National Cancer Institute®
Last Modified: August 1, 2002
UI - 8949986
AU - Raymond E; Djelloul S; Buquet-Fagot C; Mester J; Gespach C
TI - Synergy between the non-classical thymidylate synthase inhibitor AG337 (Thymitaq) and cisplatin in human colon and ovarian cancer cells.
SO - Anticancer Drugs 1996 Sep;7(7):752-7
AD - Unite INSERM U55, Institut Federatif de Recherches du Centre Hospitalo-Universitaire Paris Saint-Antoine, Hopital Saint-Antoine, France.
AG337 is the recent non-classical thymidylate synthase inhibitor with promising activity and manageable toxicity in phase I clinical trials. In this study, we investigated the cytotoxic activity of AG337 alone and in combination with cisplatin in cultured human colon (HT29) and ovarian (2008) cancer cell lines and their derived counterparts selected for their resistance to 5-fluorouracil (5-FU) (HT29-5-FU) and cisplatin (2008C13). We observed that AG337 had potent cytotoxic effects in colon (IC50 = 0.17 MicroM) and ovarian cancer cells (IC50 = 0.65 microM). The cytotoxic activity of AG337 was higher than that of 5-FU in the two models. The Activity of AG337 was not significantly affected in 5-FU-resistant HT29-5-FU colon cancer cells characterized by an amplification of the thymidylate synthase gene (IC50 = 0.27 microM, p = 0.15). Combinations of cisplatin and AG337 exert synergistic activity in both ovarian and colon cancer cells. Interestingly, this synergism was maintained in 5-FU- and cisplatin-resistant cells. Therefore, our data encourage further examination of combinations of AG337 with cisplatin in cancer chemotherapy.
UI - 10090685
AU - Glimelius B; Pahlman L
TI - Perioperative radiotherapy in rectal cancer.
SO - Acta Oncol 1999;38(1):23-32
AD - Department of Oncology, University of Uppsala, Akademiska Sjukhuset, Sweden.
Local failure of rectal cancer is one of the principal causes of morbidity and mortality. In order to lower unacceptably high local failure rates, pre- or postoperative radiotherapy has been extensively investigated. The collected information from all controlled trials reported so far shows that the proportion of local recurrences is reduced to less than half when radiotherapy up to moderately high doses is given preoperatively. This reduction is smaller after postoperative radiotherapy, even if higher doses are used. In addition, there is a positive influence on survival from preoperative radiotherapy. Improved survival has also been seen in trials using postoperative radiotherapy, but only when combined with chemotherapy. With proper radiation techniques, sufficiently high doses can be given preoperatively with little, if any, increase in postoperative mortality and morbidity. Furthermore, late toxicity can be anticipated to be low provided the technique is optimal. The beneficial effects noted so far have been achieved in trials where 'standard' surgery has been used, followed by a local recurrence rate of more than 20% (average 29%, range 23-46%) of the patients. It is, however, possible that the reduction in local failure rates is proportionally even greater added to 'optimal' surgery, although the absolute number of failures prevented is lower.
UI - 10090684
AU - Gunderson LL
TI - Indications for and results of combined modality treatment of colorectal cancer.
SO - Acta Oncol 1999;38(1):7-21
AD - Mayo Medical School and Mayo Clinic, Rochester, MN 55905, USA.
Combined modality chemoirradiation is commonly used as a component of treatment in combination with maximum resection for both high-risk resectable and locally advanced primary or recurrent rectal cancers. With surgically resected but high-risk rectal cancers, postoperative chemoirradiation has been shown to improve both disease control (local and distant) and survival (disease-free and overall) and was recommended as standard adjuvant treatment at the 1990 National Institute of Health (NIH) Consensus Conference on Adjuvant treatment for patients with rectal and colon cancers. Subsequent intergroup trials are being conducted to help define optimal combinations of postoperative chemoirradiation for resected high-risk rectal cancers and to test sequencing issues of preoperative versus postoperative chemoirradiation. With locally unresectable primary or recurrent colorectal cancers, standard therapy with surgery, external beam irradiation (EBRT) and chemotherapy is often unsuccessful. When intraoperative electron irradiation (IOERT) is combined with standard treatment, local control and survival appear to be improved in separate analyses from the Mayo Clinic and the Massachusetts General Hospital (MGH). However, routine use of systemic therapy is also needed as a component of treatment, in view of high rates of systemic failure.
