Cancer Research and Treatment

Development of Procedures of Cancer Case Ascertainment in Pusan City Area: Hai Rim Shin, Duk Hee Lee, Tae Soo Park, Yoon Ok Ahn, Hai Rim Shin, Duck Hwan Jeung; J Korean Cancer Assoc. 1996;28(6):943-951.

Abstract PDF: This study was performed to develop the method which could collect completely the cancer cases in Pusan Cancer Registry(PCR). The definite goals were ¨c to see the feasibility and completeness of PCR connected with Central Cancer Registry Program(CCRP), by calculating omitting rates based on utilization rate of hospitals in Pusan and registered hospitals ¨e to evaluate the possibility of generalization to other cities-Taegu, Incheun, Kwangju, Taejeon. Data sources were CCRP and claims from the Korea Medical Insurance Corporation (KMIC). l) In case of using data of the registered and unregistered hospitals in each city, the expected omitting rates were 6.2%(CCRP)-8.5%(KMIC) in Pusan, 4.7% in Taegu, 42.7% in Incheun, 26.3% in Kwangju and 13.5% in Taejeon, respectively. They was suggested to be transferred to the hospitals in other areas from doctor's offices directly. 2) In case of using data of CCR, the expected omitting rates were 9.3% in Pusan, 3.1% in Taegu, 4.2% in Incheun, 5.4% in Kwangju and 0.9% in Taejeon, respectively. 3) In case of using both two data resources -CCR and the unregistered hospitals in each city- the expected omitting rates were 1.2% in Pusan, 1.5% in Taegu, 0.0% in Incheun, 1.2% in Kwangju and 0.0% in Taejeon, respectively. Almost all patients using only the hospital in other areas visited registered hospital which have attended CCR. We could ensure about 100% completeness, combining the CCR and an active surveillance at unregistered hospitals. This model could be one of the most efficient population-based cancer registry in Korea.

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Comparison of Mammalian UV endeonuclase 3 Activities with Respect to Xeroderma Pigmentosum Group D Cells: Joon Kim, Jang Hee Hahm, Seong Hoe Park; J Korean Cancer Assoc. 1996;28(6):951-961.

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A Phase 1 Clinical Trial and Pharmacokinetic Evaluation of DA-125 ( A Novel Anthracycline Derivative ) in Advanced Carcer Patients: Jae Kyung Roh, Sun Young Rha, Jong In Lee, Kyung Hee Lee, Joon Oh Park, Jae Yong Cho, Nae Chun Yoo, Hyun Cheol chung, Joo Hang Kim, Jin Sik Min, Byung Soo Kim, Myung Geol Lee, Won Bae Kim, Joong Ik Y; J Korean Cancer Assoc. 1996;28(6):961-973.

Abstract PDF: Background
DA-125 {(7-0-12.6-dioxy-2-fluoro-2-L-talopyranosyl)- adriamycinone-14-b-alaninate HC1}, is a novel water soluble derivative of fluorinated doxorubicin. Our previous studies showed that DA-125 is more stable and effective than doxorubicin, especially to doxorubicin resistant tumor cell lines in vitro and in vivo. We initiated phase I clinical trial to evaluate the toxicities and the pharmacokinetics of DA-l25 in advanced cancer patients. Method: Advanced cancer patients who were refractory to the standard treatment with normal hepatic and renal functions were eligible after informed consent. Drug was administered intravenously for 5 minutes with initial starting dose of 20 mg/§³(10% of murine LD10). For each dose level, 3 patients were enrolled and the next increased dose was administered if there were no toxicities greater than WHO grade III. Blood, urine and bile (if possible) were collected for the pharmacokinetic evaluation. Result: Twenty three patients were enrolled with 22 evaluable patients (3 at 20 mg/§³, 3 at 40 mg/§³, 3 at 60 mg/§³, 6 at 80 mg/§³ and 7 at 100 mg/§³ of DA-125). All treated patients did not suffer from life-threatening side effects. Hematologic alterations especially neutropenia were major toxicities. Up to 60 mg/§³ dose, toxicities greater than WHO grade II were not observed. At 80 mg/§³ dose, one heavily pretreated patient developed grade III neutropenia. At 100 mg/§³ dose, one patient developed grade IV thrombocytopenia without evidence of clinical bleeding and 2 patients showed grade III neutropenia Grade I and II nausea and vomiting were observed at 80 mg/§³ and 100 mg/§³ dose level. Cardiac toxicities did not occur in any patient. DA-125 was rapidly hydralized to Ml(active metabolite), after IV administration. The plasma half life of M1 was 1.1~2.6 hours and that of M2 was 7.8~9.4 hours. The AUC of both metabolites were dose dependent(Ml: 0.154~0.638ug.hr/ml, M2: 0.684~3.07 ug.hr;ml). Urinary excretion of Ml wss less than 1% of administered dose until 96 hours and that of M2 was 10~22%. In one patient with periampullary cancer, 52.3% of the metabolites were excreted through bile. Conclusion: The results of the present study demonstrated that DA-125 was well tolerable to the advanced cancer patients and 100 mg/§³ was considered as maximally tolerated dose. We are planning the phase II trial on the basis of these results.

