Cancer Research and Treatment

Predictive Value of the nProfiler 1 Assay for the Efficacy of Adjuvant S-1–Based Doublet Chemotherapy in Stage III Gastric Cancer: A Post-Hoc Analysis of a Randomized Phase III Trial: Dong Ki Lee, Choong-kun Lee, Hyo Song Kim, Sun Jin Sym, Dae Young Zang, Ki Hyang Kim, Joo Han Lim, Hae Su Kim, Kyung Hee Lee, Heon Yung Gee, Sun Young Rha, Hyunki Kim, Minkyu Jung; Received July 25, 2024 Accepted November 9, 2024 Published online November 12, 2024; DOI: https://doi.org/10.4143/crt.2024.705 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
The nProfiler 1 Stomach Cancer Assay (nProfiler1), designed to predict responses to fluorouracil-based adjuvant chemotherapy, measures the expression of four gastric cancer target genes (GZMB, WARS, SFRP4, and CDX1). The randomized phase III POST trial aimed to compare the efficacies of two adjuvant S-1-based doublet chemotherapies: S-1 plus cisplatin (SP) and S-1 plus docetaxel (DS). This study aimed to validate the nProfiler1 assay using a distinct cohort from the POST trial.
Materials and Methods
The nProfiler1 assay stratifies patients into three groups (low-risk, intermediate-risk, and high-risk) using the prognostic single-patient classifier and two groups (chemotherapy-benefit and no-benefit) using the predictive single-patient classifier. The nProfiler1 assay was applied to formalin-fixed paraffin-embedded slides obtained from the POST trial. Disease-free survival (DFS) and overall survival (OS), including 5-year survival rates, were calculated for the enrolled patients.
Results
Of the 153 patients in the POST trial, 118 were included in the post-hoc analysis. With a median follow-up of 57.9 months, no significant difference in DFS or OS was observed between the SP and DS groups. The prognostic single-patient classifier predicted the OS in the SP group (p=0.043) but not in the DS group (p=0.594). The chemotherapy-benefit group exhibited numerically longer DFS than the no-benefit group in the SP and DS groups.
Conclusion
The nProfiler1 assay offers valuable insights into the prognosis and efficacy of adjuvant chemotherapy based on fluorouracil plus platinum doublet regimens but not docetaxel-containing regimens. Further validation with larger patient cohorts and different regimens is warranted.

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Public Awareness of Gastric Cancer Risk Factors and Disease Screening in a High Risk Region: A Population-Based Study: Do-Youn Oh, Kui Son Choi, Hae-Rim Shin, Yung-Jue Bang; Cancer Res Treat. 2009;41(2):59-66. Published online June 30, 2009; DOI: https://doi.org/10.4143/crt.2009.41.2.59

Purpose

This study involved a population-based survey to provide evidence of public awareness of risk factors of gastric cancer and to investigate attitudes for the screening of gastric cancer in the South Korean population.

Materials and Methods

Using a nationwide random selection method, 2014 subjects were enrolled in the study between 5 September 2006 and 25 September 2006.

Results

In terms of the awareness of risk factors, awareness was scored as the percentage of the probability of developing gastric cancer when a subject had a particular risk factor. For the risk factors, stress ranked highest with a score of 73.5%, followed by chronic gastritis (score of 72.1%), gastric ulcer (score of 71.2%) and a previous gastrectomy history (score of 68.7%). Other factors included a diet of charred foods (score of 67.3%), alcohol use (score of 65.3%), salty diet (score of 65.1%), history of smoking (score of 64.3%) and Helicobacter pylori infection (score of 57.5%). Subjects believed that 60.4% of all gastric cancers were preventable by lifestyle modification and the subjects believed that regular screening could prevent 72.1% of all gastric cancers. However, 54% of subjects did not receive regular screening and the most common reason for not undergoing screening was a lack of symptoms.

Conclusion

Public education about the risk factors of gastric cancer and of lifestyle modifications and the importance of regular screening regardless of the presence of symptoms should be emphasized to reduce gastric cancer mortality in South Korea.

Citations

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Phorbol Ester Induced - Apoptosis Mediated by Activating Serine Protease ( s ) and Caspase - 3 / CPP32 in SNU - 16 Human Gastric Cancer Cell Line: I C Park, M J Park, T B Choe, J J Jang, S I Hong, S H Lee; J Korean Cancer Assoc. 2000;32(2):270-278.