UI - 10803742
AU - van der Wilt CL; Kuiper CM; Peters GJ
TI - Combination studies of antifolates with 5-fluorouracil in colon cancer cell lines.
SO - Oncol Res 1999;11(8):383-91
AD - Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
The combined cytotoxic effects of the thymidylate synthase (TS) inhibitors 5-fluorouracil (5FU) and different antifolates were studied in seven colon cancer cell lines. Growth inhibition of the antifolates, Nolatrexed, Raltitrexed, GW1843U89, or MTA in combination with 5FU, was determined and multiple drug effect analysis showed that the drugs acted mostly additively. The only synergistic interaction was found for 5FU and Nolatrexed in the LS174T cell line. Also Raltitrexed and 5FU were slightly synergistic in WiDr/F cells grown at low folate levels, but for the other cell lines grown at high folate levels this combination was more antagonistic. GW1843U89 and 5FU were mainly additive, while 5FU and MTA showed antagonism in WiDr and additivity in LS174T. The effect of the drugs at their target was evaluated by in situ TS inhibition. We observed lower TS activity in all cells when two drugs were used instead of one. Statistical analysis revealed that none of the values of the combinations was higher or lower than could be expected from the product of the effect of single drugs. We concluded that the effects on TS inhibition were additive for all 5FU/antifolate combinations in all cell lines. DNA strand break formation, as a result of TS inhibition, was measured by means of a fluorometric analysis of DNA unwinding. Raltitrexed-induced DNA damage was significantly increased by 5FU in WiDr cells [single agent: 67% double stranded (ds) DNA, combination: 39% ds DNA, P<0.0001]. In LS174T a trend for antagonistic effects was observed for combinations of MTA, GW1843U89, or Raltitrexed and 5FU. The combinations showed additive effects in WiDr/F cells. The overall conclusion of the three assays in each of the cell lines indicated that 5FU and antifolate combinations were predominantly additive in colon cancer cells.
UI - 11049037
AU - Cassidy J
TI - Thymidylate synthase inhibitors in colorectal cancer.
SO - Semin Oncol 2000 Oct;27(5 Suppl 10):83-7
AD - University of Aberdeen, Aberdeen Royal Infirmary, Institute of Medical Sciences, Foresterhill, UK.
UI - 12092086
AU - Gislerud G
TI - [Treatment of colonic cancer in the elderly]
SO - Tidsskr Nor Laegeforen 2002 Mar 20;122(8):853; discussion 853
UI - 12046077
AU - Li J; Guo WJ; Yang QY
TI - Effects of ursolic acid and oleanolic acid on human colon carcinoma cell line HCT15.
SO - World J Gastroenterol 2002 Jun;8(3):493-5
AD - Department of Oncology, Cancer Center, Xin Hua Hospital, Shanghai Second Medical University, Shanghai 200092, China. email@example.com
AIM: Ursolic acid (UA) and oleanolic acid (OA) are triperpene acids having a similar chemical structure and are distributed wildly in plants all over the world. In recent years, it was found that they had marked anti-tumor effects. There is little literature currently available regarding their effects on colon carcinoma cells. The present study was designed to investigate their inhibitory effects on human colon carcinoma cell line HCT15. METHODS: HCT15 cells were cultured with different drugs. The treated cells were stained with hematoxylin-eosin and their morphologic changes observed under a light microscope. The cytotoxicity of these drugs was evaluated by tetrazolium dye assay. Cell cycle analysis was performed by flow cytometry (FCM). Data were expressed as means +/-SEM and Analysis of variance and Student' t-test for individual comparisons. RESULTS: Twenty-four to 72 h after UA or OA 60 micromol/L treatment, the numbers of dead cells and cell fragments were increased and most cells were dead at the 72nd hour. The cytotoxicity of UA was stronger than that of OA. Seventy-eight hours after 30 micromol/L of UA or OA treatment, a number of cells were degenerated, but cell fragments were rarely seen. The IC(50) values for UA and OA were 30 and 60 micromol/L, respectively. Proliferation assay showed that proliferation of UA and OA-treated cells was slightly increased at 24h and significantly decreased at 48 h and 60 h, whereas untreated control cells maintained an exponential growth curve. Cell cycle analysis by FCM showed HCT15 cells treated with UA 30 and OA 60 for 36 h and 72 h gradually accumulated in G(0)/G(1) phase (both drugs P<0.05 for 72 h), with a concomitant decrease of cell populations in S phase (both drugs P<0.01 for 72 h) and no detectable apoptotic fraction. CONCLUSION: UA and OA have significant anti-tumor activity. The effect of UA is stronger than that of OA. The possible mechanism of action is that both drugs have an inhibitory effect on tumor cell proliferation through cell-cycle arrest.
