한국형 자궁경부 촬영진 ( New Cervicography ) , 세포검사 그리고 HPV-DNA 검사를 이용한 새로운 자궁경부암 검진 모델 ( Model ) 개발

김승조(SJ Kim),박찬규(CK Park),이효표(HP Lee),남궁성은(SE Namkoong),강순범(SB Kang),서호석(HS Saw),이재관(JK Lee),김수녕(SN Kim),김재원(JW Kim),배석년(SN Bae),김찬주(CJ Kim),이근호(KH Lee),이선영(SY Lee),김인호(IH Kim),이찬(C Lee),이정노(JN Lee) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.5

N/A Objective : The false negative rate of conventional cytology is reported to range from 18 to 45%. It is necessary to develop more effective screening strategies that would ideally be more accurate than conventional cytology. This study is designed to investigate the potential of conventional cytology, cervicography, HPV-DNA testing and their combinations as primary screening techniques for cervical neoplasia. The purpose of this project is to develop the models and guidelines for screening tools of cervical cancer of the uterus by evaluating sensitivity, specificity and cost-effectiveness of all the screening methods. Study design : We conducted a screening of random sample of women who visited the department of OB-Gyn. of five different major university hospitals such as Catholic University Hospital, Korea University Hospital, Seoul National University Hospital, Yeonsei University Hospital and Pochon CHA University Bundang CHA Hospital, from May 1, 1996 to April 30, 1999. In a cohort women with an age range of 20 to 70 who underwent routine cytologic screening at Catholic University, Hospital Bundang CHA General Hospital and local clinics from April 1, 1996 to Decomber 31, 2000. cervicography (n=417,125) and testing for HPV-DNA (n=1,347) by the hybrid capture assay were studied for the ability of the cervical cancer screeuing. A new cervicography system with Kim's classification which was developed by Prof. Kim Seung Jo as an adjunctive method for the cervical cancer screening was applied in this cohort study. And then, accuracy, effectivencess, cost-effectiveness of the single or combined screening method were analysed. Result : Sensitivity and specificity of Pap smear were ranged from 55.6% to 83.1% and 72.8% to 88.3% respectively. The combination of Pap smear and cervicography had sensitivity from 89.7% to 98.6%, specificity from 68.2% to 93.2%. With combination of Pap smear, HPV DNA test and cervicography, sensitivity became also highest accuracy among all screening methods from 92.8% to 98.8%. Considering medical charges for diagnosis and social cost occurred by false positive and false negative results, the most cost-effective diagnostic modality was thought to be the combination of Pap smear and cervicography(91,433 won). In patients who were diagnosed as LSIL, colposcopic examination confirmed progression to high grade intraepithelial lesion(HSIL) in 10.7% patients, persistence of LSIL in 55% patients during the 3 year follow-up period. Accuracy of the screening for cervical cancer and CIN can significantly be improved by cytology with new cervicography rather than cytology alone. We concluded that cervicography can be important adjunctive tests for cervical cytology, improving the effectiveness of cervical screening by allowing a more sensitive detection of cervical neoplasia.

임신부 빈혈치료에 있어서 Iron Protein Succinylate (Hemo-Q) 의 임상적 효과

김장흡,김수평,김진홍,김휘준,김찬주,박미숙 대한산부인과학회 1994 Obstetrics & Gynecology Science Vol.37 No.5

Iron protein succinylate (Hemo-Q) is a new iron preparation for oral administration. Clinical efficacy and safety of iron protein succinylate were evaluated in 40 pregnancy and postpartum women under serum hemoglobulin level 10 gm/dl. The aim of this study was to assess the efficacy and tolerability of iron protein succinylate in iron deficiency anemia of pregnant and postpartum women. Most women received 2 bottles (30ml) every day for 60 days. Improvement was measured by hematologic variables and clinical symptom or sign after 30 days and 60 days respectively. In Conclusion 1. Efficacy of iron protein succinylate showed significant difference among pretreatment, 30 and 60 days treatment group in serum hemoglobulin and iron level. 2. Improvement of clinical symptom (polypnea, asthenia, anorexia) and sign (cutaneous, mucous pallor) of iron deficiency anemia were noted in both 30 and 60 days treatment. 3. Side effects (vomiting, constipation, diarrhea, gastric discomfort) were reported with 1(2.5%) to 2(5%) of 40 women.

