최신임상강좌 : 자궁체부암 임상시험의 세계적 현황

유희석 ( Hee Sug Ryu ) 대한산부인과학회 2007 Obstetrics & Gynecology Science Vol.50 No.10

Smooth Muscle Tumor of Uncertain Malignant Potential ( STUMP ) 의 임상적·병리학적 고찰

이희종(Hee Jong Lee),유희석(Hee Sug Ryu),박영한(Young Han Park),주희재(Hee Jae Joo),양성천(Seung Chun Yang),오기석(Kie Suk Oh) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.10

목적 : 본 연구는 Smooth muscle tumor of uncertain malignant potential(이후 STUMP로 표기함)을 평활근 육종과 비교하여 임상적. 병리학적으로 고찰하고, 1994년 개정된 자궁평활근종 분류법으로 재분류후 그 결과를 임상경과와 비교하여, 새로운 분류법의 실용성을 검토하였다.연구방법 : 1995년부터 1999년까지 아주대학교병원 산부인과를 내원한 환자들 중 STUMP로 진단된 11례와 평활근 육종으로 진단된 7례의 의무기록과 조직표본을 통해 임상적 병리학적 소견을 검토하였고, 1994년 Kempson과 Hendrickson에 의해 정립된 자궁평활근종의 분류법에 의해 재분류하였다.결과 : 환자의 연령분포/ 분만력/ 폐경유무/ 호르몬제재 복용 기왕력은 양군에서 유의한 차이가 없었다. 가장 흔한 임상증상은 불규칙한 자궁출혈이었고 (STUMP 54%, 평활근 육종 62%), 수술전 초음파상 악성종양이 의심된 경우는 STUMP 군에서 1례(9%), 평활근 육종군에서 2례(29%)였다. STUMP 군 2례에서는 근종 절제술만으로 치료를 종결하였고 총 18례중 나머지 환자들은 전자궁 적출술 및 선택적 자궁부속기 절제술을 시행하였으며, 모든 예에서 재발이나 전이소견은 없었다. 총 18례 중 STUMP 10례와 평활근 육종 4례는 유사분열지수가 증가된 평활근종으로, STUMP 1례는 비정형 평활근종으로, 평활근 육종 3례는 같은 진단명으로 재분류되었다.결론 : STUMP에서 유사분열지수가 증가된 평활근종(leiomyoma with increased mitotic index)으로 재분류된 종양의 환자들은 모두 양호한 임상경과를 보여 본 연구에서 자궁평활근종의 새로운 분류법은 임상경과와 일치하였다. 이 경우 임신을 원하는 여성이면 근종 절제술만으로 치료를 종결할 수 있다. 그러나 재발가능성이 적은 비정형 평활근종(atypical leiomyoma with low risk recurrence)이나 저급악성도를 갖는 평활근종(smooth muscle tumor of low malignant potential)으로 분류된 예는 악성 임상경과의 가능성이 있어, 예후에 대한 장기적인 추적조사가 필요할 것으로 본다. Objective : To evaluate clinical-pathological aspects of smooth muscle tumor of uncertain malignant potential (STUMP), comparing those of leiomyosarcomas and to reclassify them according to the revised classification of smooth muscle tumor, and to investigate the clinical value of new classification.Methods : A retrospective review of clinical and pathological characteristics of 11 cases of STUMP and 7 cases of leiomyosarcoma was done at department of obstetrics and gynecology of Ajou university hospital from 1995 to 1999. They were reclassified according to the revised classification by Kempson and Hendrickson in 1994.Results : Patients' age, parity, status of menopause, history of hormonal use were not significantly different. Vaginal bleeding was most common clinical symptom in both groups(STUMP 55%, leiomyosarcoma 63%) and sarcomatous change was suspected in 1 case of STUMPs and 2 cases of leiomyosarcomas with preoperative transvaginal sonographic examination. Two cases of STUMP were treated with myomectomy only and hysterectomy with or without salpingo-oophorectomy was performed in all cases of leiomyosarcomas and 9 cases of 11 STUMPs. No adjuvant therapy was done and none recurred. Ten cases of STUMP and four cases of leiomyosarcoma were reclassified into leiomyoma with increased mitotic index, one STUMP into atypical leiomyoma, and three leiomyosarcomas remained in the same category by revised classification.Conclusion : Such tumors reclassified into leiomyoma with increased mitotic index showed benign clinical course and the results of this study support new classification. However, atypical leiomyoma with low risk recurrence and smooth muscle tumor with low malignant potential still have possibility of malignant clinical course.

