Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.

Since after 2006 when the first edition of practice guidelines for gynecologic oncologic cancer treatment was released, the Korean Society of Gynecologic Oncology (KSGO) has published the following editions on a regular basis to suggest the best possible standard care considering updated scientific evidence as well as medical environment including insurance coverage. The Guidelines Revision Committee was summoned to revise the second edition of KSGO practice guidelines, which was published in July 2010, and develop the third edition. The current guidelines cover strategies for diagnosis and treatment of primary and recurrent ovarian cancer. In this edition, we introduced an advanced format based on evidence-based medicine, collecting up-to-date data mainly from MEDLINE, EMBASE, and Cochrane Library CENTRAL, and conducting a meta-analysis with systematic review. Eight key questions were raised by the committee members. For every key question, recommendations were developed by the consensus meetings and provided with evidence level and strength of the recommendation.
Committee Membership ; Consensus* ; Diagnosis ; Drug Therapy ; Evidence-Based Medicine ; Insurance Coverage ; Korea* ; Ovarian Neoplasms*

OBJECTIVE: The aim of this study is to investigate the incidence of genetic instability, defined as microsatellite instability (MI) or loss of heterozygosity (LOH) in cervical carcinoma and its relationship with clinical characteristics. MATERIALS AND METHODS: Twenty-four patients with cervical carcinoma were studied. Genomic DNA was extrected from tumor tissues collected from consenting patients undergoing surgery. MI and LOH were analyzed with five microsatellite regions on chromosome 2, 3 and 6 (D2S123; 2p16-2p16 and 2p21-2p16, D3S1619; 3p24.2-3p22, D6S291; 6p21.3-6p21.2, D6S308; 6q16.3-6q27, D6S270; 6q22.3-6q23.2) by polymerase chain reaction (PCR) and automatic laser fluorescent DNA sequencer. MI was defined as tumor-associated alteration in at least of one of five dinucleotide microsatellite markers examined. The relationship between genetic instability and clinical profile was analyzed. The significance of BAT-26 sequence size as a marker of replication error (RER) phenotype was assessed. RESULTS: Total genetic instability was detected in 79%(19/24) of cervical carcinoma. MI was detected in 50% of the cervical carcinomas and LOH in 45.8%. BAT-26 size variation was observed only in one case. There was no statistically significant difference between the groups of positive and negative genetic instability in human papillomavirus (HPV) 16 or 18 positive rate, stage, 2 year-survival rate. CONCLUSION: This results suggest that MI and LOH are present in a subset of cervical carcinoma and may have a role for carcinogenesis as co-factors. BAT-26 has no value as a marker of RER in cervical cancer.
Carcinogenesis ; Chromosomes, Human, Pair 2 ; DNA ; Humans ; Incidence ; Loss of Heterozygosity ; Microsatellite Instability ; Microsatellite Repeats ; Phenotype ; Polymerase Chain Reaction ; Uterine Cervical Neoplasms

PURPOSE: This study was undertaken to analyze whether the p53 codon 72 single nucleotide polymorphism might be correlated with the risk and/or the prognosis of cervical cancer in Korean women. MATERIALS AND METHODS: Peripheral blood samples derived from patients with cervical squamous cell carcinoma (SCC) (n=68), cervical adenocarcinoma (n=37), cervical intraepithelial neoplasia (CIN) III (n=98) and normal controls (n=98) were examined. Germline genomic DNA was extracted from peripheral blood leukocytes and examined by PCR amplification of the specific alleles assay described by Storey et al.5 Statistical analysis was performed using the Chi-Square test or the Kaplan-Meier survival analysis, logistic regression analysis. RESULTS: The proportions of individuals who were homozygous for the proline allele, and heterozygous for the two allele, homozygous for arginine allele in each group were 15%, 47%, 38% in the SCC group; 6%, 7%, 24% in the adenocarcinoma group; 7%, 33%, 60% in the CIN III group; and 11%, 38%, 51% in the control group. No significant difference was found between the three groups (p>0.05). However there was a significant difference in the adenocarcinoma group (p<0.05). Arg/Arg homozygote reduced the risk of adenocarcinoma. No significant difference existed in 5-year survival rates in the three groups (p=0.22 in SCC, p=0.91 in adenocarcinoma). CONCLUSION: These findings suggest that Arg/Arg homozygocity of the p53 codon 72 would be a protective factor against the development of cervical adenocarcinoma.
Adenocarcinoma* ; Alleles ; Arginine ; Carcinoma, Squamous Cell ; Cervical Intraepithelial Neoplasia ; Codon* ; DNA ; Female ; Homozygote ; Humans ; Leukocytes ; Logistic Models ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Prognosis ; Proline ; Survival Rate ; Uterine Cervical Neoplasms

