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Volume 26(3); 1994
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Original Articles
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Clincial Analysis of Gastric Cardia Cancer
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Jin Pok Kim, Hwan Young Yoo, Song Cheol Kim, Han Kwang Yang
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J Korean Cancer Assoc. 1994;26(3):361-369.
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Abstract
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- Gastric cardia cancers comprise gastric cancers which involve stomach of distal 2cm from gastroesophageal junction. It has been reported that cardia cancer has relatively poorer prog- nosis than gastric cancer of the other sites. To evaluate clinicopathological characteristics of gastric cardia cancer and to determine prognostic factors, we analyzed retrospectively 198 pa- tients who underwent operations for gastric cardia cancers between 1970 and l991 and had the following results. Gasric resection was performed in 176 patients. The ratio of gastric cardia cancer to gastric cancers of the other sites was slightly decreased in 1980s than in l970s (over- all 3.8% of gastric cancers). Gastric cardia cancer had poorer 5-year survival rate than those of gastric cancers of other sites (34.2% for cardia, 38.5% for fundus, 54.1% for body, 48.9% for an- trum). In cardia cancer, 2.5% was early gastric cancer, 89.3% had more than serosal invasion, 66. 5% had positive lymph node involvement and 75.2% were in stage III 4 IV. There was esophageal involvement in 33.5%; despite clear proximal resection mergin on frozen biopsies, there were positive resection margin of 21.4% (3/14) in cases with resection margin of less than 2 cm and 3.7% (6/162) in cases with resection margin of 2cm or more than 2cm (p<0.05, Fisher's exact test). These results suggest that the length of proximal resection margin should be at least 2 cm to get a cancer-free proximal resection margin in gastric cardia cancer. Multivariate analysis revealed that depth of invasion, length of proximal resection margin and lymph node metastasis were significant prognostic factors. We conclude that poorer prognosis of gastric cardia cancer is due to more advanced stage at the time of diagnosis. Therefore, to improve the survival of gastric cardia cancer, better means of early diagnosis should be developed.
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Treatment of Advanced Gastric Cancer with Oral UFT and Leucovorin
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Seong Kyoon Cheong, Ki Chan Kim, Yeul Hong Kim, Sang Won Shin, Jun Suk Kim
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J Korean Cancer Assoc. 1994;26(3):369-377.
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Abstract
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- We conducted a phase II trial of oral administration of UFT and leucovorin in patients with advanced gastric adenocarcinoma. Sixteen patients entered on this study from September 1992 to November 1993. The treatment regiman consisted of oral administration of UFT (480 mg/m/day), and leucovorin (25 mg/ m(2)/day) for 21 consecutive days. The dosage of UFT was adjusted after each treatment and the treatment was repeated every 4 weeks. The total number of administered treatments in 16 patients was 55 and the median number was 4. Among 14 evaluable patients, 1 patient (7.2%) had a complete response and 3 patients (30%) achieved paritial response resulting in an overall response rate of 28.5%. The median duration of response was 15 weeks (4+- 48+). The median survival time for all 16 patients was 24 weeks (4+- 48+). Gastrointestinal toxicity was common and toxicity over grade 3 included diarrhea in 7 patients (43.8%), mucositis in 2 patients (12.5%) and anorexia, nausea and vomiting in 1 patient respectively. Grade 1 leukopenia was observed in 3 patients (18.8%). In conclusion, oral administration of UFT and leucovorin in patients with advanced gastric cancer who have poor general condition seems to be comparable to ther chemotherapy regi- mens in efficacy and toxicity.
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Induction Chemotherapy and Surgery in Locally Advanced Stomach Cancer Showing Pancreas Involvement
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Kyung Hee Lee, Jin Hyuk Choi, Sun Young Rha, Hye Ran Lee, Nae Chun Yoo, Ho Yeong Lim, Hyun Cheol Chung, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim
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J Korean Cancer Assoc. 1994;26(3):377-385.
