Platinum 제제를 기본으로 한 화학요법에 실패한 난소암 환자에서 Taxol 구제요법의 효용성

김용범,박노현,김대연,김재원,송용상,유상영,강순범,이효표 대한부인종양 콜포스코피학회 1997 Journal of Gynecologic Oncology Vol.8 No.2

Background & Aims: Management of ovarian carcinoma presents most commonly by surgery and subsequent platinum-based chemotherapy, but most patients will have either residual or recurrent disease. Taxol, a new antimicrotubule agent, has been indicated as a salvage measure after failure of first-line or subsequent chemotherapy. The purpose of this study is to investigate the efficacy and toxicity of Taxol used as a salvage therapy. Materials & Methods : Between January 1994 and Jun 1996, 19 patients aged 38-64 years(median 52) with ovarian carcinoma were given Taxol-containing regimen. Taxol was administered at a dose of 135mg/㎡ intravenously with cisplatin or carboplatin every 3 weeks. The patients who treated with Taxol only were received 175mg/m2 intravenously with same interval. The median treatment cycle was 6.6 cycles(range, 3 to 15 cycles). Patient's response were evaluated with tumor marker(CA-125) and CT or MRI before and after chemotherapy. Responses and toxicities were defined according to the Gynecologic Oncology Group criteria. Results : The overall response rate was 26.3%(5/19), including 2 complete response(CR) and 3 partial response (PR). Better response was observed in patients who had complete response with prior platinum based chemotherapy(3/8, 37.5%) than who did not(2/11, 18.2%). The median duration of follow up was 10.8 months(range, 3 to 16 months). Neutropenia was the most frequent and does limiting toxicity. Conclusion : Taxol is useful agents in patients with previously platinum-sensitive patients with acceptible toxicity, but has limited role in refractory or relapsing cases. Further work is required to assess the optimal role of this drug in the management of ovarian carcinoma.

한국여성의 자궁경부암에서 인유두종바이러스의 감염 양상

김용범 ( Yong Beom Kim ),전용탁 ( Yong Tark Jeon ),서상수 ( Sang Soo Seo ),김재원 ( Jae Weon Kim ),박노현 ( Noh Hyun Park ),송용상 ( Yong Sang Song ),강순범 ( Soon Beom Kang ),이효표 ( Hyo Pyo Lee ) 대한산부인과학회 2003 Obstetrics & Gynecology Science Vol.46 No.4

목적 : 최근에 그 효용성이 확대되고 있는 DNA chip을 이용하여 우리나라 자궁경부암 환자에서 발견되는 고위험군 HPV 감염 빈도와 아형의 분포를 알아보고 동시에 자궁경부암의 각 조직병리학적 종류에 따라 발견되는 고위험군 HPV 아형의 빈도와 분포에 따른 차이의 여부를 알아보고자 하였다. 연구 방법 : 1998년 2월부터 2001년 2월까지 서울대학교병원 산부인과에서 자궁경부암 (FIGO stage Ⅰa1-Ⅱa)으로 자궁절제술 혹은 근치적 자궁절제술 Objective : To evaluate the prevalence and genotype of high risk HPV infection with oligonucleotide microarray based DNA chip in cervical cancer. Methods : The presence of HPV and its type were tested with oligonucleotide microarray based DNA chip in 84 s

난소암에서 HER-2/neu 유전자 증폭과 Platinum-based 항암화학요법 반응도와의 연관성에 관한 연구

김용범,박노현,이철민,김재원,송용상,강순범,이효표,노주원 대한부인종양 콜포스코피학회 1999 Journal of Gynecologic Oncology Vol.10 No.2

