Sensitivity of AutoPap Primary Screening System with Location-Guided Screening in Uterine Cervical Cytology

최종순,장회숙,김희숙,전이경,김혜선,박지영,박인서,홍성란,Choi, Jong-Sun,Jang, Hoi-Sook,Kim, Hy-Sook,Chun, Yi-Kyeong,Kim, Hye-Sun,Park, Ji-Young,Park, In-Sou,Hong, Sung-Ran The Korean Society for Cytopathology 2003 대한세포병리학회지 Vol.14 No.2

Objective: The sensitivity of the AutoPap Primary Screening System with Location-Guided Screening (AutoPap LGS) for Identifying atypical cells in cervicovaginal smears was evaluated. Methods: Two hundred forty one slides with atypical cervical cytology randomly sampled were rescreened both manually and by the AutoPap LGS. The AutoPap LGS localized the atypical cells as 15 fields of view(FOVs), which were reexamined by manual review. The sensitivity was also evaluated in accordance with the cellularity of the smears. Results: The AutoPap LGS successfully processed 232 out of 241 slides. The sensitivity of the AutoPap LGS identifying the atypical cells in successfully processed slides was 97.4%(226/232). The false negative rate was 2.6%(6/232). There was no false negative case on high grade squamous intraepithelial lesion (HSIL) or squamous cell carcinoma(SCC) smears in the AutoPap LGS. The FOVs localized the diagnostic-atypical cells in 97.8%(221/226). The number of diagnostic-atypical FOVs was increased in higher-degree of atypical cytology. The AutoPap LGS localized the atypical cells in 100% of adequately cellular smears and in 92.5% even in low cellular smears. Conclusion: The AutoPap LGS showed relatively good sensitivity to detect atypical cells. It can be a valuable system to localize atypical cells, especially in HSIL or cancer slides, even in smears with low cellularity.

체외 실험상 원인불명 습관성 유산환자에서 얻은 말초혈액 단핵구와 태반항원 반응 후 제일형 보조 T 세포 사이토카인 ( IFN - γ ) 의 분비 양상

유근재(Keun Jai Yoo),송인옥(In Ok Song),최범채(Bum Chae Choi),강인수(Inn Soo Kang),박인서(In Sou Park),변혜경(Hye Kyung Byun),이지애(Ji Ae Lee),김정욱(Jeong Wook Kim),김현주(Hyun Joo Kim) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.12

N/A Objective: A dichotomous Thl and Th2 cytokine profile has been associated with reproductive failure and success, respectively. The purpose of our study was to determine the levels of Thl cytokine (IFN- y ) secreted by peripheral blood mononuclear cells (PBMCs) form women with unexplained recurrentabortion (URA) and fertile controls in response to trophoblast antigen. Methods: PBMCs were isolated from 30 nonpregnant women with URA and from 10 nonpregnant fertile controls. Following 4 days of culture (1 * 10(6) cells/mL) with and without a protein extract derived from a trophoblast cell line (30 ug/mL, protein). None of the women had allergies, atopy or recent infection. Cytokines were measured in supernatants with enzyme-linked immunosorbent assay (ELISA) kits. IFN- r kit was obtained from BOISOURCE (lower limit of sensitivity, 15.6 pg/mL for IFN- r ). All values below the lowest limit of sensitivity as determined by test kit standards were considered negative. The cytokine stimulation test is considered positive if the IFN- r concentration increases by 200% or more with the trophoblast antigen stimulation. Datas are presented as mean+ SEM. Nonparametric testing (Mann-Whitney U) was used for analysis with P<0.05 considered statistically significant. Results: The Thl-type cytokine (IFN- r ) was detected in 20(67%) of 30 supernatants from women with URA. In contrast, 2 (20%) of trophoblast-activated PBMC culture supernatants from the 10 parus women with normal reproductive histories was detected IFN- r and but were significantly lower than levels in women with URA who had secreted IFN- r upon trophoblast stimulation (99.80+ 18.17 pg/mL versus 166.47 + 36.96 pg/mL, p<0.05). Spontaneous secretion of IFN- r was significantly higher in culture supernatants from women with URA than in supernatants from women with successful reproductive histories (41.36.09+6.99 pg/mL versus 25.89+9.34 pg/mL, p<0.05). Conclusion: These data indicate that there are significant differences between women with URA and women with normal reproductive histories in their regulation of the Thl-cytokine (IFN- r) in response to trophoblast. Thl-type immunity to trophoblast is associated with URA and may play a role in reproductive failure.