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Abstract
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- Gastric cancer is the most common malignancy in Korea. Cure for patients with gastric carcinoma can be achieved only by radical surgery. From August 1988 to May 1992, 25 patients with locally advanced unresectable gastric cancer received 5-FU(Fiuorouracil) + adriamydn + mitomycin-c or 5-FU + cisplatin based induction chemotherapy before surgem. The partial response rate after me- dian 3 cycles of induction cemotherapy was 52%, stable disease 12%, progressive disease 36%. Gastric resection was performed in 18 patients(72%); 13 patients(52%) underwent radical surgery and 5 patients(20%) underwent palliative surgery. Median survival of the patients who underwent cura- tive and palliative surgery was 24. 2 and 27 months, respectively. However, median survival of the patient who didnt undergo any surgery was only 6.5 months. The difference of median survival between curative surgery and none surgery group were significant statistically(P<0.03). Side effects of induction chemotherapy were acceptable and there were no life threatening toxicities In this study, half of the patients can undergo curative surgery after induction chemotherapy. We observe the long term survival in some patients after induction chemotherapy and surgery in loco-regionally advanced gsstric cancer. This therapeutic approch for the locally advanced stomach cancer seems to be feasible. But, prospective tandomized clinical trial is warranted in the future.
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Are There Any Clinicopathologic Differences Between Mucosal And Subumucosal Cancer Of Stomach ?
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Byung Wha Chung, Cho Hyun Park, Seong Taek Oh, Jong Soe Lee, Woo Bae Park, Byoung Kee Kim, Sang Yong Choo, In Chul Kim
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J Korean Cancer Assoc. 1994;26(3):385-392.
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Abstract
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- From 1980 through 1991, 17Z9 patients underwent operation for gastric cancer at Department of Surgery, Catholic University Medical College in Seoul, Korea. Three hundred and twelve patients (18.0%) were early gastric cancer (EGC): mucosal cancer were 107 cases (34.3%) and submucosa1 cancer were 205 cases (65.7%). The purpose of the present study was to compare the clinicopathologic features of EGC between mucosal cancer and submucosal cancer. Submucosal cancer developed in older age than mucosal cancer (average 55 vs 49 years old). No differences, however, were noted in clinical manifestations and duration of symptoms. Macroscopically, elevated lesions (type I or IIa predominant) were frequently encountered in submucosal cancer than mucosal cancer (24.6 vs 9.7%). Histologically, differentiated carcinoma or intestinal type by Lauren's classification was more common in submucosal cancer than mucosal cancer. The incidence of lymph node metastasis of EGC was 15.1% (47/312): 2.8% (3/ 107) in mucosal cancer and 21.5% (44/205) in submucosal cancer. Lymph node involvement of submucosal cancer was significantly higher in patients with elevated lesions (35.3%) than in depressed lesions (13.5%). No lymphatic or venous invasion was noted in mucosal cancer. In submucosal cancer, however, incidence of venous and lymphatic invasion was 7.2% and 20.3%, respectively. Kaplan-Meier estimates for 5-year survival were 98% for mucosal lesions and 79% for submucosal lesions (overall 5-year survival rate; 86.3%). The Syear survival rate in patients of submucosal cancer with lymph node metastasis was only 60% comyared with 88.5% in pa- tients of submucosal cancer without lymph node involvement. All recurrent cases were submucosal cancer patients. Six out of the 9 recurrent patients were macroscopically elevated type and had lymph nade metastasis. The authors conclude that there is definite difference in terms of clinicopathologic findings between mucosal and submucosal cancer of stomach even though EGC includes both lesions by definition. So, therapeutic approach of submucosal cancer should be different from mucosal cancer.
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Expression of p21 Protein in Benign and Malignant Colorectal Tumors
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Ki Young Sung, Jung Soo Kim, Suk Kyun Chang, g Soo Chun, Sang Yong Choo
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J Korean Cancer Assoc. 1994;26(3):399-409.