Background: The HER-2/neu proto-oncogene (also known as c-ErbB-2) encodes a 185 kD transmembrane glycoprotein with intrinsic tyrosine kinase activity. Many studies revealed the correlation between the aberrant overexpression of HER-2/neu oncogene and poor prognosis of the malignant tumors such as breast, stomach, colon, lung cancers. But the significance of HER-2/neu oncogene overexpression as a prognostic factor in ovarian cancer remains controversial. Objective: The aims of this study were to assess the prevalence of HER-2/neu oncogene amplification by polymerase chain reaction(PCR) and to evaluate the prognostic significance of HER-2/neu oncogene overexpression in terms of chemo-responsiveness and survival rate. Materials and methods: This study included 32 patients with advanced ovarian cancers(24 epithelial ovarian cancers, 2 Brenner tumors, 2 malignant mixed miillerian tumors, 2 granulosa cell tumors, 1 struma ovarii, 1 Krukenberg tumor). All patients had underwent staging laparotomy, and postoperative adjuvant chemotherapy with platinum-based combination chemotherapy. PCR was performed using tissues preserved in liquid nitrogen at the time of debulking operation. Overexpression of HER-2/neu oncogene was defined as being equal to or greater than 1.5 a.u. We analyzed whether the HER-2/neu overexpression correlated with chemoresponsiveness and 5-year survival rate(5-YSR). Result: HER-2/neu oncogene amplification was present in all of the ovarian cancers(32/32). Significant overexpression[gene copy number(GCN) ≥1.5 a.u.] was present in 13 of 32 ovarian cancers(41%) and 12 of 24 epithelial ovarian cancers (50%). The clinical response rate to chemotherapy in high copy group(GCN ≥ 1.5 a.u.) was 67%(8/12) and that of low copy group(GCN $lt;1.5 a.u.) was 92%(11/12)(p$gt;0.05). Pathologic response rate to chemotherapy was 0%(0/5) and 50%(3/6), respectively(p$gt;0.05). 5-YSR was 8% in high copy group and 25% in low copy group, but this difference was not statistically significant(p=7). Conclusion: HER-2/neu overexpression might be a poor prognostic factor, but this difference was not definitely elucidated by statistical analysis in this study. Larger scaled prospective randomized study is needed to define the prognostic significance of the HER-2/neu overexpression in ovarian cancer.

4 세 여아에서 발견된 질내 이물질 1 례

강순범,이효표,송용상,박노현,김용범,노주원,김문홍,김진오 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.10

Vaginal foreign bodies in children are often associated with intermittent vaginal disch-arge, vaginal bleeding and create a clinical scenario similar to that of certain cases of sex-ual abuse and isolated premature menarche. Intravaginal foreign body of especially long duration can pose a diagnostic dilemma, since a number of diagnostic modalities may fail to detect its existence. A 4-year-old girl who suffered from a bloody, malodorous vaginal discharge visited SNUH. She had had such problems for over a year and had been evaluat-ed by several gynecologists. Preoperative evaluations including ultrasound was performed and pelvis MRI strengthened the suspicion that some foreign bodies could be an etiologic factor. A vaginal inspection performed under general anesthesia with 0°endoscope and nasal speculum size no. 43 revealed $quot;pen top of ink pen$quot; lodged in her vaginal mucosa of posterior fornix area. We were allowed to remove a foreign body without trauma of genital tract by nasal forceps. We report a case of intravaginal foreign body in a 4-year-old girl with a brief review.

Platinum제제를 기본으로 한 화학요법 후 재발한 난소암 환자에서 Taxol 포함 항암요법의 효용성

강순범,이효표,송용상,김재원,박노현,김용범,이철민,김미하 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.9