PURPOSE: To examine the distribution of HPV 16 E6 polymorphisms and analyse the possible association between the polymorphisms and cervical cancer development in Korean women. MATERIALS AND METHODS: Fifty-four cases of uterine cervical tissues containing HPV 16 DNA confirmed by polymerase chain reaction (PCR) from Korean women were subjected to investigate the E6 gene mutations. PCR-amplified products were sequenced by the fluorescent dideoxy ter mination method and the results obtained from sequencing were analysed. And newly designed PASA method was tried to develop rapid test for identification of the most commonly detected variation. RESULTS: Among the 27 cervical cancer cases, only two (7.4%) was found as a prototype. Among 11 kind of variants identified in total, 4 variants (5 nucleotide sites) which were never reported before has been found, registered firstly to GenBank. The most frequently found variation was D25E, absolutely different from the previous reports from the western country. There was no statistically significant trend for the D25E variation to be more frequently detected in cancerous lesions than in noncancerous lesions. All of the DNA sequencing results observed could be confirmed by PASA method. CONCLUSION: These results suggest that Korean-specific genetic factors might operate during the cervical carcinogenesis.
Carcinogenesis ; Databases, Nucleic Acid ; DNA ; Female ; Human papillomavirus 16 ; Humans* ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Uterine Cervical Neoplasms

PURPOSE: The aim of this study was to determine whether certain genotype of p21WAF1/Cip1 might be associated with risk of cervical cancer in Korean women. MATERIALS AND METHODS: We used the specimens derived from cervical cancer (n=111) composed of two histologic groups; SCCA (n=67) and adenocarcinoma (n=44), CIN III (n=101) and controls (n=98). For the determination of p21WAF1/Cip1 polymorphism, DNA was examined by PCR-RFLP using BsmAI. We compared the distribution of p21WAF1/Cip1 genotype of Korean women with that of other ethnic groups and analyzed the distribution of invasive cancer, CIN III and controls. RESULTS: The genotype frequency of controls was different from that of Caucasian and Chinese (p<0.001) but similar to that of Japanese (p=0.21). There was no difference in the genotype frequency of p21WAF1/Cip1 among SCCA, CIN III and controls (p>0.05). A significant increase of Ser/Ser genotype was found in adenocarcinoma patients with high-risk HPV compared with the controls (p=0.009). The OR was 3.59, 95% CI=1.55~8.31, when comparing that group with controls. However, we could not find differences of prognosis. CONCLUSION: We found that codon 31 Ser/Ser homozygote of the p21WAF1/Cip1 would be a risk factor for the adenocarcinoma of cervix associated with high-risk HPV in Korean women.
Adenocarcinoma ; Asian Continental Ancestry Group ; Cervix Uteri ; Codon* ; DNA ; Ethnic Groups ; Female ; Genotype ; Homozygote ; Humans ; Prognosis* ; Risk Factors ; Uterine Cervical Neoplasms*

