Biomedical subjects

Jen-Kou Lin

Publications and source records attributed to Jen-Kou Lin.

At least 19 recordsLinked to original sources

PubMed2006

p53 protein accumulation as a prognostic marker in sporadic colorectal cancer.

BACKGROUND AND AIMS: p53 protein plays a crucial role in the pathogenesis of a large number of malignancies. In this study, our goal was to elucidate the prognostic role of p53 overexpression and its relationship to clinicopathological variables in colorectal cancer. MATERIALS AND METHODS: Between 1999 and 2004, surgical specimens of 258 patients who received surgical treatment for colorectal cancer at the Veterans General Hospital, Taipei were collected. p53 expression in tumor tissue was evaluated by immunohistochemical analysis using the human p53-specific mouse monoclonal antibody, PAb 1801. RESULTS: Of the 258 patients, 97 (37.6%) had overexpression of p53 in tumor tissues. The accumulation of p53 protein in tumor tissues did not correlate with age, gender, preoperative serum carcinoembryonic antigen (CEA) level, mucin content, nodal status, and tumor stage. A statistically significant correlation was found between p53 overexpression and location of the tumor in the rectum (p=0.038). Well to moderately differentiated tumors had significantly higher frequency of p53 overexpression than poorly differentiated tumors (40.0 vs 20.0%, p=0.050). Each patient was followed up for a minimum of 2 years (median 35 months). In univariate analysis, 3-year cancer-specific survival rate was significantly higher in patients with tumor p53 overexpression (88.2%) than in patients without overexpression (log rank test, p=0.037). However, in multivariate analysis, the tumour node metastasis stage remained the most significant independent prognostic factor. CONCLUSION: The accumulation of p53 protein might have a favorable prognostic value in colorectal cancer, but it is not an independent prognostic factor.

Adolescent↗

PubMed2006

Distinctive clinicopathological features of Ki-ras mutated colorectal cancers.

BACKGROUND AND OBJECTIVES: We explored the relationship between the mutation pattern of Ki-ras and the clinicopathological features of colorectal cancers (CRCs). METHODS: Relationships between clinicopathological parameters and Ki-ras mutation status were analyzed in 255 CRC patients using the chi-square and student t-tests. Kaplan-Meier survival curves were compared using the log-rank test. RESULTS: Ki-ras mutation occurred in 43.9% of tumors, and 83% affected codon 12. The most frequent mutations were GGT->GAT (Gly->Asp) (37.5%), followed by GGT->GTT (Gly->Val) (31.3%), both in codon 12. The frequency of Ki-ras mutation was similar for different tumor stages (38.2-47.8%). The mucin component of tumors was significantly associated with Ki-ras mutation. The 4-year overall and disease-free survival was 61% and 54%, respectively, for patients with Ki-ras mutated tumors, and 73% and 60% for patients with nonmutated tumors (not statistically significant). Patients with Ki-ras mutated tumors had lower plasma folate (24 ng/dl) than those bearing nonmutated tumors (37 ng/dl). Patients with G->T Ki-ras mutations had the lowest folate level (22 ng/dl), followed by those with G->A mutations (25 ng/dl). CONCLUSIONS: Ki-ras mutated colorectal tumors have a higher mucin production and higher differentiation, and are associated with lower plasma folate levels and a relatively poorer disease outcome.

Aged↗

PubMed2006

Role of MTHFR polymorphisms and folate levels in different phenotypes of sporadic colorectal cancers.

