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Volume 31(3); June 1999
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Original Articles
Expression of p53 Protein and Proliferating Cell Nuclear Antigen in Epstein - Barr Virus-associated Gastric Adenocarcinoma
Jeong Hee Kang, Chang Hoon Lee, Kang Suek Suh
J Korean Cancer Assoc. 1999;31(3):429-440.
AbstractAbstract PDF
PURPOSE
Recently, it has been reported that Epstein-Barr virus (EBV) is associated with some gastric cancers. But EBVs role in EBV-associated gastric carcinomas (EBVaGCs) has not been fully elucidated. This study was undertaken to evaluate the characteristics of EBVaGCs and to compare those with non-EBVaGCs.
MATERIALS AND METHODS
EBV infection was studied using paraffin-embedded tissue blocks of 119 cases of gastric adenocarcinomas by in situ hybridization for EBV-encoded small RNAs (EBERs). In EBVaGCs and non-EBVaGCs, molecular characteristics were evaluated by immunohistochemical staining for latent membrane protein (LMP)-1, p53 protein, and proliferating cell nuclear antigen (PCNA).
RESULTS
EBERs were detected in 12 cases (10.1%) of 119 gastric adenocarcinomas. LMP-1 was negative in all carcinomas tested, p53 protein was positive in 7 cases (58.3%) of 12 EBVaGCs and in 51 (47.7%) of 107 non-EBVaGCs, the difference between two groups being not significant. Mean PCNA index was 38.2+-26.1% in EBVaGCs and 22.8 +- 20.0% in non-EBVaGCs. The index was significantly higher in the former than in the latter.
CONCLUSION
These results suggested that neoplastic progression in EBVaGCs was implicated with high expression of PCNA, but not consistently with overexpression of p53 protein or LMP-1.
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Effectiveness of Gastrectomy in Stage 4 Gastric Cancer with Hepatic Metastasis
Jeong Hwan Yook, Sung Joon Kwon, Byung Ki Kim, Byung Jae Kim, Sung Kim, Seung Moon Noh, Young Jae Mok, Kyung Kyu Park, Byung Ju Park, Cho Hyun Park, Ho Yoon Bang, Jae Moon Bae, Young Jin Song, Du Hyun Yang, Dae Hyun Yang, Sung Tae Oh, Hyo Yung Yun, Moo Son Lee, Jong Inn Lee, Yong Kwan Cho, Dong Wook Choi, Sang Uk Han
J Korean Cancer Assoc. 1999;31(3):441-447.
AbstractAbstract PDF
PURPOSE
The prognosis for patients with stage IV gastric cancer is very poor. However, recently, some studies have reported benefits from a gastric resection for metastatic gastric cancer. This clinical study was performed to evaluate the effectiveness of a noncurative gastrectomy in treating stage IV gastric cancer with hepatic metastasis.
MATERIALS AND METHODS
A retrospective analysis was performed on 98 gastric cancer patients who had undergone gastric resection, in spite of hepatic metastasis, between January 1990 and December 1996 at the Department of Surgery in 11 General Hospitals in Korea.
RESULTS
The average age was 58 years old, and the male-to-female ratio was 69: 29. The laboratory tests were unable to predict hepatic metastasis. In 54 cases, hepatic metastasis was not identified before the surgery. The most common location of gastric cancer was antrum (72 cases). The most common gross type was Bonmann type III (78 cases). The serosa-exposed cases were 80. The peritoneal seeding was combined in 17 cases. A total gastrectomy was performed in 18 cases and a distal gastrectomy in 80. Lymph-node dissection was performed in 23 Dl, and 51 D2 cases. Hepatic resection was performed in 36 cases, The frequent histologic types were moderately differentiated and poorly differentiated tubular adenocarcinoma. Postoperative adjuvant chemotherapy was done in 70 cases. The complication rate (7%) was low. The median survival time was 15 months, with mean survival time of 18 months. The 2-year and 3-year survival rates were 23%, and 7%, respectively. In the univariate analysis, good survival was closely related to limitation of hepatic metastasis to one lobe, a few metastases to both lobes, negativity of peritoneal seeding and lymph node dissection more than D2 (p<0.05), CONCLUSIONS: An aggressive gastric resection for stage IV gastric cancer with hepatic metastasis might be beneficial in lengthening the survival period. A prospective study is needed, especiaUy one with an exact evaluation and analysis of the quality of life between the gastrectomy and nonresection groups.
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Combined Resection in Advanced Gastric Cancer
Dong Woo Shin, Chang Hak Yoo, Sung Hoon Noh, Jin Sik Min
J Korean Cancer Assoc. 1999;31(3):448-457.
AbstractAbstract PDF
PURPOSE
Prognosis of primary gastric cancer invading neighboring organs is very poor. However, with en bloc resection, a relatively favorable prognosis can be expected even in patients with such advanced cancer. But there has been controversy on the effectiveness of gastrectomy combined with en bloc resection of the invaded organs, and we conducted this study to evaluate the prognostic effects as well as the outcome of the combined resection.
MATERIALS AND METHODS
Among 2,603 who underwent gastrectomy due to gastric carcinoma from January 1987 to December 1994 at the Department of Surgery, Yonsei University College of Medicine, 157 patients (6.0%) in whom curative combined resections of grossly invaded adjacent organs (cT4) were perfonned entered this study. Any case with distant metastasis was excluded. Comparisons and multivariate analysis between the invasion (pT3) group and the non-invasion (pT4) group were made for age, sex, tumor size, location, Borrmann type, depth of invasion, lymph node metastasis, histologic type and 5-year survival rate.