SEMM방식의 골반경 자궁적출술 (CISH) 300 예에 대한 임상적 연구

김인현,정창조,조진호,김종욱,신명철,김경률,이정노 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.5

Laparoscopic hysterectomy, introduced by Reich et al in 1988, has proven to be an effective alternative to abdominal hysterectomy for women. Several modalities were introduced by some laparoscopists, among which the supracervical modality was particularly suitable for laparoscopic surgery because it has some advantages. The surpracervical hysterectomy requires less dissection of the bladder and the technique minimally alters the anatomy and integrity of the pelvic floor and vagina, therefore the risk of bleeding, surgical injuries to the bladder, ureters and lower intestinal tract were decreased. These factors may be responsible for the apparently less compromised bladder and sexual Function and decreased long term morbidity. The purpose of the study described below was to show that laparoscopic supracervical hysterectomy can be performed safely with minimal morbidity, and to establish the validity of replacing the vast majority of traditional abdominal hysterectomies. During the period October, 1992-June, 1996, 300 women underwent Classical Intrafascial SEMM Hysterectomy(CISH) at Cha Hospital, Seoul, Korea and KyungHee Bundang Cha Hosptial, Seongnam, Korea. Most common age groups were 41~50, and average age of patients was 43.2 years old. Most common parity groups was 2, and average parity was 2.4. Myoma and adenomyosis of uterus were common preoperative surgical indications. Most common uterine size was 8~10 weeks gestational size. The common operation time ranged from 151~180 minutes with a mean of 156 minutes. The common Hgb loss range was 1.5~1.0gm/dl, and average was 0.78gm/dl. The common hospitalization period were 5~6 day with a mean of 5.9days. The complications were 23 cases, among which intra and postoperative bleeding were most common.

고위험 자궁경부암환자에서 Quick Cisplatin-VP16 을 이용한 신보조항암요법의 효과

김승조,김진우,배석년,남궁성은,박종섭,이준모,김찬주,김재훈,박동춘,박용규 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.8

The potential role and determinants of response to a cisplatin-based regimen of neoadju-vant chemotherapy in women with a histologically confirmed first diagnosis of stage IB-Ⅲ cervical cancer were analyzed. From 1993 to 1996, 92 patients with bulky(designated as more than 3×3 cm2 size) mass were treated with cisplatin 60 mg/m2 and etoposide 100 mg/m2, admi-nistered intravenously at 7 day intervals. Seventy cases of radical hysterectomy with pelvic lymph node dissection and 22 cases of radiation therapy were performed 2 to 3 weeks after chemotherapy. At the end of the cycles, the overall clinical response rate of portio was 83.7 %(34.8 % with a complete response and 48.9 % with a partial response). The older ages, lower stages, and squamous cell types correlated favorably with the clinical response of the portio, but neither with the parametrium nor with the vagina. After the operation, we found the diff-erences in histologic responses, with the following parameters:lymphovascular space invasion, 3 mm below stromal invasion and lymph node metastasis. Theses parameters correlated with the clinical responses, and the down-staging of cases were 70 %. In comparison with radiolog-ical findings of pretreatment and postoperative tissue pathology, we could find a decrease in pelvic LN metastasis. The tumor-free survival rate calculated by the Kaplan-Meier product limit method was 75 % but it was 86.1 % for cases without the occurrence of persistent disease after the completion of the treatments. All patients suffered from nausea and vomiting, but grade 4 toxicity was not detected after the routine use of antiemetics. There were no events that delayed the next step in the treatment or caused difficulty during the operation. The results of this study suggest that the neoadjuvant chemotherapy should be accepted as a routine tool in treating high risk cervical cancer in order to improve the likelihood of favorable outcomes.