BACKGROUND AND AIMS: By altering both DNA methylation and nucleotide synthesis, folate metabolism is thought to contribute to colorectal carcinogenesis. We examined the role of folate metabolism in three different phenotypes of sporadic colorectal cancers (CRCs), phenotypes that were classified by the status of microsatellite instability (MSI) and chromosomal instability (CIN): MSI-H, microsatellite stability (MSS)/aneuploidy, and MSS/diploid. PATIENTS AND METHODS: A total of 195 sporadic colorectal tumors and another 195 age- and gender-matched healthy volunteers in Taipei-Veteran General Hospital and Taipei City Hospital were collected. We analyzed for MTHFR (methylenetetrahydrofolate reductase) polymorphisms (C677T, A1297C), folate, and vitamin B(12) levels. We determined MSI status and DNA ploidy with fluorescent polymerase chain reaction and flow cytometry. Relations between clinicopathological variables and molecular variables were analyzed by chi (2) tests (with Yates' correction) for categorical variables and Student's t test for numerical variables. RESULTS: Folate levels (5.02+/-4.43 ng/ml) were significantly lower in cancer patients than in controls (7.22+/-4.46 ng/ml). Vitamin B(12) level was similar between cancer patients and controls. The frequency of the TT genotype of MTHFR C627T (12.3%) was slightly higher than controls (8.2%), but it did not reach statistical significance (p=0.174). Within the low-folate group (<5 ng/ml), the frequency of the TT genotype in cancer patients (14.4%) was significantly higher than in controls (4.6%). Sixteen patients who had MSI-H CRC (8.2%) had a significantly higher frequency of TT MTHFR (37.5%) and lower folate levels (3.56+/-2.41 ng/ml) than patients with MSS tumors (10.1%, 5.14+/-3.72 ng/ml). Patients with MSS/aneuploid tumors had significantly lower folate levels (4.50+/-3.06 ng/ml) than those with MSS/diploid tumors (6.69+/-4.73 ng/ml). CONCLUSION: Folate deficiency and the MTHFR genetic polymorphism play an important role in colorectal carcinogenesis, including MSI and CI. SYNOPSIS: Folate metabolism plays an important role in colorectal carcinogenesis. We demonstrate that patients with MSI-H tumors had higher frequency of TT MTHFR C627T (37.5%), and patients with MSS/aneuploid tumor had lower folate level (4.50+/-3.06 ng/ml).

Adult↗

PubMed2006

Relationship between genetic alterations and prognosis in sporadic colorectal cancer.

Because chromosomal chromosomal instability (CIN) and microsatellite instability (MSI) are important genetic alterations in colorectal cancers, we classified the sporadic colorectal cancers (CRC) on the status of the CIN and MSI and explored their molecular profiles. A total of 213 colorectal tumors were collected for analysis of DNA ploidy, MSI, loss of heterozygosity (LOH), mutation of p53 (exons 5 to 9), Ki-ras (exons 1 and 2) and BRAF (V599E). Relationships between clinicopathological variables and molecular analyses were analyzed with the chi(2) test (Yates' correction). Kaplan-Meier survival curves were compared using log-rank test. Variables with p < 0.1 were entered into the Cox regression hazard model for multivariate analysis. High microsatellite instability (MSI-H) existed in 19 tumors (8.9%), which were more likely to be right-sided (31.6%) with poor differentiation (26.3%). Seventy-one (33.3%) tumors were diploid and 142 (66.7%) were aneuploid. Mutations in p53, Ki-ras and BRAF were found in 45.1%, 41.8% and 4.2% of tumors, respectively. Based on MSI, and CIN, 3 classes were defined: (i) High microsatellite instability MSI-H tumors: young age, high carcinoembryonic antigen (CEA) level, right colon, poorly differentiated, mucin production, high BRAF mutation, lower allelic loss and relatively good prognosis; (ii) Microsatellite stability (MSS) diploid tumors: right colon, poorly differentiated, less infiltrative tumor, mucin production, lower allelic loss and low p53, BRAF mutation; (iii) MSS aneuploid tumors: more infiltrative invasion, greater allelic loss and high p53 mutation. According to multivariate analysis, tumor stage and p53 mutation were significantly associated with disease progression. The MSS diploid and MSS aneuploid CRCs could be subtyped with p53 mutation and had different prognostic outcome and molecular profiles. The 4-year disease-free survival (DFS) of patients with MSS-diploid, wild-type p53 tumors was 67% and significantly higher than those of patients with MSS-diploid, mutant p53 CRC (30%, p = 0.003). The same trend was found in patients with MSS-aneuploid CRC(wild p53 vs. mutant p53, 64% vs. 41%, p = 0.009). We concluded that CIN, MSI and p53 mutation status might be used as a multiple parameter profile for the prognosis of sporadic colorectal cancer.

Aged↗

PubMed2005

Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma.