UI - 12034030
AU - Galizia G; Lieto E; De Vita F; Romano C; Orditura M; Castellano P;
TI - Imperatore V; Infusino S; Catalano G; Pignatelli C Circulating levels of interleukin-10 and interleukin-6 in gastric and colon cancer patients before and after surgery: relationship with radicality and outcome.
SO - J Interferon Cytokine Res 2002 Apr;22(4):473-82
AD - Division of Surgical Oncology, F. Magrassi and A. Lanzara Department of Clinical and Experimental Medicine, Second University of Naples School of Medicine, Naples, Italy. firstname.lastname@example.org
Elevated interleukin-10 (IL-10) and IL-6 serum levels in advanced gastrointestinal cancer patients have been shown previously. To investigate the behavior and the prognostic role of IL-10 and IL-6 serum levels in gastric and colon cancer patients undergoing surgery, we studied the relationship between these cytokine levels and surgical radicality and outcome. Seventy-eight patients with gastric or colon cancer were admitted to the study, and 50 underwent radical surgery. Cytokine serum levels were measured by ELISA the day before surgery and 16 days after surgery. Circulating levels of IL-10 and IL-6 were found to be higher in cancer patients than in controls. Both IL-10 and IL-6 serum levels were demonstrated to be able to predict likelihood to perform radical surgery. IL-10 serum levels returned to normal in all but 8 radically resected patients. These 8 patients had tumor recurrence. In contrast, IL-6 serum levels were shown to significantly decrease in all patients but not to normalize regardless of the radicality of the operation. On multivariate analysis, basal IL-10 serum levels were found to be among the variables significantly affecting the disease-free survival rate. Stepwise regression selected tumor stage, number of metastatic resected nodes, and basal IL-10 serum level as the best combination of variables for prediction of likelihood of tumor recurrence. Preoperative IL-10 serum levels may be a useful marker to predict likelihood of performing radical surgery. Abnormally high postoperative IL-10 values negatively affected disease-free survival and tumor recurrence. IL-6 serum levels were found to have a more limited prognostic role.
UI - 11843249
AU - Gray B; Van Hazel G; Hope M; Burton M; Moroz P; Anderson J; Gebski V
TI - Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer.
SO - Ann Oncol 2001 Dec;12(12):1711-20
AD - Royal Perth Hospital, Sir Charles Gairdner Hospital, University of Western Australia, Australia. email@example.com
PURPOSE: SIR-Spheres are radioactive yttrium90 microspheres (SIR-Spheres, Sirtex Medical Limited, Australia) used to selectively target high levels of ionising radiation to tumors within the liver. This trial was designed to measure any increased patient benefit by adding a single administration of SIR-Spheres to a regimen of regional hepatic artery chemotherapy (HAC) administered as a 12 day infusion of floxuridine and repeated at monthly intervals, vs. the same chemotherapy alone. PATIENTS AND METHODS: A phase III randomised clinical trial entering 74 patients was undertaken on patients with bi-lobar non-resectable liver metastases from primary adenocarcinoma of the large bowel. Patient benefit criteria assessed in the trial were tumor response, time to disease progression in the liver, overall survival, quality of life, and treatment related toxicity. Tumor response was measured by serial changes in both cross-sectional tumor areas and total tumor volumes, provided any response lasted not less than three months as well as changes in serum carcino-embryonic antigen (CEA). RESULTS: The partial and complete response rate (PR + CR) was significantly greater for patients receiving SIR-Spheres when measured by tumor areas (44%) vs. 17.6%, P = 0.01) tumor volumes (50% vs. 24%, P = 0.03) and CEA (72% vs. 47%, P = 0.004). The median time to disease progression in the liver was significantly longer for patients receiving SIR-Spheres in comparison to patients receiving HAC alone when measured by either tumor areas (9.7 vs. 15.9 months, P = 0.001), tumor volumes (7.6 vs. 12.0 months, P = 0.04) or CEA (5.7 vs. 6.7 months, P = 0.06). The one, two, three and five-year survival for patients receiving SIR-Spheres was 72%, 39%, 17% and 3.5%, compared to 68%, 29%, 6.5% and 0% for HAC alone. Cox regression analysis suggests an improvement in survival for patients treated with SIR-Spheres who survive more than 15 months (P = 0.06). There was no increase in grade 3-4 treatment related toxicity and no loss of quality of life for patients receiving SIR-Spheres in comparison to patients receiving HAC alone. CONCLUSION: The combination of a single injection of SIR-Spheres plus HAC is substantially more effective in increasing tumor responses and progression free survival than the same regimen of HAC alone.