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- Tumorigenesis from the benign and precancerous lesion has long been thought to be a multistep process. Among them, point mutation of ras oncogene was studied in several investigations as an initial event of tumorigeriesis of human colorectal cancer. Ras oncogene encoded protein product p21 has been known to regulate cell proliferation and differentiation by p21 GTP(guanosine 5-triphosphate) or GDP(guanosine diphosphate) complex with point mutation. Activation of cellular ras genes is caused by single base mutation resul- ting in sn amino acid substitution yielding p21 species with increased transforming ability. Immunohistochemical and molecular cytogenetic studies of colon and rectal neoplasms indicat- ed that in 40-50% of cases mutated ras oncogenes can be identified. But, the function of p21 has not been known precisely, yet. We undertook the immunohistochemical study of the ras p21 protein product in a series of normal colorectal tissues, benign tumors, colorectal cancers and metastatic lymph node tissues with K-ras and H-ras monoclonal antibody. Benign tumors were divided into three groups by dysplasia, size and pattern of nuclear arrangement and mucinous component in cytoplasm. Malignant tumors were dassified into 4 groups by Astler Collers modification of Dukes classifi- cation. The purpose of this study was to find out the importance and clinical application of malignant teansformation of benign tumors by detection of expression of p21 encoded by K-ras or H-ras oncogene. The results were obtained as follows: 1) The expression of the p2l of K-ras oncogene in normal tissues, benign tumors, malignant tumors and metastatic lymph nodes were 13.3%, 34.8%, 40.2% and 20.0%, respectively. And ex- pression of the p21 of H-ras were 13.3%, 50.7%, 16.7% and 35.0%, respectively. 2) The expression of the p2l of K-ras and H-ras in benign tumor was divided into 3 groups. And the rate of the group 1 showed lowest rate as 11.1% and 27.8%. The expression rate was in- creased to 40.0% and 80.0% in group 2, 61.5% and 69.2% in group 3. 3) The expression of the p21 in colorectal cancer was slightly different in various stages using the K-ras monoclonal antibody 50%, 50%, 33.3% snd 36%, repectively. But, the result of H- ras p21 was varied 58.3%, 70%, 70% and 64%, respectively. 4) In according to the differentiation of the colorectal cancer, the expression of the p2l K-ras was 44.4% in well differentiation group, 34.2% in moderate group, 46.1% in poorly group. In the case of p21 of H-ras, 75.0% in well differentiated group, 63.2% in moderate differentiated group and 53.9% in poorly differentiated group were evaluated. 5) In a point of intensity of staining, the proportion of strong stained specimen was slightly different in each group, but there was no significant discrimination statistically. With above results, authors considered that ras oncogene encoded protein product p21 plays an important role in colon and rectal carcinogenesis at the early stage, especially in the pro- gression of adenoma, and may be useful in early detection and prediction of progression of colorectal cancer.
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The Recurrence of Breast Cancer after the Breast Conservation Surgery
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Ji Yeon Kim, Eil Sang Chang
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J Korean Cancer Assoc. 1994;26(3):415-425.
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- Breast cancer, like many other cancers, often follows a tortuous course marked by remissions and subseguent recurrences and, its disease free interval is of varying duration. There are several clinical factors which might be associated with recurrence of breast cancer such as tumor size, axillary 1ymph node involvement, histologic type, patient age and selected treatment modalities. But it is not yet settled that a certain factor closely related with recurrence among those prognostic factors. For this reason, we had carried out this clinical study for the purpose of knowing such factors during the period from March of 1990 to February of 1993 at department of Surgery, College of Medicine, Chungnam National University. 50 cases out of l41 breast cancer patients who had recieved the breast conservation surgery were elected for this study. By the time of follw-up, recurrence had occurred of 7 of those 50 patients, for an incidence of 14%. The sites of vast majority of locoregional recurrence at the time of discovery were interpectoral nodes and remnant breast. The supraclavicular nodes, contralateral breast and skin of forearm were the sites of systemic recurrence. The most common symptoms of reccurence at the time of discovery was the palpable mass, and the others were erythematous skin change on forearm. But, in one case, there was not any symptoms except that a certain recurrence had been suspected on mammographic finding. The tumor size lesser than 2 cm(T2)had a recurrence rate af 8.3%, compared with 13.6% for those larger than 2 cm(T,). The rateof recurrece for N, N, and N were 10.3%, 13.3% and 33.3%, respectively. The recurrence rate according to treatment modalities were 7.7% in surgery with chemotherapy group, 20% in combination of surgery, chemotherapy and Tamoxifen, 14.3% in combination of surgery, chemotherapy and radiotherapy. But, there was not noted any recurrence in patients with combination of surgery, chemotherapy, radiotherapy and Tamoxifen. The disease free intervals were more shorter in larger tumor size, more involvement of axillary lymph nodes, and in the invasize lobular carcinoma on histopathology. But, the interval was not related with the patients age and the radiotherapy.