난소암은 조기진단이 어려워 진단 당시 이미 진행된 경우가 많으며, 일반적으로 종양감축술 후 platinum 제제를 기본으로 한 항암화학요법이 표준치료법으로 사용되고 있다. 그러나 치료 후 재발된 난소암과 치료 중에 나타나는 약제에 대한 저항성이 난소암의 치료에 있어서 가장 중요한 문제로 대두되고 있으며, 이를 극복하려는 노력의 일환으로 Taxol등을 비롯한 새로운 약제의 개발이 이루어지고 있다. 저자들은 platinum 제제를 기본으로 한 화학요법 후 재발하거나 저항성이 있는 난소암 환자들을 대상으로, Taxol을 포함한 항암요법의 치료 효과 및 부작용을 연구함으로써 임상적 유용성을 평가하고자 하였다. 1994년 4월부터 1997년 10월까지 서울대학교병원에서 진행성 난소암으로 platinum 제제를 기본으로 한 화학요법 치료 후 재발하거나 저항성이 있는 환자 31명을 대상으로 하였으며, 이 중 platinum 반응군은 11명, platinum 저항군은 20명이었다. Taxol은 cisplatin 혹은 carboplatin과 병합한 경우는 135 mg/m2를, Taxol 단독요법을 시행한 경우는 175 mg/m2를 24시간 동안 정맥 주사하였으며 매 3주마다 반복하였다. 치료 결과의 평가는 매 cycle마다 종양 표지 물질로서 CA-125 및 CEA를 측정하여 변화 추이를 관찰하였으며, CT나 MRI는 화학요법 시작 전과 끝난 후에 시행하였고, 치료에 대한 반응 및 부작용은 GOG 기준을 적용하였다. 평균 7.4회(3∼12회)의 항암화학요법 후, 9명이 완전관해, 2명이 부분관해를 보여 전체 반응률은 35.5%(11/31)이었으며, Platinum 반응군은 54.5%(6/11), platinum 저항군은 25%(5/20)의 반응률을 보였다. 전체 환자의 추적검사 기간은 13.4개월(3∼40개월)이었고 치료반응 기간은 10.1개월(1∼22개월)이었으며, platinum 반응군은 15.5개월(11∼22개월)이었고 platinum 저항군은 8.3개월(1∼16개월)이었다. Grade 3 이상의 과립구 감소증이 20%에서 나타났고, 이 중 1예에서는 감염에 의한 고열 증상이 있었다. Grade 3 이상의 간독성은 8%, Grade 3 이상의 소화기계 부작용은 8%이었으며 기타 다른 Grade 3, 4 독성은 발생하지 않았다. Taxol을 포함한 항암요법은 진행성 난소암에서 platinum 제제를 기본으로 한 화학요법 후 재발하거나 치료에 실패한 환자들의 일부에서 유용한 치료법이다. 그러나 cisplatin 저항군에서는 반응군에 비해 효과가 낮았으며, 이러한 제한점을 극복하기 위한 연구가 필요하다. Second-line Salvage chemotherapy with Taxol Containing Regimen in Recurrent or Refractory Ovarian Carcinoma after Platinum-Based Chemotherapy. Objectives: This study is to investigate the efficacy and toxicity of Taxol containing regimen used as a salvage therapy. Methods: Between April 1994 and October 1997, 31 patients aged 20∼70 years (median 53) with recurrent or refractory ovarian carcinoma were given Taxol-containing regimen. Taxol was administered at a dose of 135 mg/m2 intravenously with cisplatin or carboplatin every 3 weeks. The patients who treated with Taxol only were received 175 mg/m2 intravenously with same interval. The median treatment cycle was 7.4 cycles (range, 3 to 12 cycles). Patient`s response were evaluated with tumor marker (CA-125) and CT or MRI before and after chemotherapy. Responses and toxicities were defined according to the Gynecologic Oncology Group criteria. Result: The overall clinical response rate was 35.5% (11/31), including 9 complete response (CR) and 2 partial response (PR). Better response was observed in patients who had response with prior platinum based chemotherapy (6/11, 54.5%) than who did not (5/20, 25%). The median duration of follow up was 13.4 months (range, 3 to 40 months) and the median progression free interval was 10.1 months (range, 1 to 22 months); 15.5 months (range, 11 to 22 months) in platinum sensitive group and 8.3 months (range, 1∼16 months) in platinum resistant group. The most common and dose limiting toxicity was neutropenia, and grade 4 toxicity occurred in 10% of courses. Conclusion: Taxol containing regimen is useful combination chemotherapy in patients with previously platinum-sensitive patients with acceptable toxicity, but has limited role in chemo-refractory cases. Further prospective randomized trials are required to assess the optimal role of this drug in the management of ovarian cancer.