불임환자의 자궁경부 인자 평가시 질식 초음파촬영을 이용한 난포 성장관찰의 유용성

김병기,최영민,이진용,장윤석,문신용,김정구,신창재,김석현 대한산부인과학회 1994 Obstetrics & Gynecology Science Vol.37 No.11

서울대학교병원 산부인과 불임클리닉에 내원한 108명의 불임환자를 대상으로 하여 성교후 검사시 가장 중요한 자궁경부 점액평가를 기초체온 측정과 함께 질식 골반 초음파검사를 동시에 시행하였다. 대상환자중 기초체온표만으로 시행한 자궁경부 점액검사상 불량 자궁경부 인잘 평가된 환자느 ㄴ14명(12.9%)이었으며 이중 10명(71.4%)에서 배란일 하루 이내에 체온 상승을 보여 이러한 환자에서는 기초체온 상승이 배란일과 반영에 부적절함을 알 수 있었다. 그리고 이들 환자에서 질식 초음파검사를 동시에 시행함으로써 5명의 자궁경부 인자 불량 판정의 위양성 및 2명의 자궁경부인자 불량 위음성군을 감별하였고 아울러 불량 자궁경부 인자를 보인 9명중 난포성장의 이상에 의한 5명과 자궁경부의 반응이 적절하지 못한 4명의 환자를 감별진단하였다. 이상에서 기초체온표만을 기준으로 자궁경부인자를 평가할 경우 37%의 위양성율과 2.4%의 위음성율을 나타내므로, 질식초음파검사를 병행함으로써 이러한 위양성, 위음성율을 감소시키고 또한 적절한 치료의 선택을 할 수 있으므로 불임환자의 자궁경부인자 평가에 있어서 질식 초음파검사는 매우 유용하다고 생각된다. A prospective study was performed to evaluate the relationship between the cervical mucus test(CMT), follicle size, and basal body temperature in infertile women. One hundred eight patients were examined with serial transvaginal ultrasonography for follicular growth in conjunction with CMT. Six patterns were observed including normal follicular growth and vervical mucus(80/96), narrow cervical mucus window(1/96), premature luteinization(2/96), insensitivity to thermogenecity(4/96), abnormal cervical mucus with normal(4/96) or abnormal follicular growth (5/96). False positive(5/14) and false negative(2/82) cervical factor problems were diagnosed by ultrasonography and etiologies of abnormal cervical mucus were easily recognized. Thus transvaginal ultrasonography may be useful in eliminating false positive and false negative cervical factor diagnosis and in differentiating two types of true positive abnormal cervical factor.

완전포상기태 예후인자로서 접합체형의 임상적 의의

김승조,배석년,신진웅,김찬주,김재훈,이상형,김재동,윤수철 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.10

To evaluate the possible correlation between the origin of complete hydatidiform mole(CHM) and subsequent persistent gestational trophoblastic tumor(GTT) after molar evacuation, we have studied genetic origin patterns against conventional clinical parameters -patient`s age, gestational age, uterine size for gestational age, serum β-hCG levels before molar evacuation- in 69 patients with CHM. In our study, each of large uterine size for gesta-tional age, serum β-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 chemotherapy), serum β-hCG levels before molar evacuation and before initiation of chemotherapy- according to the origin of CHM. There are no differences in the analysis of sex-chromosome and variable number tandem repeat sequence YNZ22 and APOB gene in the extracted 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-chromosome and polymorphism of YNZ22 and APOB gene from the extracted DNA of paraffin block 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.

유아 측뇌실에 발생한 맥락총 유두종

김철진,최병욱,김수천,김형동,김수휴,심재홍 대한신경외과학회 1988 Journal of Korean neurosurgical society Vol.17 No.4

Choroid-Plexus papilloma is benign neoplastic growth arising from the ventricular choroid plexus, and has communicating hydrocephalus frequently. There has been significant surgical mortality and morbidity associated with resection of neonatal or infantile choroid plexus papillomas because these tumors are ususally large and highly vascular, whereas the total volume of neonates is small. It's site of occurrence is usually lateral ventricle and rarely the 3re or 4th ventricle in childhood. We present a case of lateral ventricle choroid plexus papilloma in an infant with a brief review of the literature

자궁경부암 환자에서 ELISA를 이용한 HPV-16 VLP에 대한 혈청반응

김승조,남궁성은,박종섭,김현수,김찬주,박순희,안희경,황은성,정근택 대한산부인과학회 1996 Obstetrics & Gynecology Science Vol.39 No.1

