Wei-Shone Chen

Anti-angiogenic effect of silymarin on colon cancer lovo cell line

OBJECTIVEnThis study was designed to evaluate the anti-angiogenic effect of silymarin (SM) and its major pure component silibinin (SB), and also thalidomide (TH).nnnMATERIALS AND METHODSnA modified in vitro system using a coculture of endothelial (EA.hy 926) and colon cancer (LoVo) cell lines was adopted in this study.nnnRESULTSnIn cytotoxicity assay, SM/SB/TH concentrations causing 20% (IC(20)) inhibition of cellular growth were 41.8 microg/ml/0.22 mM/0.088 mM for EA.hy 926 cells, and 16.1 microg/ml/0.12 mM/0.099 mM for LoVo cells, respectively. All 3 drugs showed concentration dependent inhibition of migration and differentiation assay. The IC(50) inhibiting chemotaxis migration of EA.hy 926 towards LoVo by SM/SB/TH was 1.15 microg/ml/0.66 microM/1.98 microM, respectively. In differentiation assay, SM/SB/TH inhibited in vitro capillary tube formation by 50% at 1.25 microg/ml/2.6 micro/6.3 microM, respectively. In an analysis of vascular endothelial growth factor secreted by LoVo cells, SM/SB/TH decreased 50% secretion at 6.52 microg/ml/6.6 microM/131.7 microM, respectively.nnnCONCLUSIONnSM/SB has a strong anti-angiogenesis effect on the colon cancer cell line, and this might provide an alternative treatment option for anti-cancer treatment.

Early postoperative CEA level is a better prognostic indicator than is preoperative CEA level in predicting prognosis of patients with curable colorectal cancer

PurposeCarcinoembryonic 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.MethodsBetween 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.ResultsSix 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; HRu2009=u20092.28) but that of preoperative CEA was lost (95% CI, 0.82–1.33; HRu2009=u20091.05). CRC recurred earlier in patients with high postoperative CEA concentrations; metastasis to the liver was common (72.3%) among patients in this group.ConclusionsEarly 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.

Risk and patterns of brain metastases in colorectal cancer

PURPOSE: In patients with colorectal cancer, brain metastasis is infrequent. This study aims to elucidate the risk, pattern of occurrence, and survival time after different treatment modalities. METHODS: A retrospective review of all patients with colorectal cancer admitted to the Veterans General Hospital-Taipei between 1970 and 1996 from our hospital was performed. Univariate analysis for survival determination was performed. RESULTS: Brain metastases developed subsequent to surgery for colorectal cancer in 53 well-documented patients, at a median of 36 months after surgery. Brain metastases were more commonly seen in rectal cancer and often occurred concurrently with lung metastases. Forty of these patients received active intervention in terms of surgery, chemotherapy, or radiotherapy, with surgical intervention achieving a significantly increased mean survival time (± standard deviation) compared with chemotherapy or radiotherapy or both of 86.6±17.35vs. 2.9±0.59 months (P<0.05). CONCLUSION: Increased awareness of the possibility of brain metastases, early diagnosis, and aggressive therapy can provide increased survival time for patients with colorectal cancer with brain metastases.

Metachronous colorectal cancer: necessity of post-operative colonoscopic surveillance

Background and aimsThe 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 methodsThe 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 12xa0months 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.ResultsIn 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±46.6xa0months. 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.ConclusionLifelong regular post-operative colonoscopic surveillance is essential for colorectal cancer patients.

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 transcriptase-polymerase 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)] (> 102 FTCs/106 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 (≤ 102 FTCs/106 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.

Trend of large bowel tuberculosis and the relation with pulmonary tuberculosis.

From 1965 to 1989, 60 cases of large bowel tuberculosis among 116 cases of abdominal tuberculosis are reviewed and analyzed. Lesions located in the cecum or ileocecal region were found in 49 of the 60 cases. Most of the patients (50/60) received surgical intervention, but the definite diagnoses had never been proved until surgery. The diagnoses were proved by histopathologic examination in these 50 cases. Antituberculosis medications were given for at least nine months in all patients. Twenty-nine of the 50 patients who received operations had primary anastomosis during the operations, and no leakage occurred. Evidence of pulmonary tuberculous lesions could be found in 40 of the 60 cases. Positive findings of tubercle bacilli in sputum smear or culture were noted in 13 cases. The positive rate of sputum examinations decreased during 1980 to 1989; 25.6 percent (10/39) were positive from 1965 to 1979 and 14 percent (3/21) were positive from 1980 to 1989. In the meantime, there was a steady decline in the cases of large bowel tuberculosis in the most recent few years. An antituberculosis program has been carried out in the past 40 years with remarkable effect in the Taiwan area, but the possibility of intestinal tuberculosis still exists. The authors suggest that surgeons keep tuberculosis in mind when they are dealing with patients who suffer from intestinal obstruction of unknown origin with the suspected findings of pulmonary tuberculosis in chest x-ray films.

