Cancer Research and Treatment

Volume 31(1); February 1999

Original Articles

Alterations of the DPC4 Gene in Human Stomach Cancers: Jeong Wook Kim, Jun Hyun Joe, Chul Moon, Cheol Heang Heo, Sae Kyung Chang; J Korean Cancer Assoc. 1999;31(1):1-8.

Abstract PDF: PURPOSE
Allelic loss on chromosome 18q is a hallmark of presence of a tummor represser gene. Recently, DPC4 (deleted in pancreatic carcinoma, locus 4), a candidate tumor suppressor gene, has been localized at 18q21. Inactivation of DPC4 gene was reported in pancreatic carcinomas, coloretal carcinomas, and prostatic carcinomas. The aim of the present study was to determine if it might be altered in stomach cancer.
MATERIALS AND METHODS
We tested for DPC4 gene mutations and allelic status at 18q21 using a modified 'cold SSCP' method in 48 primary gastric carcinoma and correlated the findings with various clinicopathologic characteristics of the patients.
RESULTS
The frequency of mutations in primary gastric cancer was 27.1% (13/48). Mutations of exon 1, 8, 10 were found in 2 (4.1%), 4 (8.2%) and 7 cases (14.6%), respectively. DNA sequencing of 13 cases with DPC4 mutations identified six cases (46.1%) with substitution, four cases with deletion (30.7%), and two cases (23.1%) with insertion. No significant difference was observed in the frequency of DPC4 mutations in terms of other various clinicopathologic characteristics.
CONCLUSION
These findings suggest that DPC4 mutations may play a significant role in the establishment and progression of the primary gastric cancer.

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Correlation of Radiologic and Pathologic Lymph Non Involvement with TIMP-2 ( tissue inhibitors of metalloproteinase-2 ) in Gastric and Colon Carcinomas: Soo Youn Ham, Jong Hwa Lee, Byung Kyun Ko, Hong Rae Cho, Dae Wha Choi, Chang Woo Nam, Sung Sook Kim, Woon Sup Han, Min Young Kim; J Korean Cancer Assoc. 1999;31(1):9-15.

Abstract PDF: PURPOSE
To evaluate the correlation between the expression of TIMP-2 (tissue inhibitors of metalloproteinase-2) and negative lymph node involvement of colon and gastric carcinoma.
MATERIALS AND METHODS
We studied 26 cases (13 each) of gastric and colon carcinoma specimens along with dissected lymph nodes by immunohistochemical staining to investigate the correlation of the expression of TIMP-2. Lymph nodes involvement by CT scan was defined by size criteria and the presence of central low density.
RESULTS
Eight cases with positive lymph node involvement by CT scan showed weak expression of TIMP-2. Ten cases with positive lymph node involvement had weak expression of TIMP-2. Among eight cases with strong expression of TIMP-2 7 patients were negative by radiologic exam. Good correlation between strong TIMP-2 expression and negative lymph node involvement by CT scan was found (<0.05).
CONCLUSION
As the expression of TIMP-2 had a good correlation with radiologic involvement of lymph nodes, the study of expression of TIMP-2 in patients with stomach and colon carcinoma might be helpful in planning surgery and predicting the prognosis.

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Clinicopathologic Significance of Lymphatic Vessel Invasion and Blood Vessel Invasion in Gastric Cancer: Sang Wook Kim, Ki Hyeok Lah, Chang Hak Yoo, Yong Il Kim, Sung Hoon Noh, Jin Sik Min; J Korean Cancer Assoc. 1999;31(1):16-23.

Abstract PDF: PURPOSE
The vessel invasion by cancer cells can be easily detected with the photomicroscope, but still there is an arguement on the value as a prognostic factor. The following study was conducted to evaluate the clinicopathologic significance of blood vessel invasion (BVI) and lymphatic vessel invasion (LVI) as a potential prognostic factor in gastric cancer treatment.
MATERIALS AND METHODS
618 patients who had undergone gastrectomies for gastric cancer at the Department of Surgery, Yonsei University College of Medicine, from August, 1993 to December, 1994, were retrospectively reviewed. Patients, based on the presence of BVI and/or LVI by HE stain, were arranged into three groups: Group 1 (n=338) consisted of patients with no evidence of BVI and LVI; group 2 (n=224), with evidence of either BVI or LVI; group 3 (n=56), with evidence of both BVI and LVI. The clinicopathologic features were analyzed and the survival rates of BVI, LVI and the three groups were studied.
RESULTS
BVI-positive patients were seen in 10.5% of all patients, and LVI-positive, in 43.9%. Certain factors such as tumor size, gross type, depth of invasion, lymph node metastasis, distant metastasis, and TNM staging showed significant differences among the three groups by univariate analyses. Survival rates between the BVI-positive (48.1%) and the BVI-negative (73.9%) and between the LVI-positive (55.4%) and the LVI-negative (82.6%) showed significant differences. 3-year survival rates of group 1, 2, and 3 were 82.5%, 59.7%, and 42.0%, respectively, with significant differences. But multivariate analysis demonstrated that distant metastasis, lymph node metastasis, depth of invasion, age, and gross type served as significant prognostic parameters while BVI and LVI did not.
CONCLUSION
Patients with BVI and/or LVI were associated with larger tumor size, infiltrative type tumor, deeper gastric wall invasion, more lymph node metastases, and advanced stages of tumor. BVI and LVI also played significantly adverse influence in the survival time in univariate analysis. With further studies on their roles in clinicopathologic features, lymphovascular invasion would be a useful prognostic factor in gastric cancer.

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Free Cancer Cell Detection in Peritoneal Cavitr of Gastric Cancer Patients by RT-PCR for CEA: See Young Kim, Jong Inn Lee, Nan Mo Moon, Nam Sun Paik, Dong Wook Choi, Ho Yoon Bang, Woo Chul Noh; J Korean Cancer Assoc. 1999;31(1):24-30.