1993년 1월부터 1994년 12월까지 가톨릭대학교 의과대학 강남성모병원 산부인과 종양학부에서 진단 및 치료를 받았던 환자들에서 치료전 채취한 혈청과 자궁경부 세포를 이용한 실험결과 다음과 같은 결론을 얻을 수 있었다. 1. 자궁경부암 전구병변 환자 20명은 HPV-16에 양성이었고, 나머지 4명은 다른 아형의 DNA HPV가 있거나, 발견되지 않았다. 96명의 자궁경부암 환자에서 69명은 HPV-16 DNA, 9명은 HPV-18 DNA에 양성이었고, 그외 3명은 HPV-16과 HPV-18이 동시에 발견되었다. 또한 7명에서는 다른 아형의 HPV DNA가 있었고, 나머지 8명은 HPV DNA를 발견할 수 없었다. 2. HPV-16 L1, L2 VLP에 대한 ELISA 결과는 정상 대조군의 9%에서 양성이었고, 자궁경부 전구병변의 환자에서는 50%(12/24), 자궁경부암 환자의 62.5%에서 각각 양성으로 나타나 자궁경부의 종양성 변화가 있는 환자에서 유의한 진단적 가치가 있었다. 3. HPV-16 DNA에 양성인 자궁경부암 환자의 68%(47/69)에서 HPV-16 VLP ELISA에 양성이었고, HPV-18 DNA에 양성인 환자의 44%(4/9)에서 HPV-16 VLP ELISA에 양성이었으나 HPV-16/18이외의 다른 HPV 아형에 양성인 환자에서는 14%(1/7)에서 ELISA 양성으로 나타나서 HPV-16또는 HPV-18 DNA 양성인 환자들과 다른 종류 HPV DNA에 양성인 환자들 사이에서 항체 반응 여부는 통계학적인 차이가 있었다. 4. 자궁경부암 환자의 임상기와 조직학적 특성에 따른 HPV-16 VLP에 대한 항체 형성을 관찰해 본 결과 각 임상기와 조직형에 따른 차이를 관찰할 수 없었다. 이상의 결과로 자궁경부암과 전구 병변 환자들의 대다수에서 ELISA 방법으로 HPV-16 VLP에 대한 항체 형성을 관찰할 수 있었다. 또한 HPV-16 VLP ELISA 검사는 HPV-16 DNA 검사의 보조진단법으로 유용하며, HPV와 연관된 자궁경부 종양성 질환의 혈청학적 역학 연구에도 도움을 줄 수 있을 것으로 사료된다. Background: The late structural proteins of HPV-16 have recently been shown to self-assemble into virus-lide particles(VLPs) from baculovirus system when expressed in insect cells. The ability to generate preparative amounts of HPV-16 L1-L2 VLP may have implications for the development of a serologic assay to detect anti-HPV-16 virion immune responses to conformational epitopes and for immunoprophylasis against HPV-16 infection. Methods: We attempted to investigate serologic responses in the sera obtained from Korean women with cervical neoplasia by ELISA using HPV-16 VLPs. PCR method using L1 consensus primers and type-specific oligomer probes was used to determine the presence and type of HPV infection in the study population(normal control; 23 cases, preinvasive lesions; 24 cases, and invasive cervical cancers; 96 cases). Result: 1) The sera of 93%(21/23) of women, who didn`t have HPV-ralated cervical lesions, were negative for HPV-16 VLPs in ELISA assay. The sera of 50%(12/24) of patients with preinvasive cervical lesion and 63%(60/96) of patients with invasive cervical cancer were ELISA positive for HPV-16 VLPs(p$lt;0.01). 2) The positive reactivities for ELISA of HPV-16 VLPs in cervical cancer patients according to clinical characteristics were nor signific antly different. 3) Among women with cervical neoplasia, HPV 16 VLP was positive in 50%(10/20) of HPV-16 positive cases with preinvasive cervical lesion and 72%(50/72) of HPV-16 positive cases with invasive cervical cancer. Conclusion: These results suggest that the considerable number of patients with cervical neoplasia generated an IgG antibody response to the HPV 16 VLPs that can be detected by ELISA. These HPV-16 VLP ELISA may be useful in adjunctive diagnostic asay to HPV-16 DNA test and seroepidemiologic study of HPV-related cervical neopl-asia.