OBJECTIVES: To review the clinical features, histological types and the mode of treatment of malignant gynecologic tumors in childhood and adolescence, and to analyze the survival according to the histologic types. METHODS: We analyzed clinicopathologic data for 29 patients aged less than 20 years who were referred to Dept. of Ob/Gyn in SNUH for the years Jan. 1986 through Mar. 1999. RESULTS: Of the 29 cases, 26 cases were ovarian malignancy, 2 metastatic cancers from other organs, and 1 uterine adenosarcoma. Of the 26 ovarian malignancy, histologic distrubutions were follows: 18(69%) cases were germ cell tumor, 7(27%) epithelial ovarian cancers, l(4%) stromal cell tumors. Main symptoms of the patients were abdominal pain(41.4%), abdominal distension(24.1%), and palpable mass(17.2%). The stage of the 20 cases (80%) with the ovarian malignancy was the stage 1. The most frequent treatment modality was the USO(ineluding contralateral wedge biopsy) and postoperative chemotherapy(83%). Five-year survival rate of the patients with germ cell tumor was 83% and that of the patients with epithelial ovarian malignancy was 38%, but the numbers of the cases was too small to get a statistical significance(P>0.05). CONCLUSION: Ovarian malignancy, especially germ cell tumor, was the most frequent tumors of the gynecologic malignancies developed in childhood and adolescence and mainly the stages of the cases were stage 1. Our data showed the trend that the survival rate of the patients with the germ cell tumors was better than that of the patients with the epithelial ovarian cancer. Larger scaled analysis is needed to get a final conclusion.
Adenosarcoma ; Adolescent* ; Humans ; Neoplasms, Germ Cell and Embryonal ; Ovarian Neoplasms ; Stromal Cells ; Survival Rate

OBJECTIVE: This study was performed to identify the prognostic factor for survival of patients with recurrent cervical cancer. METHODS: Sixty-eight patients were diagnosed as recurrent cervical cancer at the Seoul National University Hospital from January, 1988 to December, 1998. Recurrence was defined as new evidence of tumor after 6 months of disease free survival. Retrospective analysis was done in terms of clinical features and the Cox proportional hazard model was used to identify independent variables associated with an improved survival rate. Histopathologic types were distributed as follows; squamous cell carcinoma in 70.6%, adenocarcinoma in 11.8%, adenosquamous cell carcinoma in 11.8%, and small cell carcinoma in 1.5%. Distribution of FIGO stage was as follows; stage I in 25.0%, stage II in 66.2%, and stage III in 4.4%. Sites of recurrence were as follows; central pelvic recurrence in 44.1%, pelvic side wall recurrence in 11.8%, and distant metastasis in 44.1% and the most common site of distant recurrence was extrapelvic lymph nodes (29.4%). 29.4% of recurrences were observed within the first 12 months after initial therapy, 50.0% within 2 years and 64.7% within 3 years. RESULTS: Positive rate of SCC-Ag at initial diagnosis was 45.2% with cutoff value of 2.0 ng/ml. Positive rate of SCC-Ag at the diagnosis of recurrence was 60.0%. Overall response rate to the treatment was 29.1%. Complete response rate was higher in central pelvic recurrrence than pelvic side wall recurrence and distant metastasis (P = 0.002) and also higher in normal SCC-Ag level (< or = 2.0 ng/ml) at the diagnosis of recurrence than elevated level (P = 0.032). Cumulative survival rates of 1 year after recurrence was 66.8%, 2 year 36.7%, and 5 year 18.7%. Central recurrence showed higher cumulative survival rate than pelvic side wall or distant recurrence (P = 0.029). The patients with elevated SCC-Ag level at the time of diagnosis of recurrence showed lower cumulative survival rate than those with normal SCC-Ag level (P < 0.001). Cox proportional hazard model showed that SCC-Ag elevation at the time of diagnosis of recurrence retained significant values in predicting survival(OR = 2.56; 95% CI = [1.22-5.39]; P = 0.01). CONCLUSION: SCC-Ag elevation at the diagnosis of the recurrence is a strong independent prognostic indicator for survival of patients with recurrent cervical cancer.
Adenocarcinoma ; Carcinoma, Small Cell ; Carcinoma, Squamous Cell ; Diagnosis ; Disease-Free Survival ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Proportional Hazards Models ; Recurrence ; Retrospective Studies ; Seoul ; Survival Rate ; Uterine Cervical Neoplasms*