Abstract PDF: PURPOSE
This study is aimed to evaluate the efficacy of a novel method (RT-PCR for CEA) to diagnose free cancer cells in peritoneal cavity of gastric cancer patients, which can be used as a indication of prophylactic treatment to prevent peritoneal recurrence after curative resection of gastric cancer.
MATERIALS AND METHODS
114 gastric adenocarcinoma patients were included for this study. With pellet of peritoneal washing fluid, cytology and RT-PCR for CEA were performed with specific primers.
RESULTS
Positive rate of PCR as a whole was 55.3% (63 cases); however, that of cytology was 15.8% (18 cases). Positive rate of PCR increased with depth of invasion of the lesion (p=0.026); however, that of cytology didn't (p=0.233). In early gastric cancer and seeding cases, PCR was not more sensitive than cytologic examination in detection of free cancer cell, but in pm, ss and si cancers, PCR was much more sensitive than cytology (p<0.001).
CONCLUSION
PCR was more sensitive to diagnose free cancer cells in peritoneal cavity of gastric cancer patients especially in pm, ss and si cancers than conventional cytologic examination, and it can be a good candidate of indication of prophylactic treatment to prevent peritoneal recurrence after curative resection.

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Clinical Results of Para-aortic Lymph Node Dissection in Advanced Gastric Cancer: Ik Haeng Jo, Dae Hyun Yang, Jin Pok Kim, Won Jin Choi, Il Myung Kim, Jin Youn, Sang Su Park, Byung Ook Yoo, Seung Ik Ahn, Shin Eun Choi; J Korean Cancer Assoc. 1999;31(1):31-42.

Abstract PDF: PURPOSE
In gastric cancer, metastasis to the paraaortic lymph nodes had been regarded as an incurable factor, but many cases of long term survival have been reported with dissection of metastatic paraaortic nodes. And several reports suggested survival benefit with paraaortic lymph node dissection (D4) in advanced gastric cancer. In patients with advanced gastric cancer who underwent paraaortic lymph node dissection we tried to evaluate the factors predisposing metastasis in these nodes and survival data.
MATERIALS AND METHODS
The authors analyzed retrospectively pathological features of 95 patients who underwent paraaortic lymph node dissection for advanced gastric cancer at Kangnam General Hospital Public Corporation from May 1991 to Feb. 1998. And we also analysed survival results of 72 cases among them. We excluded 18 cases of distant metastasis (3 liver metastasis, 15 peritoneal seeding), 2 operative mortalities, 1 other disease mortality, and 2 unknown causes of death in survival analysis.
RESULTS
The frequencies of paraaortic lymph node metastasis were 0.0% (0 of 32 cases) in T2, 19.2% (10 of 52 cases) in T3, 18.2% (2 of 11 cases) in T4. And those of paraaortic lymph node metastasis were 5.8% (3 of 52 cases) in antrum, 14.3% (3 fo 21 cases) in body, 20.0% (3 of 15 cases) in cardia, and 42.9% (3 of 7 cases) in whole area. The five-year survival rates (5 YSR's) in relation to the paraaortic lymph node (No16) status was 0.0% in No16 , and 57.8% in No16 with D4 of advanced gastric cancer. The 5 YSR's were 78.1%, 40.8% and 0% in T2, T3 and T4, respectively and 93.8%, 64.2%, 24.2% and 0.0% in n0, n1, n2 and n3, respectively and 88.9%, 80.5%, 57.9% and 0.0% (47.6%) and 0.0% in stage IB, II, IIIA, IIIB and IV, respectively.
CONCLUSION
The depth of gastric wall invasion and the location of primary tumor were significant predisposing factors to para-aortic lymph node metastasis in multivariate analysis (p<0.05). Survival of No16 metastasis was very poor. And three factors of T stage, n stage, and Borrmann type were also prognostically significant in terms of five year survival in cases of D4 of advanced gastric cancer in multivariate analysis (p<0.05).

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Comparision between New Version of UICC-TNM Classification with Old Versions Including Japanese Classifications of Gastric Cancer Patientw: Sung Sik Bae, Jong Inn Lee, Nan Mo Moon, Nam Sun Paik, Dong Wook Choi, Dae Yong Hwang, Ho Yoon Bang, Woo Chul Noh; J Korean Cancer Assoc. 1999;31(1):43-53.

Abstract PDF: PURPOSE
This study was designed to examine the reliability and easy applicability of new version of UICC-TNM classification (UICC, 1997) compared with old version of UICC-TNM classification (UICC, 1992) and JRSGC (Japanese Research Society for Gastric Cancer) classification of gastric cancer.
MATERIALS AND METHODS
For 1043 patients who underwent curative resection from Jan. 1992 to Dec. 1996 in Korea Cancer Center (KCCH), old version of UICC-TMN classification and JRSGC classification were compared with the new version of UICC-TNM classification.
RESULTS
Correlation coefficient between topographic classification (old UICC-TNM, JRSGC) of lymph node and numeric classification was 0.9 (p<0.05). 5-year survival rates according to old UICC, TRSGC, new UICC classification were 94.9% at stage Ia; 96.6, 96.5, 97.1% at stage Ib; 73.8, 73.8, 73.0% at stage II; 54.1, 55.8, 58.0% at stage IIIa; 35.5, 42.0, 36.0% at stage IIlb; 25.9, 22.3, 23.9% at stage IV. 5-year survival rates of each classification had significant difference among stages (p<0.0001), but there was no significant difference among each classification.
CONCLUSION
The new version of UICC-TNM classification based on the number of involved lymph nodes allows a staging system as reliable as the old version of UICC-TNM and JRSGC classification. In addition, the new version of UICC-TNM classification can be applied without methodologic problems and seems more convenient and reproducible.

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Evaluation of the New UICC Staging System for Gastric Carcinoma: Hyeong Myeong Back, Sung Joon Kwon, Oh Jung Kwon, Pah Jong Jung, Kwang Su Lee, Jin Young Kwak, Kyu Young Jun, Chi Kyu Won; J Korean Cancer Assoc. 1999;31(1):54-61.