AIM: To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with histologically confirmed metastatic colorectal cancers receiving treatment at Taipei Veterans General Hospital were enrolled. All patients had measurable metastatic lesions and life expectancies of more than 3 mo. Plasma vWF levels were measured by immuno-turbidimetric assay and compared with results from 40 non-metastatic colorectal cancer patients and 22 healthy controls. Patients with metastatic colorectal cancer were divided into two groups according to serum vWF levels and the differences between these two groups were analyzed using chi2 test. Data on age, gender, performance status, location of primary tumor, extent of metastasis, site of metastases, histological differentiation, serum CEA and plasma vWF levels were analyzed to determine association with survival. Survival curves were constructed by Kaplan-Meier product limit method and the data was analyzed using log-rank test on a microcomputer. Multivariate analysis using the Cox's proportional hazards regression model was then performed to determine the independent prognostic indicators among all of the possible variables. RESULTS: Colorectal cancer patients were identified as having significantly higher plasma vWF concentrations than healthy controls (P<0.05). Moreover, higher vWF plasma levels were associated with advanced tumor stage (P<0.05) and the presence of multiple metastases (P = 0.014). Patients with lower vWF plasma levels (< or =160%) survived significantly longer than those with a higher plasma vWF level (log-rank test, P = 0.0043). By multivariate analysis, plasma vWF levels (P<0.001), the extent of metastasis (P = 0.012), and the performance status (P = 0.014) were identified as independent prognostic factors. CONCLUSION: Our data indicates that high plasma vWF concentrations correlate with advanced diseases and significantly poor prognosis of patients with metastatic colorectal carcinoma. It may serve as a potential biological marker of disease progression in these patients.

Adult↗

PubMed2005

Pre-operative chemoradiotherapy with oral tegafur-uracil and leucovorin for rectal cancer.

BACKGROUND: To evaluate the efficacy and toxicity of pre-operative radiotherapy (RT) combined with oral tegafur-uracil (UFUR) plus leucovorin (LV) in rectal cancer. PATIENTS: Sixty-five patients with rectal adenocarcinoma (clinical staged T2-4N0-2M0) received pelvic RT of 45 Gy in 20 fractions over 28 days. Concurrent chemotherapy consisted of UFUR (200 mg/m(2)/day) and LV (45 mg/day) on day 1-28. UFUR (250 mg/m(2)/day) and LV were continued on day 36-63. Surgery was performed on day 70. RESULTS: Sixty-three patients completed the concurrent chemoradiotherapy (CCRT) and 56 received curative or palliative surgery. Among the 52 patients receiving curative resection, downstaging (DS) occurred in 39 (75%), pathological complete response in 13 (25%), and sphincter preservation was achieved in 16 of 29 (55%) with lower-seated tumors. With a median follow-up time of 33 months, local failure developed in 4 (8%) and distant metastases occurred in 7 (14%). The 3-year overall survival was 92% and disease-free survival 76%. For all 65 patients, grade 3-4 diarrhea developed in 6 (9%) and grade 3-4 leucopenia observed in 2 (3%). CONCLUSIONS: Oral UFUR + LV administered with pre-operative RT are effective in tumor DS, pathological complete response, and sphincter preservation with tolerable toxicity in rectal cancer.

Adenocarcinoma↗

PubMed2005

Loss of heterozygosity: an independent prognostic factor of colorectal cancer.