젊은 여성에서 발생한 초기 자궁내막암에서 고용량 Megestrol Acetate의 치료 효과

김용범,김재원,박노현,이규창,이철민,송용상,이효표,최수희,강순범 대한부인종양 콜포스코피학회 1998 Journal of Gynecologic Oncology Vol.9 No.3

The effectiveness of progestogens in advanced and recurrent endometrial carcinoma has been widely accepted. But the use of progestogens in young women with early stage of endometrial carcinoma (Stage Ia) is controversial. Some authors reported that progestogens alone therapy improved or cured the endometrial pathology in young patients with early stage of endometrial carcinoma. The response to the progestogens has known to be better in cases of early stage, well-differentiated histologic type and narrow depth of invasion. We used the high-dose megestrol acetate (Megace ) as the primary treatment in four young women with early stage of endometrial carcinoma (Stage Ia) for the purpose of saving the fertility. We made the patients to have 320 ∼400 mg of Megace per day for 3 months, and then repeated the endometrial curettage for the purpose of finding changes of endometrial pathology. Three cases revealed no response to the Megace , so they were operated later. One case showed the resolution of endometrial pathlogy and delivered a baby following therapy. There have been no evidences of clinical recurrence in all cases. Even though the therapeutic efficacy is limited, high-dose therapy with megestrol acetate can be used as primary therapy in young women with early stage of endometrial carcinoma.

일반연제 발표 : 부인종양학 1 ; 말기 부인암 환자에서 MEGACE 요법의 효용성에 관한 연구

김용범,고창원,김재원,박노현,송용상,강순범,이효표 대한산부인과학회 1996 대한산부인과학회 학술대회 Vol.78 No.-

자궁경부상피내종양의 치료에서 환상투열요법 (LLETZ) 시행 후 잔류병변의 예측인자

김용범,박노현,이철민,김재원,송용상,강순범,이효표,김성일,심순섭 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.3

