Cancer Research and Treatment

Inhibitory Effect of Chinese Cabbage Extract on Diethylnitrosamine - Induced Hepatic Foci in Sprague - Dawley Rats: Yun Sil Lee, Won Suk Jang, Mi Jung Eui, Sun Ju Lee, Ja June Jang; J Korean Cancer Assoc. 1990;22(3):355-360.

Abstract PDF: The modifying effect of Chinese cabbage extract on the development of preneoplastic hepatic enzyme altered foci was examined in an in vivo mid-term assay system. Diethylnitrosamine (DEN) of 15 mg/kg body weight was injected to newborn Sprague-Dawley rat subcutaneously within 24 hours, and after 3 weeks, Chinese cabbage (95% ethanol extract) was given at a dose of 2 mg/ml in drinking water. All rats were sacrificed at week 12. The modifying effect was evaluated comparing the number of foci and area/cm of induced glutathione S-transferase placental form positive (GST-P ) foci in the liver with those of the corresponding control group given DEN alone. Chinese cabbage extract showed statistically significant decrease in the number and area of GST-P+ foci. The result suggests that Chinese cabbage could have inhibitory effect on rat hepatocar- cinogenesie.

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Proto - oncogene Expression in Human B - cell Malignancies: Jung Shin Lee, Kyoo Hyung Lee; J Korean Cancer Assoc. 1990;22(3):360-367.

Abstract PDF: The proto-oncogenes have the capacity for conversion to an oncogene that is capable of inducing or maintaining the transformed state when they are overly expressed or altered by mutation or rearrangement. To study the possible involvement of these genes in the neoplastic transformation of B-cell malignancies, we have analyzed their expression in 18 fresh samples obtained from the peripheral blood of patients with a variety of B-cell malignancies. C-myc (2.3 kb) and c-raf(3.8 kb) were expressed in all samples including normal lymphocytes without significant variation in the level of expression. C-fos (2.2 kb) was expressed in 13 samples and normal lymphocytes with a wide range in the level of expression. C-h-ras (2.9 kb, 1.4 kb) was expressed at a low .level in 11 and 12 samples, but not in norrnai Ivmphocytes. C-myb (3.7 kb) and c-fes (2.7 kb) were expressed at a low level in 5 and 10 wimples, respectively, including normal lymphocytes. C-sis (4.0 kb) was not detected in any sample including iwrmal lymphocytes. Our study indicates that certain oncogenes are expressed in different patterns in the various types of B-cell malignancies which suggest biological heterogeneity of B-cell malignancies at t.he malecular level.

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Induction of Differentiation of Leukemic Cells in Vitro: Mi Jeong Lee; J Korean Cancer Assoc. 1990;22(3):367-374.

Abstract PDF: Appropriately stimulated, leukemic cells can be made to differentiate suggesting new approaches to cancdr treatment. We tried various inducers to leukemic cell lines, Ml originated from mouse myeloid leukemia and U 937 originated from human histiocytic lymphoma. Induction of differentia- tion was initiated by adding cyclosporin A(CSA), bacterial lipopolysaccharide (LPS), retinoic acid (RA) and phorbol l2-mvristate 13-acetate(PMA) to M1 and U-937 cells growing in defined mediunm. Cell growth and differentiation markers such as reduction of nitro blue tetrazolium(NBT) dye, Fc receptor expression and cell adhesion were observed. CSA and LPS stimulated differentiation and growth inhibition of Ml cells. RA and PMA stimulated differentiation and growth inhibition of U-937 cells. Tamoxifen (TMF), protein kinase C (PKC) inhibitor, inhibited the differentiation of U-937 cells induced to differentiate by PMA. This result suggests that PKC is an important enzyme in the differentiation of U-937 cells.

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Study on the Growth Pattern and Histogenetic Classification of Peripheral Adenocarcinomas in the Lung: Jeong Wook Seo, In Ae Park, Eui Keun Ham; J Korean Cancer Assoc. 1990;22(3):374-386.

Abstract PDF: The relationships between gross, microscopic and ultrastructural features of pulmonary adenocarcinomas and the morphologic significance of lepidic growth are studied using nine cases of peripheral adenocarcinomas with lepidic growth. They include three bronhioloalveolar carcinomas ( BAC's), two acinar adenocarcinomas, two papillary adenocarcinoms and two metastatic adenocarcinomas. Ill-defined consolidating mass was seen in three cases of BAC's and one acinar adenocarinoma. Other cases of acinar, papillary types and metastatic tumors were classified into secretory type or poorly differentiated type and metastatic adenocarcinomas showed mixture of the types. Mucin secreting cell by light microscopy showed apical clustering of electron-lucent mucin vacuoles by electron microscopy, but non-secretory type showed variable features of electron microscopy, but non-secretory type showed variable features of Clara cell, type II pneumocytes of indeterminate cells. Tumor growing along the alveolar wall was encountered in every type of the cases byt the distribution and microscopic findings were different according to the light microscopic types. The lepidic pattern was seen homogeneously in the whole tumor field in BAC's but was seen only at the peripheral zone of the tumor in the other instances. We could classify the microscopic features of lepidic growth into three patterns based on the findings in BAC's. Regular lepidic growth confined to the alveolar wall was seen only in BAC. One paillary adenocarcinoma and one BAC showed multicentric nodules which was composed of micropapillary projections into the alveolar spaces in addition to the tumor cells covering the preexisting alveolar wall. Other cases showed intraluminal polypoid growth and shedding into the lumina and numerous tumor balls were scattered. The significance of these morphologic patterns of lepidic growth is undetermined, however we could speculate that first and second patterns are well differentiated forms but polypoid shedding pattern is poorly differentiated form with rapid aerogenous spread and has more frequent chance to be detected by sputum cytology.