AIM: Colorectal cancers result from the accumulation of several distinct genetic alterations. This study was to investigate the frequency and prognostic value of loss of heterozygosity (LOH) and microsatellite instability (MSI) at 14 genetic loci located near or within regions containing important genes implicated in colorectal tumorigenesis. METHODS: We studied colorectal cancers with corresponding normal mucosae in 207 patients (139 males and 68 females, mean age at the time of tumor resection 66.2+/-12.4 years, range 22-88 years). There were 37 right-sided colonic tumors, 85 left-sided colonic tumors and 85 rectal tumors. The distribution of tumor staging was stage I in 25, stage II in 73, stage III in 68, and stage IV in 41. We analyzed the LOH and MSI of HPC1, hMSH2, hMLH1, APC, MET, P53, NH23-H1, DCC, BAT25, BAT26, D17S250, MYCL1 and D8S254 with fluorescent polymerase chain reaction and denatured gel electrophoresis. High-frequency LOH was determined to be greater than three, or more than 50% of the informative marker with LOH. High-frequency MSI (MSI-H) was determined as more than four markers with instability (>30%). Correlations of LOH and MSI with clinical outcomes and pathological features were analyzed and compared. RESULTS: The occurrence of MSI-H was 7.25%, located predominantly in the right colons (7/15) and had a higher frequency of poor differentiation (6/15) and mucin production (7/15). LOH in at least one genetic locus occurred in 78.7% of the tumors and was significantly associated with disease progression. Of the 166 potentially cured patients, 45 developed tumor recurrence within 36 mo of follow-up. Clinicopathological factors affecting 3-year disease-free survival (DFS) were TNM staging, grade of differentiation, preoperative CEA level, and high LOH status. Patients with high LOH tumors had a significantly lower DFS (50%) compared with patients with low LOH tumors (84%). Of the patients developing subsequent tumor recurrence, the number and percentage of LOH were 2.97 and 46.8% respectively, similar to the stage IV disease patients. TNM staging had the most significant impact on DFS, followed by high LOH status. CONCLUSION: Clinical manifestations of LOH and MSI are different in colorectal cancer patients. High-frequency LOH is associated with high metastatic potential of colorectal cancers.

Adult↗

PubMed2005

Genetic changes and clonality relationship between primary colorectal cancers and their pulmonary metastases--an analysis by comparative genomic hybridization.

About 10% of colorectal carcinoma patients develop pulmonary metastases during their lifetime. We address whether and how the chromosomal abnormalities differ between the primary cancers and their metastatic counterparts, what the clonality relationship (CR) is between them, and whether certain genomic aberrations contribute to this disease progression. Comparative genomic hybridization (CGH) experiments were performed on 18 paired samples of primary and pulmonary metastases obtained from patients who had undergone two consecutive surgeries and from whom clinical data had been collected. The CGH profiles also were used as indexes for determining the CR between the cancers. The overall CGH abnormality profiles were similar for the primary colorectal carcinomas and their pulmonary metastases. Frequent gains were found on chromosome arms 20q, 8q, 13q, and 7q, whereas common losses were found on 18q, 8p, and 18p. The pulmonary metastases, however, contained more CGH abnormalities than did the primary carcinomas (total aberration events per tumor: 12.6 +/- 5.0 vs. 8.3 +/- 5.7, respectively, P = 0.024; gains: 7.6 +/- 3.1 vs. 5.1 +/- 3.5, respectively, P = 0.036; losses: 5.0 +/- 2.8 vs. 3.3 +/- 2.9, respectively, P = 0.076). Comparing CGH profiles between individual primary and metastasis pairs, we found that 10 of the 18 (56%) paired samples examined exhibited a high degree of CR, indicating that they were likely to have originated from the same clone and/or that not many additional chromosomal changes had occurred in the metastases, except for 4q loss, whose incidence was much higher in the metastases than in the primaries (60% vs. 10%; P = 0.030). Also, the primary tumors of the high-CR group carried more genomic aberrations, especially 8p loss, than did the primary tumors in the low-CR group. We found more chromosomal changes associated with the pulmonary metastases of colorectal cancer compared with the corresponding primary tumors. We concluded that primary cancers containing more genomic lesions, especially 8p losses, are more likely to metastasize to the lungs. Loss of 4q is potentially a supplementary factor contributing to the dissemination of this disease.

Adult↗

PubMed2005

How accurate is magnetic resonance imaging in restaging rectal cancer in patients receiving preoperative combined chemoradiotherapy?