정상 자궁난관조영을 보이는 불임 환자에 있어서 복강경술의 의의

권종희 ( Jong Hee Kwon ),서성석 ( Seong Seog Seo ),김미란 ( Mi Ran Kim ),황경주 ( Kyung Joo Hwang ),장혜진 ( Hye Jin Chang ),장석준 ( Suk Joon Chang ),유희석 ( Hee Sug Ryu ) 대한산부인과학회 2005 Obstetrics & Gynecology Science Vol.48 No.2

목적: 불임의 원인을 정확히 찾아내어 그 원인에 따라 적절한 치료 계획을 세워 성공적으로 임신에 도달하는 것이 불임 검사의 목적이다. 자궁난관조영술은 난관내부 및 자궁내강의 환경을 평가하는데 유용한 방법이기는 하나 난관주변의 유착 및 자궁내막증과 같은 골반강내 질환 등의 진단에는 한계가 있다. 본 연구는 경상 자궁난관조영을 보인 불임환자에서의 복강경술의 의의를 알아보고자 한다. 연구 방법: 본 연구에서는 후향적으로 79명의 자궁난관 조영술상 정상을 보인 Objective: To evaluate the value of laparoscopy in infertile women with normal hysterosalpingograms. Methods: Retrospectively analyzed the laparoscopic findings of 79 infertility patients with normal hysterosalpingograms. Results: Of the 79 patients, 28 (

중복자궁 산모가 임신중기에 임신된 자궁강으로부터 탈락막원주 배출 후 만삭분만한

문세희 ( Se Hee Mun ),이정필 ( Jung Pil Lee ),장석준 ( Suk Joon Chang ),김현진 ( Hyun Jin Kim ),유희석 ( Hee Sug Ryu ),장기홍 ( Ki Hong Chang ) 대한산부인과학회 2005 Obstetrics & Gynecology Science Vol.48 No.10

태아 난소 낭종의 예후 인자로서의 초음파 소견

권종희 ( Jong Hee Kwon ),장석준 ( Suk Joon Chang ),임윤경 ( Yun Kyong Lim ),양정인 ( Jeong In Yang ),김행수 ( Haeng Soo Kim ),유희석 ( Hee Sug Ryu ) 대한산부인과학회 2005 Obstetrics & Gynecology Science Vol.48 No.4

초기 자궁경부암 수술 후 재발 고위험 군에서 보조적 동시 항암화학 방사선치료의 적정성 및 효용성 평가

장혜진 ( Hye Jin Chang ),유희석 ( Hee Sug Ryu ),전미선 ( Mi Sun Chun ),박재선 ( Jae Sun Park ),권종희 ( Jong Hee Kwon ),장기홍 ( Ki Hong Chang ),이정필 ( Jung Pil Lee ) 대한산부인과학회 2004 Obstetrics & Gynecology Science Vol.47 No.6

