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Volume 20(3); June 2004
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Original Articles
Expression of Vascular Endothelial Growth Factor and Tumor Necrosis Factor-alpha in Angiogenesis Induced by Lipopolysaccharide and Thalidomide in CT26 Murine Colon Cancer of BALB/c Mouse.
Choi, Dong Lak , Cho, Chang Ho , Jeong, Jin Sook , Hong, Sook Hee , Yoon, Ghil Suk
J Korean Soc Coloproctol. 2004;20(3):125-132.
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PURPOSE
The growth, progression, and metastasis of malignant neoplasms are influenced by the environment of the tumor and by proliferation of the tumor itself. Angiogenesis of a malignant neoplasm is a very important environmental factor of tumor growth and metastasis. Also, it is a prognostic factor for malignant neoplasms. The mechanism of angiogenesis, such as the effects of cytokines and angiogenesis-promoting factors, is incompletely understood.
METHODS
This study was designed to define the role of tumor necrosis factor-alpha (TNF-alpha) and the vascular endothelial growth factor (VEGF) in angiogenesis induced by lipopolysaccharide (LPS) and thalidomide (anticytokine drug) in CT26 murine colon cancer transplanted to BALB/c mice.
RESULTS
The tumor size in the LPS-treated group (n=3, 2.1+/-0.26 cm) was larger than it was in the LPS thalidomide-treated group (n=4, 1.95+/-0.19 cm) and in the control group (n=3, 1.6+/-0.20 cm) (P<0.05). The microvessel density determined by CD31 immunostaining was lowest for the control group and highest for the LPS- treated group, but the differences were not statistically significant. An immunohistochemical study showed that the expressions of TNF-alpha (P<0.01) and VEGF (P<0.05) were higher in the experimental groups than they were in the control group. Also, the LPS thalidomide-treated group had lower expressions of TNF-alpha (P<0.01) and VEGF (P<0.05) than the LPS-treated group. Western blots revealed that the TNF-alpha and the VEGF levels semiquantitatively increased from the control group to the LPS thalidomide-treated group to the LPS-treated group.
CONCLUSIONS
Our study revealed that low doses of LPS stimulated angiogenesis through increased expression of TNF-alpha and VEGF. Thalidomide decreased angiogenesis, probably through suppression of TNF-alpha with a decreased expression of VEGF. We conclude that TNF-alpha, suppressed by thalidomide, in the model of transplanted colon cancer may inhibit angiogenesis through coincident decrease in the expression of VEGF.
Early Experience of Virtual Colonoscopy on Colorectal Cancer.
Lee, Han Il , Lee, Tae Soon , Jung, Soon Jai , Park, Ki Hyuk , Choi, Dong Rack , Joo, Dae Hyun , Park, Sung Hwan , Yoo, Yong Oon , Park, Ki Ho , Lee, Young Hwan , Kim, Jin Cheon
J Korean Soc Coloproctol. 2004;20(3):133-137.
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PURPOSE
Virtual colonoscopy (VC) is a newly developing non-invasive technique used to detect polyps and cancers of the colon. The aim of this study is to assess the efficacy of VC in the detection of synchronous polyps or cancers in preoperative patients as well as metachronous polyps of postoperative colorectal cancer patients.
METHODS
Both VC and conventional colonoscopy (CFS) were performed on 40 patients with colorectal cancer (10 cases of preoperative state and 30 cases of postoperative follow-up) during Sep. 2002 to June 2003 in Daegu Catholic Medical Centre, Catholic University of Daegu, Republic of Korea. The success rate and the detection rate of polyps or cancers along with the locations and sizes of masses and the findings of anastomotic site were compared between VC and CFS.
RESULTS
The entire colon was clearly visualized by CFS in all cases. In the preoperative group, VC was successfully performed in 8 out of 10 cases (80%). 8 out of 10 cancers, 4 out of 4 polyps (5 mm or more in diameter) and 3 out of 6 polyps (5 mm or less in diameter) were identified. The success rate of VC in the postoperative group were 58% of low anterior resection (LAR) from cecum to hepatic flexure, 89% of LAR, 45% of right hemicolectomy (RHC) from hepatic flexure to splenic flexure, 63% of LAR, 45% of RHC from splenic flexure to sigmoid colon, and 53% of LAR, 72% of RHC in rectum. The causes of failure were inadequate bowel distension and retained fluid. In postoperative group, VC identified only 3 of 7 polyps(5 mm or more in diameter), 1 of 10 polyps (5 mm or less in diameter) and 1 of 1 recurrent cancer. The anastomotic site was clearly seen by VC in 9 of 19 cases (47%) of LAR and 3 of 11 cases (27%) of RHC. VC also identified 28 extracolonic findings.