Abstract PDF: PURPOSE
There are several kinds of classificatian dealing with the staging of the gastric adenocarcinoma. However, such different staging systems pose difficulty in the inter- institutional or intemational comparison of the disease status and the treatment results. The purpose of this study is to evaluate each staging system and to assess the usefulness of the new UICC-TNM staging system (1997) for gastric adenocarcinoma. MATERIAL AND METHODS: We retrospectively analysed 473 cases of gastric adenocarcinoma who were operated at the Department of General Surgery, Hanyang University Hospital during the period from 1992 to 1996. Using these cases, we analyzed their cumulative 5-year survival rate according to three kinds of staging systems; old UICC-TNM staging system (1987), new UICC-TNM staging system (1997), and the Japanese staging system for gastric carcinoma (1993).
RESULTS
The follow up rate was 94.3% and the median follow up period was 30.3 months. All of these three systems showed a statistically significant survival difference according to their different classifications. When the distribution of stage between old and new UICC-TNM staging system was compared, 95 cases (20.1%) were subjected to stage shifting, which involves 12.1% of up-staging and 8.4% of down-staging. Stage shifting was most prominent in stage IIIb (68.8%). The cumulative 5-year survival rate according to the new UICC-TNM staging system was 99.1% in stage Ia, 81.4% in stage Ib, 75.2% in stage II, 45.9% in stage IIIa, 21.0% in stage IIIb, and 19.4% in stage IV.
CONCLUSION
We conclude that the new UICC-TNM staging system is simple, practically convenient, and highly reproducible, and it showed a statistically significant survival difference according to their staging classification.

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Clinicopathologic Findings of Early Gastic Cancer: Young Bae Ko, Won Gon Kim, Joon Mee Kim; J Korean Cancer Assoc. 1999;31(1):62-71.

Abstract PDF: PURPOSE
The prognosis forearly gastric cancer (EGC) is generally excellent after curative gastrectomy alone. However, the EGC of young patients was generally more invasive and metastasizing, and the prognosis of them was poorer than those of the elderly. We performed a retrospective study to evaluate clinica1 and pathological factors influencing the prognosis of EGC.
MATERIALS AND METHODS
The authors investigated 66 cases of EGC resected at Inha Hospital in Song-Nam, from January 1987 to December 1996. We analyzed 9 clinicopathologic factors: age, sex, macroscopic type, tumor size, depth of invasion, location, lymph node metastasis, Williss classification and Laurens classification.
RESULTS
Out of 66 cases (42 males, 24 females) of EGC, the sex ratio (M: F) was 1.75: 1, and the mean age was 55.5 years in male and 54.3 in female. The age incidence revealed a greater prevalence on 6th decade (33.3%). The most common macroscopic type of EGC was IIb and its combined type (43 cases, 65.2%). In tumor size, 16 cases (24.2%) were between 2.0 and 2.9 cm, and 13 cases (19.6%) between 1.0 and 1.9 cm, 10 cases (15%) between 3.0 and 3.9 cm. The tumors smaller than 2.0 cm were 33.2% but greater than 5.0 cm were 18.8%. In male, mucosal lesions were more common (66.6%) than submucosal lesions (33.4%); but in female, the incidence of both types of lesions were the same. The submucosal lesion in female was the most frequent at 4th decade. The major location of EGC was antrum (51.5%). Lymph node metastases were found in 3 females and 1 male. By Williss classification, poorly differentiated adenocarcinoma and signet ring cell carcinoma were more common in female (29.2%, 25%) than in male (11.9%, 14.3%). By Laurens classification, the diffuse type was more common in female (50%) than in male (33.3%). This type was the most frequent in 4th decade female patients. However, none of the above data reached statistical significance.
CONCLUSION
We found the generalized tendency, though not statistically confinned, that the young female patients of EGC frequently had larger and poorly differentiated, diffuse adenocarcinomas with more frequent lymph node metastasis than male. The authors emphasizes that a further study would be needed in young female patients of EGC on hormonal factors influencing its clinicopathologic findings.

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Relation between Body Size and Body Mass Index and Breast Cancer by Menopausal Status in Korea: Se Hyun Ahn, Mi Kyung Kim, Suk Il Kim; J Korean Cancer Assoc. 1999;31(1):72-81.

Abstract PDF: PURPOSE
Because the breast cancer is one of the major causes of mortality among women, it is important to identify modifiable risk factors for this disease. Some reported that overweight/obesity is a risk factor for breast cancer, but the results are not consistent. Human breast cancer has different characteristics according to the status of menopause (premenopause and postmenopause). For the premenopaused women, the majority of the relevant prospective studies support an inverse relationship between body mass index and the development of breast cancer. In contrast, for the postmenopaused women, a positive relationship between body mass index and development of breast cancer has been reported in only half of prospective studies on this topic. This study was undertaken to determine the role of body size and body mass index by status of menopause in development of breast cancer in Korea using retrospective case-control study.
MATERIALS AND METHODS
The breast cancer cases (n=683) and controls (n=501) were recruited from January 1993 to April 1998 at the Asan Medical Center. The authors collected information on demographic, reproductive and anthropometric characteristics by interviews. Quetelets index was calculated using height and weight. Multiple logistic regression was done to estimate adjusted odds ratios (ORs) by menopausal status, controlling age, age at first full-tenn pregnancy, age at menarche, number of parity, family history of breast cancer.
RESULTS
Overall, there was a moderate, but significant association between obesity and breast cancer. Among premenopausal women, in comparison with women whose weights were less than 50 kg, the ORs for the upper quintile group of weight was 1.71 (95% confidence interval (CI), 1.01~2.89). The heaviest premenopausal women had a higher risk (OR=1.16, 95% CI, 1.05~1.29, P=0.005). The adjusted OR for the highest quintile of BMI relative to the lowest was 2.02 (95% CI, 1.18~3.45). Higher body mass index was significantly associated with increased risk of premenopausal breast cancer (OR=1.08, 95% CI, 1.02~1.15, P=0.006). Among postmenopausal women, higher body mass index and weight were associated with increased risk of breast cancer. In comparison with women whose weights were less than 50 kg, the OR for the upper quintile group of weight was 2.08 (95% CI, 1.064.08). The adjusted OR for the highest quintile of BMI relative to the lowest was 2.02 (95% CI, 1.02~4.01).
CONCLUSION
Our findings suggest that overweight/obesity may play an important role in the incidence of premenopausal and postmenopausal breast cancer in Korea.