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Multiple Primary Cancers Associated with Lung Cancer
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Won Young Huh, Han Sik Kim, Eun Hwa Kim, Soon Heung Lee, Min Chul Kim, Kwi Wan Kim, Hye Kyung Lee, Kwang Min Lee
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J Korean Cancer Assoc. 1994;26(3):425-431.
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Abstract
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- We experienced 6 cases of multiple primary cancers associated with lung cancer and report these with a brief review of the literature. During 13 years and 7 months from January 1979 to July 1993, 1312 cases of primary lung can- cer were registered at the Presbyterian Medical Center. Among them, 6 cases were multiple primary cancers compatible with Warren and Gates Criteria. We reviewed the clinical characteristics of theses 6 cases retrospetivly of the basis of medical record. We analyse these 6 cases as below; 1) The incidence of multiple primary cancers associated with lung cancer was 0.46%. 2) Male: female ratio was 5: l. 3) The average time interval between the first and the second cancer was 3.98years. 4) The involved sites were aerodigestive tract in 5 cases and endometrium in 1case. 5) Above 5 cases had heavy smoding history. According to the analysis of our 6 multiple primary cancers associated with lung caner, there seems to be a tendency of developing secondary cancers along the aerodigestive organs which are contiguous with lung. Although we cannot find-out the common etiologic relationship, 5 cases out of 6, has a heavy smoking history. We believe that it is mandatory to have nationwide statistics of mutiple primary cancers associated with lung cancer and to sesrch for the common etioloies, if any.
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Grnulocyte Colony - Stimulating Factor , Filgrastim ( G - CSF , Filgastrim ) in Acute Leukemia after Remission Induction Chemotherapy
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Cheol Won Suh, Sung Bae Kim, Sang Hee Kim, Young Ran Chae, Byoug Soon Doh, Sang We Kim, Myung Ju Ahn, Kyoo Hyung Lee, Jung Shin Lee
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J Korean Cancer Assoc. 1994;26(3):431-438.
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Abstract
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- Objectives
Colony stimulating factors have been shown to accelerate recovery from severe neutropenia after intensive chemotherapy. To prove its clinical effectiveness, we conducted controlled study to administer G-CSF in acute leukemia after induction chemotherapy. Methods: Forty patients with newly diagnosed and relapsed or refractory acute leukemia after remission induction chemotherapy were randomly assigned to one of two groupa (20 G- CSF treated group, 20 control grouP). Treatment with G-CSF(200 ug/m(2)/d) was started 48 hours after the end of chemotherapy and continued until the neutrophil count rose above 1,500 /mm(3). Results: Treatment with G-CSF shortened neutropenic period after chemotherapy, i.e., median duration of neutrophil counts less than 1,000/mm(3) was 21 days in control group and 12 days in G-CSF treated group. The incidence of infection was 80%in control group, 70% in G-CSF treated group, but it did not show any statistically significant difference. Microbiologically documented infection was 40% in control group, 20% in G-CSF treated group. Febrile periods and duration of antibiotic administration were decreased to 7 days and 18 days respectively. In G- CSF treated group, two Patients reported mild bone pain. There was no evidence that G-CSF could increase remission duratian and survival. Conclusion: It appears that recombinant G-CSF is safe and useful in neutropenic patients after intensive chemotherapy, accelerating neutrophil recovery and thereby reducing the incidence of documented infection and duration of antibiotic ad#ministration.
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Neoadjuvant Chemotherapy Combined Carboplatin in High Risk Carvial Cancer
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Ho Sun Choi, Ji Soo Byun, Woong Ki Chung
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J Korean Cancer Assoc. 1994;26(3):438-445.