목적 : 초기 자궁경부암 (병기 IA, IB, IIA) 환자에서 근치적자궁적출술과 골반림프절절제술 후에 치료실패율이 높은 고위험군에게 보조적 동시 항암화학방사선치료 (GOG #109 protocol)에 따른 치료의 효용성 및 적정성을 알아보고자 하였다. 연구 방법 : 1994년 7월부터 2001년 6월까지 아주대학교 병원에서 초기 자궁경부암 (병기 IA2, IB, IIA)으로 진단 받고, 근치적 자궁적출술과 부대동맥 및 골반림프절절제술을 시행한 환자 151명 중에서 부대동맥림프절 전이가 있거나 선행화학요법 혹은 방사선치료를 시행한 환자들을 제외한 144명을 대상으로 연구를 시행하였다. 이들 중에서 암세포의 골반림프절 전이, 절단면 침윤 혹은 자궁방 침윤을 보인 30명을 치료군으로 하여 보조적 동시 항암화학방사선요법 (adjuvant concurrent chemoradiotherapy)을 시행하고 치료 효과와 부작용을 후향적으로 임상 분석하였다. 보조적 치료는 수술 후 2-3주 이내에 항암화학치료를 시작하였고, 매 4주마다 총 4주기를 시행하였고, 제 1일에 cisplatin 70 mg/m^2, 2일에서 5일까지 5-FU (1000 mg/m^2)를 주사하였다. 2주기에서 3주기에 방사선치료는 5주간 병용되었다. 결과 : 수술적 치료를 받은 144명의 환자 중에서 9명 (6.3%)이 재발하였고, 치료군에서 3명 (10%), 대조군에서 6명 (5.3%) 이었다. 5년 생존율은 치료군이 100%, 대조군이 96.8%로 통계적인 차이는 없었고, 5년 재발률 (9.5% vs 6.3%)과 5년 무병생존율 (90.5% vs 93.7%)에서도 치료군과 대조군의 유의한 차이는 보이지 않았다. (p>0.05) 결론 : 본 연구로 근치적자궁적출술 및 림프절절제술 후 치료 실패 고위험 인자를 가진 초기 자궁경부암환자에서 보조적 동시 항암화학방사선치료를 함으로써 5년 재발률 및 5년 무병생존율을 위험인자가 없는 대조군 수준으로 향상 시킬 수 있음을 확인하였다. Objective : This study was undertaken to evaluate the efficacy of postoperative concurrent chemoradiotherapy (CCRT) and to investigate the recurrence and survival rates after adjuvant CCRT in high risk early cervical cancer (stage IA2, IB, IIA) patients who were treated by radical hysterectomy and pelvic lymphadenectomy. Methods : From July 1994 to June 2003, we reviewed the chart of 146 patients who underwent radical abdominal hysterectomy and pelvic lymphadenectomy at Ajou University Hospital for early cervical cancer (stage IA2, IB, IIA). CCRT was performed in 30 patients with high risk factors such as positive pelvic lymph node, positive parametrial involvement, or positive surgical margins. Chemotherapy consisted of cisplatin ( 70 mg/m^2 on day 1) and 5-FU (1000 mg/m^2 on day 2-5) for 4 cycles every 4 weeks beginning 2-3 weeks after operation. Pelvic radiotherapy were started with 2nd and 3rd cycle of chemotherapy concurrently. We compared the recurrence rate and survival rate with 114 patients who received no adjuvant therapy after operation. The mean follow up period was 49 months (24-94 months). Results : Disease recurred in 9 of 144 patients treated with surgery (6.3%). There were recurrences in 3 patients after CCRT (10.0%), and in 6 patients in the control group (5.3%) respectively. The actuarial 5- year overall survival rates for patients with adjuvant CCRT, and with no adjuvant treatment were 100%vs. 96.8% (p>0.05). The recurrence and progression-free survival rates were 9.5% vs 6.3%, 90.5% vs. 93.7% (p>0.05). Conclusion : This study shows good local control and 5 years overall and progreesion free survival rates in the high-risk cervical cancer patients after CCRT which is similar results seen in control group. Our results indicate that adjuvant concurrent chemoradiotherapy seems to be effective in stage IA2-IIA cervical concer patients with high risk.

자궁경부 상피내 종양과 인유두종 바이러스 Viral Load와의 상관관계

박재선 ( Jae Sun Park ),유희석 ( Hee Sug Ryu ),장석준 ( Suk Jun Chang ),김용미 ( Yong Mi Kim ),장기홍 ( Ki Hong Chang ),이정필 ( Jung Pil Lee ) 대한산부인과학회 2005 Obstetrics & Gynecology Science Vol.48 No.12

자궁내막암 두 가지 형태의 임상적 특성

박영한(Young Han Park),유희석(Hee Sug Ryu),주희재(Hee Jae Joo),이정필(Jung Pil Lee),오기석(Kie Suk Oh) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.3