CONCLUSIONS
Although the efficacy of VC in postoperative colorectal cancer follow up seems to be disappointing, but it can be used as an alternative method for patients with incomplete conventional colonoscopy due to anastomotic site stricture or for other failed cases. Further technological advancement of VC is needed in order for it to replace conventional colonoscopy as a postoperative follow-up test.
Clinical Results of Postoperative Chemoradiation on Advanced Rectal Cancers: Tumor Response, Toxicities, and Morbidity.
Lee, Dong Ryul , Lee, Han Il , Kim, Ho Gak , Kim, Eun Young , Ryoo, Hyun Mo , Yun, Sang Mo , Kim, Jin Cheon
J Korean Soc Coloproctol. 2004;20(3):138-144.
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PURPOSE
Adjuvant chemotherapy and radiotherapy have been considered effective treatments in advanced rectal cancers. Recently, several studies have reported that preoperative chemoradiation (CRT) may have advantages over postoperative CRT, particularly in reducing local recurrence and preserving the anal sphincter. We studied the short-term efficacy of preoperative CRT for locally advanced rectal cancers.
METHODS
Between Jun. 2000 and Aug. 2003, 23 patients were treated with preoperative CRT, followed by surgery (pre-CRT) and 31 patients were treated with chemoradiation postoperatively (post-CRT). We compared these two groups for the incidence and degree of side effects from CRT, postoperative complications, type of surgery, including anal sphincter preservation, and short-term recurrence.
RESULTS
The average age and male-to-female ratio of the pre- and the post-CRT groups were 58+/-11, years and 13:10, and 61+/-14 and 14:17, respectively. T downstagings were observed in 17 of 23 (74%) pre-CRT patients. On the RTOG-EORTC scale, the patients who showed hematological, intestinal and dermal side effects in the pre-CRT group and in the post-CRT group were 5, 5, 2 and 5, 2, 4, respectively and the difference was not statistically significant (P=0.41). Anal sphincter preserving surgical procedures were performed 91.3% (21/23) and 83.9% (26/31) of the patients in the pre- and the post-CRT groups, respectively. But this difference was not statistically significant (P=0.4). Postoperative complications in the pre-CRT group were anastomosis site leakages (n=3) and rectovaginal fistula (n=1). In the post-CRT group, complications were two anastomosis site leakages. Four of the 31 post-CRT group patients had recurrences such as locoregional area (n=2), liver (n=1), and lung (n=1) while no patient was observed in pre- CRT group.
CONCLUSIONS
Although pre-CRT group showed higher incidence of complications than post-CRT group, these were managed easily and safely. Pre-CRT seems to be an effective modality for treating advanced rectal cancers particularly for preserving anal sphincter. Long-term follow- up data are needed to clarify the effect of pre-CRT.
Clinical Significance of PTEN Expression in Colorectal Cancer.
Kang, Won Kyung , Choen, Joon Sung , An, Chang Hyeok , Sung, Kwan Su , Lee, Sang Chul , Lee, Kwang Real , Kim, Jeong Su , Oh, Seong Taek
J Korean Soc Coloproctol. 2004;20(3):145-150.
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PURPOSE
Tumor suppressor gene called PTEN has been localized to 10q23 in 1997 and its mutation has been implicated in some malignancies. Loss of the PTEN gene has been clinically associated with unfavorable histology and influencing tumor staging and recurrence in the determination of a prognosis in patients suffering from other cancers, its role in colorectal cancers is inconclusive as of yet. The purpose of this study is shed light on PTEN expression in colorectal cancer and its significance associated with pathological findings and clinical findings.
METHODS
A total of 217 patients who had been diagnosed with colorectal cancer, had undergone radical colectomy from October of 1993 to December of 2000, and for whom follow-up was possible were selected for this study. Their clinical records were analyzed and specimens were stained immunohistochemically RESULTS: In comparing the PTEN positive group (48 patients, 22.1%) with the negative group (171 patients, 77.9%), there was a significantly (P=0.021) higher frequency of recurrence in the negative group (29.0%) than in the positive group (12.5%), and an especially higher frequency of distant metastasis in the negative group (18.3%) than in the positive group (4.2%), with P=0.010. Although there was no meaningful difference in the overall five year survival rate, the five year disease free survival rate was significantly (P=0.029) higher in the positive group.
CONCLUSIONS
The results of this study reveal the possibility of using PTEN as a prognostic indicator in colorectal cancer.
Thymidylate Synthase Gene Polymorphism as a Prognostic Factor for the Colorectal Cancer.