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Pharmacokinetics and Toxicities of High - Dose Methotrexate in the Treatment of Primary Osteogenic Sarcoma: Goo Hyun Baek, Soo Yong Lee, Seok Il Hong; J Korean Cancer Assoc. 1990;22(3):386-395.

Abstract PDF: From December 1989 to July l990, we have tried 70 courses of high-dose methotrexate therapy, which was combined with adriamycin and cisplatin, in the treatment of 13 patients with primary wteogenic sarcoma. The dosage of methotrexate in our protocol was 8 grams per square meter of body surface and the intravenous infusion was done for 4 hours. Using fluorescence polarization immunoassay (FPI) method, we measured the plasma level of methotrexate at 4, 5, 6, B, 24, 48 and 72 hours from the start of infusian. The toxicities were analyzed according to the WHO guidelines. The mean plasma level was 1343.89uM/L at 4 hours (S.D.: 474.63, range: 795.40 to 2870.00), 736.58 (S.D.:291.33, range: l53.00 to 1495.90) at 5 hours, 601.26 (S.D.:329.69, range:36.10 to 1251.20) at 6 hours, 353.44 (S.D.: 179.02, range: 3.60 to 720.23) at 8 hours, 7.32 (S.D.: 9.79, range: 0.08 to 68.50) at 24 hours, 0.40(S.D.: 0.55, range: 0.02 to 3.90) at 48 hours and 0.15 (S.D.: 0.09, range: 0.01 to 0.63) at 72 hours. Twenty two point nine percents at 24 hours and 17.1 percents at 48 hours needed increase of citrovorum factor rescue and 14.3 percents needed prolonged administration of citrovorum factor at 72 hours. Myelosuppression, alteration of hepatic function such as increase of sGOT and sGPT, and other infrequent toxicities were observed, but they were reversible and did not result in permanent dysfunction.

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Immunohistochemical and Genetic Changes in Putative Preneoplastic Lesion in Rat Liver: Kye Yong Song, Dae Young Kim, Hyung Chun Kim, Mi Kyung Kim, Young Ho Rha, Sang Chul Park; J Korean Cancer Assoc. 1990;22(3):395-410.

Abstract PDF: Immunohistochemical and electron microscopic studies were carried out on the preneoplastic nodule, to observe the morphological and immunohistochemical changes of the transformed preneo- plastic hepatacytes by immunohistochemical method using antibodies to the various marker enzymes such as glutathione S-transferase of placental form (GST-P), glutathione S-transferase of basic form (GST-L), Glucose 6 phosphate dehydrogenase (G6PDH), gamma glutamyl transpeptidase (GGT) The results obtained were as follaws; l) The transformed preneoplastic hepatocytes could be detected easily by use af GST-P antibody especially in the clear cell nodule from the 2nd month and is significantly increased from the 12th month compar'ed with the 2nd month, while basophilic nodule was observed from the 10th month. 2) Immunohistochemical staining revealed strong positive reaction to GST-P and weakly positive to G6PDB, GST-L and focally poitive to GGT in clear cells, while weak or negative reaction to GST-P, G6PDH, GST-L and GGT in eosinophilic cells. and Basophilic cells showed negative reaction to GST-P, GST-P, GST-L, G6PDH and positive to GGT. 3) Electron microscopically, clear cells revealed abundant glycogen particles and well developed endoplasmic reticulum, while eosinophilic cell reveaied abundant mitochondria and vacuoles with a few glycogen, basophilic cells revealed abundant rER and ribosomes. Immunohistochemically, GST-P is abundantly distributed in the cytoplasm especially around the rER, vesicles and alsp in nucleus. 4) Therefore, glutathione S-transferase is a good marker for early detection of genetically transformed and preneoplastic hepatacytes especially clear cell while GGT is positive marker for basophilic cell. GST-P is abundantly present in the cytosol and around the rER and vesicle. The clearness of preneoplastic hepat.ocytes were thought as the result of marked increase of glycogen while basophilic cells were the result of marked incresed rER.

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Expression of cellular Oncogenes During the Radiation - induced Leukemogenesis in CBA Mice: Woo Yoon Park, Jeong Sun Seo; J Korean Cancer Assoc. 1990;22(3):410-424.