Abstract PDF: PURPOSE
Protein kinase C (PKC) is a family of phospholipid dependent serine/threonine protein kinases that have important role in differentiation, development and tumor promotion. PKC also has been reported to be implicated in the induction of apoptosis in a number of studies, but the efforts to define a role for PKC in the induction of apoptosis have been complicated by conflicting reports.
MATERIALS AND METHODS
To determine the effect of phorbol 12-myristate 13-acetate (PMA) on the induction of apoptosis, DNA fragmentation was detected by agarose gel electrophoresis and morphological changes of apoptotic cells were detected by Hoechst 33258 staining. For the detection of caspase-3/CPP32 activity, we used the enzyme substrate Ac-DEVD-pNa and anti- D4-GDI antibody.
RESULTS
In the present study, PMA, a PKC activator, induced apoptosis in SNU-16 human gastric cancer cell line, whose apoptosis was significantly inhibited by the PKC inhibitor, chelerythrine chloride. The caspase-3/CPP32 protease activity was increased in PMA-induced apoptosis. Furthermore, 4-(2-aminoethyl) benzenesulfonyl fluoride (AEBSF), a serine profease inhibitor, also significantly suppressed PMA-induced cell death in an upstream of caspase-3/CPP32.
CONCLUSION
These findings indicate that PMA induces apoptotic cell death in the SNU-16 adenocarcinoma cells through PKC activation, which activates AEBSF-sensitive serine proteases and caspase-3/CPP32. Therefore, our results suggest that PKC would be a potential target for induction of apoptosis.

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Diagnostic Value of Tumor Markers in Stomach Cancer: Jeong Hwan Yook, Byung Sik Kim, Yong Ho Kim, Byung Sun Suh, Wan Soo Kim, Sung Tae Oh, Kun Chun Park; J Korean Cancer Assoc. 1999;31(6):1094-1100.

Abstract PDF: PURPOSE
CEA, CA19-9, and CA72-4 are the most commonly used tumor markers in stomach cancer. This clinical study was performed to evaluate the diagnostic value of these tumor markers in stomach cancer patients.
MATERIALS AND METHODS
A retrospective analysis of 170 stomach cancer patients who had undergone curative gastrectomy between January 1991 and December 1996 at the Department of Surgery was performed. The preoperative and postoperative serum levels of these tumor markers were measured in 170 patients.
RESULTS
The preoperative positive cases were 28 cases (16%) in CEA, 15 (9%) in CA19-9, and 24 (14%) in CA72-4. The postoperative positive cases among 48 recurrences were 21 cases (44%) in CEA, 10 (21%) in CA19-9, and 10 (21%) in CA72-4. The combination of CEA with CA19-9 or CA72-4 had higher positivity rate (58%) than single tumor marker. The highest positivity rate was found in CEA at recurrences of anastomotic site, in CA19-9 at recurrences of lymph node, in CA72-4 at peritoneal seeding and distant metastasis. In multivariate analysis, these tumor markers were not independent prognostic factors.
CONCLUSION
CEA, CA19-9, and CA72-4 have proved unhelpful in initial diagnosis of stomach cancer because of their low positivity rate. And the combination of 3 tumor markers was the useful method for raising positivity rate in diagnosis of recurrences.

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Prognostic Significance of VEGF in Human Stomach Cancer: Gue Sung Han, Sung Jae Cha, Young Kum Park, Kyong Choun Chi, Sung Jun Park, Hyun Mook Lim, Sung II Park, Un Sub Park; J Korean Cancer Assoc. 1999;31(6):1087-1093.

Abstract PDF: PURPOSE
Angiogenesis plays an important role in the growth, progression and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) was thought to be one such angiogenic factor and was also thought to be a selective mitogen for endothelial cells. The purpose of this retrospective study was to evaluate for prognostic significance of VEGF in stomach cancer.
MATERIALS AND METHODS
The sections of formalin-fixed, paraffin embedded from 55 stomach cancer were stained immunohistochemically for VEGF. The rate of VEGF expression and correlation between expression of VEGF and other prognostic factor of stomach cancer were studied.
RESULTS
There were 20 cases (36.4%) of VEGF-positive and 35 cases (63.6%) of VEGF- negative. There were no significant difference between VEGF expression and the histologic type, differentiation, depth of invasion of histologic stage, lymph node involvement. The frequency of hepatic recurrence was higher in patients with VEGF-positive tumor than that af patient with negative tumor (p=0.007). The prognosis of the patients with VEGF positive tumor was worse than that of patients with VEGF negative tumor (p=0.0214).
CONCLUSION
There was a closely significant between positive expression of VEGF and a high incidence of hepatic metastasis, low survival rate. The expression of VEGF could be considered to be one of useful prognostic factor in human gastric carcinoma

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Genetic Alterations of p16Ink4A and p15Ink4B in Gastric Carcinomas: Kwon Hur, Han Kwang Yang, Ja June Jang, Jin Pok Kim, Dae Young Kim; J Korean Cancer Assoc. 1999;31(5):887-897.