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A Phase 2 Study of VP-16 Ifosfamide and Cisplatin ( VIP ) Combination Chemotherapy Plus Early Concurrent Thoracic Irradiation ( TI ) for Limited Small Cell Lung Cancer: In Sook Woo, Young Suk Park, Young Lee Park, Jung Ae Lee, Myung Jae Park, Ki Suk Jung, In Gyn Hyun, Do Hoon Oh, Hoonsik Bae, Won Suk Kim, Keunchil Park, Hojoong Kim; J Korean Cancer Assoc. 1996;28(6):973-981.

Abstract PDF: The emergence of combination chemotherapy and thoracic irradiation has improved both quality of life and survival in patients with small cell lung cancer. Most patients respond to initial treatment but unfortunately most also subsequqntly relapse and cure for most patients with small cell lung cancer remains elusive because of the develpment of drug resistant SCLC and metastasis to distant organs. The probability that thoracic irradiation would eliminate chemoresistant tumor should be inversely proportional to elapsed time. So early thoracic irradiation is recommended. Ifosfamide, an analogue of cyclophosphamide, is relatively nonmyelosuppressive drug. According to the recent report to evaluate the effect of ifosfamide, VIP(VP-16, ifosfamide, cisplatin)combination chemotherapy is assocated with an improved time to progression and overall survival over VP(VP-16, cisplatin)therapy in patients with extensive SCLC. We studied a phase II trial of VIP combination chemotherapy with early concurrent thoracic irradiation in previously untreated patients with small cell lung cancer. Treatment consisted of VP-l6 100mg/§³ i.v. days 1~3, Ifosfamide 1,000mg/§³ i.v. days 1~2 with mesna and cisplatin 100 mg/§³ i.v, day 1, cycles were repeated every 21 days. Concurrent thoracic irradiation was given as total 40Gy for 4 weeks beginning within 24 hours of cycle l, day l. Eligibility requirements included a histoioaically proven small cell lung cancer with limited stage, measurable disease, adequate renal function, bone marrow reserve. Patient characteristics(N=20) were male 17 patients, female 3 patients, median age 60 years(40~76 years). Responses were seen in all 20 patients including 8 CR's with a median follow up of 8.4 months. Hematologic side effects(WHO Gr¡A3) of evaluable 89 cycles of chemotherapy were anemia in 17 occaisions(19%), leukopenia in 10 occasions(11%). On adverse effects associated with radiation therapy 15 of all patients showed esophagitis but the severity was mild. Radiation pneumonitis was 5 patients(25%). Side effects of the treatment were tolerable and there was no treatment related mortality. In conclusion VIP combination chemotherapy with early concurrent thoracic irradiation in limited SCLC is considered to be an active regimen with acceptable toxicity but it is too early to comment on survival and effects of treatment.

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Clinical Analysis of Invasive Papillary Carcinoma of the Breast: Seon Mi Moon, Nam Sun Paik, Nan Mo Moon, Jong Inn Lee, Dong Wook Choi, Woo Chul Noh, Shin Kwang Khang; J Korean Cancer Assoc. 1996;28(6):981-988.

Abstract PDF: Invasive papillary carcinoma of the breast is an uncommon cancer and its incidence in different series ranges between 0.3% and 3% of all breast cancers. It has been reported that in western countries papillary carcinoma generally presents in the seventh decade and is more frequently found in postmenopausal, non-white women. Generally the gross appearance of papillary carcinoma is well circumscribed or may appear to be encapsulated. The size of invasive papillary carcinoma is usually small but varies. Clinically, this tumor has lower freguency rate of axillary nodal involvement and better 5-year or 10-year survival rate than the other common types of breast cancer. To determine clinical and histopathologic characteristics of this tumor, the medical records of 14 women with invasive papillary carcinoma treated at KCCH between 1983 and 1995 were reviewed retrospectively. The results were as follows: ¨c The incidence of invasive papillary carcinama was 0.48% (14/2935) of all breast cancers. ¨e The mean age at the diagnosis was 45.8 years. ¨e The most common clinical manifestatian was a palpable mass. ¨e The mean size of tumor was 4.2 cm in diameter. ¨e The rate of ER positivity was 50%(4/8). ¨i The rate of axillary nodal involvement was 30.8%(4/13). ¨i There was one case of systemic recurrence at 16 months after modified radical mastectomy and the patient expired at 29 months after operation. There was one case of ipsilateral cervical lymph node metsstasis at 21 months after modified radical mastectomy and the patient is still alive. In conclusion, the incidence and prognosis of invasive papillary carcinoma in this study was similar to western series, but the peak age group with invasive papillary carcinoma was younger than in western countries. To determine the clinical, histopathologic chracteristics of Korean papillary carcinoma of the breast, multicenter data should be collected.