Abstract PDF: To explore whether the development of the specific tumor type in experimental animal model for the study of radiation-induced carcinogenesis is caused by genetic predisposition, such as species or strain, or irradiation method, and also to find out the role of cellular oncogenes in radiation-induced carcinogenesis, an experimental study was made using female CBA mice. After total 450 cGy of whole-body irradiation with 3 fractionations at weekly intervals, histopathologic changes and expression of cellular oncogenes were examined with thymus and bone marrow serially till postirradiation 150 days in 18 female CBA mice. Simultaneously unirradiated 12 mice were studied as a control. The results are as follows. 1) Thymic lymphoma/leukemia did not develop in CBA mice with the fractionated whole-body irradiation which has been known to be an effective method af inducing thymic lymphorna/leukemia in C57BL mice. Increment of blasts in bone marrow, which suggests the development of myeloid leukemia, was observed in 33%(2/6) of irradiated mice elapsed 150 days after irradiation. These findings suggest that the development of the specific tumor type in experimental animal is not related to irradiation method but to genetic predisposition, such as differences in species or strain. 2) The expressian of two cellular oncogenes, c-fps and c-myc, as a parameter of chemical changes were examined at thymus serially till postirradiation 150 days. No abnormal expression of c-fps or c-myc was observed as with the findings of histopathology. 3) In the examination of two cellular oncogenes in bone marrow, there was no change in c-myc, but there was strong expression of c-fps in one of mice elapsed 150days after irradiation. The expression of c-fps at preleukemic state suggests that the chemical changes develop before the appearance of malignancy as a phenotype. This result is very meaningful in that specific oncogenes might play a role in radiation-induced carcinogenesis.

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Establishment and Chemosensitivity ( 5 - FU ) Test of Colon Cancer Cell Lines with Enhanced Invasive Potential: Jae Gahb Park, Song Kim, Yung Jue Bang, Hynda K. Kleinman, Jin Pok Kim; J Korean Cancer Assoc. 1990;22(3):424-431.

Abstract PDF: The in vitro chemosensitivity of 3 human colorectal cancer cell lines and those invasive cells which were repeatedly selected with in vitra matrigel invasion assay to the anticancer agent, 5-FU, was determined using a semiautomated tetrazolium-based colorimetric assay (MTT assay). The IDvalues of control cells of SNU-C1, SNU-CZA, SNU-61 were 2.37+-4.S2ug/ml, 0.85+0.40ug/ml, 23.9+-13.3ug/ml, respectively, and those of invasive cell groups obtained by matrigel invasion assay were 0.37+-0.24ug/ml, 1.37+1.04ug/ml, 40.5+19.1ug/ml. There were no statistically significant differences between the ID,. values of control cell groups, SNU-C1(0), SNU-C2A(0), SNU-61(0) and those of invasive cell groups(p>0.05). This result was considered to be caused by the homogenization of the established cell lines during passage and maintenance cultivation.

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Anticarcinogenic Activity of Copolang : Suppression of N , N'-Dimethyl Nitrosamine - Induced Activation of Hepatic Glutathione S-Transferase: Tai Ho Chung, Jung Chul Kim, In Sun Lee, In Su Lee, Moon Kyu Kim; J Korean Cancer Assoc. 1990;22(3):431-440.

Abstract PDF: Dimethylnitrosamine (DMV)-induced renal mesenchymal preneoplastic loci and hepatic glutath- ione S-transferase P (GST-P) gene expression in weanling F344 male rats were used as early carcinogenic biomarkers to evaluate anticarcinogenicity of Copolang. Continuous daily intake of 0. 85 1.1 g Copolangiday/kg b. wt. for 3 weeks immediately following a single intraperitoneal administration of DMN (15, 30 and 60 mg/kg body weight) significantly blocked these DMN-induced biomarkers. The dose response slopes for DMN with or without Copolang treatment (1% Copolang in drinking water) were 0.27 and 0,47, respectively. Copolang treatment significantly inhibited DMN-induced small renal mesechymal cell proliferation, Likewise hepatic GST-P enzyme expression in the lowest DMN dose group (15 mg/kg) and the highest dose (60 mg/kg) was blocked nearly completely. In the highest dose group, multicellular GST-P enzyme loci were not observed in this experimental group, however, there was GST-P positive single cells were observed. On the other hand, in the middle dose group, GST-P histochemical staining was much more diffuse and not as intense. The results of this study demonstrate that Copolang treatment significantly inhibits expression of DMN-induced early carcinogenic biomarkers. A long term whole animal carcinogenic bioassay study is necessary to confirm anticarcinogenic activtiy of Copolang.

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Expression of Carcinoembryonic Antigen by Immunohistochemical Staining Method in Primary Male Breast Cancer: Hyun Cheol Chung, Dong Lip Kim, Eun Hee Koh, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Kyung Shik Lee, Woo Ik Yang, Byung Soo Kim, Byung Soo Kim; J Korean Cancer Assoc. 1990;22(3):440-451.

Abstract PDF: Carcinoembryonic antigen (CEA) immunohistochemistry was evaluated with 12 sections of male breast cancer diagnosed at Severance Hospital during the year of 1979-1990. Ten of twelve (83.3%) primary breast masses and four of five (80%) metastatic lymph nodes were CEA positive. There was concordance of CEA positivity and CEA positivity grade between primary mass and metastatic lymph nodes. The grade of CEA positivity did not appear to be related to size, tumor depth (T) and pathological stages. It was difficult to find a relationship between nuclear grade and CEA positive grade, because there was no nuclear grade 3 patient. Tumor heterogeneity was a constant feature of CEA staining with positivity varying from region to region.