Abstract PDF: PURPOSE
p16Ink4A and p15lnk4B, encoded by the genes located on chromosome 9p21, are cyclin-dependent kinase 4 inhibitors and are the upstream regulators of pRB (retinoblastoma protein) function and are involved in the regulation of cell cycle in mammalian cells. It has been demonstrated that p16 and p15 genes are frequently deleted, mutated, and hypermethylated in many malignancies and cancer cell lines. This study was performed to investigate the genetic alteration and immunohistochemical profile of p16 and p15 in gastric carcinomas.
MATERIALS AND METHODS
We examined 30 primary gastric cancer samples using PCR- SSCP (Polymerase chain reaction-single strand conformation polymorphism), DNA sequencing, PCR-based hypermethylation assay, and immunohistochemistry.
RESULTS
No homozygous deletion was detected in either pl6 or p15 gene, and only one gastric carcinoma sample showed mutation of p16 gene and p15 gene. However, hyper-methylation of 5' CpG islands was observed in 53.6% of exon1 of p16 gene and in 46.4% of exon 1 of pl5 gene. By immunohistochemistry of p16, nuclear under-expression was observed in 58.6%, whereas nuclear over-expression was detected in 31% of formalin-fixed, paraffin-embedded gastric cancer tissues.
CONCLUSIONS
Our results suggest that the p16 and p15 tumor suppressor genes may play an important role in gastric carcinogenesis and may be inactivated not by deletions or mutations but mainly by hypermethylation of their 5' CpG islands. There was a good correlation between methylation study and immunohistochemical results in p16 genes.

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Correlation between Proliferative Index by DNA Flow Cytometry and Histological Features in Stomach Cancer: Hyoung Kug Kim, Myeong Soo Lee, Hong Yong Kim, Se Hwan Han, Seok Yong Rhu, Hong Joo Kim, Young Doug Kim; J Korean Cancer Assoc. 1998;30(6):1078-1088.

Abstract PDF: PURPOSE
Stomach cancer is the most prevalent malignancy in Korea. The survival rate in advanced stage disease has stayed in less than 50%. One of the possible explanation for dismal outcome of stomach cancer is various biologic behavior of cancer cells of heterogeneous clones. Introduction of flow cytometric analysis has provided objective information of cancer cell kinetics, and it could help us in deciding the appropriate adjuvant therapy. The prospective study was undertaken to evaluate the clinical implication of DNA ploidy and each proliferative fraction by DNA flowcytometry. The other aim of the study was to evaluate which one is the most valuable index for proliferative activity of cancer cells.
MATERIALS AND METHODS
One hundred and fifty-four patients who underwent gastric resection for primary stomach cancer were included in this study. Male to female ratio was 2.1: 1, and mean age was 58.2 years (range: 26-81). Resected cancer tissues were immediately transported to the flow cytometry laboratory, and analyses for DNA content and cell cycle distribution were carried out by FACScan. The results of flow cytometric analysis were studied in correlation with clinical and histologic parameters; depth of invasion, lymph node metastasis, distant metastasis, stage, Laurens classification, histologic types and grade.
RESULTS
The frequency of aneuploid cancer was 40.3% (62 cases). The mean value of GO/Gl fraction was 75.9% and that of S-phase was 16.0%. Decrease of GO/Gl correlates with lymph node metastasis (p 0.015) and stage (p-0.046). Aneuploid cancer exhibited significant decrease of GO/Gl fraction. However, there was no significant conelation between decreased GO/Gl and depth of invasion, distant metastasis, Laurens classi- fication, differentiation of the cancer cells. Patients with metastasis to the lymph node or distant organs had increased S-phase fraction (p-0.032). High S-phase fraction also correlates with advanced stage (p-0.011) and ploidy of the oancer cells (p=0.001). When the ploidy of the tumor was analysed with clinical variables, aneuploid pattern was increased in cancer cells with intestinal type according to Laurens classificatian (p=0.042), Diploid cancer had significantly lower level of S-phase fraction than aneuploid cancer (p 0.001).
CONCLUSION
Ploidy and growth fraction of the stomach cancer reflected the extent of disease in different aspects. However, there was no single parameter which reflected the extent of disease and degree of malignant potential. Furthermore, there is a possibility that S-phase & action alone is not an accurate parameter for the proliferative activity of stomach cancer cells. In conclusion, flow cytometric analyses is a valuable study providing us more precise information about biologic properties of cancer cells. However, further evaluation with longer follow-up period is imperative because the ultimate value as an prognostic factors can be estimated in respective of clinical outcomes.