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The Induction Chemotherapy with MMM Regimen on Breast Cancer: Eil Sang Chang, Kyung Hun Kim, Ji Young Sul, Wan Hee Yoon, Chin Sun Bae, Ki Sub Son; J Korean Cancer Assoc. 1996;28(6):988-996.

Abstract PDF: At the department of general surgery, college of medicine Chungnam National University, from Mar. 1993 to Oct. 1995, 34 patients with breast cancer were treated with the primary combination chemotherapy with MMM regimen. The MMM regimen was consisted of mitoxantrone, methotrexate, given on days 1 and 21 at a dose of 7 mg/§³, 35 mg/§³ respectively, and Mitomycin-C, given on days 1 at a dose of 7 mg/§³. After 3 cycles of primary chemotherapy, operation was performed in 2 weeks. The results were as follows; 1) The most prevalent age was fifth decade in 12 cases(35.3%) and premenopause was 25 cases(73.5% ). 2) After primary chemotherapy and operation, the axillary lymph node metastasis was not involved in 21 cases(61.8%). 3) The histopathological diagnostic methods were needle biposy in 20 cases(58.8%) and fine needle aspiration cytology in 14 cases(41.2%). 4) After primary chemotherapy, overall objective response rate was 61.8% with complete response, 11.8% and partial response, 50.0%. 5) The down staging effect was happened in 19 cases(55.9%). 6) After primary chemotherapy, berast-preserving operation was performed in 22 cases (64.7% ). 7) Of the side effect, amenorrhea was significant and present in 25 cases, whole premenopausal women.

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Expression of Epidermal Growht Factor Receptor mRNA by In Situ Hybridization in Breast Cancer: Won Jong Lee, Soo Jung Lee, Dong Sug Kim, Koing Bo Kwun, Min Chul Chim; J Korean Cancer Assoc. 1996;28(6):996-1010.

Abstract PDF: Epidermal growth factor(EGF) and epidermal growth factor receptor(EGFR) have been identified as one of the prognostic factor for breast cancer. EGFR status has been determined by several methods including competitive binding assay(BA), immunohistochemical stain(IHC), enzyme immunoassay(EIA). But EGFR could be masked by endogenous ligands in some proportion of tumors. So many different methods have been developed to detect EGFR mRNA. Among these methods, in situ hybridization with biotinylated probe found to be simple and rapid. In addition, it can determine intratumoral heterogenicity in gene expression and identify specific cells that contain a particular mRNA transcript. The author investigated the expression of EGFR mRNA in 81 human breast cancers by in situ hybridization(ISH) and compared the result with EGFR detected by IHC. The author also examined the relationship between EGFR mRNA expression and clinical parameters and other prognostic markers(estrogen receptor, progesterone receptor, p53, c-erbB-2). The author also studied the relationship between EGFR mRNA and recurrence and mortality rate. According to the degree of cytoplasmic staining in ISH assay, negative were 13 cases(16.1%), + were 41 cases(50.6%), ++ were 26 cases(32.1%) and +++ was 1 case(1.2%). The overall expression of EGFR mRNA was 84%. The positive staining of EGFR by IHC was observed either on the cell membrane alone or on both cell membrane and cytoplasm. EGFR by IHC were detected in 69.l%. The 19 cases(23.5%) of EGFR negative cases by IHC were demonstrated as + or more EGFR mRNA by ISH study. On the contrary, 7 cases(8.6%) of EGFR positive by IHC were not detected by ISH. The findings in the majority of the cases were same in two methods. EGFR mRNA had shown a significant positive correlation with c-erbB-2(p<0.009). But an inverse correlation with both estrogen receptor(p<0.027) and progesterone receptor(p<0.02) status, when ++ or more were regarded as positive staining in ISH. There were no correlation was found between positive EGFR by IHC and clinical parameters and other prognostic markers except c-erbB-2(p<0.05). Among the 11 cases of tumor containing both invasive ductal carcinoma and ductal carcinoma in situ(DCIS), there were 5 cases of + and 4 cases of ++ in invasive ductal carcinoma, but negative in these cases of DCIS by ISH. Although the cases with overexpression of EGFR mRNA showed a tendency of more recurrent rate and mortality rate, but there were no statistic significance during the short follow up period (24 months). In summery, EGFR mRNA thought to be a useful prognostic factor especially when over expression is more than ++ by ISH. In situ mRNA hybridization technique is more sensitive and more accurate than immunohistochemistry.

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Significance of Hormaone Receptors and nm23 Protein Expression in Human Breast Cancer: Ki Hoon Jung, Eun Sook Lee, Won Jun Choi, Jeoung Won Bae, Young Chul Kim, Bum Hwan Koo, Chul Hwan Kim, In Sun Kim; J Korean Cancer Assoc. 1996;28(6):1010-1021.