자궁내막암 환자의 수술 전 자궁경부 세포진 검사 - 임상병리학적 연관성

성석주(Seok Ju Seong),김태진(Tae Jin Kim),임경택(Kyung Taek Lim),정환욱(Hwan Wook Chung),이기헌(Ki Heon Lee),박인서(In Sou Park),심재욱(Jae Uk Shim),박종택(Chong Taik Park),김혜선(Hye Sun Kim),김희숙(Hy Sook Kim) 대한산부인과학회 2002 Obstetrics & Gynecology Science Vol.45 No.10

목적 : 자궁내막암 환자에서 수술 전에 악성 예후인자를 미리 알 수 있다면 치료 계획을 세우는데 많은 도움이 된다. 이 연구의 목적은 자궁내막암 환자에서 수술 전에 시행한 자궁경부 세포진 검사 결과와 악성 예후인자와의 상관관계를 알아보는 것이다. 연구 방법 : 1989년 1월부터 2000년 6월까지 삼성제일병원에서 수술을 시행받은 자궁내막암 환자 중에서 수술 전에 자궁경부 세포진 검사를 하였던 163예의 환자를 대상으로 하였다. 모든 환자에서 전자궁적출술 및 양측 부속기 절제술과 복강 내 세포진 검사를 시행하였고, 골반 림프절 절제술은 79예에서, 또 부대동맥 림프절 절제술은 81예에서 시행하였다. 이들 환자의 수술 전에 시행한 자궁경부 세포진 검사 결과를 정상, AGUS, adenocarcinoma로 나누어 자궁내막암의 예후인자와의 상관관계를 검토하였다. 통계는 카이 제곱 테스트를 이용하였다. 결과 : 163예 환자의 평균 나이는 49세 (24-75세)였고, 50세 미만이 65예 (39.9%)이고 50세 이상이 98예 (60.1%)였다. 수술 전 자궁경부 세포진 검사에서 72예 (44.2%)는 정상, 38예 (23.3%)는 AGUS, 53예 (32.5%)는 adenocarcinoma였다. 자궁경부 세포진 검사는 고령 (p=.014), 나쁜 조직학적 분화도 (p=.000), 자궁경부 침윤 (p=.015), 심부 자궁근층 침윤 (p=.000), 림프-혈관 침윤 (p=.000) 및 진행된 수술병기 (p=.049)와 통계적으로 유의한 상관관계를 보였고, 조직학적 분류 (p=.328), 복강내 세포진 검사 (p=.067), 자궁부속기 침범 (p=.602), 골반 림프절 침윤 (p=.266) 및 부대동맥 림프절 침윤 (p=.220)과는 통계적으로 유의하지 않았다. 결론 : 자궁내막암 환자에서 수술 전 자궁경부 세포진 검사상 발견된 AGUS나 adenocarcinoma는 예후인자 중 고령, 나쁜 조직학적 분화도, 자궁경부 침윤, 심부 자궁근층 침윤, 림프-혈관 침윤 및 진행된 수술병기와 통계학적으로 유의한 상관관계가 있었다. 따라서 자궁경부 세포진 검사는 자궁내막암 환자의 수술 전 평가방 법으로 중요시되어야 할 것이다. Objective : The aim of this study was to evaluate the correlation between preoperative Pap smears and known poor prognostic factors in patients with endometrial carcinoma. Methods : Between January 1989 and June 2000, preoperative evaluation of Pap smears were done in 163 patients with endometrial carcinoma who underwent total abdominal hysterectomy with bilateral salpingooophorectomy, peritoneal cytology, and pelvic and/or para-aortic lymphadenectomy. All Pap smears and histologic sections were reviewed. Pathologic parameters of hysterectomy specimens were evaluated and correlated with the findings of Pap smears. Chi-square test was used for statistical analysis. p-values<0.05 were considered significant. Results : The mean age of patients was 49 years with range between 24 and 75 years old. 72 patients (44.2%) had normal, 38 patients (23.3%) had atypical glandular cells of undetermined significance (AGUS), and 53 (32.5%) had adenocarcinoma on preoperative Pap smears. Statistically significant associations were found between Pap smears and age (p=.014), histologic grade (p=.000), cervical involvement (p=.015), depth of myometrial invasion (p=.000), lymph-vascular space invasion (p=.000), and surgical stage (p=.049). Patients with malignant cytology were more likely to have older age, poorly differentiated malignancies, deeper myometrial invasion, cervical metastases, lymphvascular invasion and higher surgical stage. However, histologic subtypes (p=.328), peritoneal cytology (p=.067), adnexal involvement (p=.602) and pelvic and/or para-aortic lymph node metastases (p=.266 and p=.220) were not statistically significant. Conclusion : This study revealed that preoperative abnormal Pap smears in patients with endometrial carcinoma were significantly associated with age, histologic grade, cervical involvement, depth of myometrial invasion, lymphvascular space invasion and surgical stage. Therefore, Pap smears could be an important part of the preoperative evaluation in patients with endometrial carcinoma.