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A Phase 2 Trial of PEF ( Cispatin , Etoposide , 5-Fluorouracil ) Chemotherapy for Metastatic Stomach Cancer: Yoon Koo Kang, Kwang Seob Yum, Hee Jun Cho, Jhin Oh Lee, Taik Koo Yun; J Korean Cancer Assoc. 1998;30(5):900-906.

Abstract PDF: PURPOSE
To determine the activity and toxicities of PEF (Cisplatin, Etoposide, 5-Fluorouracil) chemotherapy for stomach cancer.
MATERIALS AND METHODS
Patients with previously untreated metastatic stomach cancer were treated with PEF regimen which consisted of cisplatin (20 mg/m2 i.v. days 1~5), etoposide (100 mg/m2 i.v. days 1, 3, 5), and 5-fluorouracil (5-FU)(800 mg/m2 i.v. infusion for 12 hours days 1~5). Chemotherapy was repeated every 3 weeks until disease progressed or toxicities were intolerable.
RESULTS
Between May 1989 and July 1990, 40 patients were enrolled in this protocol. Twelve patients were lost to follow up after one cycle of chemotherapy and inevaluable. After 2~8 cycles (median 3) of chemotherapy, 20 out of 28 evaluable patients showed objective responses without any complete response, making the response rate 71% (95% confidence interval: 54~89%). The responses lasted from 4+ to 39 weeks (median: 38 weeks). The overall survival of total evaluable patients was 4+ ~50+ weeks (median 38 weeks). Among total 109 cycles of chemotherapy, cycles were delayed or doses were reduced in 48 cycles (44%) because of leukopenia (in 61 cycles: 56%) and/or thrombocytopenia (in 14 cycles: 13%). However, there was no treatment-related death. Nausea/vomiting and alopecia were experienced in most of patients. The stomatitis was experienced in 7 patients (25%) but completely reversible. In contrast, the peripheral neuropathy which developed in 4 patients (14%) after 5 cycles of chemotherapy was not reversible.
CONCLUSION
The PEF regimen was active and tolerable in stomach cancer.

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A Case of Early Gastric Cancer Associated with Small Cell Lung Cancer: Mi Kyeong Park, Tae Hun Kwon, Jin Hong Park, Seol Young Yun, Seong Ho Choi, Seong Pyo Son; J Korean Cancer Assoc. 1998;30(2):414-420.

Abstract PDF: The incidence of multiple primary cancers is low than that of single primary cancer. In gastric cancer, incidence of occurrence of multiple primary cancer is 3 to 11.3%. Because stomach and lung are unrelated organs, the combination of gastric cancer and lung cancer is rare. Its estimated incidence is about 10% of all multiple primary cancers. The histologic types of secondary lung cancer in one series, squamous cell carcinomas were 49%; adenocarcinomas were 28%; large cell carcinomas were 14%; small cell carcinomas were 9%; others were 6%. This patient had been diagnosed as early gastric cancer 3 years ago, but he refused operation for cancer and wasnt followed up. After 3 years, he revisited us for dry coughing and diagnosed as small cell lung cancer. At this time, previous gastric cancer was remained as well differentiated, early gastric adenocarcinoma. For its rarity, we report this case with review of literatures.

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Clinical Analysis of 329 Cases of Total Gastrectomy: Woo Sung Lee, Nam Sun Paik, Seon Mi Moon, Woo Chul Noh, Ho Yoon Bang, Dong Wook Choi, Jong Inn Lee, Nan Mo Moon; J Korean Cancer Assoc. 1998;30(1):63-71.

Abstract PDF: PURPOSE
This study was designed to evaluate the safety including the morbidity and mortality of total gastrectomy and combined organ resection, to examine the survival rate and the prognostic factors of gastric cancer following the total gastrectomy and to assess the prognostic predictability of new UICC staging system after surgery in gastric cancer patients. MATERIAL AND METHOD: To evaluate demographic features, clinical presentations, preoperative diagnostic accuracy, postoperative complications and prognostic factors, we analyzed 329 patients who underwent the total gastrectomy or the total gastrectomy with combined resection for gastric malignancy at KCCH from Jan. 1990 to Dec. 1993 retrospectively.
RESULTS
The early postoperative complication rates of overall patients and combined resection group were 9.1% and 8.9%. Mortality of these were 0.9% and 1.1%(p>0.05). The overall 5YSR was 52.8% and there was no significant differrence in the survival rate between the total gastrectomy only group and the combined resection group. The accuracy of preoperative UGIS and abdominal CT for determiantion of resectability were over 80%. The depth of invasion and lymph node metastasis were independent prognostic factors.
CONCLUSION
The total gastrectomy with combined resection should be considered when indicated, because the postoperative morbidity and mortality is low and long term survival is expected. The new UICC staging system seems to be good to predict prognosis in gastric cancer patients.

