in the differential diagnosis between invasive mole and choriocarcinoma.

Clinical Significance of Zygosity as a Prognostic Factor in Complete Hydatidiform Mole / 대한산부인과학회잡지

To evaluate the possible correlation between the origin of complete hydatidiform mole(CHM) and subsequent persistent gestational trophoblastic tumor(GTT) after molar evacua-tion, we have studied genetic origin patterns against conventional clinical parameters -pati-ent's age, gestational age, uterine size for gestational age, serum beta-hCG levels before mol-ar evacuation- in 69 patients with CHM. In our study, each of large uterine size for gesta-tional age, serum beta-hCG levels before molar evacuation, and genetic origin of CHM had a prognostic significance of subsequent persistent GTT. However, each of gestational age and patient's age is not a good prognostic indicator for subsequent persistent GTT. Among the patients with persistent GTT, there are no differences in clinical parameters- patient's age, gestational age, tumor age(the interval between evacuation of CHM and initiation of chem-otherapy), serum beta-hCG levels before molar evacuation and before initiation of chemother-apy- according to the origin of CHM. There are no differences in the analysis of sex-chr-omosome and variable number tandem repeat sequence YNZ22 and APOB gene in the extr-acted DNA from frozen tissues and paraffin blocks and from EDTA treated peripheral blood and dried blood specimen on Wartman paper. It is suggested that analysis of sex-chromo-some and polymorphism of YNZ22 and APOB gene from the extracted DNA of paraffin bl-ock and dried blood specimen on Wartman paper is the valauble experiment to evaluate the origin and the classification of hydatidiform mole and seems to be the sensitive molecular genetic method in predicting subsequent persistent GTT.

Subsequent Reproductive Experiences after Treatments for Gestational Trophoblastic Disease / 대한산부인과학회잡지

For evaluating the reproductive performances of GTD patients, we found 115 cases of GTD patients, 77 HM and 38 GTT, who became pregnant after the completion of treatments and follow-up period. The results of this study suggest subsequent pregnancies after the completion of treatments may promise normal reproductive outcomes regardless of the chemotherapy.

Effect of insulin on development of mouse preimplantation embryos / 대한산부인과학회잡지

No abstract available.