UI - 11843250
AU - Wein A; Riedel C; Kockerling F; Martus P; Baum U; Brueckl WM; Reck T;
TI - Ott R; Hansler J; Bernatik T; Becker D; Schneider T; Hohenberger W; Hahn EG Impact of surgery on survival in palliative patients with metastatic colorectal cancer after first line treatment with weekly 24-hour infusion of high-dose 5-fluorouracil and folinic acid.
SO - Ann Oncol 2001 Dec;12(12):1721-7
AD - Department of Internal Medicine I, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany. Axel.Wein@med1.imed.uni-erlangen.de
BACKGROUND: In palliative first-line treatment of colorectal cancer, the secondary resection of distant metastases after downstaging has constantly gained in importance. The objective of this prospective study was to examine the tumor response rate, the toxicity, the median survival time and the prognostic impact of metastatic resection after downstaging of consecutively enrolled patients with primary nonresectable colorectal cancer treated with once weekly 24-hour (24-h) infusion of high-dose 5-fluorouracil (5-FU) and folinic acid. PATIENTS with primary nonresectable metastases were recruited for a prospective phase II study. The patients received in out-patient care 500 mg/m2 folinic acid in the form of a 1-2-hour infusion followed by 2600 mg/m2 5-FU administered as a 24-h infusion once weekly. One treatment cycle comprised six weekly infusions followed by a two week rest. Three cycles were administered, and in the event of complete remission (CR) or partial remission (PR) and good tolerability, a fourth cycle was undertaken. Thereafter, the possibility of performing a curative metastatic resection was investigated. RESULTS: Of the 53 patients treated, 7 showed a CR (13%), 15 patients a PR (28%), 26 patients stable disease (SD) (49%), and 5 patients progressive disease (PD) (10%). As the main symptom of toxicity, diarrhea (CTC grade 3 + 4) was observed in 11 patients (21%), followed by leucocytopenia (CTC grade 3 + 4) in 2 patients (4%), and the hand-foot syndrome in 1 patient (2%). The median survival time was 17 months with a median follow-up of 41 months (range: 28-59 months). In 9 patients (17%), a secondary metastatic resection was considered; in 6 patients (11%) curative resection was performed, and 4 patients (8%) showed no evidence of disease for at least three years. CONCLUSION: In this phase II study, we have been able to show prospectively that, after downstaging by palliative treatment using a weekly 24-h infusion of high-dose 5-FU and folinic acid, secondary curative metastatic resection was technically feasible in 11% of the patients. For some of these patients, long-term survival is therefore possible. Secondary metastatic resection should be carried out in close interdisciplinary cooperation, and should be further investigated in prospective phase III studies.
UI - 11843252
AU - Zeuli M; Costanzo ED; Sdrobolini A; Gasperoni S; Paoloni FP; Carpi A;
TI - Moscetti L; Cherubini R; Cognetti F; Gruppo Oncologico Italiano per la Ricerca Clinica (GOIRC) and Gruppo Oncologico Laziale (GOL) Capecitabine and oxaliplatin in advanced colorectal cancer: a dose-finding study.