습관성유산 및 불임환자에서 자궁중격절제술 후 임신의 결과

송지홍(Ji Hong Song),유근재(Keun Jai Yoo),송인옥(In Ok Song),백은찬(Eun Chan Paik),최범채(Bum Chae Choi),손일표(Il Pyo Son),전종영(Jong Young Jun),박인서(In Sou Park),궁미경(Mi Kyoung Koong),강인수(In Soo Kang) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.12

N/A Uterine anomalies have been reported in 4% of women with infertility and in up to 15% of those with recurrent abortion. One of the major intrauterine disorder associated with infertility and recurrent abortions is intrauterine septum, The reproductive outcome of 41 patients of intrauterine septum (7 complete, 34 incomplete) with repeated abortions or infertility was assessed after the uterine septotomy. 5 of 7 patients with comlete uterine septum undergone uterine septotomy (3; hysteroscopic metroplasty, 2; abdominal metroplasty) had total 6 pregnancies and all of them had live biths. 28 patients with incomplete uterine septum got the hysteroscopic intrauterine septotomy and the viable pregnancy rate was 62% (3 ongoing pregnancies, 13 live biths of total 26 pregnancies). 6 patients with incomplete uterine septum had not the operation and 5 patients had 5 live births after total 6 pregnancies with 1 spontaneus abortion. Even though, the number of cases were small, the live birth rate in the group of septotomy of the patients of complete uterine septum (100%, 6/6) was higher than that in the group of not-done (50%, 1/2). The live birth rate in the group of not-done of the patients with incomplete uterine septum (83%, 5/6) was higher than that in the group of hysteroscopic uterine septotomy (62%, 16/26), but 5 of 6 had short uterine septal length (<1 cm), 1 had 1.5 cm septal length in the group of not-done. All the patients with successful pregnancy outcome had no other co-factors at the diagnostic laparoscopy, but the 5 primary infertility patients with no live birth even after treatment (all were with incomplete septum; 3 undergone hysteroscopic septotomy, 2 not-done with one abortion) had other co-factors such as endometriosis, peritoneal or tubal facor. In conclusion, hysteroscopic uterine septotomy would be useful for the patients with habitutal abortion or infertility and more advanced managemnet protocols should be applied to the patients having other co-factors if there was no pregnancy even after the uterine septotomy.

