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Purpose: Carcinoembryonic antigen (CEA) measurements performed preoperatively and during the early postoperative period were examined prospectively to assess their prognostic value for colorectal cancer (CRC) patients receiving curative surgery. Methods: Between 2000 and 2004, 1,361 patients with CRC who underwent curative surgery at the Taipei Veterans General Hospital were enrolled prospectively. CEA was measured prior to surgery and during the third or fourth postoperative week. The endpoint was length of postoperative disease-free survival, and prognostic importance was determined using the log-rank test and Cox regression hazard model. Results: Six hundred (44.1%) CRC patients had high CEA concentrations preoperatively, and 188 (13.8%) patients retained high values postoperatively. Within the median follow-up period of 61 (6-108) months, CRC recurred in 313 patients. By univariate analysis TNM staging, tumor differentiation, lymphovascular invasion, preoperative CEA concentration, and postoperative CEA concentration affected the outcome. By multivariate analysis, the prognostic importance of postoperative CEA was retained (95% CI, 1.73-3.01; HR = 2.28) but that of preoperative CEA was lost (95% CI, 0.82-1.33; HR = 1.05). CRC recurred earlier in patients with high postoperative CEA concentrations; metastasis to the liver was common (72.3%) among patients in this group. Conclusions: Early postoperative CEA concentration is an independent prognostic factor for CRC. Patients with high postoperative CEA values should receive aggressive follow-up examinations for early relapse of CRC, with special attention paid to recurrence at the liver. [ABSTRACT FROM AUTHOR]

Purpose: We studied whether HSP90α was associated with the special carbohydrate structures IMH-2 epitopes, and investigated its mRNA expression and clinical relevance in colorectal cancer (CRC) patients. Methods: The lysates and the culture media of colon cancer HCT-8 cells were immunoprecipitated with IMH-2 antibody, and the immunoprecipitates were subsequently analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or by immunoblotting with anti-HSP90α antibody. In vitro wound-healing assay was done to evaluate the role of IMH-2 epitope-associated HSP90α in HCT-8 cell migration. Real-time RT-PCR was performed to detect the levels of HSP90α mRNA expression in paired tumor and non-tumor tissues of 56 CRC patients. The correlation of tumor HSP90α mRNA overexpression with CRC metastasis and poor survival outcome was determined by statistical analyses. Results: HSP90α was first identified as an IMH-2 epitope-associated protein by immunoprecipiation, mass spectrometry, and immunoblotting analysis. IMH-2 epitopes were detected in both cellular and secreted HSP90α. HCT-8 cell migration induced by serum starvation-conditioned medium was blocked by anti-HSP90α antibody or the HSP90α inhibitor geldanamycin (GA) as efficient as by IMH-2 antibody, suggesting that IMH-2-associated HSP90α was involved in serum starvation-induced CRC cell migration. On the other hand, HSP90α mRNA expression was induced in HCT-8 cells after serum starvation. Clinically, 15 (26.8%) of 56 CRC patients exhibited tumor HSP90α mRNA overexpression and had higher rates of metastatic occurrence ( P = 0.003) and poor prognosis ( P = 0.028). Conclusions: HSP90α was an IMH-2 epitope-associated protein. Tumor HSP90α overexpression was correlated with the metastasis and poor prognosis of CRC patients. [ABSTRACT FROM AUTHOR]