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- Objective: Survival of patients with bulky cervical cancer treated with surgery or radiotherapy has been poor. This has led to the another therapeutic modality. Neoadjuvant chemotherapy with cisylatin combination has been employed extensively. Carboplatin is an an- alog of cisplatin with minimal nephrotoxicity and neurotoxicity at conventional dosage. The purpose of this study was to assess the local response and toxicity of carboplatin combination therapy for high risk cervical cancer. Methads: Neoadjuvant chemotherapy with carboplatin, vinblastin, bleomycin combination(20 patients) or cisplatin, vinblastin, bleomycin combination (20 patients)were tried to high risk squamous cell cancer of the uterine cervix. Randomization was well balanced for age, clinical stage and histologic type. Both drugs were given every 21 days with carboplatin 300 mg/m, vinblastin 4 mg/m(2), bleomycin 20 mg and cisplatin 75 mg/m, vinblastin 4 mg/m(2), bleomycin 20 mg. Results: The response rate of carboplatin combination and cisplatin combination were 25% and 30% of patients. The major toxic effects for carboplatin combination and cisplatin combination included nause and vomiting in 70% and 80% of patients, leukopenia in 40% and 60%, thrombocytopenia in 25% and l0%, and anemia in 35% and 40%, respectively. Conclusion: The activity of carboplatin combination for high risk cervical cancer is similar to the activity of cisplatin combination. However, the toxicity of the former is substantially better than that of the latter.
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p53 Mutationas and Human Papiloma Virus Infections in Carcinoma of the Uterine Cervix in Korean Women
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Youl Hee Cho, Bong Yoon Kim, Yong Kyun Paik, Jin Woo Kim
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J Korean Cancer Assoc. 1994;26(3):445-460.
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- Inactivation of two tumor suppressor gene products, P53 and pRb, either by complex formation with the E6 and E7 proteins of oncogenic Human papilloma virus (HPV) or by mutations of the two tumor suppressor genes is known as an important step in carcinogenesis of the uterine cervix. Some experiments with established cervical cancer ceIl lines have confirmed this hypothesis. The present study was designed to clarify the association between p53 mutation and oncogenic HPV infection in primary carcinomas of the uterine cervix. Thirty primary cervical cancer tissues were examined for the presence of HPV DNA by polymerase chain re- action (PCR) with Ll consensus primers, HPV type 16 specific primers, and type 18 specific primers. With LI consensus primers, 25 (83%) of 30 were positive, with HPV type 16 specific primers, 16 (53%) were positive, and with HPV type 18 specific primers, 5 (17%) were positive. Mutations in the highly conserved regions of p53 gene were further examined by PCR-single strand conformation polymorphism (SSCP) and direct sequencing method. Point mutation was detected in only one case which was positive for HPV type 18. The mutation was an AAA to TAA transversion at codon 101 of exon 4, resulted in nonsense mutation. These observations suggest thst, in contrast to data derived from established cervical carcinoma cell lines, inactivation of the P53 gene by sllelic losses or by point mutations is infrequent in clinical samples of carcinomas tissues of the uterine cervix irrespective of the presence or absence of HPV infection.
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Clinical Significance of Endometrial Cavity Fluid Detected by Ultrasonography in Patients with Gynecologic Neoplasm
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Keun Jai Yoo, Soo Nyung Kim, In Jae Cho, Doo Ho Kim, Hae g Jeon, Jeong Hee Park
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J Korean Cancer Assoc. 1994;26(3):460-466.