SO - Ann Oncol 2001 Dec;12(12):1737-41
AD - Department of Medical Oncology A, Regina Elena Cancer Institute, Rome, Italy. firstname.lastname@example.org
PURPOSE: Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer (ACRC). The aim of this dose-finding trial was to determine the maximum-tolerated dose (MTD), the dose-limiting toxicities (DLTs) and the activity of the combination in patients with advanced colorectal cancer. PATIENTS AND METHODS: Twenty-five chemotherapy-pretreated patients received the combination of capecitabine and oxaliplatin. Capecitabine was administered orally twice a day continuously for 14 days in doses ranging from 1,650 to 2,500 mg/m2/d, and oxaliplatin was administered as a two-hour infusion on day 1 using dose, ranges from 100 to 130 mg/m2 repeated every three weeks. RESULTS: Twenty-five patients were assessable for toxicity, and DLTs were diarrhea (grade > or = 3: 27%) and stomatitis (grade > or = 3: 9%) at dose level VI. Dose level V (capecitabine 2500 mg/m2 and oxaliplatin 120 mg/m2) was found to be the MTD. Hematological toxicity was minimal, overall neurotoxicity (grade 1-4) was 27% with 1% grade 3-4. A global response rate was 17% (95% confidence interval (95% CI): 2%-32%) and the median overall survival was 12 months. CONCLUSION: The recommended dose for further phase II studies is capecitabine 2,500 mg/m2/d with intermittent schedule and oxaliplatin 120 mg/m2 every three weeks. The toxicities were mainly gastrointestinal: diarrhea, stomatitis and vomiting. This combination should be studied in phase II trials in advanced colorectal.
UI - 12131153
AU - Shia J; Tickoo SK; Guillem JG; Qin J; Nissan A; Hoos A; Stojadinovic A;
TI - Ruo L; Wong WD; Paty PB; Weiser MR; Minsky BD; Klimstra DS Increased endocrine cells in treated rectal adenocarcinomas: a possible reflection of endocrine differentiation in tumor cells induced by chemotherapy and radiotherapy.
SO - Am J Surg Pathol 2002 Jul;26(7):863-72
AD - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
The presence of focal endocrine cells in colorectal adenocarcinoma is a relatively common phenomenon. However, endocrine differentiation in treated adenocarcinomas of the gastrointestinal tract has received little attention. We noted striking numbers of cells with endocrine morphology and phenotype in the residual tumor of six randomly encountered cases of rectal adenocarcinoma that were subjected to neoadjuvant therapy. All six cases had a substantial treatment response (> or =50%). To validate our initial observation and to explore its clinicopathologic significance, further morphologic and immunohistochemical studies were performed on 53 cases of rectal adenocarcinomas treated with preoperative radiation with (33 cases) or without (20 cases) chemotherapy. Pretreatment biopsies from 20 of the 53 cases and 79 resection specimens of rectal adenocarcinoma that received no neoadjuvant therapy were used as controls. Chromogranin positivity was identified in the posttreatment resection specimens in 36 of the 53 study cases (67.9%). Twenty of the 36 showed positive staining in > or =20% of the residual tumor cells. The chromogranin-positive cells in these cases often formed cords or nests. On hematoxylin and eosin sections these cells had markedly eosinophilic cytoplasm and round and uniform or sometimes pleomorphic nuclei with an often dense chromatin pattern. The proportion of chromogranin-positive cells was significantly associated with the extent of treatment response (p = 0.0005). Tumors treated with both chemotherapy and radiotherapy were more likely to have abundant chromogranin-positive cells compared with tumors treated with radiotherapy alone (p = 0.0004). In contrast, only 30% of the pretreatment biopsies and 17.7% of the control resection specimens of untreated rectal carcinomas showed chromogranin-positive cells, predominantly arranged as scattered individual positive cells, constituting <10% of the tumor. No significant correlation was observed between pretreatment and posttreatment specimens with regard to chromogranin positivity (p = 1.0). Ten of 15 patients (66.7%) whose resection specimens showed positive chromogranin staining failed to demonstrate any chromogranin positivity in their pretreatment biopsy specimens. In addition, groups or nests of chromogranin-positive cells noted in posttreatment specimens showed a very low Ki67 labeling index (<5%) but showed a frequency of abnormal p53 protein expression comparable with that observed in tumor foci resembling conventional adenocarcinoma (66.7% vs 62.5%). Our findings demonstrate that there is an increased frequency and density of cells with an endocrine phenotype in rectal adenocarcinomas that were subjected to neoadjuvant therapy and that the extent of endocrine cells appears proportional to the degree of treatment response. The possible mechanism for the increased endocrine cells in treated rectal adenocarcinomas may be related to induction of endocrine differentiation in tumor cells by cytotoxic insult.