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Induction of Natural Killer and Lymphokine Activated Killer Cell Activities in Patients with Advanced Cancer Treated with Combination of Interleuki: Kyoo Hyung Lee; J Korean Cancer Assoc. 1990;22(3):451-458.

Abstract PDF: Peripheral blood lymphucytes were obtained from 14 patients with advanced cyncer receiving combination therapy with interleukin-2 (IL-2) and a-interferon (a-IFN) as a part of a phase I study and killer cell activities were assayed against k-562 and Daudi cell lines before, during, and after the therapy. There was significant natural killer (NK) activity before the treatment (74+-77 Lytic Unit) and it increased during the treatment (day 5, 262+195 L.U., p<0.01); day 15, 431+-328 L.U., p<0.01; and day 26, 743+-506 L.U., p<0.01). Lymphokine activated killer (LAK) activity before the treatment was low (13+9 L.U.) but also increased significantly during and after the treatment (day 5,71+59 L. U., p<0.01; day 15. 63+-77 L.U.; and day 26, 290+419 L.U.). In l0 patients same assay was repeated during the second course of therapy and showed similar increase in killer cell activities without evidence of cumulative increment. Out study showed that immunotherapy with combination of IL-2 and rz-IFN induces significant levels of NK and LAK cell activities in patients with advanced cancer. This biological phenomena can be utilized as a paramenter with which the IL-2 therapy can be tailored to augment clinical efficacy and tolerability.

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The Combined Effects of 5 - Fluorouracil and Recombinant Interferon - gamma on Human gastric Cancinoma Cell Lines: Heung Tae Kim, Jae Gahb Park, Jin Pok Kim, Seong Hoe Park, Noe Kyeong Kim; J Korean Cancer Assoc. 1990;22(3):458-476.

Abstract PDF: Stomach cancer is a leading malignant disease in many countries. Conventional combination chernotherapy approaches to advanced gastric cancer only produce paitial response and there has been no impact on patient survival from these approaches as well. Of several promising new approaches the combination of interferon (IFN) and chemotherapeutic agents are now being made to improve the effectiveness for the treatment of cancer. Preclinical studies suggested that IFN may biochemically modulate the cellular uptake or metabolism of 5-fluorouracil (5-FU) resulting in s synergistic antitumor effect. Based on these data, Wadler reparted a promising result with combina- tion of 5-FU and IFN-alpha in patients with advanced colorectal carcinoma. This study was conducted to investigate the combined effects af 5-FU and recombinant IFN- gamma at cellular level against four gastric carcinoma cell lines (SNU-1, SNU-5, SNU-16, and NCI-NB7). We used a semiautomated tetrazolium-based colorimetric (MTT) assay for cytotoxicity and an isobologram analysis to evaluate the effect of the combination. The experiment was perfor- med three times on each of the three cell lines. Only two experirnents for SNU-16 and NCI-N87 showed supraadditivity (p< 0.02). On isobologram plotted by the mean value of three experiments for each cell line, supraadditivity was suggested for only SNU-16 (p = 0.055). In conclusion, our result did not document in vitro synergy between 5-FU and IFN-gamma for gastric carcinoma cell lines but additivity within clinically achievable dose range. Because in vivo immunomodulatory effect of IFN-gamma on host is more important rather than antiproliferative effect, the combination of 5-FU and IFN gamma is expected to improve the treatment of advanced gastric cancer.

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Significance of Serum Total Lactate Dehydrogenase ( LDH ) Level and Isoenzyma Patterns in Non - Hodgkin's Lymphoma as a Prognostic Factor: Jee Sook Hahn, Hyun Cheol Chung, Joo Hang Kim, Sun Ju Lee, Eun Hee Koh, Jae Kyung Roh, Hyon Suk Kim, Yun Woong Ko, Byung Soo Kim; J Korean Cancer Assoc. 1990;22(3):476-490.

Abstract PDF: Serum total lactate dehydrogenase (LDH) and LDH isoenzyme activities were studied in 33 cases w i th non-H odgk in's lymphom a to compare the cl inical significance of serological staging with these two serological markers to anatomical staging. Serum total LDH activity correlated with tumor burden as determined by clinical stage at presentation. Initially, LDH-3 was the major fraction of increment for the reflection of increased serum total LDH activity. With the increment of tumor burden (total LDH >200 IU/L), LDH-3 with additional LDH-4 fraction increased, which resulted in LDH-1/LDH-3 flipped pattern. These changes were normalized if complete remission state was induced with treatment. A high pretreatment LDH level (total LDH> 200 IU/L) correlated significantly to a decreased survival rate IP.0.01l> Furthermore, the flip pattern of LDH-I/LDH-3 isoenzyme at diagnosis showed a decreased survival rate (p<0.05), in which 4-year survival rate of patients with non-flipped pattern was 73.8%, comparable to 25.4%; of patients with flippd pattern. The 4-year survival rate of the low risk group Itotal LDH 200 IU/L with unftipped pattern: serological stage A) was 73g while 2-year survival rate of the high risk group (total LDH>200 IU/L withflipped pattern: serological stage D) was 0%, which showed a significant difference (p<0.05). Stepwise Cox regression analysis to identify the important prognostic factors among the serum total LDH, LDH1/LDH-3 flip, serological stage, anatomical stage, B symptoms, cell type, hepatos- plemomegaly, mediastinal mass reveated that the serological stage was the only prognostic factor. In conclusion, based on results of the multivariate analysis, we propose a new prognostic classification of patients with serological staging system in non-Hodgkins lymphoma. Furthermore, the reproducibility and therapeutic stratigies will be warranted.