Abstract PDF: The nm23 gene was originally identified by differential hybridization between two murine melanoma cell sublines which have low and high metastatic potential, and located in the chromosome 17q22. This gene has known to be involved in metastasis of several cancers and its down-regulation usually associated with metastasis or disease progression in breast cancer. This study was designed to determine the significance of overexpression of the entimetastatic gene nm23 protein in human breast cancer and to compare it with established clinicopatholoaical prognostic factors such as the tumor size, number of involved lymph nodes, grade of differentiation, and hormone receptor status. 118 surgical specimens, which were obtained from breast cancer between July of 1989 and June of 1993 were used to evaluate nm23 protein expression using immunohistochemical staining. All patients were female. The nm23 protein expression was positive in 74 cases(63%) and was negative in 44 cases(37%). There was a significant inverse relationship between nm23 pratein overexpression and Bloom and Richardson histologic grade(p=0.023). Also overexpression of nm23 was significantly correlated with estrogen and progesterone receptor(p=0.031, 0.001) and with longer disease free survival and overall survival(p=0.0048, 0.0026). In conclusion, nm23 protein overexpression is one of good prognostic indicators independently in human breast cancer.

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Analysis of Recurrence and Survival Rate in Early Gastric Castric Cancer Patients: Seong Kwang Chang, Nam Sun Paik, Nan Mo Moon, Ho Yoon Bang, Jong Inn Lee, Dong Wook Choi; J Korean Cancer Assoc. 1996;28(6):1021-1032.

Abstract PDF: The prognosis of surgically treated early gastric cancer(EGC) is usually excellent and the recurrence rate is quite low. From January l985 to December l993, 708 cases of EGC among 4408 cases of gastric cancer underwent gastrectomy in Korea Cancer Center Hospital. Among them 619 cases could be followed-up, and disclosed 24 cases(3.9%) of recurred EGC. 5 and 10 year survival rate in EGC exclusive of other cause of death were 95.8% and 95.4%. Mean interval between surgery and recurrence was 31.7 month and mean survival time was 40.3 month. Retrospective analysis was performed to evaluate the clinicopathological factors which relate to recurrence and survival rate. In univariated and multivariated analysis of factors, statistically significant prognostic factors are regional lymph node metastasis and macroscopically elevated type(p<0.05). Mode of recurrence in EGC was commonly hematogenous metastasis(69.7%), and frequent metastatic sites were liver, bone and lung

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Histocompatibility Antigens in Primary Gastric Carcinoma in Young Korean Adults: Tai Ho Chung, Jung Chul Kim, Da Mi Lee, Suk Joo Lee, Soo Il Chang, Wan Sik Yu, In Sun Lee; J Korean Cancer Assoc. 1996;28(6):1032-1040.

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Immunohistochemical Analysis of Transforming Growth Factor - β Isoforms ( TGF-β1 , TGF-β2 , TGF-β3 ) Expression in Gastric Adenocarcinoma: Jae Hyung Yoo, Weon Sub Park, Mi Kyung Kim, Tae Jin Lee, Sang Jun Lee; J Korean Cancer Assoc. 1996;28(6):1040-1050.

Abstract PDF: Immunohistochemical studies using polyclonal antibodies to transforming growth factor beta isoforms(TGF-￥a1, TGF-￥a2 & TGF-￥a3), a multifunctional regulatory proteins which hoave effects on normal and transformed cells, were performed on 66 cases of gastric adenocarcinomas in order to analyze the relationship between expression of these isoforms in gastric cancer cells, adjacent mucosa of the cancer and normal control gastric mucosa. In addition to determine the relationship between expression of TGF-￥a isoforms and various clinicopathological states, including tumor location, histologic types, regional lymph node metastasis and depth of invasion of tumors were carried out. The positive staining reactivity was detected within the cytoplasm and on the cell membrane. The rate of TGF-￥a isoforms expression in gastric adenocarcinomas were 47% in TGF-￥a1, 83% in TGF-￥a2, and 27% in TGF-3, respectively. The adjacent gastric mucosa from adenocarcinomas and normal control mucosa were 40 % in TGF-￥a1, 40% and 55% in TGF-￥a2, 20% and 33% in TGF-￥a3, respectively. Among the TGF-￥a isoforms, TGF-￥a2 was strongly associated with histologic differentiation and regional lymph node metastasis. No significant association was found between expression of TGF-￥a isoforms and tumor location, histologic types and T-stages. From these results, we can postulate that the altered expression of TGF-￥a isoforms, especially TGF-￥a2, play an important role in histogenesis and gastric cancer progression and regional lymph node metastasis.