UI - 12146017
AU - Takahashi K; Mori T; Ohue M; Yamaguchi T
TI - [The prevention of negative side effects in homeochemotherapy]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1311-8
AD - Dept. of Surgery, Tokyo Metropolitan Komagome Hospital.
The purpose of the present study was to identity ways to prevent negative side effects in homechemotherapy. We conducted continuous hepatic arterial infusion chemotherapy (CHAI) in 122 cases of unresectable hepatic metastases from colorectal cancer. We continuously administered 5-FU at 250 mg/day for 7 days using a pump system. We also conducted systemic chemotherapy (FP therapy) in 145 cases of advanced or recurrent colorectal cancer in our outpatient clinic. Based on these experiences, we analyzed the problems of homeochemotherapy. The rate of negative side effects was 15.1% with CHAI. More than half were cases of abdominal pain. Because we had established an observation system for emergency cases, there were no fatal accidents. With FP therapy, about 40% of patients had gastrointestinal discomfort, but the rate of those with higher than grade 3 was low (1-2%). We conclude that it is very important to establish a hospital system to respond quickly to any negative effects of homeochemotherapy.
UI - 12147376
AU - Dzik-Jurasz A; Domenig C; George M; Wolber J; Padhani A; Brown G; Doran
TI - S Diffusion MRI for prediction of response of rectal cancer to chemoradiation.
SO - Lancet 2002 Jul 27;360(9329):307-8
AD - UK Cancer Research Clinical Magnetic Resonance Research Group, Institute of Cancer Research, Royal Marsden NHS Trust, Downs Road, Sutton SM2 5PT, UK. email@example.com
Prediction of tumour response before onset of treatment could have considerable clinical benefit. Since the apparent diffusion coefficient (ADC) of a tumour's water content can show the extent of necrosis, we looked for a possible correlation of ADC with response to treatment. We measured mean tumour water ADC before and after chemotherapy and chemoradiation in 14 patients with locally advanced rectal cancer, with a quantitative magnetic resonance diffusion imaging sequence. We found a strong negative correlation between mean pretreatment tumour water ADC and percentage size change of tumours after chemotherapy (r=-0.67, p=0.01) and chemoradiation (r=-0.83, p=0.001). Persistence of low ADC in responders after chemotherapy could represent loss of a non-viable fraction of the treated tumour.
UI - 12113029
AU - Freyer G; Ligneau B; Kraft D; Descos L; Trillet-Lenoir V
TI - Therapeutic advances in the management of metastatic colorectal cancer.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):236-46
AD - Medical Oncology Unit, Centre Hospitalier Lyon-Sud, 69495 Pierre-Benite, France. Gilles.Freyer@chu-lyon.fr
Metastatic colorectal cancer has long been considered as a short-term, poor prognosis, chemoresistant disease. Until the early 1990s, the impact of systemic chemotherapy on patient outcome was debated. Recently, the emergence of new therapeutic modalities (5-FU modulations and associations with oxaliplatin and irinotecan) has led to a significant improvement in tumor response rates and patient survival. Thus, the indications of curative surgery of visceral metastases, frequently preceded and followed by chemotherapy, systemic or intra-arterial or both, have become more frequent. In this paper we will review and comment on the results of the major clinical trials published in the past 5 years and propose some decision strategies regarding the main clinical situations met in daily practice.
UI - 12113030
AU - Graziano F; Catalano V; Baldelli AM; Cascinu S
TI - Prognostic biomarkers in resected colorectal cancer: implications for adjuvant chemotherapy.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):247-57
AD - University Hospital of Parma, via Gramsci 14, 43100 Parma, Italy.
Knowledge of the prognostic role of biomarkers in colorectal cancer is limited and the routine determination for clinical practice is not warranted. However, for some of these markers, data are promising enough for further evaluation. This review addresses a comprehensive analysis of prognostic biomarkers in colorectal cancer. Data from published studies were collected and analyzed. A sufficient level of evidence suggests that DNA indexes, angiogenesis indicators and some genetic/biochemical markers identity prognostic differences in patients with early-stage colorectal cancer. High-risk patients could be the target for future adjuvant chemotherapy trials and one or more of these markers may identify prognostic subgroups with the same TNM stage category.