Kim, Joo Hyung , Kim, Young Bae , Choi, Jin Hyuk , Kim, Jeong Mi , Jeong, Soo Hyun , Suh, Kwang Wook
J Korean Soc Coloproctol. 2004;20(3):151-156.
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PURPOSE
Thymidylate synthase (TS) expression in colorectal cancer is regarded as both a prognostic marker and a predictor of response to fluoropyrimidine-based therapies targeting TS. However, results from immunohistochemical staining of TS show wide discrepancies. The human TS gene promoter is polymorphic, having either double or triple tandem repeats of a 28-bp sequence. Here, we determined the significance of this polymorphism in predicting the clinical outcomes for patients with operable colorectal cancer treated by a curative resection.
METHODS
The cases of 121 patients with stage II or III colorectal cancer, who underwent a curative resection, were reviewed. After DNA extraction from paraffin- embedded tissues, the promoter region of the TS gene was amplified by polymerase chain reaction.
RESULTS
Sixty-eight subjects were homozygotes for the triple repeat variant (group A, L/L, 250-bp), and 53 subjects (group B) were either homozygotes for the double repeat variant (S/S, 220-bp) or heterozygotes (S/L, 220 and 250- bp). The difference between stage II and stage III patients was significant with regard to the 5-year actuarial survival (87% vs 63%, P=0.0320). Examining the survival according to the TS polymorphism, we found a significant difference between group A and B (80% vs 53%, P=0.0481). In patients with stage II disease, the difference in survival rates between group A and B did not reach statistical significance (43% vs 86%, P=0.1678). However, the difference was significant between group A and B for stage III disease (77% vs 41%, P=0.0414).
CONCLUSIONS
We found the TS polymorphism to be a significant and independent prognostic factor for operable colorectal cancer. We think assay of the TS polymorphism can overcome the technical pitfalls of immunohistochemical staining and give more solid prognostic information in the treatment of colorectal cancer.
nfluences of DNA Ploidy and Pre-operative CEA Level on the 5 Year Survival Rate in Colorectal Cancer.
Kang, Kyu Chul , Jung, Sung Teak , Yoon, Min Young , Choi, Sun Keun , Hur, Yoon Seok , Lee, Keon Young , Kim, Sei Joong , Cho, Young Up , Ahn, Seung Ik , Hong, Kee Chun , Shin, Seok Hwan , Kim, Kyoung Rae , Woo, Ze Hong
J Korean Soc Coloproctol. 2004;20(3):157-162.
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PURPOSE
The role of DNA ploidy in colon cancer as a prognostic factor and the correlation of DNA ploidy with the established prognostic factors have been studied for the past 20 years. The purpose of this study was to look into the correlation of DNA ploidy with the prognostic factors and to assess the influence of pre-operative CEA level and DNA ploidy on survival in colorectal cancer.
METHODS
A total of 319 patients with colorectal cancer received radical operations, and DNA flow cytometric analyses of DNA ploidy patterns were performed at the Department of Surgery, Inha University Hospital, from June 1996 to July 2002. The patients were divided into 2 groups according to the DNA ploidy patterns.
RESULTS
The DNA ploidies of the colorectal tumors were compared to various prognostic factors, the pre-operative CEA level and lymph-node metastasis. The latter two showed correlations to the DNA ploidy. The 5-year survival rate for patients with a normal pre-operative CEA level and DNA diploidy was 85.6% compared to 47.8% for patients with both high pre-operative CEA level and DNA aneuploidy, a statistically significant correlation (P= 0.0003).
CONCLUSIONS
This study suggests that DNA ploidy in patients with colon cancer has a significant correlation with pre-operative CEA level and lymph-node metastasis. Especially, the pre-operative CEA level and DNA ploidy in patients with colorectal cancer may play a role as useful prognostic factors.
Clinical Comparison of Hepatic Resection and Radiofrequency Ablation of Hepatic Metastases from Colorectal Cancer.
Kang, Sin Jae , Park, Chi Min , Jeong, Keuk Won , Park, Sung Bae , Yun, Seong Hyeon , Chang, Weon Young , Lee, Woo Yong , Chun, Ho Kyung
J Korean Soc Coloproctol. 2004;20(3):163-168.
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PURPOSE
The aim of this study was to compare the clinical characteristics between hepatic resection and radiofrequency ablation (RFA) in hepatic metastases of colorectal cancer.
METHODS
Among 183 patients who were diagnosed as having colorectal cancer with hepatic metastases from May 1999 to Dec. 2002, excluding 56 patients who did not undergo a hepatic resection or RFA due to multiple hepatic metastases or other distant metastases, 127 patients who were treated with a pure hepatic resection (N=68), pure RFA (N=35), or a hepatic resection with RFA (N=24) synchronous or metachronous were reviewed in this study. The study included metastatic hepatic tumor size, number, distribution, disease-free survival rate, and overall survival rate.