RESULTS
One-organ combined resection was done in 60 (38.2%) patients; Two-organ, in 80 (51.0%) patients; and three-organ, in 17 (10.8%) patients. Most commonly combined organ was distal pancreas and transverse colon was the next. Histologic confirmation of invasion was made in 40.9%. 157 patients with T4 were divided into pT3 or pT4. Significant differences were found in type of operation, location of tumor, and TNM staging. Postoperative complications of combined resection were observed in 48 cases (30.6%) and the wound infection was the most frequent one. There were only 2 cases (1.3%) of immediate postoperative mortality in the combined group, and the causes of death were pulmonary complication and acute renal failure. Five-year survival rate (5-YSR) of pT3 group was 43.0% and that of pT4 was 26.2%. In comparison of 5-YSR according to TNM stages, no significant difference was found between pT3 and pT4 (45.0% vs. 66.7% in IIIa; 25.4% vs. 18.4% in IV). No difference of 5-YSR was observed in the groups categorized according to the number of resected organs. The comparison of 5-YSR between the 157 curatively-combined cases and the 63 palliatively-combined cases showed a significant difference (35.6% vs. 4.2%, p=0.000). Multivariate analysis showed that lymph node metastasis and microscopic tumor invasion served as significant parametets.
CONCLUSION
En bloc combined resection of adjacent invaded organs along with systematic lymph node dissection would be beneficial to gastric cancer patients with neighboring organ invasion.
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Results of Surgical Treatment and Analysis of Prognostic Factors in Primary Gastric Adenocarcinoma
Cheol Hun Chung, Young Jae Mok, Gil Soo Son, Seung Joo Kim, Sae Min Kim
J Korean Cancer Assoc. 1999;31(3):458-465.
AbstractAbstract PDF
PURPOSE
Despite gsstric cancer is one of the most common ma1ignancies, its prognosis has not been improved significantly. Therefore, it is important to know what clinical and pathological factors relate to survival in gastric carcinoma in order to improve survival rate. The aim of this retrospective study was to evaluate treatment results and to analyze the factors that affect the survival of patients with gastric carcinoma.
MATERIALS AND METHODS
A total of 1,580 patients with primary gastric adenocarcinoma who had been treated surgically during the period 1983-1996 at the Department of Surgery, Korea University College of Medicine was studied to evaluate the treatment outcome. Prognostic factors were investigated by univariate and multivariate analyses in 1,407 resected patients.
RESULTS
The 5-year survival rate was 57.1% in all case, 62.4% in resected cases, and there was no survivor at 2.5 year in unresectable cases. In univariate analysis, gross type, maximum tumor diameter, depth of invasion, lymph node involvement, distant metastasis, histologic type and type of operation were found to correlate significantly with survival. Multivariate analysis indicated that lymph node involvement, depth of invasion and type of cancer were independently conelated with survival. The stage-related survival rates (UICC, 1987) were 95.8% (stage Ia), 87.6% (stage Ib), 76.7% (stage II), 51.3% (stage 1IIa), 25.5% (stage IIlb), 9.4% (stage IV) and the stage-related survival rates (UICC, 1997) 95.8% (stage Ia), 87.6% (stage Ib), 76.4% (stage II), 55.2% (stage IIla), 24.0% (stage IIIb), 13.4% (stage IV). There was no difference between two staging systems.
CONCLUSIONS
These results suggest that lymph node involvement, depth of invasion, and gross type were the most important prognostic factors, indicating that they may be helpful as predictors of long-term survival and in planning the treatment.
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Pattern of Recurrence after Curative Resection of Gastric Cancer
Jae Hong Jang, Young Jin Kim, Dong Yi Kim, Hyung Rok Kim, Shin Kon Kim
J Korean Cancer Assoc. 1999;31(3):466-472.
AbstractAbstract PDF
PURPOSE
Despite radical lymph node dissection and combined resection, the operative result of progressive gastric cancer remains unsatisfactory. The prognosis of gastric cancer has not been improved. In case of recurred gastric cancer, the problem is low curative resection rate. We tried to study the pattem of recurrence after curative resection for gastric cancer.
MATERIALS AND METHODS
We had retrospectively analyzed the recurrence pattern of 191 patients who recurred after curative resection of gastric cancer. We analyzed the interval between operation and recurrence, primary tumor location, tumor histologic type, Borrmann's type, pathologic stage, DNA ploidy pattem and lymph node metastasis.
RESULT
The number of recurred gastric cancer patients was 191. The M: F ratio was 2.03: 1. Seven cases were early gastric cancer. The interval between operation and recurrence was from 1 month to 130 months. The early recurrence within 24 months was found in 147 patients (77.0%), the intermediate recurrence from 25 months to 60 months was found in 38 patients (19.9%), the late reeurrence after 60 months was found in 6 patients (3.1%). The pattems of recurrence were as follows: loco-regional recurience, including lymph node and site of anastomosis, was found in 51 cases, liver metastasis in 37 cases, peritoneal metastasis in 74 cases, extraperitoneal metastasis in 29 cases including Virchows node. In undifferentiated cancer, peritoneal metastasis was higher than in other histologic types (p<0.05). 59 cases was found in stage IV, 47 cases in stage IIIb, 43 cases in stage IIIa, 31 cases in stage II, 8 cases in stage Ib, and 3 cases in stage Ia. We found peritoneal metastasis was very high in stage IIIb. The 5-year survival was better in loco-regional group than that of other patterns of recurrence.
CONCLUSION
Recurrence after operation was found within 24 months, that in most of patients, so the follow up is very important in this period and the recurred pattem after curative resection for gastric cancer was related with cell differentiation of primary tumor and stage. In local recurrence, the survival rate was higher than the other pattern of recurrence.
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Restoration of Hormone Dependency in Estrogen Receptor - Lipofected MDA-MB-231 Human Breast Cancer Cells
Young Jin Suh, Jae Hee Chang, Chung Soo Chun
J Korean Cancer Assoc. 1999;31(3):473-482.