자궁경부세포진에 있어서 AutoPap 300 QC System의 임상경험과 민감도 검사

홍성란,박종숙,장회숙,김의정,김희숙,박종택,박인서,Hong, Sung-Ran,Park, Jong-Sook,Jang, Hoi-Sook,Kim, Yee-Jeong,Kim, Hy-Sook,Park, Chong-Taik,Park, In-Sou 대한세포병리학회 1998 대한세포병리학회지 Vol.9 No.1

OBJECTIVE: False negatives of cervical smears due to screening errors pose a significant and persistent problem. AutoPap 300 QC System, an automated screening device, is designed to rescreen conventionally prepared Pap smears initially screened by cytotechnologists as normal. Clinical experience and sensitivity of the AutoPap 300 QC System were assessed and compared with current 10% random qualify control technique. MATERIALS AND METHODS: In clinical practice, a total of 18,592 "within normal limits" or "benign cellular changes" cases classified by The Bethesda System were rescreened by the Autopap System. In study for sensitivity of The AutoPap System to detect false negatives, a total of 1,680 "within normal limits" or "benign cellular changes" cases were rescreened both manually and by the AutoPap System. The sensitivity of the AutoPap System to these false negatives was assessed at 10% review rate to compare 10% random manual rescreen. RESULTS: In clinical practice, 38 false negatives were identified by the AutoPap System and we had achieved 0.2% reduction in the false negative rate of screening error. In study for sensitivity, 37 false negatives were identified by manual rescreening, and 23 cases(62.2%) of the abnormal squamous cytology were detected by the AutoPap System at 10% review rate. CONCLUSONS: The AutoPap 300 QC System is a sensitive automated rescreening device that can detect potential false negatives prior to reporting and can reduce false negative rates in the laboratory. The device is confirmed to be about eight times superior to the 10% random rescreen in detecting false negatives.

난소과자극 증후근의 예측인자와 임상 양상에 관한 연구

송지홍(Ji Hong Song),유근재(Keun Jai Yoo),송인옥(In Ok Song),백은찬(Eun Chan Paik),최범채(Bum Chae Choi),궁미경(Mi Kyoung Koong),손일표(Il Pyo Son),전종영(Jong Young Jun),강인수(Inn Soo Kang),박인서(In Sou Park) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.11

N/A Objeetive: Ovarian hyperstimulation syndrome (OHSS) is one of the well known complication of conttolled ovarian hyperstimulation. Though there have been numerous protocols for the prevention of OHSS, it has not been completely preventable until now. This study was performed to identify clinical predictors for early and late OHSS. Methods: A retrospective analysis of all IVF cycles in 1993 up to June 1996 was performed. OHSS was diagnosed using the criteria of Rabau modified by Schenker. All cases of OHSS reported in this study presented with marked ovarian enlargement, ascites, oliguria, hemoconcentration and electrolyte disturbance. Ovarian stimulation was carried out using a combination of gonadotrophin releasing hormone-agonist, follicle-stimulation hormone and human menopausal gonadotrophin. 27 patients has moderate or severe OHSS presenting 3-7 days post-human chorionic gonadotrophin (hCG), and 21 patients had severe OHSS presenting 12-17 days post-hCG. Results: No patient with early OHSS went onto develop late OHSS, and no patient with late OHSS had demonstrated early OHSS. Logistic regression showed that early OHSS was predicted by the number of oocytes retrieved and the estradiol concentration on the day hCG injection (P<0.05). Late OHSS was predicted by the transferred embryos, B-hCG on 14 day after hCG injection (P<0.05). Conclusion: Early OHSS was an acute effect of the hCG administered prior to egg retrieval in women with high estradiol and large number of retrieved oocytes. Our analysis of the risk factors for early OHSS indicates that cryopreservation of all embryos will not alter the risk of early OHSS even though it should prevent late OHSS. Late OHSS was induced by the rising serum concentration of hCG produced by the early pregnancy, the number of transferred embryos must be adjusted carefully, since it was associated with multiple gestation.