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Clinical Analysis of the Favorable Type of Breast Cancer - Medullary , Mucinous , Papillary and Tubular Carcinoma: Chang Wan Jeon, Woo Chul Noh, Nan Mo Moon, Nam Sun Paik, Jong Inn Lee, Dong Wook Choi, Ho Yoon Bang; J Korean Cancer Assoc. 1999;31(1):82-89.

Abstract PDF: PURPOSE
The favorable types of the breast cancer - medullary, mucinous, papillary and tubular carcinoma are uncommon subtypes and their incidences in different series ranges between 2.0% and 8.0%, 1% and 2%, 0.3% and 3%, less than 2% of all breast cancers, respectively. In westem countries these subtypes have been reported to have good prognosis and slow growth rate. Clinically, these tumors have lower frequency of axillary nodal involvement and better 5-year or 10-year surviral rate than the other common types of breast cancer.
MATERIALS AND METHODS
To determine the clinical characteristics and to evaluate the correlation between the progrostic factors and survival rate of these tumors, the medical records of 83 women with medullary, mucinous, papillary and tubular carcinoma treated at Korea Cancer Center Hospital between Jan. 1987 and Dec. 1997 were reviewed retrospectively.
RESULTS
The incidences of medullary, mucinous, papillary and tubular carcinoma were 0.51%, 1.45%, 0.71% and 0.14% of all breast cancer, respectively. There were 1 case of local recurrence and 5 cases of systemic relapse during the follow-up (median follow-up peroid of 56 months). Overall 5-year survival and 10-year survival rate were 98.5% and 94.2%, respectively. No significant difference in overall survival rate was detected according to histologic types of these tumors but disease-free survival was significantly lower in papillary carcinoma than the other types of these tumors (p=0.042). Standard prognostic factors of breast cancer such as tumor size, lymph node status, age of the patient and ER status did not affect the prognosis of these tumors.
CONCLUSION
Medullary, mucinous, papillary and tubular carcinoma revealed very excellent prognosis in this study regardless of tumor size, lymph node status, age of the patients and ER status.

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A Clinical Study of Infiltrating Lobular Breast Cancer: Jung Mo Kim, Young Chul Kim, Dong Young Noh, Yeo Kyu Yong, Seung Keun Oh, Kuk Jin Choe; J Korean Cancer Assoc. 1999;31(1):90-97.

Abstract PDF: PURPOSE
Infiltrating lobular carcinoma of the breast was known to have a high incidence of multicentricity and bilaterality in patients. We analyzed the clinical features of infiltrating lobular breast cancer.
MATERIALS AND METHODS
We studied 29 patients with infiltrating lobular carcinoma of the breast, from Jan. 1980 to Mar. 1997 in the Department of Surgery, Seoul National University Hospital.
RESULTS
The age of the patients ranged from 32 to 71 years with an average of 45.2 years. The main complaining symptom was a painless mass. The diameter of the tumor ranged from 0.7 to 7 cm with a mean size of 2.8 cm. The axillary lymph node was positive for malignancy in 12 cases. The number of multicentric breast cancers were 7 cases (24.1%), and the number of bilateral breast cancers were 3 cases (10.3%). The estrogen receptor was positive in 66.7%, and the progesterone receptor was positive in 75% of the cases. There were one local recurrence and three distant metastases during a mean follow-up period of 4.5 years. The 5-year survival rate and 5-year disease free survival rate were 89.6% and 88.6%, respectively.
CONCLUSION
Infiltrating lobular breast cancers are at greater risk of developing multicentricity and bilaterality than nonlobular breast cancers. Careful program of frequent follow-up examinations and thorough histopathological studies are needed for patients with infiltrating lobular breast cancers.

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Mucinous Carcinoma of the Breast: Seung Sang Ko, Byung Chan Lee, Kyung Shik Lee; J Korean Cancer Assoc. 1999;31(1):98-104.

Abstract PDF: PURPOSE
Mucinous carcinoma of the breast is relatively rare among the malignant breast lesions. It has distinctive pathological and behavioral characteristics to separate from other types of breast cancers. Accoding to the WHO definition, mucinous carcinoma of the breast is a carcinoma containing large amounts of extracellular epithelial mucus, sufficient to be visible grossly, and recognizable microscopically surrounding and within tumor cells. Mucinous carcinoma shows the characteristic features clinically and histologically because of the mucus production by the tumor.
MATERIALS AND METHODS
We reviewed 29 cases of mucinous carcinoma that had been treated from 1985 to 1996 in the Department of General Surgery, Yonsei University College of Medicine.
RESULTS
The results were as follows: The prevalent age group was the fifth decade (37.9%). The 27 cases were female and 2 were male. The most common sign and symptom was a palpable mass (100%). The most patients visited the hospital within 2 months of onset (55.2%). Most frequent tumor size was 2-3 cm in diameter, found in 10 cases (34.5%), and 13.8% of cases was more than 5 cm in diameter. The most frequent site of tumor was the upper outer quadrant in 16 cases (55.2%). The operations performed were as follows: Modified radical mastectomy (Auchincloss or Patey) in 24 cases (82.8%), quadrantectomy with axillary lymph node dissection in 4 cases (13.8%), simple mastectomy with lower axillar dissection in 1 cases (3.4%). Axillary lymph node metastasis was present in 3 cases (10.3%). The most common stage at diagnosis was stage IIa in 13 cases (44.8%).
CONCLUSION
This study shows some characteristics of mucinous carcinoma of breast distinict from those previously proposed Further studies are needed to identify clinical parameters which characterize mucinous carcinoma of the breast.

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Prolonged Oral Etoposide in Combination with Intravenous Cisplatin for Advanced Non-small Cell Lung Cancer: Ki Hyun Kim, Sung Yong Oh, Hun Sik Jeong, Jong Tae Lee, Won Seng Kim, Ho Joong Kim, Sung Soo Yoon, Won Ki Kang, Hong Ghi Lee, Chong Heon Lee, Chan Hyung Park, Keun Chil Park; J Korean Cancer Assoc. 1999;31(1):105-111.