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Abstract
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- There are a number of different causes of endometrial fluid collections. Hematometra, hematocolpos, pregnancy and its complications, pelvic inflammatory disease, menstruation or exogenous estrogen administration have been reported to cause uterine fluid collections. The sonographically detected endometrial cavity fluid in the postmenopausal women has been described as indicative of uterine malignancy. The purpose of this study was to determine whether sonographic detection of the endometrial cavity fluid might be useful in the evaluation of gynecologic neoplasm. The results were as follows; 1) The sonographic detection rate of endometrial fluid in endometrial hyperplasia, endome- trial cancerm uterine myoma, cervical cancer, benign ovarian tumor were 33%(8/24), 50% (3/6), 11%(7/66), 9%(1/l1), 10%(l/10) respectively. 2) The sonographic detection rate of endometrial cavity fluid in vaginal bleeding was 56%(66/ 117) which was not significantly higher than that of other sy mptoms. 3) The sonographic detection rate(37%) of endometrial fluid in endometrial hyperplasia and cancer was significantly higher than that of other gynecologic neoplasms(10%)(P<0.05). 4) The frequency(10/1l) of vaginal bleeding in endometrial hyperplasia and cancer with endometrial cavity fluid detected by ultrasonography was significantly higher than that of other gynecologic neoplasms(P < 0.05). 5) The amounts of endometrial cavity fluid(mean+1SD) were 1.76+-1.35ml in endometrial hyperplasia, 2.33+-1.16m1 in endometrial cancer, 1.76+-1.35ml in uterine myoma, 8.00+-0.00ml in cervical cancer and 1.000.00ml in benign ovarian tumor. 6) In premenopausal and postmenopausal women, endometrial fluid collections were found in 15(18%) and 5(15%) cases respectively and there was no significant difference between the two groups.
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DNA Content and Ki - 67 Antibody Expression by Means of Image Analyzer for Laryngeal Lesions
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Hyung Ro Chu, Sun Hee Lee, Jong Ouck Choi, In Sun Kim
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J Korean Cancer Assoc. 1994;26(3):466-474.
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Abstract
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- The laryngeal epithelial cell kinetics of 26 laryngeal lesions(invasive squamous cell carcinoma 14, epithelial hyperplasia 5, laryngeal nodule 7) were studied by immunohistochemical analysis with the monoclonal antibody Ki-67, which reacts with a nuclear antigen in proliferating cells using paraffin embedded tissue. For DNA analysis, touch imprint with fresh biopsy specimens were stained with Feulgen and analyzed by image analyzer in 22 cases. 1) The positive nuclear area of Ki-67 were 32.65+-11.59% in invasive squamous cell carcino- ma, 20.14 +- 3.38% in epithelial hyperplasia and 11.66+ 3.02% in laryngeal nodule. 2) DNA aneuploidy was found in 7 cases of 10(70%) invasive squamous cell carcinomas, 2 cases of 5(40%) epithelial hyperplasia and none of laryngeal nodules. 3) Average proliferative index(S phasa+ G2/M phase) was 24.32+- 1l.33% in spuamous cell carcinama, 13.09 +- 10.90% in epithelia1 hyperplasia and 4.50 +- 1.19% in laryngeal nodule. As the results, the measurement of the DNA content and Ki-67 positive nuclear area on the small biopsy obtained by microscopic surgery used as effective factors predicting prognosis.
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Comparison of Serum Prostate Specific Antigen and Pathologic Findings on Patient with Benign Prostatic Hyperplasia
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Sung Goo Chang, Chur Chill Sin, Choong Hyun Lee, Ju Hie Lee, Soo Eung Chai
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J Korean Cancer Assoc. 1994;26(3):474-484.
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Abstract
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- Prostate specific antigen(PSA) is a serine protease produced by both benign and malignant prostatic epithelium that can be measured in serum samples by immuoassay. Although recent studies suggest that serum PSA may be useful in the early detection of prostate cancer, it is known that PSA elevations occur in men with benign prostatic hyperplasia and that men with prostate cancer can have normal PSA leveL We evaluated serum prostate specific antigen and pathologic findings on patient with benign prostatic hyperplasia. The most significant factor affecting high serum PSA levels in patient with B.P.H. was P.I.N. Identification of PIN will be helpful to detect early prostatic cancer because PIN is consid- ered a precursor of prostatic cancer.
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Anti - tumor Effect of Mycoplasma hominis on Transplanted Sarcoma 180 in Mice
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Mu In Park, Kwang Hyuk Kim, Myung Woong Chang
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J Korean Cancer Assoc. 1994;26(3):484-495.