PURPOSE: Preoperative combined chemoradiotherapy is currently the main neoadjuvant therapy used to treat locally advanced middle and low rectal adenocarcinoma. A restaging work-up with magnetic resonance imaging was hoped to provide information about the effects related to combined chemoradiotherapy. The goal was to evaluate the correlation between pathologically verified tumor stages and clinical stages predicted by magnetic resonance imaging after combined chemoradiotherapy. METHODS: Between August 2000 and June 2003, 50 patients with biopsy-proven middle and lower rectal adenocarcinoma, with initial stage T3-T4 or N+, M0, were recruited in this series. Pelvic magnetic resonance imaging was used to stage the tumor before and after combined chemoradiotherapy. A protocol of the standard external radiation dose and oral combined uracil and 5-fluorouracil plus leucovorin was used. The results of magnetic resonance imaging restaging after combined chemoradiotherapy were correlated with the pathologic staging. RESULTS: The overall predictive accuracy in T stage was 52 percent, whereas overstaging and understaging occurred in 38 percent and 10 percent of patients, respectively. Most of the inaccurate T staging was a result of the overstaging of superficial tumors (T0-T2). In N stage, accurate staging was noted in 68 percent of all patients, whereas 24 percent were overstaged and 8 percent were understaged. CONCLUSION: In restaging irradiated tumors, magnetic resonance imaging had the accuracy of 52 percent in T stage and 68 percent in N stage. Poor agreement between post-combined chemoradiotherapy magnetic resonance imaging and pathologic staging was observed in both T (k = 0.017) and N (k = 0.031) stages. Most of the inaccuracy in both T and N stages was caused by overstaging. The problem with magnetic resonance imaging was believed to be that it could not completely differentiate fibrosis from viable residual tumors.

Adenocarcinoma↗

PubMed2005

Curative resection of T1 colorectal carcinoma: risk of lymph node metastasis and long-term prognosis.

PURPOSE: The features of T1 colorectal adenocarcinoma and the risk determination of lymph node metastasis were reviewed. Prognostic factors were assessed to verify whether the risk of lymph node metastasis would influence the long-term prognosis. METHODS: Patients undergoing curative resection of T1 colorectal adenocarcinoma at the Taipei Veterans General Hospital from December 1969 to August 2002 were retrospectively studied. Patients with synchronous colorectal cancer, distant metastasis, familiar adenomatous polyposis, or inflammatory bowel disease were excluded. The associations between lymph node metastasis and clinicopathologic variables were evaluated univariately using chi-squared test, Fisher's exact test, or Student's t -test, and multivariately using logistic regression. Univariate analysis by the log-rank test and multivariate analysis by Cox regression hazards model determined the factors influencing the overall survival. RESULTS: A total of 159 patients were included. Sixteen patients (10.1 percent) had lymph node metastasis. The risk of lymph node metastasis included histologic grade (P = 0.005), lymphatic vessel invasion (P = 0.023), inflammation around cancer (P = 0.049), and budding at the invasive front of tumor (P = 0.022). Age (P = 0.001) and number of total sampling lymph nodes (P < 0.0001) were found to be the factors influencing the overall survival. CONCLUSIONS: Variables that predict lymph node metastasis in surgically resected T1 colorectal carcinoma may not impact the long-term prognosis.

Adenocarcinoma↗

PubMed2005

Transabdominal anastomosis after low anterior resection: A prospective, randomized, controlled trial comparing long-term results between side-to-end anastomosis and colonic J-pouch.

PURPOSE: Colonic J-pouch has been constructed to overcome reservoir dysfunction after restorative rectal surgery, whereas no effort has been made for sphincter dysfunction. We conducted a prospective, randomized study comparing surgical and functional outcomes between side-to-end anastomosis and colonic J-pouch after low anterior resection in which the anastomosis was constructed from the abdomen. METHODS: Fifty-six consecutive patients with middle-to-low rectal cancer undergoing low anterior resection were randomly assigned to side-to-end or colonic J-pouch group preoperatively. Surgical outcomes of all the patients were recorded. Patients underwent functional evaluation, including anorectal manometry and functional assessment, preoperatively and then 3 months, 6 months, 1 year, and 2 years postoperatively. RESULTS: Twenty-four patients in each group completed the study. The demographic data and preoperative functional assessment did not differ between the two groups. There was no significant difference in surgical outcomes with regard to anastomotic height (5 cm), blood loss, protective colostomy, operative time, complications, and adjuvant therapy. Anal pressures showed no significant change postoperatively and during the follow-up period; there were no differences between the two groups. Temporal minor fecal incontinence was noted in the early postoperative period in both groups. With regard to bowel function, a significant reduction of volume of urgency and maximal tolerable volume was found postoperatively in both groups; however, a faster recovery was noted in the colonic J-pouch group. Stool frequency increased significantly after surgery in both groups; however, in contrast to rectal volume, a faster recovery was noted in the side-to-end group. CONCLUSIONS: Anastomosis after low anterior resection for middle to low rectal cancer could be performed safely from the abdomen. It minimized sphincter injury and showed good continence preservation. On the other hand, the surgical outcomes and long-term functional results of side-to-end anastomosis were comparable with colonic J-pouch. Side-to-end anastomosis provides an easier, alternative way for reconstruction after restorative rectal surgery.