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Phase 2 Trial of FLP ( 5-FU , Leucovorin , Cisplatin ) Combination Chemotherapy for Advanced Gastric Cancer: Young Iee Park, Moon Hee Lee, Sung Woo Han, Woo Jung Park, Dong Gyu Kim, Jin Lee, Jin Seok Ahn, Jung Ae Rhee, In Sook Woo, Young Suk Park; J Korean Cancer Assoc. 1998;30(1):55-62.

Abstract PDF: PURPOSE
Advanced gastric cancer, the most common malignancy in Korea is a kind of systemic disease. At dignosis, 50~80% of patients have systemic cancer. Therefore, the most patients require systemic chemotherapy. Cisplatin and 5-FU have been suggested to be active in the treatment of gastric cancer, a high response rate was observered with a combination of 5-FU infusion and cisplatin, and the biochemical modulation of 5-FU by leucovorin has been demonstrated to enhance the activity of 5-FU in gastrointestinal tract cancer.
MATERIALS AND METHODS
The patients with advanced gastric cancer whose disease had relapsed or unresectable were treated with 5-FU(800 mg/m2 12 hr IV infusion, D 1~5), leucovorin(20 mg/m2 IV, D 1~5, max. 30 mg), cisplatin(100 mg/m2 15min IV dripping, D1). The cycles of treatment were repeated at 3-weeks intervals.
RESULTS
Between Sep. 1994 and Aug. 1996, previously untreated 44 patients(39 eligible patients) were admitted to this study, the median age was 55 years(range 17~73) and male to female ratio was 20:19. The rate of complete remission was 5%(2/39), the rate of partial remission was 21%(8/39). The median-response duration was 26 weeks(5+~38+ ). The median-time to progression was 25 weeks(4+~62+). The range of overall survival time was from 4 to 62+ weeks. 24 weeks survival rate was 71.5% but the median survival time was not reached. The leukopenia and anemia were the main hematologic toxicities. Non-hematologic side effects were nausea, vomiting, diarrhea, stomatitis, peripheral neuropathy. These toxicities were observed commnonly, but tolerable. Two treatment-related deaths were associated with sepsis.
CONCLUSION
Based on these results, FLP combination chemotherapy seems to be a moderate efficacy for advanced gastric cancer with tolerable toxicities. To confirm the efficacy further, the long-term follow up and a large scale of clinical studies are needed.

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Effects of Lovastatin in Combination with 5-FU on Stomach Cancer Cells: Chaehwa Park, Won Ki Kang; J Korean Cancer Assoc. 1997;29(5):785-790.

Abstract PDF: No abstract available

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The Postoperative Adjuvant Chemotherapy with Combined 5-Fluorouracil and Mitomycin-C following curative resection for gastric Cancer: Young Suk Park, Chang In Suh, Won Ki Kang, Heung Tae Kim, Yung Jue Bang, Noe Kyeong Kim, Jae Gahb Park, Kuhn Uk Lee, Kuk Jin Choe, Soo Tae Kim; J Korean Cancer Assoc. 1989;21(2):406-413.

Abstract PDF: The postoperative adjuvant chemotherapy with 12 cycles of 5-FU and mitomycin-C has been administered in 162 patients with stage II or lll gastric adenocarcinoma after curative gastric resection. 1) After a median follow-up time of 81 months, 94/163 treated patients recurred (58%). The sites of recurrent cancer were as follows: loco-regional, 419, peritoneal, 24%, distant metastases, 26%, multiple sites, 9%. 2) The 5-year disease free survival rates were 36.8% 3) The 5-year overall survival rates were 45.0% and the median survival was 50.2 months. 4) The number of lymph nodes involvement and the T stage affected disease free and overall survival. 5) The FM regimen was well tolerated, and produced moderate bone marrow suppression, anorexia, nausea, vomiting and diarrhea.

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A Clinical Study of Early Recurrence after Curative Gastric Resection for Stage 3 Stomach Cancer: Gi Jun Kim, Tae Seok Lee, Ho Chul Park, Choong Yoon; J Korean Cancer Assoc. 1994;26(2):188-198.