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Abstract
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- Sarcoma 180(S.180) tumor cells were transplanted to the peritoneal cavity and subcutaneous tissue of the inguinal region of mice, and then, Mycoplusma kominis were inculated into the peritoneal cavity of the mice 7 times. Inhibitory effect of tumor growth, effect of life prolongation, and changes of T cell subsets in the spleen, and changes of phagocytic rate of the macro- phages were examined. The growth of S. 180 in the peritoneal cavity was suppressed and the survival rate of those mice was increased in the group of mice inoculated with M, hominis after transplantation with S. 180. The growth of tumor was suppressed and the suppression rate of the tumor growth was 43.6% in the group inoculated with M. hominis after transplanta- tion with S. 180. In the spleen, the number of total T cells and T helper cells of each study groups was not different from that of the control group. In the group, however, inoculated with M. #homi#nis alone and the group preinoculated with M. hoinis 7 times before transplantaton with S, 180, T suppresor cells were decreased in number. In the spleen, in both group transplanted with S. 180, and inaculated with M. hominis after 7 days, and the group transplanted with S. 1SO after M. hominis was inoculated 7 times, the number of NK cells was increased. In other groups, however, the number of NK cells was decreased. The rate of phagocytosis of peritoneal macrophage from the mice inoculated with M. kominss was increased. The titers of serum antibody against M. hominis in the group of mice inoculated with M. hominis at different times after transplantation with S. 180 were increased from 320 to 1280 folds. All above results suggest that the tumor growth was inhibited by inoculation with M. hominis in the mice transplanted with S. 180., and propose that the tumor growth inhibition is not caused by the changes of number of T cell subsets but by number of NK cells and activity of macrophages.
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Phase 1b Clinical Trial and Pharmacokinetic Evaluation of Recombinant Human Granulocyte - Macrophage Colony
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Jae Kyung Roh, Jin Hyuk Choi, Hyung Keun Roh, Sun Young Rha, Kyung Hee Lee, Hye Ran Lee, Jee Sook Hahn, Pum Soo Kim, Byung Soo Kim
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J Korean Cancer Assoc. 1994;26(3):495-510.
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Abstract
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- To define the clinical safeties and hematologic effects of subcutaneously administered yeast- derived recombinant human granulocyte-macrophage colony stimulatina factor(rh GM-CSF, LBD-005h and to determine the maximally tolerated dose(MTD) and the pharmacokinetics. Sngle arm open non-randomized phase Ib study was carried in 15 cancer patients#(14 patients evaluable) with chemotherapy induced bone marrow depression. Rh GM-CSF by once-daily subcutaneous administration to groups of 3-6 patients at doses of 50, 100, 150, 250, 350, 500, 700 ug/m/d for 10 consecutive days was escalated unless greater than WHO grade III toxicites were observed. Intrapatient dose escalation was permitted. Clinical safeties and toxicities were observed with frequent hematologic monitering. Blood and urine were collected on day 1, and 8 of rh GM-CSF administration to evaluate the parmacokinetic parameters. Of the 15 enrolled patients, 14 patients were evaluable. Male to female ratio was 8: 6 with median age 32 y-o(10~70 y-o). Seven patients had osteosarcoma, 2 malignant lymphoma, 2 gastric carcinoma, 2 lung cancer and 1 had uterine leiomyosarcoma. The total administered cycles of rh GM-CSF were 24. At each dose step, 3 patients were treated with exception of 6 patients at 500 ug/m/d dose. At all the doses administered, fever and flue-like syndrome were common side effects. Grade I fever and flue-like syndrome 50~150 pg/m dose, and grade II fever flue- like syndrome were observed at the dose of grater than 250 u/m(2)/d dose. Even at the 700 ug/m(2)/ d dose, no greater than grade III toxicities were observed. Leucocytosis were dose dependent with 120-480% increment of baseline. Pharmacokinetic parameters are as follows; Cmax were dose dependent(0.42-11.7 ng/ml) with 2-4 hours of Tmax. AUC were also dose dependent(3.93~87.9ng.hr/ml) with sustained serum levels(0.2-2ng/ml) up to 12 hours after rh GM-CSF administration. Urinary excretion(0-24 hours) after GM-CSF was less than 1% of administered dose. Yeast-derived rh GM-CSF induces leucocytosis in the dose range of 150~500ug/m(2)/d with tolerable side effects. Subcutaneously administered rh GM-CSF has sustained serum levels up to 12 hours after administration. The doses of 150-500 ug/m/d would be appropriated for the further trials.