목적: LLETZ(Large loop excision of transformation zone)는 자궁경부상피내종양(CIN)의 정확한 진단목적 뿐만 아니라 치료목적으로도 사용되고 있다. 그러나 LLETZ 후 자궁경부내 잔류병변의 가능성 및 예측인자에 대하여 명확히 밝혀져 있지 않기 때문에, CIN 치료 방법으로서 LLETZ의 안정성, LLETZ 시술 후 어떤 경우에 자궁절제술 등의 추가 치료를 실시할 것인가에 대하여 논란이 있다. 따라서 본 연구에서는 LLETZ시술 후 잔류병변 여부를 예측할 수 있는 관련인자들을 확인하고 절단면 양성의 임상적 의의를 알아보고자 하였다. 연구방법: 1993년 8월부터 1995년 7월까지 서울대학교 산부인과에서 LLETZ 시행 후 자궁절제술을 시행한 133명을 대상으로 임상기록을 검토하였다. 잔류병변 양성이란 자궁절제술 후 최종병리학적 소견에서 CIN이나 침윤암 등의 잔류병변이 확인된 경우로 정의하였고, 잔류병변이 없는 경우를 LLETZ를 통한 치료에 성공한 것으로 하였다. 잔류병변의 존재 여부에 연령, 병변의 등급, 절단면의 상태 등의 인자들이 관여하는지 확인하였으며, 통계학적 분석 방법으로 Student t-test, χ2 test와 Fisher's exact test를 사용하였다. 결과: LLETZ 후 자궁절제술을 시행한 환자의 85.7%(114/133)에서는 잔류병변이 없었으나 14.3%(19/133)에서 잔류병변이 발견되었고 이 중 미세침윤암이 3례에서 확인되었다. 잔류병변이 없는 환자군의 평균연령은 42.5세(27-71세)인 반면 잔류병변이 있는 환자군의 평균연령은 49.1세(33-72)로서 유의하게 높았다(p=0.005). LLETZ 후 조직검사에서 절단면 음성인 군에서 잔류병변이 발견된 경우는 9.6%(9/94)이었고 절단면 양성인 군에서 잔류병변이 발견된 경우는 25.6%(10/39)로서 두 군간에 유의한 차이를 보였다(p=0.032). LLETZ 후 조직검사에서 CIN II인 군과 CIN III인 군에서 잔류병변이 발견된 경우는 두 군에서 모두 14.3%(2/14, 17/119)로서 두 군간에 차이가 없었다. 결론: LLETZ 후 절단면 양성 여부가 잔류병변의 존재 여부와 일치하지 않는 경우가 많으며, 폐경 이후의 연령이 많은 여성이나, 절단면 양성인 경우 등 잔류병변 양성 가능성이 높은 환자의 경우에는 보다 철저한 추적관찰 혹은 광범위 원추생검술이나 자궁절제술 등의 보다 적극적인 치료가 고려되어야 할 것으로 사료된다. Objective: Large loop excision of transformation zone(LLETZ) is gaining popularity as an alternative to other ablative or cone methods for the treatment of cervical intraepithelial neoplasia(CIN). The optimal management of CIN after LLETZ, however, remains controversial and the reliable predictors of residual disease after LLETZ have not been consistently identified. This study was performed to identify factors to predict residual disease after LLETZ. Methods: From August 1993 to July 1995, 133 patients who received subsequent hysterectomy after LLETZ in Department of Obstetrics and Gynecology at Seoul National University Hospital were retrospectively reviewed. Residual disease was defined as positive findings of CIN or further advanced findings in hysterectomy specimen. The age of patients, the severity of disease and the status of resection margin(RM) were analyzed for predictive values of residual disease. The Chi-square test, Fisher's exact test and Student t-test were used for statistical analysis. Results: The residual disease after hysterectomy was negative in 85.7%(114/133) and positive in 14.3%(19/133). Among 19 cases with positive residual disease, 3 cases were revealed to be microinvasive cervical cancer. The mean age of patients with no residual disease was 42.5 years(range; 27-71) and that of patients with residual disease was 49.1 years(range; 33-72). Nine out of 94 cases(9.6%) with negative RM and 10 out of 39 cases(25.6%) with positive RM in LLETZ had residual disease. Two out of 14 cases(14.3%) with CIN II and 17 out of 119 cases(14.3%) with CIN III in LLETZ had residual disease. The success of LLETZ which means no residual disease was influenced by the age of patients(p=0.005) and the status of resection margin of LLETZ(p=0.032). Conclusion: The negative resection margin in LLETZ does not always guarantee that there is no residual disease. Close preoperative workup and more aggressive treatment plan(wide conization or hysterectomy) should be considered in patients who has higher possibility of positive residual disease such as old age and positive resection margin in LLETZ.

재발성 자궁경부암의 임상양상에 관한 고찰

김용범,김정화,박노현,이철민,김재원,송용상,강순범,이효표 대한부인종양 콜포스코피학회 2000 Journal of Gynecologic Oncology Vol.11 No.4