Abdomen↗

PubMed2005

Is it reasonable to add preoperative serum level of CEA and CA19-9 to staging for colorectal cancer?

BACKGROUND: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the most common tumor markers for colorectal cancer. The aim of this study was to evaluate the possibility of adding them into the current staging system by analyzing their prognostic significance. MATERIALS AND METHODS: The study population was patients (n = 574, 67.1 +/- 11.3 years old, 397 males) who received potentially curative resection of colorectal adenocarcinoma (stage I-III) between January 1994 and August 2002, including preoperative measurements of CEA and CA19-9. Clinicopathological characteristics and associated follow-up data were retrospectively collected by reviewing available medical charts. CEA higher or equal to 5 ng/ml was defined as abnormal (CEA+). The CA19-9 level was set at 37 U/ml (CA19-9+). Patients were further divided into four groups (1, 2, 3, 4) according to the results of these two markers (CEA/CA19-9: -/-, -/+, +/-, and +/+). Survival was analyzed for AJCC staging, CEA (+) versus (-), CA19-9 (+) versus (-), and four groups. RESULTS: CEA and CA19-9 survival curves were not significantly different. However, the combined use of the two markers revealed a significant survival benefit (P = 0.035) of group 1 ("-" for both markers) over 4 ("+" for both) in stage II. CONCLUSIONS: Patients with an elevated level of both CEA and CA19-9 in stage II of colorectal cancer have a significantly poorer prognosis than those with normal levels of these markers. We recommend adding both CEA and CA19-9 to the current staging system.

Adenocarcinoma↗

PubMed2005

Silibinin inhibits angiogenesis via Flt-1, but not KDR, receptor up-regulation.

BACKGROUND: Our previous study found that silymarin (SM) and its major pure component silibinin (SB) have anti-angiogenic effects via decreased vascular endothelium growth factor (VEGF) secretion of LoVo cells (colon cancer). We designed this consecutive study to evaluate the anti-angiogenic effects of SM/SB in vivo, and on VEGF receptor (VEGFR) gene expression. MATERIALS AND METHODS: We used LoVo cells exposed to SM/SB in a modified chicken chorioallantoic membrane assay (CAM) to evaluate anti-angiogenic effects. We used EA.hy 926 cells (endothelial cells) exposed to SM/SB to evaluate the effect on VEGFR-1 (Flt-1) and VEGFR-2 (KDR), with 1-step, real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In CAM, SM/SB showed a dose-dependent decrease on the vascular density index (VDI) induced by LoVo cells, as did thalidomide in a concentration of 10 microg/ml. Adding escalating dosages of VEGF successfully reversed this inhibitory effect. RT-PCR revealed that SB up-regulated Flt-1 mRNA expression of EA.hy 926 cells. SM had a similar trend, although the effect was not statistically significant (P = 0.19). Neither drug effected KDR mRNA expression. CONCLUSION: We conclude that anti-angiogenic effects of SM/SB are associated with the up-regulation of VEGFR-1 (Flt-1) gene expression and that they are good candidates for combination therapy to treat colorectal cancer.

Angiogenesis Inhibitors↗

PubMed2005

Genetic alteration of p53, but not overexpression of intratumoral p53 protein, or serum p53 antibody is a prognostic factor in sporadic colorectal adenocarcinoma.