AbstractAbstract PDF
PURPOSE
The loss of estrogen and progesterone receptors appeats to be associated with a progression to less differentiated and hormone-independent tumors. The gain of hormone independency over time even in estrogen receptor-positive tumors has become another obstacle to endocrine therapy for breast cancer. We tried to regain the hormone dependency in estrogen receptor-negative breast cancer cells by lipofecting estmgen receptor cDNA.
MATERIALS AND METHODS
The mutant human estrogen receptor cDNA (pSGS-HEO) was lipofected into estrogen receptor-negative human breast cancer cell line MDA-MB-231, in an attempt to restore their sensitivity to antiestrogen. Then the effects of 17p-estradiol and tamoxifen were studied by counting viable cell numbers after treating the lipofected cell line with either one or together.
RESULTS
Culture medium cantaining phenol red, a weak estrogen, has growth advantages compared with culture medium without it. In both culture conditions, cell growth was most profoundly inhibited in 4 days after lipofection with mutant human estrogen receptor cDNA, which was overcome after that day. Tamoxifen, as an antiestrogen, showed a growth inhibitory effect slightly stronger tban combined conditions of tamoxifen and 17- estradiol compared to estrogen-treated group and to control, and the inhibitory effect was lasted 4 days.
CONCLUSION
The temporary induction of estrogen receptor by lipofection with pSGS-HEO on estrogen receptor-negative human breast cancer cell line MDA-MB-231 showed negative growth control on these cells by tamoxifen, indicating that liposome-mediated estrogen receptor transfection may be used as a novel therapeutic strategy for hormane independent human breast cancers in the near future.
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Correlation between VEGF Expression and Prognostic Factors in Breast Cancer
Jung Eun Jang, Sang Yun Choi, Chan Hyung Park, Young Hyeh Ko, Ki Hyun Kim, Hyun Sik Jeong, Kwang Sung Ahn, Jung Hyun Yang, Seok Jin Nam, Sung Soo Yoon
J Korean Cancer Assoc. 1999;31(3):483-491.
AbstractAbstract PDF
PURPOSE
Archival tissues of breast cancer patients were examined for VEGF expression to evaluate the relationship with other clinicopathologic factors and prognostic significance of VEGF in breast cancer.
MATERIALS AND METHODS
Paraffin sections from 76 patients with invasive breast cancer who have been treated at Samsung Medical Center from December, 1994 to April, 1998 were examined for VEGF expression by immunohistochemical staining using anti-VEGF antibody. We analyzed relationships between VEGF expression and tumor size, tumor stage, metastasis, steroid honnone receptors, p53, disease recurrence and survival.
RESULTS
Immunostaining showed variable VEGF positivity in the malignant cells and VEGF was detected more frequently in tumors than in adjacent non-tumorous breast tissues. 74 out of 76 (97.4%) was positive for VEGF. We found that the expression of VEGF was strongly correlated with the stages of breast tumor (P=0.020), lymph node metastasis (P=0.043) and PR (P=0.016). However, we could not find statistically significant relationship between VEGF expression and tumor size, ER, p53 and distant metastasis.
CONCLUSION
VEGF may be a useful prognostic indicator in patients with breast cancer, especially correlated with tumor stage and lymph node metastasis. This result warrants further study to confirm our findings.
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Reduced Expression of p27 Correlates with High Grade Malignancy and is Associated with Poor Clinical Outcome in Human Greast Cancer
Se Hwan Han, Hong Yong Kim, Kyeong Mee Park, Myeong Soo Lee, Hong Joo Kim, Young Doug Kim, Hyun Suk Suh
J Korean Cancer Assoc. 1999;31(3):492-498.
AbstractAbstract PDF
PURPOSE
The cyclin-dependent kinase inhibitor p27Kipl is a negative regulator of cell proliferation. Its expression is known to be altered in proteasome-dependent manner without changes in DNA level. Reduced expression of p27Kipl is associated with aggressive behavior in a variety of human cancers. We investigated expression of p27Kipl protein in human breast cancer using immunohistochemistry to assess its biologic implication along with cell cycle analysis by flow cytometry.
MATERIALS AND METHODS
We peformed immunohistochemical assay for expression of p27 in total 68 patients with invasive ductal cancer along with 27 benign ductal hyperplasia and 10 ductal carcinoma in situ. The data were analyzed in association with proliferative activity of the same tissues and biologic parameters.
RESULTS
In epithelial cells of normal and benign breast disease, expression of p27Kipl was well preserved while its expression markedly decreased in breast cancer (45 of 68). Expression of p27Kipl was significantly reduced in poorly differentiated cancers and in advanced stage of the disease. Levels of p27Kipl expression correlated with cell populations in GO/Gl phase of the cell cycle. In survival analysis, p27Kipl was useful to predict disease-free survival but not overall survival of the patients after adjuvant chemotherapy.
CONCLUSION
p27Kipl seems to have a role in cell proliferation and differentiation process during carcinogenesis of breast cancer. The results of present study suggest that p27Kipl can be used in predicting response to systemic chemotherapy in a subset of patients with breast cancer.
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Breast Cancer Detected by Screening Mammography
Byung Ho Son, Jung Mi Park, Gyeong Yeop Gong, Se Hyun Ahn
J Korean Cancer Assoc. 1999;31(3):499-508.
AbstractAbstract PDF
PURPOSE
The early detection of breast cancer by screening mammography is important to reduce breast cancer mortality rate. The purpose of this study was to investigate the characteristics of breast cancer patients detected by screening mammography.
MATERIALS AND METHODS
Surgically treated 1,265 patients at Asan Medical Center from Jul. 1989 to Dec. 1997 were evaluated. Among them, 119 patients (9.4%) were detected by screening mammography. These patients were compared with clinically detected symptomatic breast cancer group.