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Synergistic Effect of Cisplatin and 5 - Fluorouracil Against Gastric and Colon Cancer Cell Line: Yoon Sik Kang, Dong Young Noh, Jae Gahb Park, Kuk Jin Choe; J Korean Cancer Assoc. 1990;22(3):490-505.

Abstract PDF: The purpose of this study was to elucidate the synergistic effect of cisplatin and 5-fluorouracil against human gastric and colon cancer cell lines. Since it is virtually impossible to document supraadditive tumor cell kill in vivo, this in vitro experiment implicates the interaction of these agents at a cellular level. We used an in vitro tetrazolium-based colorimetric assay for cytotoxicity (MTT assay) and an isobologram analysis to test combination effects of the two drugs against gastric and colon cancer cell lines, SNU-1, SNU-5, SNU-16, SNU-CI, SNU-C2A, SNU-C4, SNU-C5 those were established at cancer research institue of Seoul National University and NC1-N87 from NCI, VSA. As a resuh, those drug combination applied to this experiment didnt show a synergistic effect except in SNU-1 cell line demonstrated partly synergistic effect. Then we conclude that there are lack of in vitro synergistic effect between cisplatin and 5- fluorouracil against gastric and colon cancer cell lines, and that methodology we adopted can be one index ta check the combinatian effect of anticancer drugs.

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Cislatin , Vincristine , Bleomycin and Methotrexate ( PVBM ) Combination Chemotherapy for Advanced Uterine Cervix Cancer: Young Hyuk Im, Kee Hyung Lee, Young Suk Park, Chang In Suh, Won Ki Kang, Hyo Jin Kim, Heung Tae Kim, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim, Soon Beom Kang, Hyo Pyo Lee, Jin Yong Lee, Seung Wook; J Korean Cancer Assoc. 1990;22(3):505-518.

Abstract PDF: Twenty-nine patient with advanced cervix cancer were treated with a combination chemotherapy of cisplatin, vincristine, bleomycin, and methotrexate between January, 1987 and December, 1988. 1) Among 19 evaluable patients, 4 patients (20.1%) achieved complete response and 6 patients (31. 6%) achieved partial response, giving an overall response rate of 51.7%. The median duration of remission was 23 weeks in the responders. 2) The median survival of overall patients was 50 7 weeks. The median survival of the responders did not reach the median value during the follow-up period of 15-81 weeks. In contrast, the median survival of the non-responders was 30.7 weeks, which was significantly shorter than that of the responders (p<0.05). 3) The only factor influencing remission rate was the pattem of failure, and the patients with distant metastasis showed higher remission rates (p<0.01). There were no prognostic factors influencing the remission duration. The factors improving survival rates were the early stage at diagnosis (p< 0. 005), the previous history of curative operation (p<0.005), and the presence of distant metastasis (p<0.01). 4) Considerable number of patients experienced toxicities. Among these, leukopenia (50%) and thrombocytopenia (4.7%) were the main hematologic toxicities. Most patients experienced nausea, vomiting, diarrhea (89.49o), stomatitis (26 3%), and alopecia (73.7%). Neurotoxicity due to vincristine or cispatin was found in 36.896 of patients, and 2 patients showed pulmonary fibrosis due to bleomycin toxicity. In conclusion, this regimen (PVBM) seems to be effective in terms of remission rates, but did not show any additional benifits in terms of remission duration or overall survival. In addition, the large number of patients experienced considerable side effects. Based on these findings, further studies are needed to find out the new regimen which is more effective and less toxic for the patients with advanced uterine cervix cancer.

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Efficacy of Combined Modality , Multidisciplinary Treatment ( Neoadjuvant Chemotherapy , Difinite Local Treatment , and Adjuvant Chemotherapy ) in Locally Advanced Head and Neck Squamous Cell Carcinoma: Jae Kyung Roh, Wha Young Lee, Hyun Cheol Chung, Young Joon Park, Hyung Keun Roh, Chang Ok Suh, Gwi Eon Kim, Jun Kyu Loh, Won Pyo Hong, Cheong Soo Park, Byung Soo Kim; J Korean Cancer Assoc. 1990;22(3):518-532.