Abstract PDF: 69 cases of early recurred stomach cancer within 2 years from the point of initial curative gastric resection among the 211 cases of stage III stomach cancer have been analysed with regard to factors influencing early recurrence, which were operated at the Department of General Surgery, Kyung Hee Medical Center from January 1988 to April 1991. The results were as follows; 1) Curative gastric resection was performed in 211 cases and 69 cases(32.7%) of them were recurred within 2 years. 2) In 69 cases, the most frequent age group was under 30 years of age(50%), but that was not statistically significant, and male to female ratio was 5.9: 1. 3) The most common site of recurrence was peritoneum(40.5%), and the next was distant me- tastasis such as bone and lung(23.1%), liver(l4.5%), lymph nodes(8.6%), peritoneum and liver(7.2 %), remnant stomach(5.8%), in order of frequency. 4) The larger size of tumor, the higher early recurrence rate, but that was not statistically signif icant(p > 0.05). 5) The early recurrence rate was higher in antral lesion(p<0.05). 6) The early recurrence rate was higher in Borrmann type III and IV(p < 0.05). 7) When the distance of proximal & distal resection margin were shorter than 5 cm or 2 cm, the early recurrence rate was higher(p<0.005). 8) The early recurrence rate was higher in T, and T, lesion for the depth of invasion(p< 0.005). 9) The larger number of involved lymph nodes, the higher early recurrence rate(p<0.005), and that of R operation only was higher than R+a operation(p<0.05). 10). The early recurrence rate was higher in well differentiated tubular adenacarcinoma, but was not sigmificant(p>0.05). 1 1) The early recurrence rate was higher in under 3 cycles of postoperative adjuvant chemo- therapy(FAM) than in over 3 cycles(p<0.05).

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Induction Chemotherapy and Surgery in Locally Advanced Stomach Cancer Showing Pancreas Involvement: Kyung Hee Lee, Jin Hyuk Choi, Sun Young Rha, Hye Ran Lee, Nae Chun Yoo, Ho Yeong Lim, Hyun Cheol Chung, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim; J Korean Cancer Assoc. 1994;26(3):377-385.

Abstract PDF: Gastric cancer is the most common malignancy in Korea. Cure for patients with gastric carcinoma can be achieved only by radical surgery. From August 1988 to May 1992, 25 patients with locally advanced unresectable gastric cancer received 5-FU(Fiuorouracil) + adriamydn + mitomycin-c or 5-FU + cisplatin based induction chemotherapy before surgem. The partial response rate after me- dian 3 cycles of induction cemotherapy was 52%, stable disease 12%, progressive disease 36%. Gastric resection was performed in 18 patients(72%); 13 patients(52%) underwent radical surgery and 5 patients(20%) underwent palliative surgery. Median survival of the patients who underwent cura- tive and palliative surgery was 24. 2 and 27 months, respectively. However, median survival of the patient who didnt undergo any surgery was only 6.5 months. The difference of median survival between curative surgery and none surgery group were significant statistically(P<0.03). Side effects of induction chemotherapy were acceptable and there were no life threatening toxicities In this study, half of the patients can undergo curative surgery after induction chemotherapy. We observe the long term survival in some patients after induction chemotherapy and surgery in loco-regionally advanced gsstric cancer. This therapeutic approch for the locally advanced stomach cancer seems to be feasible. But, prospective tandomized clinical trial is warranted in the future.

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Molecular Characteristics of Tumorigenesis in Human Gastric Carcinomas: In Ho Kim, Joong Shin Kang, Min Ho Suh, Soo Sang Sohn, Suk Kon Kim, Won Ki Baek, Seong Il Suh; J Korean Cancer Assoc. 1994;26(5):688-702.

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The Postoperative Adjuvant Chemotherapy of Gastric Cancer with 5 - Fluorouracil , Adriamycin and Mitomycin - C ( FAM ): Young Suk Park, Heung Moon Chang, Keun Chil Park, Dae Seog Heo, Yung Jue Bang, Jae Gahb Park, Kuhn Uk Lee, Kuk Jin Choe, Soo Tae Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1994;26(6):853-860.

Abstract PDF: The postoperative adjuvant chemotherapy with FAM combination chemotherapy has been administered to 167 patients with stage IB, II, IIIA or IIIB gastric adenocarcinoma after cura- tive gastric resection between March l984 and December 1986. Chemotherapy was started within 4 weeks of surgery in most patiente. Treatment consisted of 5-FU 600 mg/m(2) (day 1, 8, 29 and 36), adriamycin 30 mg/m(2) (day l and 29), mitomycin-C 10 mg /m(2) (day 1) of an 8-week cycle. The cycle was repeated 3 times. Appropriate dose adjustment was made for hematologic and other toxicities. Twelve patients were ineligible for the study and excluded from the analysis. After median follow-up of 79 months, 65 of 155 treated patients recurred (41.9%). The sites of recurrent cancer were as follows: loco-regional, 35%, peritoneal, 23%, distant metastases, 23%, multiple sites, 19%. The 5-year disease-free survival rate was 57.1% and the 5-year overall survival rate was 60.6%. Treatment was well tolerated by the majority of patients and the common side effects were nausea and vomiting (51%). Sex, N stage and the number of involved lymph nodes affect- ed disease-free and overall survival. In conclusion, the postoperative adjuvant chemotherapy with FAM combination chemotherapy was safe and well tolerated. Although the results of FAM chemotherapy were more effec- tive than those of FM chemotherapy as historical control, we concluded that adjuvant chemo- therapy as given in this trial is not indicated as routine trestment in operable gastric cancer. So new trials of adjuvant chemotherapy for gastric cancer must be prospectively randomired and include a no-treatment control arm.