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Determination of Preoperative Serum CEA Level in Curativeal Resected Gastric Cancer: Jin Hyuk Choi, Sun Young Lee, Kang Sup Shim, Hye Young Son, Ki Youl Seo, Jong Seon Kim, Jin Ah Park, Eun Soon Hong, Hyo Jeong Kim, Su Young Park, Min Gyeu Hwang, Kang Sup Shim; J Korean Cancer Assoc. 1996;28(6):1050-1055.

Abstract PDF: Background
Although the role of serum carcinoembryonic antigen(CEA) as a tumor marker in gastric cancer remains unanswered, several reports suggested the usefulness of serum CEA as prognostic factor or indicator of recurrence. Methods: Preoperative serum levels of CEA were determined in 79 patients with curatively resected gastric cancer and its correlation with clinicopathologic characteristics was investigated. Results: Serum CEA was positive(defined as>5ng/ml) in 16 patients(20.3%). The mean age of CEA positive group(62.9¡¾7.5 years) was significantly older than that of the negative group(53.2¡¾12.7 years)(p=0.005), and Borrmann type III cases were more frequent in CEA positive group(56.3% vs. 19.0%)(p=0.026). There were no significant differences between two groups in other clinicopathologic characteristics, including tumor size, tumor location, differentiation of tumor, and stages. Conclusion: Serum CEA does not seem to be standard. tumor marker of gastric cancer, in terms of screening or diagnosis. However, it could be useful as prognostic factor or for early detection of recurrence in curatively resected gaxtric cancer

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Prognostic Fastors in Gastric Leiomyosarcoma: Jin Suk Hu, Han Kwang Yang, Ik Jin Yun, Jong Kwon Park, Gyeong Hoon Kang, Ja June Jang, Seung Keun Oh, Jin Pok Kim, Ja June Jang, Dong Young Noh, Yeo Kyu Yong, Seung Keun Oh, Kuhn Uk Lee, Kuk Jin Choe; J Korean Cancer Assoc. 1996;28(6):1055-1061.

Abstract PDF: Objectives
The aim of our study was to analyze prognostic factors in gastric leiomyosarcoma. Method: We retrospectively reviewed the medical records of 33 patients with pathologcally proven leiomyosarcoma diagnosed from 198l through August 1995. All 33 gastric leiomyosarcoma were histologically confirmed by the pathologist. The factors analyzed are patient age, sex, tumor location, surgical procedure, tumor size, histologic grade, p53 and nm23. Expression of p53(positive vs. negative) and type of nm23 expression(diffuse vs. granular) were measured by immunohistochemical staining in 25 surgically resected specimens. The survival curves obtained by Kaplan-Meyer methods were compared using Log-rank test. Result: The 33 patients represents 0.39% of all patients with 8370 gastric cancer patients presenting during the same period. There were 23 males and 10 females. The mean age at the time of diagnosis was 57 years. Forty percent(13/33) of the tumors were located in the body, 30% (10/33) in fundus and 21%(7/33) in cardia of the stomach. Only three tumors(9%) were located in the antrum. Twenty seven of these tumors were treated by radical gastrectomy and 6 were treated by wedge resection. Histologically, 34.9% were low grade and 65.1% were high grade. Metastatic involvement was noted in four of patients at the time of diagnosis. p53 overexpression was positive in 28%. nm23 expression was positive in all cases; 72% were diffuse type and 28% were granular type. The 5-year survival rates of all cases were 79% and the 5-year disease free survival rates were 52%. Among the factors analyzed, the tumor size was the only significant prognostic factor. 5 year survival rete was 100% for tumors less than 10cm(n=16) and 55% for tumors larger than 10cm(n=l7). Tumor size and tumor grade were significant prognostic factor in disease free surviva. Conclusion: Our data suggest that leiomyosarcoma representing very small portion of gastric cancer were more commoly located in the upper part of stomach. Variables such as age, sex, tumor lacation, type of surgery, p53 overexpression and type of nm23 expression did not have prognostic significance. Tumor size was the only significant prognostic factor in overall survival(p<0.05). Tumor size and tumore grade were significant factors in disease free survival(p<0.05). The authors believe that these data will provide selection criteria for future clinical studies.

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Expression of Transforming Growth Factor - α in Hepatocellular Carcinoma: l Gyoon Cho, Sang Woo Choo, Soo Jin Na Choi, Young Jin Kim, Hyun Jong Kim, Gyung Soo Kim, Chang Soo Park; J Korean Cancer Assoc. 1996;28(6):1061-1071.