Abstract PDF: PURPOSE
Etoposide is a schedule-dependent agent and has a synergistic activity with cisplatin. We evaluated the response rate and the toxicity of prolonged oral etoposide in combination with intravenous cisplatin for the previously untreated patients with unresectable stage IIIB or IV non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS
Between April 1996 and February 1998, 71 patients were enrolled. The median age was 61 years (range, 36~75) and male: female ratio was 54: 17. Fourteen patients had stage IIIB disease and 57 had stage IV. Sixty-two patients had ECOG performance status of 0 or 1, and 9 had 2. Forty-eight patients had adenocarcinoma, 19 had squamous cell carcinoma and 4 had poorly differentiated NSCLC. Treatment consists of daily oral etoposide 50 mg/m in 2 divided doses for 21 days and intravenous cisplatin 60 mg/m on day 1. The treatment was repeated every 28 days.
RESULTS
Sixty-four of 71 patients were evaluable. Complete response and partial response were observed in 1 and 21 patients, respectively. The overall response rate was 34.4% (95% confidence interval 23.9~46.6%) and the median response duration was 30 weeks (range 13-53 weeks). The median survival of 71 patients was 56 weeks (range 3. 96+ weeks). There was a significantly longer survival in responders (p=0.035). Toxicities were evaluated by WHO criteria. Hematologic toxicities of grade 3, 4 were as follows: anemia 12.3%, leukopenia 8.7%, neutropenia 19.2%, thrombocytopenia 1.8%. Non-hematologic toxicities of grade 3, 4 were as follows: nausea and vomiting 5.9%, stomatitis 14.7%, diarrhea 1.5%. Early treatment-related death occurred in 2 patients (2.8%) due to sepsis.
CONCLUSION
Combination chemotherapy with prolonged oral etoposide and intravenous cisplatin is easy to administer and has moderate activity with acceptable toxicities for NSCLC.

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Changing Trends of Clinical Aspects in Lung Cancer from 1988 to 1996 - Hostipal Based Study: Jung Suk Kim, Jae Young Park, Sang Chul Chae, Moo Chul Shin, Moon Seob Bae, Ji Woong Son, Kwan Young Kim, Tae Kyung Kang, Ki Soo Park, Chang Ho Kim, Sin Kam, Tae Hoon Jung; J Korean Cancer Assoc. 1999;31(1):112-119.

Abstract PDF: PURPOSE
Lung cancer is now one of the most frequently diagnosed cancers in the world and its incidence has been increasing also in Korea. In several recent studies, the indidence of adenocarcinoma and female/male ratio have been reported to be increasing. The aim of this study is to investigate the changing trends in sex and age distribution, the histologic type and location (peripheral or central) of tumors in lung cancer.
MATERIALS AND METHODS
We performed the retrospective review of histopathology and clinical information of 1409 patients diagnosed as baving primary lung cancer, except non-epithelial tumors and undetermined histologic types, at Kyungpook National University Hospital from January 1988 to December 1996.
RESULTS
Male to female ratio was 4.6; 1. The peak incidence of age group was 7th decade (40.3%) with mean age of 61.5. Percentage of smokers in patients with lung cancer was 84.3%. Total number of patients with lung cancer has increased recently. However, the annual female/male ratio was nearly constant during the study period. Peripheral tumors, which were found in 20.6% of patients with lung cancer in 1988, increased to 33.5% in 1996 and this trend was more prominent in squamous cell carcinoma than in adenocarcinoma. Squamous cell carcinoma was the most common histologic type (62.0%), followed by adenocarcinoma (19.2%), small cell carcinoma (14.2%), large cell carcinoma (4.6%) in order. There was a predominance of squamous cell carcinoma (67.9%) in males and of adenocarcinoma (46.6%) in females. There has been a significant shift in the histology pattern with an increase in the percentage of adenocarcinoma. The incidence of adenocarcinoma was more than doubled from 7.5% in 1988 to 25.8% in 1996.
CONCLUSION
These findings suggest that the epidemiology of lung cancer is changing.

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Protracted Venous Infusion of 5-Fluorouracil as a Chemotherapy in Colorectal Cancer: Hyun Sik Jeong, Won Seog Kim, Sook In Jung, Jong Tae Lee, Ki Hyun Kim, Sung Soo Yoon, Won Ki Kang, Hong Ghi Lee, Ken Chil Park, Poong Lyul Rhee, Hae Jun Kim, Ho Kyun Chun, Chan Hyung Park; J Korean Cancer Assoc. 1999;31(1):120-125.

Abstract PDF: PURPOSE
The administration of 5-fluorouracil (5-FU) by protracted intravenous infusion is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancers. This study was performed to evaluate the response rate and toxicities of protracted infusion of 5-FU in patients with advanced or recurrent colorectal cancers who had been treated with 5-FU by bolus or shortterm continuous administration.
MATERIALS AND METHODS
Between March 1995 and June 1997, twenty-eight patients with advanced colorectal cancer previously exposed to 5-FU based chemotherapy were enrolled in this triaL Patients received 5-FU (250 mg/m(2)/day days 1-28) or 5-FU plus leucovorin (5-FU; 200 mg/m/day days 1-28, leucovorin; 20 mg/m IV days 1, 8, 15, 21) by ambulatory infusion pump. Treatment course was repeated every 42 days until disease progression.
RESULT
Twenty-eight patients entered. All 28 patients were assessable for response and toxicity. Five (19%) patients achieved a partial response, with the median response duration of 15 weeks (range; 7-22 weeks), and median survival time of entire patients was 54 weeks (range 7-151+ weeks). Gastrointestinal toxicity, specifically stomatitis was a major toxicity (grade 2, 12%; grade 3, 4%), but hand-foot syndrome was less frequent (5%) compared with other trials with protracted infusion of 5-FU reported in the literature. Hematologic toxicity was generally of low grade.
CONCLUSION
Prolonged intravenous infusion of 5-FU can produce a response rate of 19% with low toxicity among patients refractory to bolus or short-term infusion of S-FU.

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Toxicity of Bile Acids on Colon Cancer Cell Lines: Dong Kook Park, Ji Hyun Shin, Ho Jin Jun, Kyeong Jae Kim, Chan Young Lee; J Korean Cancer Assoc. 1999;31(1):126-133.