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Multiple Primary malignant Tumors following Stomach Cancer Daignosis: In Keun Choi, Soo Sang Sohn, Joong Shin Kang; J Korean Cancer Assoc. 1995;27(5):829-836.

Abstract PDF: As progressively larger percentage of long-term survivors are being reported, the proportion of patients with subsequent primary lesions are increasing. This study is the clinical analysis of 17 cases of multiple primary malignant tumors confirmed fillowing the pathologic diagnosis of gastric cancer at the Department of Surgery, Keimyung University School of Medicine during the past 10 years from 1984 through 1994. These deta show that, when cancer first appears at a specific anetomic site, certain organs are more susceptible to second primary lesions than other sites. The ratio between male and female was 2:1 and mean age of incidence was 60 years. The ratio between synchronous and metachronous lesions was 1:2. The average time interval between first and second cancer was 3.0 years in metachronous cases. After the diagnosis of stomach cancer, the most frequently involved second organ was colorectum, others were liver, cervix, thyroid, and neck in decreasing order. Pathologic stage, tumor differentiation, tumor size, lymph node metastasis of the first lesions were unrelated to subsequent malignant tumor after stomach cancer diagnosis.

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The Usefuness of laparoscope for the Staging of Gastric Cancer: Jae Bok Lee, Young Jae Mok, Ho Sang Ryu, Young Chul Kim, Jin Hai Hyun, Sae Min Kim; J Korean Cancer Assoc. 1995;27(5):836-846.

Abstract PDF: The purpose of this study is to evaluate the usefulness of preoperative laparoscopic examination in gastric cancer. A more accurate preoperative cancer staging may allow a better prepared setting in which to avdoid unnecessary laparotomy, decide preoperative neoadjuvant chemotherapy and prepare the operation far combined resections or intraoperative radiotherapy. The subjects of this study were the 105 patients who were diagnosed preoperatively by gastrofiberscopic examination with biopsy and had received gastric resections in our department from 1986 to 1993. We performed laparoscopy preoperatively in all patients to characterize the location of the tumor and its and regional infiltration. Abdomi- nal CT staging, preoperative laparoscopic staging, and staging with CT and laparoscopy were compared for serosal infiltration, lymph node metastasis, peritoneal seeding and hepatic me- tastasis. The diagnostic indices such as sensitivity, specificity, accuracy, prevalence and predictive value of each staging were calculated and compared. For the statistical interpretation of the results, diagnostic indexes were calculated in two-way contingency tables of the frequencies of positive and negative results construed as either true or false upon surgical and histo- logic evaluation. The sensitivities for laparoscopic examination of serosal invasion, lymph node metastasis, peritoneal seeding and liver metastasis were 87.3%, 26.8%, 37.5% and 10.5% respectivelym and the specificity of the above findings were 61.8%, 76.5%, 100% and 94.2% respectively. The sensitivities of CT staging for above findings were 50.7%, 39.4%, 0%, 15.8% respectively, and the specificity was 73.5% 97.1%, 99.0%, 93.0% respectively. The sensitivity of combined modalities for above findings were 94.4%, 59.2%, 50.0%, 15.8% respectively, and the specificity was 70.6%, 70.6%, 99%, 94.2% respectively, and which indicates that seosal invasion, lymph node metastasis and peritoneal seeding could be detected accurately, while liver metas- tasis could not be. 1) Serosal infiltration was more accurately diagnosed by preoperative laparoscopy (sensitivity 87.3%, specificity 61.8%, p=0.024). 2) Diagnostic indices of lymph node metastasis, peritoneal seeding and liver metastasis were not different between preoperative laparoscopy and CT (p > 0.05).

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Late Jaundice after Curative Resection of Gastric Cancer: Ki Hoon Jung, Eun Sook Lee, Jeoung Won Bae, Cheung Wung Whang; J Korean Cancer Assoc. 1996;28(1):12-19.