Purpose: Adjuvant systemic 5-fluorouracil (5-FU)-based chemotherapy improves survival after resection of synchronous colorectal liver metastases (CLMs), but not metachronous. We retrospectively examined if adjuvant chemotherapy with new regimen containing oxaliplatin or irinotecan improved survivals after resection of metachronous CLMs. Methods: Between 2000 and 2007, 52 patients having undertaken resection of metachronous CLMs with curative intent were identified from Taipei Veterans General Hospital hospitalization registry. One patient with perioperative mortality and another being lost to follow-up within 3 months after metastasectomy were excluded. Thirty-one patients experienced six to 12 cycles of FOLFOX or FOLFIRI chemotherapy while 19 patients with 5-FU/leucovorin (LV)-based chemotherapy following CLM resection. The primary end point was disease-free survival (DFS) and secondary end point, overall survival (OS). Results: By the univariate analysis, median DFS was 34.3 months in the FOLFOX/FOLFIRI group vs 14.2 months in the 5-FU/LV group ( P = 0.022). The median OS and 5-year survival rates were longer than 57.7 months (not reached, with median follow-up of 35.5 months) and 54.0%, respectively, in the FOLFOX/FOLFIRI group compared to 49 months and 34.6% in the 5-FU/LV group ( P = 0.027). FOLFOX/FOLFIRI chemotherapy was shown by multivariate analyses to be an independent factor predicting a better DFS (hazard ratio [HR] = 0.37; 95% CI: 0.15–0.94; P = 0.036) and a better OS (HR = 0.27; 95% CI: 0.083–0.86, P = 0.026) than 5-FU/LV-based. Conclusions: Adjuvant FOLFOX/FOLFIRI chemotherapy following resection of metachronous CLMs is demonstrated to have better DFS and OS than 5-FU/LV chemotherapy. [ABSTRACT FROM AUTHOR]

Carbon dioxide (CO2) pneumoperitoneum can lead to cardiopulmonary loading and complications. By comparing with conventional CO2 pneumoperitoneum approach, we introduce a novel Laparo-V lifting system for gasless laparoscopic colorectal surgery. In a prospective study, patients with colonic lesions underwent either Laparo-V gasless ( n = 20) or conventional CO2 pneumoperitoneum ( n = 19) laparoscopic colectomy. Twenty patients who underwent open surgery were enrolled as control. Intra-operative monitoring includes blood pressures, heart rate, O2 saturation, and end-tidal CO2 (ET-CO2). Serum level of interleukin 6 (IL-6), C-reactive protein (CRP), cortisol, and lymphocyte subpopulations (CD4/CD8) were measured repeatedly. Postoperative recovery was indicated by return of bowel function and postoperative hospital stay. Patient characteristics were not different between the three groups. There were three conversions in each laparoscopy group, making conversion rates 15% and 15.7% for Laparo-V and CO2 pneumoperitoneum groups, respectively. Vital signs remained stable in Laparo-V and open surgery groups; while, elevated ET-CO2 and heart rate were noted in CO2 pneumoperitoneum group. Both laparoscopy groups had a significant faster recovery and shorter hospital stay than the open surgery group. Postoperative elevation of IL-6, CRP, and cortisol level was observed in all the three groups, of note, the change was most significant in the open surgery group. Laparo-V gasless laparoscopic approach is feasible in various colorectal procedures. It carries advantages comparable with those of CO2 pneumoperitoneum; while, the intra-operative hemodynamic was more stable. Therefore, laparoscopic approach using the Laparo-V system could be beneficial to patients with high cardiopulmonary risk and represents an alternative for minimally invasive surgery. [ABSTRACT FROM AUTHOR]

Colorectal carcinoma is the most common malignancy of the gastrointestinal tract. It remains controversial for adjuvant chemotherapy in patients with stage II colon cancer. This study was designed to identify the risk factors of tumor recurrence in stage II colon cancer. Furthermore, the benefit of adjuvant chemotherapy for high-risk stage II colorectal cancer will be investigated. From May 1998 until August 2004, 375 patients with stage II (T3N0M0, T4N0M0) colon cancer received curative operation in a single hospital. The clinical data were extracted from the prospectively collected colorectal cancer database. The disease-free survival curves were calculated with Kaplan–Meier’s analysis, and the survival difference was determined by log-rank test. The p value less than 0.05 was considered to be significant. Of 375 stage II colon cancer, 66 patients received 5-FU-based adjuvant chemotherapy, either oral or intravenous (IV) form. Within the median of 48.5 months of follow-up, recurrence developed in 35 patients (9.3%). T4 lesion ( p=0.024), lymphovascular invasion ( p=0.022), obstruction at presentation ( p=0.008), and mucinous component more than 50% ( p=0.032) were associated with significantly decreased disease-free survival. High-risk patients ( n=102), but not other patients with stage II colon cancer, benefited from adjuvant therapy (3-year disease-free survival: 96.4% vs. 84.7%, p=0.045; 5-year overall survival: 100% vs. 86.4%, p=0.015). Adjuvant therapy for high-risk stage II colon cancer may be beneficial, and we suggest adjuvant therapy should be considered in high-risk stage II colon cancer patients. [ABSTRACT FROM AUTHOR]