N/A Objective : The endometrial cancer can be divided into two large groups on the base of carcinogenesis according to the pathologic findings. The hormone induced cancer group(type 1) represents the cancers developed under the effects of unopposed estrogen. And the other group(type 2) can be developed by the mechanisms of divergent variable events such as mutations or gene deletions. These two different types show definite differences in clinical characteristics. Methods : Clinical features of the 43 patients who were diagnosed and were treated as endometrial cancer in Gynecologic department of Ajou University Hospital from June 1994 to November 2000 were evaluated according to the pathologic findings. 22 patients of type 1 and 17 patients of type 2 were classified and analysed statistically. Results : Age, cell types, grade, cancer stage, endometrial thickness, invasion depth of uterine walls were definitely different with statistic significance. The lymphovascular space invasion, the number of lymph node metastasis, pap smear of cervix, adnexal involvement, diabetes, hypertension, CA125, gravida, height were not different between two groups statistically in correlations. BMI shown marked difference but had no statistical significance. Conclusion : The classification of endometrial cancer into the two types is very significant because it can allow avoidance of preceding risk factors and can provide the alteration of treatment tendency and the expectation of benign or malignant prognosis, clinically.

초기 자궁경부암 근치적자궁적출술 후 치료실패 고위험 환자군에서 보조적 항암화학방사선요법의 역할

김영아(Young Ah Kim),유희석(Hee Sug Ryu),전미선(Mi Son Chun),장기홍(Ki Hong Chang),박영한(Young Han Park),오기석(Kie Suk Oh) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.10

목적 : 초기 자궁경부암(병기 IA2, IB, IIA) 환자에서 근치적자궁적출술과 골반림프절절제술 후에 치료실패율이 높은 고위험군에게 보조적 동시 항암화학방사선요법(GOG #109 protocol)에 따른 치료의 효용성을 알아보고자 하였다.연구방법 : 1994년 7월부터 1997년 6월까지 만 3년간 아주대학교 병원에서 초기 자궁경부암으로 진단 받고, 근치적자궁적출술 및 골반림프절 절제술을 시행한 63명의 환자 중에서 암세포의 골반림프절 전이, 자궁방 또는 절단면 침윤을 보인 15명을 대상으로 보조적 동시 항암화학방사선요법을 시행하고 치료효과를 전향적으로 임상 분석하였다. 보조적 치료는 수술 후 2-3주 이내에 항암화학치료로 시작하였으며 매 4주마다 총 4주기를 시행하였고, 치료 제 1일에 cisplatin 75mg/m2, 2일에서 5일까지 5-FU(1000mg/m2/d)를 주사하였다. 2주기 및 3주기 항암화학치료는 5주간의 방사선 치료와 같이 병용하였다.같은 기간동안 근치적자궁적출술과 골반림프절절제술 후에 재발 고위험 인자와 관계없이 추가 치료를 시행하지 않은 48명을 대조군으로 하여 재발율과 생존율을 비교 평가하였다. 치료 종료 후 추적 관찰 기간은 최소 24개월에서 51개월까지로 평균 37.3개월이었다.결과 : 전체 63명의 대상 환자 중에서 3명(4.8%)이 재발하였으며 이들은 모두 대조군으로 치료군과는 통계학적 차이가 없었다(p>0.05). 추적 관찰 중 환자 사망은 없었으며 무병생존율(relapse-free survival rate)은 치료군에서 100%, 대조군에서 93.8%로 이들간의 통계학적 차이는 없었다(p>0.05).결론 : 본 연구의 결과 근치적 수술 후 치료실패율이 높은 예후인자를 가진 자궁경부암 환자군에서 modified GOG #109 protocol에 준한 보조적 치료를 함으로써 재발율 및 무병생존율을 대조군과 유사한 수준으로 향상시킬 수 있을 것으로 생각된다. Objective : The purpose of this study was to evaluate the recurrence and survival rates after adjuvant concurrent chemoradiotherapy in high risk early cervical cancer(stage IA2, IB, IIA) patients treated by radical hysterectomy and pelvic lymphadenectomy(GOG #109 porotocols). Methods : We reviewed the charts of 63 patients who underwent radical abdominal hysterectomy and pelvic lymphadenectomy at Ajou University Hospital from July, 1994 to June, 1997 for early cervical cancer(stage IA2, IB, IIA). Concurrent chemoradiotherapy(CCRT) was performed in 15 patients with high risk factors such as positive pelvic lymph nodes, positive parametrial involvement, or positive surgical margins. Chemotherapy consisted of cisplatin(75mg/m2 on day 1) and 5-FU (1000mg/m2 on day 2-5) for 4 cycles every 4 weeks beginning 2 to 3 weeks after operation. The patients started pelvic radiotherapy with 2nd and 3rd cycle of chemotherapy concurrently. We compared the recurrence rate and survival rate with 48 patients who received no adjuvant therapy after radical hysterectomy and pelvic lymphadenectomy for early stage cervical cancer with or without risk factors. The mean follow up period was 37.3 months( range: 24- 51months).Results : Three of 63 patients(4.8%) had recurrent disease, all of whom didn't receive any adjuvant treatment postoperatively. There were no recurrence in patients with CCRT(0/15). However, all patients were alive until last follow up.Conclusion : This study shows excellent local control and relapse-free survival rates in the high-risk cervical cancer patients after CCRT which is similar results seen in control group. Postoperative adjuvant therapy, GOG #109, seems to be effective in high risk patients with good local control and survival rate. But due to small size sample and short duration of follow up, further follow up of a large number of patients is necessary.