Abstract PDF: Between January, 1986 and October, 1989, 40 patients with previously untreated, locally advanced head and neck squamous cell carcinoma enrolled for combined modality treatment (CMT) with neoadjuvant chemotherapy (2 cycles of infusional 5-FU and cis-platin), definite local treatment (DLT) (surgery and/or radiotheray) and adjuvant chemotherapy (3 cycles of infusional 5-FU and cis-platin) to enhance the therpeutic efficacy. Of the 40 enrolled, all the patients were evaluable for tumor responses and treatmen#t related toxicities after neoadjuvant chemotherapy, and 35 patients finished scheduled CMT. Male to female ratio were 33:7, median age 54 year old (34-69), and median ECOG performance grade 1 (0-2). Primary sites were nasopharynx 19, oral cavity 16, larynx 3, hypopharynx 1, and maxillary sinus l. After the 2 cycles of neoadjuvnt therpay, 8/40 (20%), 23/40 (72.5%) achieved compIete remission (CR) and partial remission (PR), respectively with 92.5% over all response rates. After the DLT, 23/ 35 (67.5%) 11/35 (31.4%) achieved CR, and PR respectively with 97.1% over all response rates. Of the 35 patients who finished the DLT, 15 received the 3 cycles of adjuvnat chemotherapy with infusional 5-FU and cis-platin. The median failure-free, and overal survival duration of 35 evaluable patients were 21.7 months and 31.0 months, respectively after the CMT. The median survival duration was significantly prolonged in patients with objective respanses after the neoadjuvant chemotherapy compared to those of non-responders (p<0.05). Of the 35 patients who finished the DLT, patients who received the adjuvant chemotherapy showed trend of prolongation of survival when compared to no adjuvant chemotherapy patients Imedian overall survival duration; adjuvant group 21.7 months, no adjuvant group 17.6 month (p>0.05). This study strongly suggests that CMT can increase the median response duration and survival especially in patients with locally advanced head and neck squamous cell carcinoma who showed responses after the neoadjuvant chemotherapy with infusional 5-FU and cis-platin, but phase III randomized controlled prospective studies are warranted for the verification of this study.

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Cyclophosphamide , Adriamycin and Cisplatin ( CAP ) Combination Chemotherapy for Invasive Thymoma: Young Suk Park, Young Hyuk Im, Won Ki Kang, Chang In Suh, Kee Hyung Lee, Kyung Hae Jung, Heung Tae Kim, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 1990;22(3):532-539.

Abstract PDF: Between October 1985 and January 1990, the combination chemotherapy with cyclophosphamide, adriamycin and cisplatin (CAP) has been administered in 16 patients with invasive, recurrent or metastatic thymoma. Among 14 evaluable patients, 1 patient(7%) achieved a complete response and 4 patients (29%) had a partial response. The 4 year overall survival rates were 56.7% with a median follow-up of 11.5 months. The mast frequent hematologic toxicity was leukopenia (15.9%) and nonhematologic toxicity (WHO criteria; grade II) were alopecia (80%) and nausea/vomiting (66.7%). The CAP regimen is effective and well tolerated for the treatment of invasive thymoma, and further study is needed to confirm the relative effectiveness of CAP regimen in comparison with other regimens and to find out the prognostic factors related to response rate and survival

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Treatment of Childhood Acute Lymphoblastic Leukemia Diagnosed Jan . , 1978 Through Dec . , 1987 : Comparison between Standard - Risk and High - Risk Groups: Soon Ki Kim, Hee Young Shin, Hyo Seop Ahn; J Korean Cancer Assoc. 1990;22(3):539-549.

Abstract PDF: Of 328 children who were diagnosed as acute lymphoblastic leukemia at the Department of Pediatrics. Seoul National University Hospital from Jan., 1978 through Dec., 1987, 211 patients above one year af age were evaluable for induction chemotherapy. The leukemias were classified as standard risk (SR), comparison group (who had high-risk prognostic factors, but had been treated with standard regimen), or high- risk (HR) leukemia according to the prognostic criteria at diagnosis. Three regimens were compared and the results were as follows. 1) The complete remission (CR) rate was 97.1%(133/137), 81.0%(34/42) and 90.6%(29/32) in SR, comparison group. and HR group, respectively. And significant difference in the CR rate was seen between SR group and comparison group (p= 0.0001). 2) Of the patients remained in remission follow-up of each group showed 56.8% 5-yr disease-free survival (DFS)(+-5.9%, median follow-up 30 mo) in SR, 35.5% (+-9.1%, median 24 mo) in comparison group, and 76.0%(+- 8.5%, median 24 mo) in HR group. And significant difference in the 5yr-DFS rate were observed be(ween SR and comparison group (P = 0.007), between HR and comparison group (p = 0.002), respectively. 3) Induction failure was due to infection (n=2) bleeding (n=1) or uric acid nephropathy (n= 1) in SR drug resistance (n=3), infection (n=2), bleeding (n=2), or combind infection and bleeding (n=1) in comparison group, and bleeding (n=2) or infection (n= 1) in HR. Of the patients who were on maintenance chemotherapy in complete remission, 11 died due to infection: menigitis or meningoencephalitis (n=4), disseminated varicella (n=3), Pneumocystis carinii pneumonia (n=2), and sepsis (n=2). 4) In SR group, 29 patients experienced relapse: BM(n=18), CNS(n=3), BM and CNS(n=4), and testes (n=4). Two- third (n = 19) of them relapsed between 6mo to 2yr after initial remission. In comparison graup, 20 relapsed: BM (n= 10), CNS(n=2), BM and CNS (n=3), testes (n=4), and testes and CNS(n =1), Mostly they relapsed within the first 2 years after remission. In HR group, all patients (BM 3 and CNS 1) experienced relapse from 1 yr to 1 1/2 yr after initial remission.

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Analysis of regional Lymph Node Metastasis in Resectable Stage 3 Gastric Cancer: Ki Joo Kweon, Min Chung, Jin Pok Kim; J Korean Cancer Assoc. 1990;22(3):549-556.