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Therapeutic Implication of Intracavitary Instillation of Interferon-alpha-2b in Advanced Solid Tumors
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Yeul Hong Kim
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J Korean Cancer Assoc. 1994;26(3):510-519.
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Abstract
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- Malignant pleural effusions and ascites are distressing complications in solid cancer patients with considerable management problems. Intracavitary immunotherapy has been studied recently in a variety of solid tumors that otherwise might be incurable. Using the intraperitoneal administration of a cytokine, such as the interferons and the interleukins, some complete regressions of tumors have been documented. But those trials were applied for malignant lesions that are isolated to the peritoneal cavity, such as residual ovarian cancer. To evaluate the clinical implications of intracavitary interferon-alpha-2b(IFN-a2b) instillation with or without systemic chemotherapy in various solid tumors, thirteen patients (five with gastric, four with hepatic, two with bronchial, one with ovarian, and one with pancreatic tumor) with carcinoma- tous pleural effusions or ascites were treated with intracavitary instillation of IFN-a2b 6MU or 10MU on day 1, 8, 15, repeated every 28 days. Two patients who had recurrent ascites after ini- tial response, were retreated by same method and total IS cases were evaluable. Ten patients were treated with intracavitary IFN-a2b and systemic chematherapy (six with oral UFT and Leucovorin, two with Etoposide, Ifosfomide, and Cisplatin, one with Cyclophsphamide, Adriamycin, and Cisplatin, one with Etoposide, Leucovorin, and Cisplatin). Nine cases (60%) showed clinical evidence of therapeutic benefit by disaPPearance of malignant ascites or pleural effusion. The response ranged from 8 to 44+ weeks with a median of 12+ weeks. Especially responders treated with intracavitary IFN-a2b and systemic chemotherapy showed long- er duration of response. Fever (8/15) and abdominal pain (4/15) were the most common side effects. Patients who treated with IFN-a2b instil1ation only did not show any significant side effects and leukopenia and mucositis which developed after combined therapy with chemotherapy were not seem to be related with IFN-a2b instillation. These results suggest a role of intracavitary IFN-a2b instillation for control of malignant ascites and pleural effusion in advanced solid tumor. Also minor side effects of intracavitary IFNMb instillation suggest that this treatment can be combined safely with systemic chemotherapy.
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Myxoma of Nerve Sheath ( Neurothekeoma ) - A case report -
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Jeong Yeon Kim, Chang Won Ha, Kyung Ja Cho, Ja June Jang
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J Korean Cancer Assoc. 1994;26(3):519-524.
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- Neurothekeoma is a rare benign cutaneous tumor. We describe a case of neurothekeoma in the neck of a 51-year-old female. She complained of an anterior neck mass and tingling sensation. Wide excision and functional neck dissection were done. Histologically the tumor showed smal1 nests of tumor cells in myxomatous stroma and fibrous trabeculae. The cytoplasm was pale staining or eosinophilic and the nuclei were hyperchromatic and pleomorphic. The tumor showed reactivity for S-l00 protein but the histogenesis is uncertain until now. There is few report of neurothekeoma arising from neck on the literature, so this is a rare case of neurothekeoma.
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A Case of Retroperitoneal Synovial Sarcoma
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Day Key Song, Jun Ho An, Min Gyun Im, Joo Seop Kim, Bong Wha Chang, Bo Whan Choi, Ki Soon Park, Soo Young Chung
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J Korean Cancer Assoc. 1994;26(3):524-529.
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Abstract
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- Synovial sarcoma is uncommon, highly malignant soft tissue tumor that occurs most often in the deep soft tissue of lower and upper extremities. It almost never arise within the mediastinum and retroperitoneum. We present a case of retroperitoneal synovial sarcoma which was confirmed by microscopically sarcomatous growth of spindle cells, hyalinized vasculature, and some calcification. The treatment was performed by wide excision and radiotherapy.
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