Abstract PDF: Transforming growth Factor-￥a(TGF-￥a) which is thought to be associated in various pysioiogic processes of human body acts as the regulator of normal growth and regeneration of hepatocyte in the liver. There are many reports that TGF-￥a over-expression is observed in some kinds of human cancers, and recent animal experiments using the cancer cell lines prove that hepatocellular carcinoma(HCC) is developed in transgenic mice created with TGF-￥a gene. It is considered, therefore, that overexpression of TGF-￥a relates to the carcinogenesis of HCC. In this study, we tried to observe the expression of TGF-￥a in human HCC by immunohistochemical staining and to characterize the expression pattern according to the various clinicopathological features such as histologic type and grade of tumor, tumor size, serum AFP level, HBsAg status and preoperative hepatic artery embolization. The specimens in this study were 15 cases of HCC and 10 cases of normal liver as a control group. In cases of HCC, we examined both tumor tissue itself and adjacent non-tumorous liver tissue. Immunohistochemical staining of the specimen was performed using monoclonal Ab to recombinant human TGF-￥a by avidine-biotine-peroxidase complex technique. To see the expression rate of TGF-￥a protein in HCC, 13 cases(86.7%) out of total 15 cases were positive in tumor tissue itself and in adjacent non-tumorous tissue respectively. In the normal liver tissue, only 1 case(10.0%) showed positive expression of TGF-￥a protein. Evaluating the TGF-￥a expression in HCC according to clinicopathologic features, serum HBsAg status was related to the intensity of expression and preoperative hepatic artery embolization to the extent of expression with statistical significance, but histologic type and grade of tumor, tumor size and serum AFP level had no significanct association.In conclusion, we observed the overexpression of TGF-￥a in HCC,which may be associated with the carcinogenesis of human HCC.

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Immunologic and Oncogenic Study on the Cervical Neoplasia: Eun Yeong Seol, Sung Chul Lim; J Korean Cancer Assoc. 1996;28(6):1071-1083.

Abstract PDF: Immune response commonly is cited as a determining factor in the development or clearance of various neoplasias, but the immunobiology of neoplastic progression is poorly understood. The cervix has the largest concentration of lymphocytes found in the female genital tract and as a component of the common mucosal immune system guards against ascending infection from the microbial-laiden vagina, but cervical immunocytes have not been well characterized in the neoplasia itself. The objective of this study is to characterize the subpopulations of lymphocytes that infiltrate various grades of cervical neoplasia including metaplasia to invasive carcinoma. To establish the correlation I examined 60 cases of uterine cervix which were divided 4 categories according to the Bethesda Classification system; normal cervix(15), low grade squamous intraepithelial lesions(SILs)(15), high grade SILs(15), and invasive squamous cell carcinomas(15 cases). The degrees of T-lymphocyte infiltration were assessed after immunohistochemical staining by UCHL1, and compared to stainability of aberrant p53 and bcl-2 protein. There were significant increasing number and proportion of T-cells of invaisve cancers compared with that of preinvasive lesions. Aberrant p53 expression of invasive cancer was a little more intensive than that of low grade and high grade SILs, and there was no correlation between T-cell infiltration and aberrant p53 and/or bcl-2 expression. Bcl-2 was expressed in most of basal layer and some cases of parabasal layer of low and high grade SILs, and some minute foci of invasive cancer. In the adjacent areas of SILs and invasive lesions strong bcl-2 expression was noted in parabasal, intermediate or superficial cells case by case. In conclusion, the UCHLl-positive T cell infiltrate far exceeded in the invasive, but not in the preinvasive lesions, a finding that suggests that T cells are recruited preferentially to cervical lesions with progression to invasion. It is suggested that the T cell recruitment is not related to p53 or bc1-2, but the unknown third factors, and the bcl-2 overexpression is involved in the early step of epithelial neoplastic transforrnation and followed by recurrent overexposure to various oncogenic factors.

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Clinical Significance of Interleukin-6 and its Production in Patients with Renal Cell Carcinoma: Sung Goo Chang, Sun Ju Lee, Jai Kyung Park; J Korean Cancer Assoc. 1996;28(6):1083-1092.

Abstract PDF: Interleukin-6(IL-6) is a multifunctional cytokine with many biologic activities in vitro, including synergistic or antagonistic actions with one ar more other cytokines. The role and induction parameter of IL-6 in renal cell carcinoma(RCC) are not fully understood. To understand the capabilities of RCC to produce IL-6 and its clinical significance, we have determined the IL-6 level in the serum and urine of RCC patient at pre-treatment and during post-treatment follow up. From the results of study, we conclude there was no correlation observed between serum IL-6 level and tumor size or disease progression of RCC. There was no correlation between level of serum IL-6 and urine IL-6. The urine IL-6, however, was increased in case of renal vein thrombosis or renal capsular invasion and it was mainly increased at before operation. The IL-6 of serum and urine in patients was markedly increased after angioinfarction of RCC. There was no correlation between serum IL-6 level and synthesis of serum C-reactive protein. Therefore, measurement of urine IL-6 at preoperative period will be have more significance than those of serum IL-6 in patient with renal cell carcinoma.

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Neoadjuvant Chemotherapy with High-dose Methotrexate , Adriamycin and Cisplatin for Non - Metastatic Osteosarcoma: Keun Seok Lee, Heung Moon Chang, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim, Sang Hoon Lee, Eui Keun Ham, Han Ku Lee; J Korean Cancer Assoc. 1996;28(6):1092-1104.