RESULTS
The characteristics of breast cancer patients detected by screening mammography were as follows: The most common finding of mammography was microcalcifications (62.2%); The less invasive or more conservative minimal and non-destructive surgical treatments such as breast conserving surgery (21.0%), simple mastectomy (8.4%), breast reconstruction (8.4%) were performed more frequently; The median tumor size of invasive cancers was 16 mm; Node-negative cancers (83.2%) were more frequent; The early breast cancer of stage 0 and I was 70.6%; DCIS (29.4%) was highly proportionated; and The 5-year overall (95.8%) and 5-year disease-free survival rate (92.0%) were significantly higher than in clinically detected symptomatic breast cancer patients.
CONCLUSION
The screening mammography was significant for detecting non-palpable, early stage breast cancer. Ultrasonography was needed as an adjunct for the accurate detection in dense breast or young women. According to early detection, the 5-year survival rate was high.
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Patterns of the Recurrence of Breast Cancer in Korean Female Patients
Hark Kyun Kim, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim
J Korean Cancer Assoc. 1999;31(3):509-516.
AbstractAbstract PDF
PURPOSE
The major aim of this study is to evaluate the pattems of recurrence of breast cancer and to determine risk factom influencing the pattem.
MATERIALS AND METHODS
Medical records of 322 female patients who underwent mastectomy from 1989 till 1992 were reviewed. Recurrence pattem and the length of survival after the first relapse of each relapsed patient were identified. Factors influencing the pattem of recurrence and the length of survival after relapse were analyzed using Cox proportional hazards model.
RESULTS
Locoregional relapse was identified in the first failure sites of sixteen patients (5-year relapse rate, 5.7%). Risk of locoregional relapse was associated with the number of positive axillary lymph nodes [adjusted Relative Risk (aRR), 31.28 (95% Confidence Interval (CI), 6.81-143.77)]. The 5-year estimates of the first relapse at bone, lung, pleura, liver, and brain were 15.4%, 6.9%, 1.9%, 3.1%, and 0.8%, respectively. The multivariate analysis indicated that distant metastasis was associated with the number of positive axillary lymph nodes [aRR, 3.14 (95% CI, 1.56-6.32)] and with the age of 35 years and younger [aRR, 1.95 (95% CI, 1.01-3.75)]. The statistical association of negative estrogen receptor (ER) with distant relapse was borderline [aRR, 1.89 (95% CI, 0.99-3.61)]. Factors independently affecting the survival of relapsed patients were the pattem of metastasis and the disease-free interval.
CONCLUSION
Bone metastasis was the most frequent pattem of first relapse in Korean breast cancer patients. The number of positive axillary lymph nodes, younger age, and negative ER were independent risk factors for distant relapse in Korean female breast cancer patients.
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Correlation of Breast Cancer with Atypical Ductal Hyperplasia on Fine-needle Aspiration Cytology Speciemens
Lee Su Kim, Jin Hee Sohn, Jeong Jin Kim, Jong Hyun Kim, Kyung Ho Cha, Song Kim, Chang Sig Choi, Bong Hwa Lee
J Korean Cancer Assoc. 1999;31(3):517-522.
AbstractAbstract PDF
PURPOSE
Atypical ductal hyperplasia (ADH) is a lesion with significant malignant potential We evaluated the prevalence of breast carcinoma in surgical breast biopsies performed on palpable breast lesions diagnosed initially as ADH by fine needle aspiration cytology (FNAC).
MATERIALS AND METHODS
Between January 1, 1996 and December 31, 1997, 942 patients who underwent FNAC at the Department of Surgery and Pathology, College of Medicine, Hallym University and Department of Surgery, Central Gil Hospital were analyzed. ADH was found in 46 (4.9%) of 942 patients, and surgica1 excision subsequently was performed in 39 of these cases. In these 39 cases, cytologic and histopathologic results from FNAC and surgical biopsies were reviewed and correlated.
RESULTS
Histopathologic study of the 39 surgically excised lesions diagnosed as ADH in their FNAC specimens showed breast cancer in 15 cases (38.5%), ADH in 11 cases (28.2%) and benign disease in 13 cases (33.3%).
CONCLUSION
In our patient populatian, 15 cases (38.5%) of 39 patients with ADH at FNAC had a breast cancer. Therefore, the FNAC finding of ADH may warrant a recommendation for an excisional biopsy.
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Clinical Trial
Efficacy of Gemcitabine Chemotherpy in Advanced Non-small cell Lung Cancer ( NSCLC ): A Phase 2 Study
Hyuk Jae Chang, Joong Bae Ahn, Jun Gu Lee, Kwang Yong Shim, Sun Young Rha, Sae Kyu Kim, Jun Chang, Sung Kyu Kim, Won Young Lee, Nae Chun Yoo, Hyun Cheol Chung, Jae Kyung Roh, Byung Soo Kim, Sung Jun Choi, Tae Won Kim, Chul Won Suh, Joo Hang Kim
J Korean Cancer Assoc. 1999;31(3):523-532.
AbstractAbstract PDF
PURPOSE
To evaluate the efficacy and safety of gemcitabine, a pyrimidine antimetabolite against advanced non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS
Forty patients with unresectable stage IIIb to IV, pathologacally documented NSCLC were evaluated. Patients received gemcitabine 1000 mg/m, as a 30 to 60-min, intravenous infusion on days 1, 8 and 15, which was repeated every 28 days. Responses were assessed every two courses. Twenty-five to fifty percent dose reduction was permitted, ptovided that overall toxicity was severe according to World Health Organization (WHO) toxicity criteria.
RESULTS
Of all 40 patients (32 men, 8 women; age range 37 to 73 years; median 63 years), 3S patients were assessable for response. 15 patients had stage IIIb disease and 25 had stage IV. Nineteen patients were histologically classified as adenocarcinoma (47.5%), 17 as squamous cell carcinoma (42.5%), 1 as large cell carcinoma (2.5%), 1 as mixed carcinoma (2.5%) and 2 as undifferentiated carcinoma (5.0%). The overall response rate was 20%. None of the patients showed complete response while 7 showed partial response (20%), 5 had stable diseases (23%) and 23 had progressive diseases (57%). During a total of 119 courses, hematologic toxicity was negligible. Granulo- cytopenia worse than WHO grade 3 occured in 11.8%, anemia in O.S% and thrombocytopenia in 0.8%, respectively. Non-hematologic toxicity was minor and easily controlled. There was no case of febrile neutropenia or treatment-related death.