Mutation of p53 is a common event in colorectal cancer and can result in cellular accumulation of p53 protein and induction of p53 antibodies. We investigated the association of colorectal cancer with alterations in p53 DNA, protein and serum antibody levels to determine their prognostic value in colorectal cancer. Colorectal cancer patients (n=167) who underwent surgery in Taipei Veterans General Hospital from January 1999 to December 2000 were enrolled [age 62.91+/-12.61 years (range: 22-85); 111 (66.5%) males]. Of these, 20 were stage I (12%), 54 stage II (32.3%), 58 stage III (34.7%), and 35 stage IV (21%). Median follow-up was 36.3 months (range: 4-58). p53 alteration was detected by DNA sequencing from exon 5 to 9 and loss of heterozygosity (LOH) at two microsatellite markers near p53; and demonstrating intratumoral accumulation of p53 protein and detection of serum p53 antibodies using ELISA. p53 mutation frequency was 41.9% (70/167). Of 127 informative cases for LOH analysis, 73 (57.5%) tumors that had LOH had at least one microsatellite marker. Genetic p53 alterations were found for 56.3% of cases when LOH and DNA sequencing methods were combined. Genetic p53 alterations were associated with advanced tumor stage and tumor differentiation. Overexpression of intratumoral p53 and anti-p53 antibody positivity were 44.9% and 28.1%. The presence of p53-Ab was associated with p53 mutations (chi2 test, 42.9% vs. 17.5%, p=0.001), but not with overexpression of intratumoral p53 protein. The mutations at exon 6 (57.1%) and 7 (53.3%) were associated with presence of serum p53-Ab. Of 132 potentially cured patients, 3-year disease-free survival (DFS) was affected by: advanced TNM stage (I, II, III: 90%, 84%, and 41%), genetic p53 alteration (89% vs. 43%), intratumoral p53 accumulation (71% vs. 56%), and preoperative CEA level >5 ng/ml (74% vs. 58%). In multivariate analysis, genetic alteration of p53 was the most significant independent prognostic factor [hazard ratio (HR) = 6.09; 95% confidence interval (CI): 2.45-15.11], followed by advanced tumor stage (HR = 3.93; 95% CI: 2.14-7.23), and preoperative CEA >5 ng/ml (HR = 1.98; 95% CI: 1.12-3.17). Genetic alterations in p53 but not intratumoral p53 protein accumulation or p53-Ab appear to play a significant role in the progression of colorectal cancer.

Adenocarcinoma↗

PubMed2004

Risk factors for peritoneal dissemination of colorectal cancer.

BACKGROUND AND OBJECTIVES: The aim of this study was to clarify the risk factors associated with positive peritoneal dissemination (PPD) of colorectal cancer (CRC). METHODS: From June 2000 to September 2002, 143 CRC patients who underwent elective curative (79.0%) or non-curative (21.0%) open laparotomy were prospectively studied. Clinical evaluations including classical factors, colonoscopic evaluation, intraoperative evaluation, and pathological features were recorded. PPD was diagnosed when macro- (MAPD) or microscopic peritoneal dissemination (MIPD) was evident. Positive peritoneal cytology from initially existing ascites or washing lavage indicated MIPD. Various factors were analyzed with univariate (Chi-square test) and then multivariate analyses (logistic regression test) to search for the risk factors of PPD. RESULTS: Overall, MIPD, MAPD, and PPD were found in 2.8%, 6.3%, and 9.1%, respectively. Univariate analysis identified age (< or =59 years), CA19-9 (> or = 34.6 U/ml), poor differentiation, circumferential involvement (> or = 3 quadrants), ascites volume (>80 ml), pN+, and pT4 as risk factors of PPD. PPD did not occur in patients with well-differentiated tumors, less circumferential involvement (< 2 quadrants), or no lymph node metastasis. After multivariate analysis, CA19-9 (Odds ratio (95% CI), 8.6 (1.7-43.1)), pT4 (9.0 (1.3-61.0)), and age (5.26 (1.1-25.0)) remained significant risk factors. CONCLUSION: CA19-9 (> or = 34.6 U/ml), pT4, and age (< or =59 years) were significant risk factors of PPD.

Adult↗

PubMed2004

Metachronous colorectal cancer: necessity of post-operative colonoscopic surveillance.