Abstract PDF: three non-metastatic osteosarcoma patients were treated with high-dose methotrexate, adriamycin, and cisplatin from October 1987 to May 1993. Median age was 18. The ratio of male to female was 16: 7. The patients received methotrexate 8g/§³ IV, day 1 and 8 with leucovorin rescue, adriamycin 25mg/§³ IV day 16~18, and cisplatin 75mg/§³ IV day 16, After two cycles of neoadjuvant chemotherapy, operation was done and then six cycles of adjuvant chemotherapy were given with the same regimen. One patient developed lung metastasis after two cycles of neoadjuvant chemotherapy, and the other patient died from sepsis associated with chemotherapy-induced neutropenia before operation. Therefore, 21 patients underwent operation. Among them, l9 patients underwent limb salvage operation. Of the five patients who relapsed, two patients had lung metastasis and another two patients had local recurrence, and one patient had both lung and brain metastasis. One year, three year, and five year disease-free survival rate were 84%, 68%, and 68%. One year, three year, and five year survival rate were 91%, 64%, and 53%, respectively. The site of the primary lesion was the only significant prognosis factor. Patients with the lesion of distal femur had poor prognosis.Histologic responses were assessed in 17 patients. Observed histologic responses were grade I necrosis in 35%, grade II necrosis in 65%. There was no grade III or IV necrosis. The disease-free survival rates and overall survival rates were not significantly different between grade I necrosis group and grade II necrosis group. Toxicities grade III or IV were as follows: leukopenia 32%, thrombocytopenia 9%, hepatotoxicity 14%, and infection 6% with one chemotherapy-related death. The pharmacokinetics of high-dose methotrexate with leucovorin rescue were studied in l0 patients. The highest concentration was achieved at the end of infusion(6 hour). The decay of the plasma concentration of methotrexate after completion of the infusion followed a two-compartment model with a T(1/2)￥a of 3.4¡¾1.9 hours and T(1/2)￥a of 8.0¡¾2.6 hours. The clearance was 55¡¾13ml/min/§³ and the volume of distribution was 8.2¡¾3.0 L/§³. In conclusion, neoadjuvant chemotherapy with high-dose methotrexate, adriamycin, and cisplatin is effective for treatment of the patients of osteosarcoma with preserving the limb function.

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Effect of Combined Modality Treatment and Clinical Significance of P-Glycoprotein Overexpression in Patients with Osteosarcoma: Yong Seok Yun, Jae Kyung Roh, Hyun Cheol Chung, Jae Yong Cho, Kyoo Ho Shin, Soo Bong Han, Beom Seok Kim, Joon Oh Park, Soo Jung Gong, Sun Young Rha, Nae Choon Yoo, Joo Hang Kim, Jin Sik Min, Byung So; J Korean Cancer Assoc. 1996;28(6):1104-1117.

Abstract PDF: Osteosarcoma is a highly malignant bone tumor and usually encountered in the first three decades of life. The Prognosis of osteasarcoma treated with surgery alone had been poor, with 20% of the patients surviving 5 years. The addition of adjuvant chemotherapy after surgery has siginificantly improved the outcome of osteosarcoma. The new concept of pre-operative chemotherapy has permitted histological assessment of treatment effect and limb salvage procedures. As the role of chemotherapy has been raised, the resistance of tumors to multiple drugs, such as p-glycoprotein overexpression, has become a major problem in the treatment of osteosarcoma. We retrospectively reviewed the clinical records of 53 patients with stage IIB osteosarcoma who were treated at Yonsei Medical Center and Yonsei Cancer Center between March 1, 1986 and June 30, 1996. The purpose of this study was to assess the efficacy and toxicity of cisplatin(IA)-adriamycin(IV) combination pre-operative chemotherapy and the clinical significance of p-glycoprotein status and histologic response as prognostic factors. Among 53 patients, 33 were male and 20 were female with a median age of 21 years(range: 5~61). The tumor locations were as follows: distal femur 24(45.3%), proximal tibia 17(32.1%), humerus 7(13.2%), proximal femur 3(5.4%), fibular 1(1.9%), radius 1(1.9%). Histologic subclassifications were as follows: osteoblastic type 42(78.2%), telangiectatic type 4(7.5%), chondrablastic type 3(5.7%), fibroblastic type 2(3.8%) and undetermined 2(2.8%). The three year overall survival and disease-free survival rates were 66.1% and 61.9% respectively in all patients. Thirty-two patients were treated by pre-operative cisplatin(IA)-adriamycin(IV) combination chemotherapy and 21 patients were taken only post-operative adjuvant chemotherapy. No significant difference was found between the two groups in probability of survival and recurrence rates. The histological response ta pre-operative chemotherapy was scored by degree of tumor necrosis. Twenty-two patients had a good response [grade IV, 13(40.6%);grade III, 8(25.0%)] and 11 patients had a poor response [grade II, 6(18.8%);grade I, 5(15.6%)]. The histological response was not significantly related to the probability of the survival rate. However, the recurrence rate was higher in the poor-response group(p=0.04). Overexpression of p-glycoprotein was found in tumors from 11 of l8 patients(61.1%) who were given only post-operative adjuvant chemotherapy. No relation was found between the p-glycoprotein expression and survival rate. The degree of tumor necrosis after pre-operative chemotherapy and initial serum alkaline-phosphatase level were considered as prognositic factors. Other clinicopathologic features including age, gender, anatomical site, histological subclassification,operation types,tumor size.p-glycoprotein expression were not associate with patient outcome. Treatment-related side effects were relatively tolerable and reversible by conservative treatment. Pre-operative cisplatin(IA)-adriamycin(IV) combination chemotherapy in our study did not show improved survival than conventional post-operative chemotherapy with limited follow-up duration. The degree of histologic response after chemotherapy and the initial alkaline phosphatase level were found to be the major predictor for tumor recurrences, while p-glycoprotein overexpression did not alter the clinical outcome. Further studies are warranted to improve the efficacy of adjuvant chemotherapy and to evaluate the significance of multiple resistance gene overexpression in osteosarcoma.