Objective: Cervical carcinoma can be adequately treated when diagnosed in early stage. However, the progsnosis of recurrent cervical carcinoma remains poor. The objective of this study is to analyze the prognostic factors affecting survival of recurrent cervical carcinoma patients. Methods: The clinical characteristics of eighty-three patients who were diagnosed as recurrent cervical carcinoma from Jan 1988 to Apr 1999 were retrospecively analyzed, The initial FIGO stage of II (67.5%) was the most predominant. There were 9.6% of adenocarcinoma, 9.6% of adenosquamous carcinoma, and 1.2% of small cell carcinoma other than squamous cell carcinoma (77.1%). Diagnosis of recurrence was made by histopathologic examination, CT/MRI, Chest X-ray, intravenous pyelography. The recurrence was detected on routine follow-up in 41.0%. Comparison of Kaplan-Meyer survival curve was made with log-rank test, P-value less than 0.05 was regarded as statistically significant. Results: Overall 2-year survival rate was 37.3% and median survival was 17 [13-21, 95%CI] months. Four patients survived more than 5 years. There was no significant difference among survival rates of histopathologic types, Survival rates of patients with central recurrence were significantly higher than those of lateral and distant recurrence (P=0.009). 13 patients who did not receive any treatment after recurrence survived only for 9 [7-11] months and the survival of those were significantly lower than the survival of patients who received treatment of any kind (P$lt;0.001). The treatment modalities after recurrence did not affect survival. Conclusion: We conclude that regular follow-up of cervical carcinoma patients is very important in detecting recurrence and that treatment after recurrence does affect survival of patients.

외음부에 발생한 파제트병 4 예

강순범,이효표,송용상,김재원,박노현,김용범,이철민,박인애,임경실 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.5

외음부에 생기는 파제트병은 매우 드문 외음부 종양으로써 높은 재발율을 보이는 것으로 알려져 있다. 파제트병은 apocrine선을 포함하고 있는 신체 어느 부위에나 생길 수 있으며 비교적 느리게 진행하는 상피내 종양이다. 전세계적으로 수백례가 보고되고 있으나 정확한 발생 빈도는 알려져 있지 않으며 유방외에서 생기는 파제트병의 대부분은 외음부에서 생기는 것으로 보고되고 있다. 외음부 파제트병은 대개는 상피내에만 국한되어 있으나 약 20%에서는 선암을 동반하고 있으며, 약 30%에서는 다른 장기의 악성 종양을 동반하는데 주로 유방이나 비뇨생식기계 또는 위장관계에서 생기는 것으로 알려져 있다. 외음부 파제트병의 치료는 광범위 병변의 절제술[wide local excision]로 충분하며, 만일 동반된 선암이 있는 경우에는 광범위 외음부 절제술[radical vulvectomy]과 동측 서혜부 림프절 절제술[ipsilateral inguinal lymphadenectomy]을 시행하여야 한다. 외음부 파제트병은 그 빈도가 매우 적으며 외음부의 다른 종양들과는 다른 임상병리학적 특성을 가졌기에 저자들은 1988년부터 1998년까지 본 병원에서 경험한 외음부 파제트병 4예를 문헌고찰과 함께 보고하는 바이다. Extramammary Paget`s disease of the vulva is an uncommon vulvar neoplasm that is a slowly progressive intraepithelial carcinoma and develops in an apocrine gland-bearing areas of the body. Several hundred cases have been described worldwide, however the precise incidence remains unclear. Paget`s disease of the vulva most often presents as an intraepithelial lesion, but underlying adenocarcinoma with this process in up to 20% of cases. A second synchronous or metachronous primary neoplasia is associated with extramammary Paget`s disease in about 30% of patients. The most common presenting symptom is vulvar pruritus, and typical finding is erythematous, eczematous lesions of the vulva. Vulvar Paget`s disease is often multifocal, and histologic evidence of disease is frequently greater than is clinically apparent. So, frozen-section surgical margin evaluation is utilized as a guide to extent of excision. Treatment of Paget`s disease requires wide local excision and if there is an underlying adenocarcinoma, radical vulvectomy is required, which should be combined with at least an ipsilateral inguinal-femoral lymphadenectomy. Due to its rarity and different disease patterns, we present a clinicopathologic study of four cases seen at our hospital from 1988 to 1998.