인간자궁내막의 탈락막화 (Decudualization)에 있어서 TGF-$\beta$ (Transforming Growth Factor-$\beta$)의 역할

박동욱,최동순,김미란,황경주,조미영,안성희,민철기,유희석,Park, Dong-Wook,Choi, Dong-Soon,Kim, Mi-Ran,Hwang, Kyung-Joo,Jo, Mi-Yeong,Ahn, Seong-Hee,Min, Churl-K.,Ryu, Hee-Sug 대한생식의학회 2003 Clinical and Experimental Reproductive Medicine Vol.30 No.1

Objectives: To investigate the role of TGF (Transforming growth factor-$\beta$) involved in the paracrinic communication during decidualization between UEC (uterine epithelial cells) and USC (uterine stromal cells), we have employed a co-culture system composed of human endometrial epithelial and stromal cells in defined hormonal conditions. Design: In the co-culture, endometrial epithelial cells cultured in the matrigel-coated cell culture insert are seeded on top of the endometrial stromal cells cultured within a collagen gel. The co-culture was maintained for 48 hours under the following hormonal conditions: progesterone dominant condition (100 nM P4 and 1 nM E2) or estrogen-dominant condition (100 nM E2 and 1 nM P4). 10 ng/ ml HGF and/or 10 ng/ml TGF-$\beta$1 are added. Methods: RT-PCR is utilized to detect mRNAs quantitatively. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining are utilized to detect proteins in the tissue. Results: Prolactin mRNA is expressed in the co-cultured stromal cells under the progesterone dominant condition. TGF-$\beta$1 and its receptors are expressed in both the co-cultured epithelial and stromal cells irrespective of the steroid present, which is in contrast with no or negligible expression of TGF-$\beta$1 or its receptor in cells separately cultured. Both estrogen and progesterone significantly elevate the concentration of hepatocyte growth factor (HGF) in the conditioned medium of the co-culture with the value of 4, 325 pg/ml in E2-dominant and 2, 000 pg/ml in P4-dominant condition compare to 150 pg/ml in no hormone. In separately cultured stromal cells, administration of HGF induces the expression of TGF receptor 1 in both hormonal conditions, but induction of TGF receptor 2 is only manifest in the P4-dominant condition. Administration of TGF-$\beta$ and HGF directly induce the decidualization marker prolactin mRNA in separately cultured stromal cells. Conclusion: It is likely that steroid hormones induces prolactin mRNA indirectly by promoting the cell to cell communication between the stromal and the epithelial cells. TGF-$\beta$ and HGF are two possible paracrine mediators in the human endometrial decidualization.