RESULTS
The mean hepatic tumor sizes in the resection group, the RFA group, and the resection with RFA group were 3.3 cm, 3.0 cm, and 2.5 cm, respectively, but the differences in the sizes had no statistical significance (P>0.1). In the view of the number of hepatic metastases, single metastases were the most prevalent kind in the resection group and the RFA group (64.7% and 60.0%) while multiple metastases were the most prevalent kind in the resection with RFA (20/24, 83.3%). In the resection and the RFA groups, a unilobar distribution was the most common (88.2% and 68.6%), but a bilobar distribution was the most common (87.5%) in the resection with RFA group. The disease-free survival rates were 42.2% (resection group), 30.7% (RFA group), and 22.2% (resection with RFA group) in the third year (P=0.65). The overall survival rates were 70.9% (resection group), 68.4% (RFA group), and 62.9% (resection with RFA group) in the third year (P=0.19).
CONCLUSIONS
There were no significant statistical differences in the disease-free survival and the overall survival rates between the three groups. Radiofrequency ablation (RFA) is considered as not only a complementary but also an alternative treatment tool to hepatic resection in the treatment of hepatic metastases of colorectal cancer and has a similar survival rate.
Is Routine Chest X-ray Useful in Detection of Pulmonary Metastases after Curative Resection for Colorectal Carcinoma?.
Yun, Seong Hyeon , Park, Sung Bae , Kang, Sin Jae , Park, Chi Min , Jeong, Keuk Won , Chang, Weon Young , Lee, Woo Yong , Chun, Ho Kyung
J Korean Soc Coloproctol. 2004;20(3):169-175.
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PURPOSE
This study was performed to evaluate the effectiveness of conventional chest radiography and abdominal CT for early detection of pulmonary metastases after curative surgery for colorectal cancer.
METHODS
We retrospectively reviewed 138 cases of pulmonary metastases from a group of colorectal-cancer patients, who were recruited from 1994 to 2002 at Samsung Medical Center, Sungkyunkwan University School of Medicine, and who had been surgically treated with a curative resection.
RESULTS
The detection rates for pulmonary metastases were 34.1% by conventional chest radiography, 50.0% by abdominal CT, and 15.9% by other means. For stage I and II tumors, conventional chest radiography was superior to abdominal CT (45.7% vs. 34.3%, P<0.05) for detecting pulmonary metastases. On the contrary, for stage III tumors, abdominal CT was superior to conventional chest radiography (55.3% vs. 30.1%, P<0.05). Compared with stage I and II, pulmonary metastases in stage III had a tendency to be more numerous, bilateral, and extra-pulmonary. They also had a low detection rate by conventional chest radiography and a higher detection rate by abdominal CT, and they were associated with poor survival.
CONCLUSIONS
Conventional chest radiography is no more useful in detecting early pulmonary metastases after curative colorectal surgery than abdominal CT, especially for stage III tumors. We propose the use of routine chest CT or extended abdominal CT for screening of occult lung metastases in stage III colorectal cancer patients.
Case Report
Ischemic Pseudomembranous Colitis with Perforation due to Polyarteritis Nodosa.
Kim, Ki Nam
J Korean Soc Coloproctol. 2004;20(3):176-179.
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Polyarteritis nodosa, one of the necrotizing vasculitis involving predominantly small and medium sized arteries is a rare disease. Gastrointestinal involvements have been reported in more than 50% of patients at some time during its course. The small bowel is the frequent site of involvement in clinically apparent ischemic disease. The colon is less commonly involved, particularly at the initial presentation. We report a rare case of polyarteritis nodosa with ischemic colitis, perforation, and pseudomembrane formation.
Review
Molecular Targeted Therapy in Colorectal Cancer.
Yun, Seong Hyeon
J Korean Soc Coloproctol. 2004;20(3):180-188.
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In the last few years, the knowledge of molecular oncology has led to the development of many new biological agents whose targets are extracellular or intracellular molecules involved in the main signaling pathways that play major roles in cancer development and progression. Now new agents against epidermal growth factor receptor (EGFR), farnesyl transferase (FT), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP), cyclooxygenase (COX)-2 are developed. These agents represent a new approach to the colorectal cancer, as for many other types of tumors. Preliminary data show that the targeted therapy may enhance activity of chemotherapeutic agents. Despite the encouraging preclinical results, the majority of these compounds have not yet produced convincing clinical results. However, these new agents raise a new challenge in the treatment of colorectal cancers in the new millennium.

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