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Primary Central Nervous System Lymphoma ( PCNSL ) : Treatment Result: Hong Gyun Wu, Il Han Kim; J Korean Cancer Assoc. 1996;28(6):1117-1126.

Abstract PDF: Purpose
This study analyzed the treatment results and the prognostic factors of PCNSL. Patients and Methods: Surgical procedures were performed in 24 among 29 patients; 4 gross total removal, 9 subtotal removal, 11 open or stereotactic biopsy. Radiation fields include whole brain and reduced brain field. Whole spine field was used in 6 patients and local spinal field was used in 1 patient. The range of radiation dose to primary site was 4460 cGy to 5940 cGy with fractional dose of 180 cGy to 200 cGy. Systemic chemotherapy (6 cycles with CHOP) was used in 6 patients. Intrathecal methotrexate was used in 2 patient. Reeult: Follow-up range was 4 to 65 months. Median survival was 15 month and 2 year overall survival rate was 38%. Radiation dose and systemic chemotherapy were significant prognostic factors. Two year survival rate was 13% with dose less than 50 Gy, 49% with dose greater than or equal to 50 Gy (p=0.05). When the patients were treated radiation alone, 2 year survival rate was 27% and was 80% with radiation therapy combined with systemic chemotherapy (p=0.02). Conclusion: At least, 50 Gy should be given to PCNSL. We could not find any benefit from the prophylactic whole spinal irradiation. Survival benefit with combined chemotherapy should be confirmed after long-term analysis.

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A Case of Gastric MALT Lymphoma Successfully Treated with Anti - Helicobacter pylori Therapy: Byung Soo Kim, Tae Jin Song, Jae Seon Kim, Sang Won Shin, Yeul Hong Kim, Jong Guk Kim, Chul Woo Kim, Jun Suk Kim; J Korean Cancer Assoc. 1996;28(6):1126-1133.

Abstract PDF: A 44-years old female was adimitted to Guro Hospital because of epigastric pain. Endoscopy showed several small sized and slightly depressed erythematous 1esions on the greater curvature of upper antrum. Endoscopic biopsy was done. The microscopic examination of the biopsy specimens showed mucosa associated lymphoid tissue(MALT) lymphoma lesions at gastric submucosa with the invasion of B lymphocytes forming lymphoepithelium and many foci of Helicobacter pylori(H. pylori) infection. Therefore, the treatment to H. pylori with the combined prescription with omeprazole, amoxycillin, and metronidazole was done for 2 weeks. The follow-up endoscopic biopsy was done at 1 month after the end of antimicrobial therapy. The follow-up biopsy specimens showed only mild gastritis lesions without the invasion of B lymphocytes and H.pylories. Hence, we present a case of MALT gastric lymphoma associated with H. pylori infection and successfully treated with anti-H. ori therapy.

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A Case of Relapse in Central Nervous System during the Chemotherapy of Testicular Lymphoma Stage 1: Wook Sun Choi, Si Young Kim, Jeong Hee Kim, Hwi Joong Yoon, Kyung Sam Cho; J Korean Cancer Assoc. 1996;28(6):1133-1139.

Abstract PDF: Primary testicular non-Hodgkin's Lymphoma is very rare. It may be the systemic manifestation of nodular lymphoma. The most common symptom of primary testicular lymphoma is the painless enlargement of testis. It frequently involves Waldeyer's ring, skin and central nervous system. The combination chemotherapy and CNS prophlylaxis may be needed in the treatment of early stage primary testicular non-Hodgkin's lymphoma. We are reporting a case of primary testicular non-Hodgkin's 1ymphoma stage I, which relapsed in central nervous system during combination chemotherapy.

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