CONCLUSION
The single agent efficacy of gemcitabine is comparable to other agents commonly used to treat NSCLC. Gemcitabine has unusually mild side effect profile for such an active agent. This significant activity in conjunction with a very favorable toxicity profile supports further investigation in combination with other agents in patients with inoperable NSCLC.
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Original Articles
The Site-dependent Differences in Response to Chemotherapy in Patients with Advanced Lung Cancer
Kee Won Kim, Sook Kyung Lee, Jee Won Seo, Suk Young Park, Kyung Shik Lee
J Korean Cancer Assoc. 1999;31(3):533-538.
AbstractAbstract PDF
PURPOSE
To detennine the extent and the clinical significance of site-dependent differences in response to chemotherapy in patients with metastatic lung cancer.
MATERIALS AND METHODS
We reviewed the records of patients with metastatic lung cancer who had received chemotherapy and were evaluated for the response of primary lung and metastatic lesions simultaneously. Total 52 patients were eligible.
RESULTS
The discordance rate of response between primary lung lesion and various metastatic lesions was 0% (0/51) at regional lymph nodes, 12% (1/8) at distant lymph nodes, 45% (5/11) at hematogenous metastatic lung lesion, 0% (0/7) at liver, 50% at adrenal glands, and 21% (3/14) at bone. As a result, the concordance rate of response amang lymph nodes, liver, and primary lung lesions was high. But some differences in response were observed at intrapulmonary metastatic lesion, adrenal glands, and bone lesions in comparison with primary lung lesion.
CONCLUSION
We conclude that the effective therapeutic strategies against those discordant metastatic lesions should be developed to increase the overall treatment effect in patients with metastatic lung cancer.
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Combination Chemotherapy with Etoposide, Ifosfamide, and Cisplatin (VIP) in Small Cell Lung Cancer
Goon Jae Cho, Joo Seop Chung, Ihm Soo Kwak, Ha Yeon Rha
J Korean Cancer Assoc. 1999;31(3):539-547.
AbstractAbstract PDF
PURPOSE
Combination chemotherapy has shown promising activity in small cell lung cancer (SCLC). This study was perfonned to determine the efficacy of the combination chemotherapy with etoposide, ifosfamide and cisplatin (VIP) in previously untreated patients with SCLC.
MATERIALS AND METHODS
Patients with SCLC were treated with etoposide (75 mg/m iv. D1-4), ifosfamide (1200 mg/m iv. Dl-4 with mesna) and cisplatin (20 mg/m iv. D1-4). The treatment was repeated every 3 weeks for 6 cycles in principle. Thoracic radiotherapy was administered to patients with limited disease (LD) of SCLC after initial 2 or 3 cycles of chemotherapy subsequently. Praphylactic cranial irradiation (PCI) was given to complete responders of SCLC.
RESULTS
From April 1996 through June 1998, 42 patients were included, but 32 were eligible for the study (4 refused of treatment, 2 lost in follow-up, and 4 combined with other disease). The median age was 62 years (range, 42-74). Twelve patients had LD and 20 patients were with extended disease (ED). Complete response (CR) rate was 34% (LD 58%, ED 20%) and overall response rate was 72% (LD 83%, ED 65%). The median duration of response was 28 weeks (38 weeks in LD, 24 weeks in ED, P=0.016) With the median follow-up period of 65 weeks (6-134 weeks), overall median survival was 43 weeks (56 weeks in LD, 34 weeks in ED, P 0.001), and the median disease free survival (DFS) of eleven CR patients was 16 weeks. Stage, performance, and LDH level were significant prognostic factom (P 0.011, 0.002, 0.043, respectively), but sex and age did not affect the outcome significantly. The hematologic side effects (WHO grade 2) of evaluable 152 cycles of chemotherapy were leukopenia (53%), thrombocytopenia (31%) and anemia (16%); and nonhematologic side effects (WHO grade >2) were alopecia (84%), nausea/vomiting (45%) and stomatitis (19%).
CONCLUSION
It appears that VIP combination chemotherapy is a safe, effective and well tolerated regimen for the patients with SCLC.
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Association of Genetic Polymorphism of Glutathions S-transferase M1 and T1 and Bladder Cancer
Seung Joon Lee, Dae Hee Kang, Soo Hun Cho, Soo Woong Kim, Moon Soo Park, Han Yong Choi, Whang Choi
J Korean Cancer Assoc. 1999;31(3):548-555.
AbstractAbstract PDF
PURPOSE
Smoking and high-risk occupation are known to be the risk factors of bladder cancer. The carcinogen-metabolizing enzymes in human body such as GSTM1 and GSTT1 have also been regarded as risk factors in many cancers because the activities of those enzymes play a role in metabolizing the carcinogen. A case control study was conducted to evaluate the role of known risk factors (smoking and high-risk occupational history) and the genetic polymorphism of GSTM1 and GSIT1 in blader carcinogenesis in Korean men.
MATERIALS AND METHODS
The pathologically proven bladder cancer cases were selected from three hospitals in Seoul (Seoul National University Hospital, Boramae Hospital, and Sam-Sung Medical Center) and the patients older than 40 years of age with the nonmalig nant urinary tract diseases were selected as the controls from the same hospitals. The informations of demographical characteristics, smoking, and occupational history was obtained by the trained interviewer and the genetic polymorphisms of GSTM1 and GSTT1 were assayed by multiplex PCR. The statistical analysis was performed by multiple logistic regression.