Metronomic chemotherapy, at a minimally toxic dose and with a frequent schedule, is a potentially novel approach to the control of advanced cancer disease via a different mechanism from maximum tolerable doses chemotherapy. Taking advantage of the potential effectiveness of metronomic therapy, tegafur/uracil (UFT) was incorporated into an oxaliplation/infusioanl fluouracil (5-FU)/leucovorin (LV) protocol in this study. The primary endpoints were response rate, time to progression (TTP) and safety profile in 5-FU-pretreated metastatic colorectal cancers (CRCs). Twenty-eight patients with metastatic CRCs resistant or refractory to 5-FU/LV were enrolled. Chemotherapy was administrated every 2 weeks sequentially with 2-h infusion of oxaliplatin (85 mg/m2) and LV (200 mg/m2), intravenous bolus 5-FU (400 mg/m2), 22-h infusion of 5-FU (600 mg/m2) on day 1 and then followed by 10-day daily oral UFT (200 mg/m2)/LV (30 mg/m2). Partial response was seen in ten (35.7%) patients. The median TTP was 5.2 (95% CI: 4.16–6.31) months and the median overall survival was 13.4 (95% CI: 6.39–20.5) months. No grade 3 toxicities above 5% according to National Cancer Institute-Common Toxicity Criteria (NCI-CTC) occurred except sensory neuropathy (10.7%). No grade 4 toxicity, treatment-related mortality or hand–foot syndrome was found. This study protocol with favorable toxicity profile is thus promisingly effective against 5-FU-pretreated metastatic CRCs. Given the present experience, an evaluation of the regimen as front-line treatment of metastatic CRC is planned. [ABSTRACT FROM AUTHOR]

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. 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. 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. The accumulation of p53 protein might have a favorable prognostic value in colorectal cancer, but it is not an independent prognostic factor. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The response to chemotherapy of solid tumors is generally assessed by measuring tumors visualized by imaging. However, the response assessment based on imaging is not always feasible because patients often have disease not measurable by imaging, such as diffuse peritoneal dissemination. We evaluated the correlation between the change on imaging and change in CEA levels for assessing chemotherapeutic response of patients with metastatic colorectal cancer. Between July 1993 and August 1999 we retrospectively examined 136 patients with metastatic colorectal carcinoma, all of whom had measurable lesions. Forty patients received oral tegafur-uracil (300 mg/m2/day) plus folinic acid (60 mg/day) for 4 weeks, repeated every 5 weeks, as the first-line treatment. Another 96 patients received either a weekly intravenous bolus injection of 5-fluorouracil (400 mg/m2) plus folinic acid (20 mg/m2), or an intravenous bolus injection of 5-fluorouracil (425 mg/m2) plus folinic acid (20 mg/m2) for 5 consecutive days every month. Responders, based on CEA assessment, were defined as those with a greater than 50% drop in CEA level for more than 4 weeks. The pretreatment CEA levels were elevated beyond the normal cutoff value in 110 (81%) patients. A response rate of 18.4% (95% CI, 11.9–24.9%), including 8 complete remissions and 17 partial remissions, was achieved according to imaging studies. The response rate assessed by CEA was 25% (34/136). Sixteen responders (47%) based on CEA had no remission on imaging. The sensitivity of change in CEA levels in the prediction of true responders and progressive diseases on imaging were 72% and 81%, respectively. In terms of the positive predictive value, change in CEA levels in the prediction of true responders and progressive disease on imaging were 53% and 85%, respectively. Patients with remarkable falls on CEA levels survived significantly longer than nonresponders (P<0.001, log-rank test). At follow-up of 48 months the median survival for responders and nonresponders assessed by CEA was 28 months and 13 months, respectively. These data suggest that measurement of CEA levels might be helpful in monitoring chemotherapeutic response when imaging study is unsuitable for assessing the response in clinical practice. Furthermore, measurement of CEA levels may be helpful in determining the prognosis of patients with metastatic colorectal cancer receiving chemotherapy. [ABSTRACT FROM AUTHOR]