UI - 12160204
AU - Yabata E; Okabe S; Endo M
TI - A prospective, randomized clinical trial of preoperative bowel preparation for elective colorectal surgery--comparison among oral, systemic, and intraoperative luminal antibacterial preparations.
SO - J Med Dent Sci 1997 Dec;44(4):75-80
AD - First Department of Surgery, Faculty of Medicine, Tokyo Medical and Dental University, Yushima, Japan.
During a one year and six month period, 137 patients undergoing elective colorectal surgery for carcinoma were randomly allocated to three groups. Patients in group A received oral tobramycin and metronidazole for three days prior to surgery. Patients in groups B and C received systemic antibiotic, a second generation cephem cefmetazole, every 3 hours during surgery. Patients in group C also received a luminal preparation of tobramycin during surgery. All patients received mechanical bowel preparation in the same manner. The incidence of postoperative wound sepsis was 10.9% in group A, 9.8% in group B, and 10.0% in group C. There were no significant differences in postoperative wound sepsis among the three groups. The oral antibiotic regimen induced a greater change in intestinal flora and was associated with more frequent postoperative diarrhea. Although the preoperative bowel preparation taken for patients in group A could not sufficiently reduce the intestinal bacterial count, systemic antibiotic prophylaxis was simple and cost-effective. There was no additional advantage in combining the systemic and luminal antibiotic preparations. Therefore, for elective colorectal surgery, we recommend intravenous infusion of second generation cephem cephmetazole with mechanical bowel preparation.
UI - 11952614
AU - Wu FP; Cuesta MA; Sietses C
TI - Randomized clinical trial of the effect of open versus laproscopically assisted colectomy on systemic immunity in patients with colorectal cancer.
SO - Br J Surg 2002 Apr;89(4):497
UI - 11952615
AU - Schwenk W
TI - Randomized clinical trial of the effect of open versus laproscopically assisted colectomy on systemic immunity in patients with colorectal cancer.
SO - Br J Surg 2002 Apr;89(4):497
UI - 12109610
AU - Jansen JO; O'Kelly TJ; Krukowski ZH; Keenan RA
TI - Right hemicolectomy: mechanical bowel preparation is not required.
SO - J R Coll Surg Edinb 2002 Jun;47(3):557-60
AD - Department of Surgery, Aberdeen Royal Infirmary, Foresterhill, UK.
BACKGROUND: Mechanical bowel preparation before colonic surgery is widely advocated but remains controversial. Recent guidelines published by the Clinical Standards Board for Scotland recommend mechanical bowel preparation prior to surgery for all colorectal cancers but this may be inappropriate. This study examines the outcome of a policy of no mechanical preparation before elective right hemicolectomy. METHOD: Data on 102 consecutive patients undergoing elective right or extended right hemicolectomy for colonic adenocarcinoma were extracted from a prospective database. RESULTS: No clinical anastomotic leaks were observed. Two patients developed wound infections and one patient died with no autopsy evidence of anastomotic leak. CONCLUSION: Mechanical bowel preparation can safely be omitted prior to right hemicolectomy in patients with colonic cancer.
UI - 12107552
AU - Liu Y; Eu W; Seow-Choen F; Cheah Y
TI - Differential cytostatic effect of sodium salicylate in human colorectal cancers using an individualized histoculture system.
SO - Cancer Chemother Pharmacol 2002 Jun;49(6):473-8
AD - Department of Colorectal Surgery, Singapore General Hospital, Singapore 169608, Republic of Singapore.