RESULTS
Neither smoking nor high-risk occupational history was statistically significant risk factor of the bladder cancer. However, the GSTM1 null-type showed borderline significance (OR 1.49; 95% CI 0.92-2.41) and both GSTM1 and GSlT1 null-type was statistically significant risk factor of bladder cancer when compared with both normal genotype (OR-2.43; 95% CI 1.13-5.24) after age and smoking history were adjusted.
CONCLUSION
The concurrent null-type of GSTM1 and GSTT1 increases the risk of bladder cancer in Korean men.
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A Clinical Trial on the BTA (Bladder Tumor Antigen) Test for Monitoring and Diagnosis of Bladder Transitional Cell Carcinoma
Eun Young Choi, Je Jong Kim, Jun Cheon
J Korean Cancer Assoc. 1999;31(3):556-561.
AbstractAbstract PDF
No abstract available.
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Development of a New Nonoclonal Antibody CC5 Using a Cervical Carcinoma Cell-line Derived From Korean Woman
Jin Woo Kim, Chun Ok Seo, Eun Young Cho, Heung Kee Kim, Sa Jin Kim, Soo Young Hur, Young Wook Kim, Tae Chul Park, Joon Mo Lee, Sung Eun Namkoong
J Korean Cancer Assoc. 1999;31(3):562-574.
AbstractAbstract PDF
PURPOSE
Cancer of the uterine cervix remains the leading cause of cancer death in Korean women. Conventional examinations still have limitations with regards to sensitivity and specificity in diagnosis and to monitoring of the disease. Thus, an additional specific tumor marker is needed for early detection of recunence of uterine cervical carcinoma and for estimation of prognosis.
MATERIALS AND METHODS
Monoclonal antibodies against human cervical carcinoma were generated using hybridoma technology. These tnurine monoclonal antibodies were produced by fusion of spleen cells obtained from mice immunized with CUMC-6, a human cell line of squamous cell carcinoma derived from uterine cervix, and P3-X63-Ag8 mouse myeloma cells.
RESULTS
We obtained 415 hybridomas secreting specific monoclonal antibodies to cervical carcinoma antigen continuously. Among them, one hybridoma designated CCS that was highly reactive with cervical carcinoma was selected and examined on. the staining pattern and the reactivity with antigenic detenninants of cervical carcinoma. Immunohistochemical staining revealed that CCS monoclonal antibody reacted with all of the seven cervical carcinoma tissues, but also reacted with one of the ten (10%) normal cervical tissues. Westem blot analysis showed that CC5 monoclonal antibody detected single 19.5-kDa protein band in cervical cancer patient's sera. The detection rate was 88% (7/8). However, the antibody did not show any reactivity to 15 sera of normal healthy women tested. Sodium dodecyl sulfate polyacrylamide gel electrophoretic (SDS-PAGE) analysis of CCS monoclonal antibody immunoprecipitates of extracts of L-[S] methionine-labeled human cer vical carcinoma cells showed a major band in apparent molecular weight of 51,000 daltons. The isotype and subclass of CC5 monoclonal antibody was IgG2b in hemagglutination assay.
CONCLUSIONS
We have developed a new monoclonal antibody, CC5, against squamous cell carcinoma of the human uterine cervix. Further investigation is needed to establish this monoclonal antibody as an immunodiagnostic devise for cervical cancer.
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Analysis of 38 Cases of Metastatic Cancer of Ovary
Jae Ho Yum, Jae Weon Kim, Yong Beom Kim, Chul Min Lee, Noh Hyun Park, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee
J Korean Cancer Assoc. 1999;31(3):575-581.
AbstractAbstract PDF
PURPOSE
The relative ftequency of ovarian metastases from various organs reported in literature varies with geographic distribution. To our knowledge, there has been no comprehensive report on the subject of metastatic cancer to the ovary in Korea, so we tried to evaluate the clinical characteristics of them.
MATERIALS AND METHODS
We reviewed the files of the Department of Pathology from January 1988 to December 1997 in Seoul National University Hospital and obtained 38 cases diagnosed as metastatic cancer to ovary. We retrospectively reviewed the patients' records and evaluated the clinical characteristics, treatment modalities and clinical outcome.
RESULTS
The mean age of patients was 43.7 years (range: 19-63) and the most common symptom was pelvic pain (21.1%). The origins of primary cancer were as follows in the order of frequency: stomach (65.8%), colon (13.2%), unknown (10.5%), hematologic malignancy (7.9%) and lung (2.6%). The most common pathologic findings were metastatic adenocarcinoma in 34 cases (89.5%), among which 14 cases (36.8%, 14/38) were Krukenberg tumor. The origins of primary cancer were diagnosed preoperatively in only 18 cases (47.4%). Eleven patients (28.9%) received surgery only, while 27 patients (71.1%) received both surgery and adjuvant chemotheiapy. For all patients, the median survival was 17 (range: 11-23) months and the overall 3-year survival rate (3YSR) was 28.6%. There were no significant differences in 3YSR according to primary tumor sites, status of ovarian involvement, pathologic finding, diagnostic time and treatment modalities.
CONCLUSION
Although the overall survival rate and clinical factors which might affect survival were similar to previous reports from Westem countries, the most common origin of primary cancer was different.
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p53 and bcl-2 Gene Expression in Gastational Trophoblastic Disease
Noh Hyun Park, Ju Won Roh, Jae Weom Kim, Yong Sang Song, In Ae Park, Soon Beom Kang, Hyo Pyo Lee
J Korean Cancer Assoc. 1999;31(3):582-589.
AbstractAbstract PDF
PURPOSE
p53 and bcl-2 expressions are known as important cell survival factors and their levels of expression are related with patients prognosis in various human malignancies. But there are few data about p53 and bcl-2 expression and their role in the genesis of gestational trophoblastic disease (GTD). The aims of this study are to describe p53 and bcl-2 expression in normal trophoblast and hydatidifonn mole (HM), and to identify the role of p53 and bcl-2 in the genesis of gestational trophoblastic tumor (GlTI from HM.