Abstract PDF: We analyzed the pattern of regional lymph node metastasis in resectable stage III gastric cancers which were operated at the Department of Surgery, Seoul National University Hospital from January 1987 to June 1988. The results were as followr. 1) The number of patients was 187, 123 were males and 64 females. The average number of dissected lymph node was 29.97 (range: 10-77), and that of metastatic lymph node was 7.9(range: 1-58). 2) In total cases, the rates of metastasis in NNand N, lymph nodes were 98.5%, 24.1% and 12.4%, respectively. 3) Young patients under the age of 30 had more frequent metastasis to N, lymph nodes than older gtOUpS. 4) When the tumor was located at the lower 1/3 or posterior wall of the stomach, the rates of metastasis to N, and N, lymph nodes were higher than other cases. 5) In three cases, the metastasis was skipped to N, lymph nodes without involvement of N, nodes. 6) Gastric cancers of Borrmann type IV had more frequent metastasis to N, lymph nodes. 1) When the mean diameter of tumor was over 5 cm, metastatic rates to NN, nodes were higher than those of tumor under 5 cm. 8) There was more frequent metastasis to N2 and N2 lymph nodes in the tumors penetrating serosa. 9) Differentiated adenocarcinomas of stomach had more frequent involvement of N, lymph nodes than undifferentiated adenocarcinoma.

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Clinical Analysis on Recurrence Rattern of Gastric Cancer: Kyu Joo Park, Jae Gahb Park, Jin Pok Kim; J Korean Cancer Assoc. 1990;22(3):556-567.

Abstract PDF: In an effort to analyze recurrence pattem of gastric cancer, we have reviewed medical records of 460 patients operated for gastric cancer at department of Surgery, Seoul National University from 1980 to 1982. Of these patients, 158 patients were found to have recurrence after initial curative resectian of their tumor. Recurrences were detected based on clinical, radiological, and endoscopic findings and by reoperative findings. We analyzed in detail the site and pattern of recurrence based on morphologic and pathologic characteristics of the initial tumor. In 15S patients, total of 566 recurrences were identified. Of total recurrences, 39% were locoregional, 24% were peritoneal, 24% were distant metastasis, and 13% were liver metastasis. 1) Most common manifestation of colo-regional recurrence was obrstuctive jaundice, land loco- regional recurrence tended to occur more frequently (55%) when number of regional lymph node metastasis was less than 3 (P=0.012). 2) Peritoneal recurrence tended to occur more frequently (33%) in poorly differentiated tumors(P= 0.002). 3) Distant metastasis were more frequent(30%) in resectable Stage IV lesions (P=0.012), in tumors located in cardia (39%, P = 0,062), and when more than 10 regional lymph node metastasis was present (3%, P=0.000). 4) Liver metastasis was more frequent (21%) in T, and T, lesions (P=0.026), and in well differentiated tumors (30%, P=D.088). 2. Multivariate analysis on patterns of recurrence and various morphologic and pathologic characteristics of the initial tumor failed to show statistically significant correlation.

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Intraperitoneal Administration of 5 - Fluorouracil in Advanced Gastrointestinal Cancer: Kyu Joo Park, Jae Gahb Park, Kuk Jin Choe, Jin Pok Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1990;22(3):567-579.

Abstract PDF: In gastrointestinal malignancies such as cancer of stomach, large bowel and ovary, peritoneal involvement with metastatic tumor is a common finding at the time of initial operation or following initial curative resection of the tumor. Intraperitoneal administration of chemotherapeutic agents offers an opportunity to deliver high concentration of drug to local intraperitoneal surfaces and also to liver as most of drug administered intraperitoneally is cleared via the portal vein. Thus, Intraperitoneal (IP) chemotherapy should permit more effective treatment of peritoneal surfaces and liver while reducing systemic toxicities of the chemotherapeutic 'agents. In an effort to evaluate the efficacy and safety of IP chemotheray, we have treated 6 advanced stomach cancer patients (including 2 stage IV stomach cancer patients) and I colon cancer patient who had undergone surgery at Department of Surgery, Seoul National University HapitaL Each cycle of treatment consisted of daily intraperitoneal administration of 5-fluorouracil through Tenckhoff peritoneal dialysis catheter for 5 days in every four weeks. Initial dose of IP 5-FU was 20 ml/kg body wt, with dosage increment each cycle until toxicity was experienced by the patient. The following results were obtained: 1) Mean daily dose of 5-FU administered was 1500 mg, and maximal daily dose administered to each patient ranged from 1100 to 2030 mg (21 to 30 mg/kg body wt.) with a mean maximal dose of 1567 mg (28mg/kg body wt.) 2) Most common toxicities related to 5-FU were nausea, vomiting, and diarrhea which were self -limited. Hepatotoxicity appeared in 3 patient, but only in one patient was it severe enough to discontinue therapy. Hematotoxicity appeared in 1 patient as manifested by leukopenia (WBC< 4000/ mm(3)) but was able to continue therapy after dosage reduction. 3) Complications related to Tenckhoff catheter were catheter obstruction, leakage of fluid around the catheter and intestinal obstruction which occurred in one patient respectively. There was no incidence of skin infectian or bacterial peritonitis. 4) Common discomfort after IP administration of 5-FU was abdominal fullness and self-limited ahdominal pain, but there was no inicidence of chemical peritonitis. 5) Three advanced stomach cancer patients died at 4 months, S months and 12months postoperatively, but one patient who had peritoneal seeding at the time of operation remained disease free for 32 months after 12 cycles of 5-FU IP therapy. Remaining 3 patients are free of recurrence at 20 months postoperatively. IP chemotherapy is a relatively safe method of administrating a large dose of 5-FU to intraperitoneal space as well as to the hepatic parenchyme. Further clinical testing of this route of administration is clearly warranted both for prevention and treatment of peritoneal and hepatic metastasis of gastrointestinal cancers.