Effect of Transcutaneous Electrical Nerve Stimulation for Pain Relief on Patients Undergoing Hemorrhoidectomy: Prospective, Randomized, Controlled Trial

PURPOSE: Posthemorrhoidectomy pain control remains a challenging problem. Transcutaneous electrical nerve stimulation is known to be effective in the treatment of many diseases. Our aim was to investigate the effect of transcutaneous electrical nerve stimulation on pain relief in patients undergoing hemorrhoidectomy. METHODS: Sixty patients with symptomatic hemorrhoids were randomly allocated into two groups, the acupoint group (n=30) and the nonpoint control group (n=30). Transcutaneous electrical nerve stimulation was applied to those patients who received hemorrhoidectomy, and patient-controlled analgesia was achieved by injection of morphine through ambulatory infusion pumps. The dependent measures in this study were pain score from 0 (no pain) to 10 (agonizing pain), analgesic doses administrated through patient-controlled analgesia, and postoperative complications. RESULTS: The subjective pain scores evaluated 8, 12, 16, and 24 hours after hemorrhoidectomy in the control group and the acupoint group were 5.9±0.5 and 4.1±0.5, 5.7±0.5 and 3.5±0.4, 4.1±0.4 and 2.3±0.3, and 3.2±0.4 and 1.9±0.2, respectively (two-way analysis of variance;P<0.05). There was a significant difference between treatment groups in morphine use, with 11.6±2.2 mg in the control group and 6.2±1.3 mg in the acupoint group (P<0.05). The acupoint group tended to have less postoperative acute urinary retention (Fishers exact probability test;P=0.145) and less need for analgesics than the control group (P=0.112, Fishers exact test). CONCLUSION: Transcutaneous electrical nerve stimulation is effective for pain relief in patients receiving hemorrhoidectomy. Its efficacy and safety could assist outpatient pain management after hemorrhoidectomy.

Carbohydrate antigen 19-9 is a valuable prognostic factor in colorectal cancer patients with normal levels of carcinoembryonic antigen and may help predict lung metastasis

PurposeWe retrospectively analyzed preoperative levels of carbohydrate antigen (CA) 19-9 in colorectal cancer (CRC) patients to determine the prognostic value of CA19-9 in CRC patients with normal carcinoembryonic antigen (CEA) levels.MethodsA total of 639 patients who underwent curative surgery at Taipei Veterans General Hospital between 2002 and 2006 were enrolled. We excluded 254 patients (39.7xa0%) with high preoperative CEA levels and analyzed 385 patients with normal CEA levels. The measured endpoint was the postoperative disease-free survival (DFS). The prognostic value of CA19-9 was determined using log-rank test and Cox regression analysis.ResultsHigh CA19-9 levels were significantly associated with advanced disease and were detected in 5.8xa0% of patients with stage I disease, 11.7xa0% of those with stage II disease, and 22.5xa0% of those with stage III disease (Pu2009<u20090.001). The 5-year DFS in patients with normal CA19-9 levels was 82.0xa0%, which was significantly higher than that in patients with high CA19-9 levels (68xa0%; Pu2009<u20090.001). In a multivariate analysis, the most important independent factor affecting the 5-year DFS was tumor–node–metastasis stage (95xa0% CI, 1.26–2.36; HRu2009=u20091.72). After stratification by other factors, high CA19-9 level remained an independent prognostic factor for patients with normal CEA levels. Patients with high CA19-9 levels also showed a higher incidence of lung metastasis (23.1xa0%) than those with normal CA19-9 levels (7.2xa0%).ConclusionsCA19-9 may be a prognostic factor for CRC patients with normal CEA levels. An aggressive follow-up protocol for lung metastasis should be used for these patients.

Tumor β-1,4-Galactosyltransferase IV Overexpression Is Closely Associated with Colorectal Cancer Metastasis and Poor Prognosis

Purpose: To elucidate the significance of β-1,4-galactosyltransferase IV (β-1,4-GT-IV) in the clinical presentation and prognostication of colorectal cancer. Experimental Design: Tissue lysates from paired tumor and nontumor tissues of a colon cancer patient were labeled separately with fluorescent dyes Cy5 and Cy3 for two-dimensional difference in-gel electrophoresis. Subsequent matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and immunoblot analyses identified a down-regulated level of β-1,4-GT-IV in the tumor tissue. In the follow-up study, paired tissue lysates were obtained from 100 colorectal cancer patients with immunoblot analyses done to compare the levels of β-1,4-GT-IV expression in these patients. Results: Of 100 colorectal patients studied, 48% had down-regulated expression of β-1,4-GT-IV in the tumor tissue but 28% of patients exhibited elevated β-1,4-GT-IV levels. Increased β-1,4-GT-IV in the tumor tissue was significantly coexistent with raised serum level of CA-199 and the presence of tumor metastasis (P = 0.006 and P < 0.001, respectively) but was independent of age and gender of patient, tumor site, tumor size, serum level of carcinoembryonic antigen, grade of tumor cell differentiation, and depth of tumor invasion. The results of logistic regression analyses suggested that tumor β-1,4-GT-IV overexpression and tumor invasion, but not other patient variables such as tumor size and serum levels of carcinoembryonic antigen and CA19-9, were significantly correlated with the occurrence of metastases (P < 0.05). In a multivariate regression analysis, the patient group with tumor β-1,4-GT-IV overexpression strongly predicted for tumor metastasis (odds ratio, 10.009; 95% confidence interval, 2.992-33.484; P < 0.001). Likewise, tumor β-1,4-GT-IV overexpression was significantly associated with poor overall survival (P < 0.01). By Cox regression analysis, this association remained significant even after adjustment for tumor metastasis (P = 0.048). Conclusion: Increased β-1,4-GT-IV expression in tumor tissue was strongly associated with tumor metastases and poor prognosis in colorectal cancer.

Carcinoembryonic antigen in monitoring of response to systemic chemotherapy in patients with metastatic colorectal cancer

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 (300xa0mg/m2/day) plus folinic acid (60xa0mg/day) for 4xa0weeks, repeated every 5xa0weeks, as the first-line treatment. Another 96 patients received either a weekly intravenous bolus injection of 5-fluorouracil (400xa0mg/m2) plus folinic acid (20xa0mg/m2), or an intravenous bolus injection of 5-fluorouracil (425xa0mg/m2) plus folinic acid (20xa0mg/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 4xa0weeks. 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 48xa0months the median survival for responders and nonresponders assessed by CEA was 28xa0months and 13xa0months, 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.