Abstract PDF: PURPOSE
Cytotoxicity of the bile acids on colon cancer cell lines was studied to know which bile acid was most cytotoxic to colonic mucosal epithelium. We performed agarose gel electrophoresis whether this toxicity was caused by detergent effect of the bile acids or by apoptotic pathway.
MATERIALS AND METHODS
HT29, LoVo, SW620 colon cancer cell lines were exposed to lithocholate, cholate, deoxycholate and chenodeoxycholate with 50, 100, 150, 200, 250, 300 pM as final concentration in DMEM culture media for short time (for 2 hours) and for long time (for 5 days). Agarose gel electrophoresis was performed on each colon cancer cell lines (HT29, LoVo, SW620, SW480) after 1, 2, 3, 4, 5 days exposure to deoxycholate with 150 pM concentration to detect intemucleosomal fragmentation.
RESULTS
There was no toxicity after short time exposure in all bile acids concentration and in all colon cancer cell lines. Of the bile acids, deoxycholate was most toxic for all colon cancer cell lines. And DNA fragmentation was noticed after 2 days exposure with deoxycholate. Only LoVo cell line showed apoptotic DNA pattern after 4 days of exposure with deoxycholate.
CONCLUSION
Bile acids (especially deoxycholate) are suggested to be possible agents to cause apoptosis in colonic mucosal epithelium.

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The Efficacy of Pre - operative Chamotherapy with Intra-arterial Cisplatin and Intravenous Adriamycin for High Grade Osteosarcoma: Sun Young Rha, Soo Jung Gong, Hee Cheol Chung, Kwang Yong Shim, Joong Bae Ahn, Nae Choon Yoo, Hyn Cheol Chung, Joo Hang Kim, Hae Kyung Roh, Jin Sik Min, Byung Soo Kim, Kyu Ho Shin, Woo Ick Yang, Chong In Lee; J Korean Cancer Assoc. 1999;31(1):134-143.

Abstract PDF: PURPOSE
Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment [pre-operative chemotherapy + surgery (limb salvage or amputation) + adjuvant chemotherapy] had improved the overall survival and quality of life. To improve the local control rate, we introduced pre-operative chemotherapy combined with intra-arterial (IA) cisplatin and continuous intravenous infusion (CI) of adriamycin. We evaluated the efficacy and feasibility, such as limb salvage rate, recurrence pattern and the survival impact, based on the histologic response of pre-operative chemotherapy.
MATERIALS AND METHODS
Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1996. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72hrs CI, was administered for 3 cycles with 3 week interval, followed by surgery. Post-operative chemotherapy was applied by the tumor necrosis rate. If the tumor necrosis of the specimen was more than 90%, the same regimen af the preoperative one was administered for 3 cycles. A salvage regimen (Ifosfamide 7.5 gm/m2/5d IV + high dose MTX 10 gm/m2 IV VP-16 360 mg/m2/3d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%.
RESULTS
Of 41 patients, 37 were evaluable for efficacy and toxicities, because 4 refused further chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 female, with the median age of 16 years (8-41). The tumor locations were as follows: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (10 with grade III, 27.8%; 17 with grade IV, 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lungs. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive care.
CONCLUSION
Pre-operative chemotherapy combined with IA cisplatin and CI adriamycin induced higher good response rate without survival benefits. To improve the survival rate, the design of good salvage chemotherapy with a non-cross resistant regimen should be considered.

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The Efficacy of PEEL Chemotherapy and Identification of Favoranble Subgroups in Patients with Carcinomas of Unknown Primary Origin: Byung Kook Choi, Young Jin Yuh, Jeong Hoon Yang, Seong Bae Kim, Yeon Hee Park, Bong Seog Kim, Baek Yeo Ryoo, Tae You Kim, Young Hyuck Im, Yoon Koo Kang; J Korean Cancer Assoc. 1999;31(1):144-152.

Abstract PDF: PURPOSE
In order to evaluate the efficacy of PEFL (cisplatin, etoposide, 5-fluorouracil and leucovorin) chemotherapy and to identify favorable subsets, we conducted a phase II trial of PEFL regimen for patients with carcinomas of unknown primary origin (CUPO).
MATERIALS AND METHODS
A total of 38 patients was enrolled in this study between May 1995 and September 1997. CUPO was defined as the presence of metastatic cancer documented in the absence of an identifiable primary site. All entered patients were treated with PEFL combination chemotherapy (cisplatin 20 mg/m(2)/day i.v, days 1-5, etoposide 100 mg/m(2)/day i.v. days 1, 3 & 5, 5-fluorouracil 800 mg/m(2)/day continuous infusion days 1-5, and leucovorin 20 mg/m(2)/day i.v, days 1-5; repeated every 4 weeks). The end points of this study were response and survival. To identify favorable subsets, univariate and multivariate analyses were perfonned.
RESULTS
Among 38 patients, 29 had measurable lesions. Three (11%) out of 27 evaluable patients had a complete response and 7 (26%) had a partial response (response rate 37%; 95% confidence interval 19~55%). The median survival of the total 38 enrolled patients was 9.1 (range; 1~21.9+) months. The median progression-free survival of the 27 evaluable patients was 5.3 (range 0~ 16.0) months. Among total 132 cycles of chemotherapy, leukopenia of grade II or more was observed in 15% and thrombocytopenia of grade I in 4%. There was no treatment-related death. Main non-hematologic toxicities were nausea/vomiting (79%), stomatitis (70%), and neurotoxicity (33%). The prognostic factor analyses identified 2 favorable subgroups; One was the patient group whose disease had poorly differentiated histology and presented in cervical lymph node. This group of patients had better response rate than other patients (response rate; 71% vs 25%, p=0.02). The other was the patient group who had normal tumor markers (CEA, CA 125 and CA 19-9). This group of patients had better survival than other patients(median survival; 14.8 vs 8.4 months, p=0.05).
CONCLUSION
PEFL chemotherapy seemed to be moderately active and tolerable in patients with CUPO. Among heterogenous patients with CUPO, the subset with cervical lymph node and poorly differentiated histology responded better to the chemotherapy and those with normal tumor markers tended toward longer survival.