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Four Cases of Primary Urachal Adenocarcinoma: Don Haeng Lee, Hyun Cheol Chung, Young Jin Kim, Sin Ki Ahn, Young Ho Kim, Dong Lip Kim, Eun Hee Koh, Joo Hang Kim, Jae Kyung Roh, Young Tae Lee, Eun Kyung Han, Hyun Joo Chung, Gui Eon Kim, Byung Soo; J Korean Cancer Assoc. 1990;22(3):579-587.

Abstract PDF: The primary adenocarcinoma of bladder is a rare cancer and it was known that the prognasis is poor. The primary adenocarcinoma of bladder is divided by its embriological orign: I) nonurachal carcinoma derived from transformation of bladder epithelium, 2) urachal carcinoma arising from urachal remnant. This report represent four cases of primary urachal adenocarcinoma at Yonsei University Medical College from 1971 to 1989. The commonest sign is a painless hematuria. The specific site of origin is evaluated by measns of cystocopy, ultrasonography and computerized tomography. The choice of treatment is wide surgical resection and the role of chemotheraphy and radiotheraphy is still controversial. Our first two cases were treated only conservatively in advanced stages. The third cases was treated by curative resection and postoperative adjuvant chemotherapy. But 10 months later, intraabdominal carcinomatosis was developed. The fouth case showed metastatic lesions in both lung fields at the time of diagnosie. So we started chemotherapy of FAM regimen and a partill response was noticed after 3 cycles of chemotherapy. But after additional 3 cycles, the metastatic resions were aggrevated.

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Three Cases of Endodermal Sinus Tumor in Pediatric Age: Sang Wook Choi, Mi Jeong Lee, Kyung Ja Cho, Ja June Jang; J Korean Cancer Assoc. 1990;22(3):587-595.

Abstract PDF: We experienced three cases of Enclodermal sinus tumor (EST) during 9 months of period developed at intestine ovary and sacrococcyx. EST is the most common Gerrn cell tumor in pediatric age. The sacror occygeal area is the major site of involvement in the newborn and infant; in older children, the ovary is the chief location. Like most Germ cell tumor, EST is very sensitive to Chemotherapy and thc long term survior have been reported recently with the regimen containing CDDP (cisplatinum).

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Treatment of Olfactory Neuroblastoma with Combination Chemotherapy and radiation Therapy: Jong Youl Jin, Choon Snag Bang, Hoon Kyo Kim, Kyung Shik Lee, Dong Jip Kim, Min Sik Kim, Seung Ho Cho, Byung Do Suh, Sei Chul Yoon, Kyu Ho Choi; J Korean Cancer Assoc. 1990;22(3):595-600.

Abstract PDF: Olfactory neuroblastoma (esthesioneuroblastoma) is very rare nasal tumor, which develops in the olfactory mucosa. Since the first description by Berger et al in 1924, about 200 cases have been reported in the literature. And there have been 3 reports since 1964 in Korea. All the reported cases in Korea were treated with surgical resection and or radiotherapy. The authors have experienced complete remission with combination chemotherapy and radiation therapy in a patient with olfactory neuroblastoma. A 55-year-old male presented with advanced unresectable olfactory neurobIastoma (stage C) and he was treated with combination chemotherapy (cisplatin, adriamycin, VM-26, cycloposphamide) every 3-4 weeks for 5 times followed by radition therapy (64BO cGy/36 fractions/9 weeks), which resulted in complete remission. The patient had been free of disease and asymptomatic for 8 months after treatment. Rescently left facial nerve palsy developed, of which etiology due to recurrence or treatment related fibrosis is unclear. Now, the authors are on study the etiology of left facial nerve palsy.

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Metastatic Papillary Cystic Neoplasm of Pancreas in Child - Report of a case -: Seung Tae Han, Kyung Rae Kim, Yong Hwa Moon, Young Chae Chu, Chuhl Joo Lyu, Byung Soo Kim; J Korean Cancer Assoc. 1990;22(3):600-607.

Abstract PDF: Papillary cystic neoplasm of the pancreas is rare low grade malignant tumor, especially in children, and that occurs chiefly in young women. This type of pancreatic tumor has more benign clinical features than any other type of the tumor of the pancreas dose, and long survival or even cure can be expected by aggressive treatment. We present a 10-year-old frmle patient with a papillary-cystic neoplasm of the pancreas, she had distant metastatic evidences to the liver, omentum and peritoneum. The tumor was totally excised with the spleen and greater omentum, and chemotherapy was carried out with vincristine and 5-FU. On the follow up studies, there are neither evidence of recurrence nor evidence of disease and the child has been doing well for two years.

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