MATERIALS AND METHODS
Paraffin-embedded tissue sections from 32 cases of HM and 9 cases of normal early pregnancy placentas were obtained. Of 32 HM patients, 15 cases were cured after molar evacuation (group A), and 17 cases progressed to GT1' (group B). p53 and bcl-2 immunohistochemical stainings were done and their reactivity were graded. The positive rates of p53 and bcl-2 overexpression among normal placenta, group A, and group B were compared and analyzed.
RESULTS
p53 mutant gene overexpression was more frequently detected in HM (68%) than in normal placentas (22%)(p<0.05). bcl-2 was overexpressed in 31% of HM and 11% of normal placenta, but the difference was statistically insignificant (P > 0.05). The difference in bcl-2 and p53 expression between group A and group B was not observed (P>0.05). There was no inverse relationship between p53 and bcl-2 expression in group A, and group B (P>0.05).
CONCLUSIONS
p53 gene mutation may play a mle in the process of HM development, but p53 and bcl-2 were not associated with the genesis of GTI' from H-mole. More studies are needed to identify the molecular process in the progression of the GTD.
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Antiemetic Efficacy of 2-Hour Infusion of Granisetron in Patients Receiving High - Dose Cisplatin
Seung Taek Kim, Ji Hyun Lee, Kyung Soo Lee, Jung A Lee, Hye Young Kim, Kee Hyung Lee
J Korean Cancer Assoc. 1999;31(3):590-597.
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PURPOSE
The physiologic mechanism of chemotherapy induced emesis is poorly understood, but recently it is thought to be mediated by serotonergic (5-hydroxytryptamine-3 or 5-HT3) receptars. 5-HT3 is released by enterochromaffin cells in the gastrointestinal tract, which peaks 2-6 hours after the start of chemotherapy. In this study, the granisetron, an antiemetic agent, was given over 2-hour from the start of cisplatin administration to synchronize the peak level of the drug with that of 5-HT3 release.
MATERIALS AND METHODS
Chemotherapy-naive patients undergoing their first cycle of cisplatin ( > 60 mg/m)-based chemotherapy were included. One milligram of granisetron was given intravenously 15 minutes before the start of cisplatin as a loading dose, then 2 mg was given over 2-hour starting with the cisplatin.
RESULTS
24 of 25 patients were evaluable for efficacy and safety. Fifteen (62.5%) of the 24 evaluable patients had advanced gastric carcinoma and 21 (87.5%) received FP (5-FU/ Cisplatin) combination chemotherapy. The complete response rate for acute and delayed vomiting/retching was 58.3% (10/24) and 33.3% (8/24), respectively. The median latency time to first vomiting or retching was 20.3 hours. Side effects were tolerable, but central nervous symptoms (dizziness, headache, or anxiety) and diarrhea were frequently noted.
CONCLUSION
Two-hour infusion of granisetron with the beginning of cisplatin showed no superior efficacy compared with historical controls that used bolus administration of granisetron, but somewhat more frequent central nervous system and gastrointestinal symptoms were observed.
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Clinico-pathologic Study on Multiple Squamous Epithelial Neoplasia of the Esophagus
Kyung Ja Cho, Seung Sook Lee, Jae Soo Koh, Jae Ill Zo, Ja June Jang
J Korean Cancer Assoc. 1999;31(3):598-606.
AbstractAbstract PDF
PURPOSE
Multicentric occurrence of esophageal squamous neoplasm has been known to be significant in terms of its pathogenesis and production of detectable early lesions. This study was performed to establish the incidence, pattem and clinico-pathologic features of multiple squamous epithelial neoplasia of the esophagus in Korea.
MATERIALS AND METHODS
Forty-two consecutive cases of esophageal squamous cell carcinoma surgically treated at Korea Cancer Center Hospital in 1991 were studied. For pathological analysis, whole esophagectomy specimens were sectioned, micrascopically examined, and reconstructed. Age, sex, alcohol and smoking history, tumor location, stage, lymph node metastasis and survival were compared among different neoplastic conditions.
RESULT
Fifteen cases (35.7%) showed multiple squamous lesions, 6 (14.3%) with multiple carcinomas and dysplasias, and 9 (21.4%) with single carcinomas with separate dysplasias. Intraepithelial lesions contiguous to main tumors were commonly observed (61.9%). Lugol`s solution staining pattern was compatible with epithelial pathology. Lymph node metastasis rate was significantly higher in cases with multiple carcinomas. Smoking history was significantly more common in patients with solitary catcinomas only.
CONCLUSION
The multicentric occurrence of squamous epithelial dysplasia and carcinoma in the esophagus was confirmed in Korean patients, supporting the concept of field carcinogenesis at this region. However, lack of evidence for strong environmental influence in the patients with multiple lesions suggests yet another risk factor.
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Clinical Characteristics and Prognostic Factors of Metastatic Tumor of Unknown Primary
Eun Kyung Cho, Keun Seok Lee, Chul Won Jung, Won Seog Kim, Ki Hyeong Lee, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim
J Korean Cancer Assoc. 1999;31(3):607-616.
AbstractAbstract PDF
PURPOSE
For malignant diseases, predictions about tumor behavior and determination of appropriate therapy are based on the primary tumor sites, but 2-9% of cancer patients are diagnosed without identifiable primary tumor sites. Metastatic tumors of unknown primary origin (MUO) are a heterogeneous group of tumors with variable natural histories. The majority of these patients fall outside of treatable subjects and seldom respond to therapy. To define further the natural history of MUO and identify prognostic factors, we undertook a clinical analysis of 141 consecutive patients with a presumed diagnosis of MUO.
MATERIALS AND METHODS
One hundred forty-one patients were diagnosed with unknown primary tumor from Jan. 1, 1992 through Aug. 31, 1995. The primary end point for the study was survival, which was calculated from the first day of patient registration diagnosed histologically. The survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. To identify important prognostic factors, univariate and multivariate analyses were conducted.