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Expression of Multidrug Resistant Genes in Bone Marrow Mononuclear Cells of Patients with Myeloid Leukemia: Seok Goo Cho, Il Ho Yang, Hyeon Seok Eom, Chang Gi Min, Hee Je Kim, Dong Wook Kim, Jong Wook Lee, Chi Wha Han, Woo Sung Min, Won Il Kim, Chun Choo Kim; J Korean Cancer Assoc. 1999;31(1):153-164.

Abstract PDF: PURPOSE
Multidrug resistance mediated by several drug resistant genes impedes the successful outcome of anti-cancer chemotherapy. In this study, we investigated the expressions of drug resistant genes encoding multidrug resistance (MDR1), multidrug resistance-associated protein (MRP), topoisomerase I (Topo I), topoisomerase II g (Topo II a) in narmal volunteers (n=12) in and patients with myeloid leukemia (n=34). Material and Method: We compared the levels of their transcripts in bone matrow mononuclear cells by semiquantitative RT-PCR. The amount of specific transcripts was represented as the optical density ratio of PCR product of target gene to that of B2- microglobulin (MG). Twenty patients of acute myelogenous leukemia (eight in remission state, twelve in refractory) and fourteen patients of chronic myelogenous leukemia (nine in chronic phase and five in blastic crisis) were examined. Twelve normal healthy persons were compared with leukemic patients.
RESULTS
The expression levels of all resistant genes in normal volunteers were relatively high as those of AML patients. Regardless of the disease status including remission status of AML (complete remission versus refractory) and the phase of CML (chronic phase versus blastic phase), the expression levels of all resistant genes in patients with CML were significantly lower than in the patients with AML (p < 0.05). Of interest, the patients with refractary AML did not show any statistical difference in comparison with normal controls and even the patients with AML in complete remission. Among the four drug resistant genes, the optical density ratio of MDRl was significantly lower than that of any other genes (p<0.05). Using HL-60 cell line, we compared the changes of various resistant gene expressions before and after differentiation induced by dimethylsulfoxide. The expressions of resistant genes declined in paralle1 with granulocytic differentiation, suggesting that the induction of cell differentiation might make leukemic cells susceptible to chemotherapeutic agents.
CONCLUSION
It is impossibble to explain the mechanism of drug resistance by comparing the level of drug resistant gene expression between nonnal subjects and patients with myeloid leukemias. Therefore, we suppose that longitudinal study of drug resistant gene expression is necessary to demonstrate the development of drug resistant during chemotherapy.

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Risk Factors of Early Recurrenec after Curative Hepatic Resection for Hepatocellular Carcinoma: Jae Hun Choi, Helen Rho, Young Taeg Koh, Kyung Suk Suh, Kuhn Uk Lee; J Korean Cancer Assoc. 1999;31(1):165-172.

Abstract PDF: PURPOSE
The purpose of this study was to clarify the risk factors of early recurrence within 1 year by comparing them with patients without recurrence within 3 years after curative liver resection in hepatocellular carcinoma (HCC).
MATERIALS AND METHODS
Three hundred and twenty six patients with HCC who underwent curative liver resection between 1991 Jan, to 1995 June were observed for possible recurrence for least 3 years. These patients were divided into two groups: 79 patients who had recurrence within 1 years (early recurred group) and 132 patients who had no recurrence within 3 years (no recurred group).
RESULTS
Overall survival rates in 5 years after 1iver resection were 17.5% in early recurred group and 94.9% in no recuned group. Risk factors of early recurrence in multivariate analysis were the presence of liver cirrhosis in nontumorous parenchyme (p=0.011, relative risk (RR)=2.5), tumor size (p=0.004, RR 2.9), multiple mass (p 0.015, RR=3.4), the presence of angioinvasion (p=0.043, RR=3.7), serum alpha-fetoprotein more than 20 ng/dl (p=0.007, RR=2.7), major liver resection more than lobectomy (p=0.039, RR=3.2). However, other factors such as age, sex, preoperative transcatheter arterial embolization (TAE), several liver function tests, Child classification, reseetion margin, total necrosis of tumor after preoperative TAE, tumor encapsulation, histologic type, Edmondsons grade, were not significant in our study.
CONCLUSION
The risk factors of early recurrence were liver cirrhosis, tumor size, number of tumor, angioinvasion, serum alpha-fetoprotein, and major liver resection. Biologic characteristics of tumor were the most important risk factors of early recurrence. Because the extent of liver resection is the only risk factor that depends on surgeons decision, we must consider this factor in liver resection for HCC.

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Intraperitoneal and Retroperitoneal Sarcomas: Young Wook Jung, Woo Chul Noh, Nan Mo Moon, Nam Sun Paik, Jong Inn Lee, Dong Wook Choi, Ho Yoon Bang; J Korean Cancer Assoc. 1999;31(1):173-179.

Abstract PDF: PURPOSE
Sarcomas arising in intraperitaneal cavity and retroperitoneal space are relatively uncommon. Thus, studies characterizing the results of long-term follow-up are limited. The purpose of this study was to identify the clinicopathologic features and prognostic factors of intraperitoneal and retroperitoneal sarcomas. Materials and Method: Thirtyeight patients with intraperitaneal or retroperitoneal sarcoma who had been treated at Department of Surgery, Korea Cancer Center Hospital during the period from January 1987 to December 1997 were reviewed retrospectively.
RESULTS
The ratio between male to female was 0.9: 1. The mean age of the patients was 48.3 (32-75) years. The most common symptom was abdominal pain or discomfort (61%), followed by palpable mass (55%), GI bleeding (34%), weight loss (26%), and change of bowel habits (21%). The most comman histologic type was leiomyosarcoma (73.7%), followed by liposarcoma (23.7%), and malignant fibrous histiocytoma (2.6%). The mean tumor size was 15.5 x12.1 x 8.7 cm. Among 38 cases, 25 cases developed in intraperitoneal cavity and 13 cases arose in retroperitoneal space. Overall, 44 operations were performed in 31 patients. Among them, complete surgical resection constituted 73%. In 20 cases, combined resection of adjacent organ was performed to accomplish complete surgical resection of tumors. During the median follow up period of 23 months (3~116 months), the overall 5-year survival rate was 34.7%. The patients who had been treated by complete surgical resection showed better survival than those in whom palliative resection or biopsy only was performed (38.6% vs 0% of 5 YSR, P=0.015). Liposarcoma showed better prognosis than leiomyosarcoma (41.7% vs 34.2% of 5 YSR, P=0.0000). The size of tumor (10 cm>vs 10 cm< or =) was not a statistically significant prognostic factor.
CONCLUSION
In this series, The histologic type and complete surgical resection were important factors that can affect the survival of the patients. Aggressive surgical resections are therefore wananted to obtain better outcome of the patients with intraperitoneal and retroperitoneal sarcomas.