Abstract PDF: Surgeons and oncologists consider the development of late jaundice following curative resection in advanced gastric cancer patients to be an untreatable condition of cancer recurrence. Usually they opt for a conservative management approach rather than to attempt aggressive diagnosis and treatment. To evaluate the justify of this approach, authors retrospectively reviewed 629 cases of curative resections for advanced gastric cancer that had been performed at the Korea University Hospital during a six years time period between Jan. 1986 to Jan. 1992. Of the 629 patients, 51 patients had either bilirubin levels greater than 2 mg% or had shown signs of clinical jaundice. The patients were classified in the following method: type 1a: single liver metastasis, 1b; multiple liver metastases, 2; hepatoduodenal ligament LN metastases, 3; GB or CBD stones, 4; chemotherapy toxicity, 5; hepatitis. We observed 3 cases(6%) of type 1a, 10 cases(19%) of type lb, 14 cases(27%) of type 2, 5 cases(10%) of type 1a+2, 7 cases(14 %) of type 1b+2, 6 cases(12%) of type 3, 4 cases(8%) of type 4, 2 cases(4%) of type 5. The onset of jaundice development differed between recurrent and nonrecurrent jaundice. In nonrecurrent cases, the late jaundice developed shortly after the operative procedure, whereas jaundice usually appeared l yerar after the operation in recurrent cases. There was no significant difference in the primary site of advanced gastric cancer between recurrent and nonrecurrent jaundice. Although late jaundice usually developed in patients with TNM stage II and III cancers, there was no significant difference between the recurrent and nonrecurrent cases. Management of late jaundice consisted of aggressive procedures such as choledochotomy, cholecystectomy, PTCD(Percutaneous transhepatic cholangiography with drainage) and conservative approaches for nonrecurrent cases, and hepatectomy, PTCD, RT (Radiotheraphy) and choledochotomy was done in recurrent cases. These procedures resulted in good outcomes with symptomatic improvement and a better quality of life. The duration of survival in patient who received treatment for the jaundice was on average 8 months in the recurrent cases and 33 months in the nonrecurrent cases, whereas a surviva1 of only 2.4 months was observed in patients who received no treatment for the late jaundice. The results of this study strongly suggested that aggressive approaches in the diagnosis and treatment for late jaundice following curative resection of advanced gastric cancer leads to a longer duration of survival and a better quality of life. We concluded that aggressive treatment for patients developing late jaundice should be performed for the better outcome of patients.

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The Cytotoxic Activity of Sterol Derivatives from Pulsatilla Chinensis Regal: Jin Won Hyun, Yong Man Yang, Min Sook Sung, Ha Sook Chang, Woo Hun Paik, Sam Sik Kang, Jae Gahb Park; J Korean Cancer Assoc. 1996;28(1):145-151.

Abstract PDF: In order to search for antineoplastic components from plants, cytotoxic activity against human carcinoma cell lines was measured in 266 extracts from 236 plants using the MTT (3-[4,5-dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide) method. As a result, the root of Pulsatilla chinensis (Ranunculaceae), which has been used as an insecticide in oriental medicine, showed a cytotoxic effect. Its structure was determined to be a mixture of ￥a-sitosterol-3-O-glucoside and stigmasterol-3-O-glucoside (3:1). Its IC value was 26￥ig/ml against SNU-I stomach cancer cell line.

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5-Fluorouracil , Leucovorin and Mitomycin C ( MLF ) Chemotherapy for Advanced Gastric Cancer : Results of A Phase 2 Trial: Sung Hyun Yang, Sung Rok Kim, Eun Soo Yang, Jong Cheol Ryu, Joon Hee Kim, Chul Soo Kim, Re Hwe Kim; J Korean Cancer Assoc. 1996;28(2):191-198.

Abstract PDF: The results of systemic chemotherapy for advanced stomach cancer are still disappointing despite of numerous studies which has been performed to develop better treatment regimens. Mitomycin C (MMC) is one of the most active agents against stomach cancer and leucovorin (LV) enhance cytotoxicity of 5-fluorouracil (5-FU). This clinical phase II trial was designed to evaluate the efficacy of combination chemotherapy with MMC and LV-modulated 5-FU (MLF). Thirty nine patients were entered into the trial. All patients had measurable lesion. The MLF reaimen consisted of 5-FU 375 mg/§³ IV days 1 through 5: LV 20 mg/§³ IV just before 5-FU infusion days 1 through 5; and MMC 9 mg/§³ IV day l (7mg/§³ from the 2nd cycle). Cycles were repeated every 4 weeks. There were 19 responses (48%) including 6 clinical complete responses. The median survival of all 39 patients was 40.4 weeks. There was minimal myelosuppression; grade 3-4 leucopenia or thrombocytopenia in 26% of cycles. Non-hematologic toxicities were also tolerable; grade 3 nausea or vomiting in 8% of patients. This phase II study showed that the MLF therepy is comparable in effect for advanced stomach cancer with minimal toxicities, deserving phase III study with other regimens.

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