자궁경부 미세침윤암의 진단 및 치료에 관한 고찰

김태진,심재욱,박인서,임경택,이기헌,박종택,노성훈,송하균,안현경,함경렬,강옥림,전종수 대한부인종양 콜포스코피학회 1997 Journal of Gynecologic Oncology Vol.8 No.2

Microinvasive carcinoma of the uterine cervix(FIGO stage IA) has been reported as highly curable disease even with conservative surgery such as conization and simple hysterectomy. Nevertheless, the surgical management for microinvasive carcinomas has been proposed varying from conservative surgery to radical hysterectomy with pelvic nodes dissection according to different diagnostic criterias for microinvasive carcinoma. We reviewed 512 patients who had been diagnosed as microinvasive carcinoma of the uterine cervix at the Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center from Jan. 1988 to Dec. 1995. Among them, 376 patients were included in this study satisfying guided criterias such as proper management and follow up more than at least one year, and they were analyzed retrospectively based on the clinicopathologic characteristics, pattern of surgical management and postoperative status. The majority of patients were diagnosed at 4th and 5th decades of their lives(271/376, 72.1%). The main presenting symptoms were abnormal vaginal bleeding including postcoital spotting and leukorrhea, but considerable numbers of patients were asymptomatic(108/376, 28.7%). The majorities of patients had findings of erosion and inflammation in the cervix, but grossly normal appearing cervices were encountered in considerable numbers(97/376, 25.8%). Satisfactory colposcopic evaluations for abnormal findings were observed in 145 cases among 164 colposcopically examined patients. Abnormal findings such as aceto-white epitherium, erosion, mosaicism, atypiacal vessels were frequently observed. Overall diagnostic accuracy of Pap smear and colposcopically directed biopsies were 59.3% and 61.6%, respectively. Significant correlations were statistically observed between the rates of diagnostic accuracy and the depth of stromal invasion. Findings of positive lymph-vascular space invasion and confluent pattern of invasion were observed in 8.2% and 16.2% of cases, respectively. Both findings were observed more frequently in advanced depth of stromal invasion with statistical significance. The findings of positive lymph-vascular space invasion and/or confluent pattern of invasion in conized specimens with negative margin were also significantly correlated with relation to residual lesion in the hysterectomy specimens. The surgical managements were performed varying from conization to radical abdominal hysterectomy with pelvic nodes dissections. The conservative surgeries were performed in 218 cases and there were tendenciesnto perform conservative surgery in cases which correspond to SGO or JSOG criterias for microinvasive carcinoma. No positive node was observed in 1,294 pelvic lymph nodes dissected. There was no case of surgery-related death in this series. Including one case of central recurrence, 8 cases required postoperative treatment due to occult lesions. Among them, 5 cases did not correspond to JSOG criteria for microinvasive carcinoma and another 2 cases had positive cone margin. Accordingly we emphasized again the significance of the regular screening procedures for early detection of cervical lesions and liberal use of diagnostic conization in suspected microinvasive carcinoma cases to evaluate the exact pathologic characteristics. In addition, we suggest the JSOG criteria as a criteria for conservative surgery in microinvasive carcinoma based on the results in this study.