RESULTS
Most of the 141 patients had histologic or cytologic evidence of adenocarcinoma and had more than one site metastatically involved. The predominant sites of tumor involvement were lymph node, peritoneum, bone, liver, lung, and pleura. Univariate and multivariate analyses identified numerous important prognostic factors with a significant influence on survival, including performance status (P 0.0001), specific organ sites involved (lung P 0.0076 or liver P 0.0310), and chemotherapy group (P- 0.0480).
CONCLUSION
This study validated clinical courses and important prognostic factors that had an impact on survival in MUO.
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Midkine Expression in Cell Lines and tumor Tissues of Glioblastoma Multiforme
Jin Woo Chang, Sun Young Rha, Sang Sup Chung, Frank Czubayko, Hyun Cheol Chung
J Korean Cancer Assoc. 1999;31(3):617-626.
AbstractAbstract PDF
PURPOSE
We measured the expression of midkine (MK) gene and biophenotypes in brain tumor cell lines and tumor tissues.
MATERIALS AND METHODS
We used the cell lines purchased from ATCC: two glioblastoma cell lines (T98G, U87MG), rat bladder tumor cell line (NBT-II), NIH/3T3, and two endothelial cell lines [(human umbilical vein endothelial cell (HUVEC) and fetal bovine heart endothelial cell (FBHE)]. RNA was taken from 4 cancer tissues of glioblastoma multiforme. Tissue cytosol was obtained from 5 cancer patients and 2 tissues of epilepsy patients. Pentosanpolysulfate(PPS) was used as a competitive inhibitor of heparin-binding growth factor (HBGF). MK and pleiotrophin (PTN) mRNA expression was tested by Northem hybridization, uPA and PAI-1 levels were measured by ELISA (Monozyme, Netherlands). Cross-feeding assay was done to measure the activity of endothelial cell growth stimulation induced by cancer cell lines.
RESULTS
T98G cell line expressed both MK and PTN while U87MG expressed only PTN. In cross-feeding assay, endothelial cell growth increased in proportion to the number of administered feeding tumor cells, T98G and U87MG. This phenomenon was found in HUVEC, but not in FBHE. Conditioned media of T98G and U87MG showed similar stimulatory effect on the growth of NIH/3T3 cells. T98G cell showed higher excretion rate of uPA into conditioned media while U87MG showed higher excretion rate of PAI-1 into conditioned media. 20% of growth inhibition was induced on T98G cell with 100 pg/ml PPS, while 40% of growth inhibition was induced with 10 pg/ml PPS on U87MG cell. In four cancer tissues, thee expressed MK. In cancer tissue cytosol, uPA and PAI-1 expressions varied in individuals. No PAI-1 was found in non-tumor tissues.
CONCLUSION
MK expression was found in brain tumor cell lines and tumor tissues. Modulation of biophenotypes (angiogenic activity and growth) by PPS in tumor cells with MK expression suggested a possible biotherapy in brain tumor targeting growth factor.
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Primary Central Nervous System Lymphoma
Jin Hee Ahn, He Hwan Lee, Tae Won Kim, Jeong Gyoon Kim, Seong Jun Choi, Sung Bae Kim, Sang We Kim, Cheolwon Suh, Kyoo Hyung Lee, Jung Shin Lee, Wo Kun Kim, Hyesook Chang, Snag Hee Kim
J Korean Cancer Assoc. 1999;31(3):627-634.
AbstractAbstract PDF
PURPOSE
Primary central nervous system lymphoma (PCNSL) is defined as lymphoma limited to the cranial-spinal axis without evidence of systemic disease and its incidence has risen threefold during the last fifteen years among apparantly healthy population. This study was intended to analyze the clinicopathologic features and treatment outcome of the patient with PCNSL.
MATERIALS AND METHODS
Twenty one patients were diagnosed and treated for the PCNSL limited to brain parenchyme at Asan Medical Center between March 1989 and December 1996. We reviewed clinical records of these patients and analyzed clinicopathologic features, treatment response, survival time and prognostic factors.
RESULTS
The ratio of male to female was 1.3: 1 and the most prevalent age group was the 4th decade. Most patients had diffuse large cell (19/21) and B-cell type (8/8). Seventeen (94.4%) among 18 evaluable patients achieved complete remission (CR) as initial response, but 53% of patients showed recurence of the disease. Median times of disease-free and overall survival were 40 and 50 months, respectively and 5 year overall survival rate was 35.3 %. Prognostic factors such as age and performance status, had a statistically significant influence on the overall survival but not on disease-free survival.
CONCLUSION
CR rate of the patients with PCNSL was high, but relapses were frequent. There fore further studies are needed to define the pmgnostic factors and to decrease relapse rate.
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Case Report
A Case of Synchronous Gastric Non - Hodgkin's Lymphoma and Renal Cell Carcinoma
Je Jung Lee, Moo Rim Park, Young Eun Joo, Young Jin Kim, Hyeoung Joon Kim, Chan Choi, Ik Joo Chung
J Korean Cancer Assoc. 1999;31(3):635-640.
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We report a 58-year-old man who developed synchronous gastric non-Hodgkin`s lymphoma (NHL) and renal cell carcinoma. He presented with epigastric discomfort for 2 months. Endoscopic finding of the stomach disclosed a large inegular ulceration with nodular margin on the upper body. Constrast enhanced CT scan of the abdomen showed an ulceration and focal wall thickening in the greater curvature side of stomach, and an enhanced bulging mass in the left kidney incidentally. The tissue obtained by radical proximal gastrectomy and nephrectomy showed diffuse large B-cell lymphoma on stomach and chromophobic type of renal cell carcinoma on kidney. To our knowledge, this is the first report of synchronous gastric NHL and renal cell carcinoma in Korea.
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Cancer Res Treat : Cancer Research and Treatment
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