Inhibitory activity of 1,3-Bis-[4 -(β-D-glucopyranosyloxy)benzyl]citrate from Gastrodiae root on antigen-induced asthmatic responses in conscious guinea pigs

CJ Kim,JK Lee,SW Moon,JH Park,JH Cho,WK Whang,SS Sim 대한약학회 1999 大韓藥學會 總會 및 學術大會 Vol.48 No.-

자궁경부암에서 HPV-16 단백질을 이용한 혈청내 진단물질의 임상적 효용성

김승조,남궁성은,박종섭,김현수,김찬주,박순희,안희경,정근택,박동춘,유왕돈 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.3

Background : Most markers in current clinical use are not cancer-specific, but the ideal tumor marker should be specific for cancer, highly sensitive, clinically practicable, inexpensive, and acceptable to individual. it is still debating that SCCA and CEA are clinically useful for specific tumor markers in management of cervical cancers. Recently, a variety of HPV- related proteins have been synthesized and their utility as diagnostic and prognostic tumor markers in cervical cancers is needed to be assessed by comparing the previous tumor markers ; CEA and SCCA. The early proteins(E6 & E7) of HPV-16 which are responsible for malignant transformation could be constructed by in vitro transcription and translation and the late structural proteins(L1/L2) of HPV-16 have been shown to self-assemble into virus-like particles(VLPs) from baculovirus system when expressed in insect cells. The ability to generate preparative amounts of HPV-16 E6, E7 proteins and L1/L2 VLPs may have implications for the development of a serologic assay to detect anti-HPV-16 virion immune responses to conformational epitopes of HPV-associated cervical neoplasia. Methods : We attempted to investigate serologic response in the sera obtained from Korean women with cervical neoplasia by RIPA(radioimmunoprecipitation assay) using in vitro translated HPV-16 E6, E7 proteins and ELISA using HPV-16 L1/L2 VLPs, PCR method using E6 type-specific primers and probes for HPV-16/18 was used to determine the presence and type of HPV infection in the study population(normal controls ; 15 cases, preinvasive lesions ; 28 patients, and invasive cervical cancers; 124 cases). Result : 1) The sera of 0% of preinvasive lesions and 34%(42/124) of cervical cancers were positive for SCCA and the sera of 0% of preinvasive lesions and 18% (22/124) of cervical cancers were positive for CEA. The positivity of SCCA was increased with advancing clinical stages, but the antibody levels were not correlated with clinical outcome of disease. 2) The sera of 7%(2/28) of preinvasive lesions and 51%(63/124) of cervical cancers were positive for in vitro translated HPV-16 E6 protein(P$lt;0.05) and the sera of 11%(3/28) of preinvasive lesions and 33%(41/124) of cervical cancers were positive for in vitro translated HPV-16 E7 protein(P$lt;0.05). The levels of HPV-16 E6 proteins showed high titers in some invasive cancers, but they didn`t show any fluctuations along with clinical outcomes. In contrast, the antibody levels to HPV-16 E7 protein were correlated to clinical stage and tumor burden in a significant number of cervical cancers. 3) The sera of 7% (1/15) of normal controls, 39%(11/28) of preinvasive lesions and 56% (70/124) of cervical cancers were ELISA positive for HPV-16 L1/L2 VLPs(P$lt;0.05). The positive reactivities for HPV-16 L1/L2 VLPs in cervical cancers by clinical stage, histopathology or HPV DNA types were not significantly different. Conclusion : These results suggest that the considerable number of patients with cervical neoplasia generated positive antibody response to in vitro translated HPV -16 E6, E7 proteins and L1/L2 VLPs. These HPV-16-associated proteins might be disease-specific markers which could be useful in adjunctive diagnostic assay and seroepidemiologic study of HPV-related cervical neoplasia. Especially, the monitoring of antibody to HPV-16 E7 protein seems to be valuable in proper management of cervical cancers for specific tumor marker.