Handy-diag-EIA^(�)의 임상진단 정확도에 관한 임상적 고찰

김훈기,구은주,박찬용,박인서 최신의학사 1986 最新醫學 Vol.29 No.12

Comparative Genomic Hybridization을 이용한 자궁경부암의 유전적 변이 조사

김태진,김영미,김진미,최수경,심재욱,정환욱,박인서,임경택,이기헌,박종택,홍성란 대한부인종양 콜포스코피학회 1999 Journal of Gynecologic Oncology Vol.10 No.3

Comparative Genomic Hybridization (CGH) is a recently developed molecular cytogenetic technique, which makes it possible to detect chromosomal alteration in solid tumors. To determine whether chromosome alterations are related to cervical carcinoma, we have analyzed 33 cases (24 squamous cell carcinomas and 9 adenocarcinomas, stage Ib-IIIb) from tumor tissues and paraffin embedded tissues by CGH. The cut off value of CGH profiles was 1.15 and 0.85 (green/red ratio). Chromosomal aberrations were detected in 30 out of 33 cases (90.9%). In 32 cases, chromosome 3q was most frequently affected and had greater copy numbers in 20 of the 33 cases (60.6%). Interestingly, out of those 20 cases, 10 cases were shown to have a high-level of amplification of chr 3q. In addition to chr 3q, chromosomal gains were observed in chr 1q, 1p, 5p, Sq, 12p, 15q, 19q, 20q, Xp, and Xq. Furthermore chromosomal loss was detected, most commonly in chromosome 11q (11/33). Although less frequent, common losses were also detected in chr 2q, 4p, 4q, Sq, 11p, 17p, and 18p. In addition, there were cases of gross chromosome loss for chr 4, 6, 10, 11, 13, 14, 16, 17, 18, 19, 20, 21, 22 and X. In cases involving whole arm deletion, we utilized fluorescence in situ hybridization (FISH) using specific probes α-satellite. We performed HPV typing for 16 and 18 usiag polymerase chain reaction (PCR) and Southern blot analyses. Out of 33 tumor samples, 24 cases (72,7%) were HPV 16 positive, while only 6 cases were positive for HPV 18. two cases were positive for both HPV 16 and 18. We believe that a gain of chromosome 3q as a reeurrent chromosomal aberration may contribute to the tumorigenesis of cervical cancer. However, we could not correlate a pattern of chromosomal aberration with tumor stage or histologic type in cervical cancer.

자궁경부암의 발암과정과 세포자연사의 연관성

김태진,김정욱,심재욱,백두진,정환욱,박인서,임경택,이기헌,전이경,박종택,김혜선 대한부인종양 콜포스코피학회 1999 Journal of Gynecologic Oncology Vol.10 No.2

Apoptosis, including the programmed cell death, is important event in normal cell turnover and maintenance of adult tissues. Apoptosis exerts a homeostatic function in relation to tissues dynamics, as the steady state of continuously renewing tissues achieved by a balance between cell replication and cell death. This study was undertaken to investigate the association between apoptosis and development of the cervical neoplasia. Archival cervical samples from normal epithelium (n = 10), low-grade squamous intraepithelial lesions (LSIL, n = 10), high-grade squamous intraepithelial lesions (HSIL, n = 10), microinvasive squamous cell carcinomas (n = 10), and invasive squamous cell carcinomas (n = 10) were evaluated for apoptosis. We used in situ end-labeling of DNA strand breaks by terminal deoxynucleotidyltransferase incorporation of biotinylated deoxyuridine to 3-OH ends of DNA, identified by nickel-avidine-peroxidase. The apoptotic index (sum of apoptotic bodies divided by the total nuclei times 100) significantly decreased (P $lt; 0.05) as the degree of neoplasia increased: 3.1 ± 0.9 % in normal epithelium, 5.5 ± 1.4 % in LSIL, 1.6 ± 0.4 % in HSIL, 1.9 ± 0.5 % in microinvasive carcinomas, and 0.6 ± 0.3 % in invasive carcinomas. Compared to normal epithelium, the total cell number per 200x field increased significantly (P $lt; 0,05): 379 ± 47 in normal epithelium, 462 ± 228 in LSIL, 670 293 in HSIL, 1035 ± 254 in microinvasive carcinomas, and 1389 ± 247 in invasive carcinomas. Consequently, these results suggest that progression of cervical carcinogenesis is associated with a decrease in apoptotic index and an increase in the number of the total cell.