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Liposomes as Acitivators of Lipophilic Platinum (2 ) Complexes: In Sook Han, Young Jae Lee; J Korean Cancer Assoc. 1999;31(1):180-187.

Abstract PDF: PURPOSE
The goal of this study is to understand the activation processes that take place within the liposomal formulation of lipophilic diaminocyclohexane platinum (DACH-Pt) complexes, to identify the activated species of this class of compounds, and to use that information to develop a reproducible liposomal formulation of DACH-Pt complexes.
MATERIALS AND METHODS
Liposomal DACH-Pt complexes were prepared by lyophilization-rehydration method using PC, PG and PA. Their intraliposomal stability and biological activity were determined by HPLC and in vitro/in vivo experiments.
RESULTS
DACH-Pt complexes in a liposomal formulation have shown significant promise in preclinical studies and clinical phase I, II trials. Interestingly, they are prodrugs which converts into one or more undetennined activated platinum species within the liposomes ex vivo. Our studies have shown that the stability of liposomal DACH-Pt complexes is inversely related with the antitumor activity of those complexes. The configuratian of leaving group in the complexes and pH of the liposome suspension affect significantly the degradation/activation process that takes place within the liposomes. DACH-Pt complexes with linear (L10) leaving groups are more stable than complexes with branched ones (B10 and NDDP), but also significantly less potent. The presence of PG and PA in the liposome is a prerequisite for the degradation/activation process of DACH-Pt complexes. As PG and PA formulation gave more dramatic changes of the original complexes than PC alone due to lower pH, the cytotoxicity and antitumor activity at those fonnulations increased against PC alone. DACH-Pt complexes are very stable in liposomes containing PC alone but inactive in vitro/in vivo experiments.
CONCLUSION
These results also support that the active species produced within the liposomal DACH-Pt complexes is DACH-Pt-Cl2.

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Primary Gastric Small Cell Carcinoma: Heung Rae Min, Yeon Myung Shin, Seung Do Lee, Sung Do Lee, Bang Hur; J Korean Cancer Assoc. 1999;31(1):188-193.

Abstract PDF: Small cell carcinoma is derived from APUDcells of any parts of the body. Usually the cases are discovered in the lungs and have poor prognosis. Small cell carcinoma has been increasingly reported in various organ outside the lungs, such as the larynx, thymus, esophagus, stomach, pancreas, uterine cervix, and prostate. Primary small cell carcinoma of the stomach is extremly rare. The histology of the tumor was similar to that of ordinary small cell carcinoma of the lung, and the secretory granules were identified by electron microscopy. We report a patient with gastric pure small cell carcinoma who treated by a radical total gastrectomy and chemotherapy.

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Case Reports

A Case of Angiosarcoma of the Maxillary Sinus: Young Chang Choi, Kun Ho So, Chun Dong Kim, Jeong Rye Kim, Bong Seog Kim; J Korean Cancer Assoc. 1999;31(1):194-200.

Abstract PDF: Angiosarcomas are extremely rare in the nasal cavity and para-nasal sinus. Upto the present only nineteen cases have been reported in the literature. A 31-year-old male presented with right facial swelling and large oral cavity mass. He was treated with wide excision of the tumor by radical maxillectomy. The tumor was diagnosed as angiosarcoma by immunohistochemical staining with factor VIII-reactive antigen. No adjuvant radiotherapy after surgery was done. After 9 montbs from surgery, the tumor recurred in the primary sites of oral cavity and right maxillary sinus and metastasized to the both lungs. He was treated with palliative chemotherapy and showed a stable disease in follow-up magnetic resonance image of para-nasal sinus and simple chest X-ray after second cycle of chemotherapy. He is undergoing further chemotherapy without any problems. We report first in Korea a case of primary angiosarcoma of the right maxillary sinus in a 31-year-old male.

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A Case of Pancreatic Serous Cystadenoma Associated with Papillary Thyroid Cancer: Jin Hong Park, Chang Ryoul Lee, Jun Ho Lee, So Jin Choi, Seong Ho Choi, Seong Pyo Son; J Korean Cancer Assoc. 1999;31(1):201-207.

Abstract PDF: The most common pancreatic cystic lesion is pancreatic pseudocyst which represents about 85%. Primary cystic neoplasms represent about 10 to 15% of the lesion. Pathologically cystic neoplasms can be classified into serous cystadenoma, mucinous cystadenoma and papillary cystic neoplasm by epithelial lining-cell, whereas pseudocyst is characterized by fibrotic capsules. Mucinous form is known to be premalignant or malignant and serous cystadenoma was known to be benign in the past, but recently 4 cases of malignant transformation have been reported. Serous cystadenoma is described under a variety of names, including microcystic adenoma and glycogen-rich cystadenoma but recently macroqystic variants have been reported. Serous cystadenoma is most commonly seen in middle aged women with symptoms of vague upper abdominal pain or palpable mass. It is sometimes associated with extra- pancreatic diseases such as gallstones, diabetes mellitus, hypertension, duodenal ulcers, sterility, obesity and thymic dysfunction, but coexisting papillary thyroid cancer have been reported in only 2 cases to our knowledge. The pathogenesis of associated diseases is unknown and appears to be due to function of age of the patients or incidental occurrence. Herein, we report a patient who had a pancreatic serous cystadenoma coexisting with papillary thyroid cancer. Since pancreatic serous cystadenoma can occur in association with papaillary thyroid cancer, examination of thyroid seems to be advisable when pancreatic serous cystadenoma is found.

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