BACKGROUND AND AIMS: The aim of this study was to identify the occurrence and analyze the characteristics of metachronous colorectal cancers, and to compare the characteristics of these cases (index tumor) with the control group to find any predicting factor that may influence the occurrence of metachronous cancer. PATIENTS AND METHODS: The database of colorectal cancer in the Veterans General Hospital-Taipei, from January 1981 to September 2001 was reviewed. In total, 3,846 cases of adenocarcinoma of the colon and rectum, which received curative resection during this period, were found. The criteria of metachronous cancer were: occurrence more than 12 months after curative surgery; with pre-operative complete colonoscopy or one negative post-operative colonoscopic follow-up to rule out synchronous tumor; tumor arising from mucosa at a site other than anastomosis. The age, gender of the patients, the location, pathological characteristics of the metachronous tumors, occurrence of associated adenomas, the number of lesions, and the tumor stage were analyzed and compared with the control group. RESULTS: In total, 43 cases of metachronous cancer were identified, giving an annual incidence of 0.18%. The distribution of the location of the index tumor of metachronous cases was predominantly left-sided, which was not different from that of the control group. The mean duration of occurrence of metachronous cancer after the primary operation was 71+/-46.6 months. The association of adenomas had no relationship with the occurrence of the metachronous cancer. No significant predicting factors for the development of metachronous tumors were found. CONCLUSION: Lifelong regular post-operative colonoscopic surveillance is essential for colorectal cancer patients.

Adenocarcinoma↗

PubMed2004

Impact of circulating free tumor cells in the peripheral blood of colorectal cancer patients during laparoscopic surgery.

Despite widespread use of laparoscopic surgery for colorectal operations, its application for curative resection of colorectal cancer is still controversial. One of the major concerns is the impact of the laparoscopic procedure on dissemination of tumor cells. The main purpose of this study was to investigate the impact of laparoscopic surgery on circulating tumor cells in colorectal cancer patients. Quantitation of circulating free tumor cells (FTCs) was performed preoperatively, during the operation, and 14 days later by means of real-time quantitative reverse transcriptasepolymerase chain reaction (RT-PCR) targeting guanylyl cyclase C (GCC) mRNA in 42 colorectal cancer patients undergoing laparoscopic resections. Despite an increasing trend of FTC detection in patients with advancing stage, there is no significant difference in the preoperative FTC level by disease stage. No elevation in FTC level was found during the laparoscopic procedure in most patients compared with their preoperative FTC value. Patients with a persistently high FTC load [per nucleated blood cells (NBCs)] (> 10(2) FTCs/10(6) NBCs) 2 weeks postoperatively portends a poor prognosis regarding disease recurrence and tumor-related mortality when compared to those with an undetectable or low FTC load (< or = 10(2) FTCs/10(6) NBCs). We concluded that the laparoscopic procedure itself had no significantly deleterious effect on circulating FTCs and that the detection of FTCs by real-time qRT-PCR might be of clinical importance during the postoperative follow-up for colorectal cancer patients.

Adult↗

PubMed2004

Long-term prognosis of patients with obstructing carcinoma of the right colon.

BACKGROUND: The long-term prognosis of patients with colon cancer is dependent on many factors. The aim of this retrospective study was to assess the long-term prognosis of patients with obstructing carcinoma of the right colon. METHODS: From 1981 to 1988, 256 patients at the Veterans General Hospital-Taipei who were status postcurative resection of right colon adenocarcinoma were classified as obstruction group (n = 35) or nonobstruction group (n = 221) as appropriate. RESULTS: Analysis revealed no differences in age, sex, tumor location, or stage (P >0.05) between the two groups. However, the overall and distant recurrence rates were significant higher in obstructed patients than in nonobstructed patients. Further, long-term crude and cancer-specific survival rates were significantly lower in obstructed patients when examining either overall patient outcome or stage-matched outcomes. Multivariate analysis demonstrated that obstruction and tumor stage were both independent prognostic factors. CONCLUSIONS: Obstruction status was an independent prognostic factor for patients with right colon carcinoma. The long-term prognosis of patients with obstructing carcinoma of the right colon was poor.

Adenocarcinoma↗