PURPOSE: Tumor metastasis is the major cause of colorectal cancer (CRC) mortality. Nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin have been shown to have an antineoplastic effect in CRC cell lines. Different patients, however, exhibit different chemosensitivity. In this study, we assessed the chemotherapeutic potential of sodium salicylate, an aspirin metabolite, by measuring its cytostatic effect in an individualized three-dimensional histoculture system. METHODS: Histocultured cancer tissues were treated with sodium salicylate at concentrations from 1 to 10 m M for 24 or 48 h. Inhibition of DNA synthesis was measured in terms of inhibition of bromodeoxyuridine (BrdU) incorporation.RESULTS: The concentration response of individual cancer tissues could be categorized into four groups ranging from the most to the least sensitive to sodium salicylate. Of 20 cancer tissues, 12 (60%) showed a concentration-effect relationship with sodium salicylate in the clinically relevant concentration range (IC50 1.2+/-0.4 to 3.8+/-0.5 m M). Doubling the exposure time decreased the IC50 in four specimens, suggesting that a similar inhibition might be achieved with a lower concentration over an extended time. None of the right-sided cancers was sensitive to sodium salicylate ( P=0.002). CONCLUSIONS: Sodium salicylate had a cytostatic effect on the majority of histocultured CRC tissues. The varying chemosensitivity of the cancers possibly reflected underlying differences, for example in relation to cancer site, thus emphasizing further the usefulness of this clinically relevant system in tailoring chemotherapy to the individual patient.
UI - 11511236
AU - Liu J; Kolar C; Lawson TA; Gmeiner WH
TI - Targeted drug delivery to chemoresistant cells: folic acid derivatization of FdUMP enhances cytotoxicity toward 5-FU-resistant human colorectal tumor cells.
SO - J Org Chem 2001 Aug 24;66(17):5655-63
AD - Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Current chemotherapy protocols that include fluoropyrimidines, such as 5-fluorouracil (5-FU), are limited by the development of chemoresistance during the course of treatment. Our laboratory has developed a novel class of fluoropyrimidines, FdUMP[N], that are oligodeoxynucleotides (ODNs) composed of some number, N, of 5-fluoro-2'-deoxyuridine-5'-O-monphosphate (FdUMP) nucleotides. Novel synthetic procedures are described that permit conjugation of folic acid to the 5'-OH of FdUMP via a phosphodiester linkage using automated synthesis. The synthetic methods developed are generally applicable for ODN conjugation with folic acid. The folic acid conjugate FA-FdUMP showed improved cytotoxicity toward human colorectal tumor cells (H630), and 5-FU-resistant colorectal tumor cells (H630-10). Enhanced cytotoxicity was observed for FA-FdUMP relative to nonconjugated FdUMP for cells grown under folate-restricted conditions, consistent with cellular uptake being, in part, receptor-mediated. Folate receptor alpha (FRalpha) mRNA was shown by RT-PCR to be overexpressed 26.3-fold in 5-FU-resistant H630-10 cells relative to H630 cells. Thus, FA-FdUMP[N] may prove useful for the treatment of 5-FU-resistant malignancies.
UI - 11866136
AU - Black JB; Feigal EG; Gore-Langton RE
TI - Clinical trials referral resource. Clinical trials and NCI resources for cancer in HIV-positive patients.
SO - Oncology (Huntingt) 2002 Feb;16(2):200-2, 205, 207
AD - National Cancer Institute, USA.
UI - 12113038
AU - Anonymous
TI - New studies highlight benefit of Xeloda in new combination treatments for colorectal cancer.
SO - Expert Rev Anticancer Ther 2002 Jun;2(3):241-2
UI - 12048454
AU - Black PK; Hyde C
TI - Parents with colorectal cancer: 'What do I tell the children?'.
SO - Br J Nurs 2002 May 23-Jun 12;11(10):679-85
AD - Stoma Care/Coloproctology, Coloproctology Department, The Hillingdon Hospital, Uxbridge, Middlesex.
Whatever the age of the child, there is no easy way for a parent to explain serious, life-threatening illness. For children to hear that their parent is ill is devastating, especially if the parent has cancer and needs a permanent colostomy. The diagnosis of cancer can produce feelings of fear, confusion and uncertainty in patients and their close relatives. How difficult does this then become for the child battling to understand long medical words, alien hospital environments and an ill parent? The social taboos that surround body matter elimination are legion and therefore the surgical outcome of having a permanent stoma changes the individual's body image perception long-term. The two case studies presented in this article highlight this problem as well as the lack of suitable available literature.
UI - 12099653
AU - Secco GB; Fardelli R; Gianquinto D; Bonfante P; Baldi E; Ravera G;
TI - Derchi L; Ferraris R Efficacy and cost of risk-adapted follow-up in patients after colorectal cancer surgery: a prospective, randomized and controlled trial.
SO - Eur J Surg Oncol 2002 Jun;28(4):418-23
AD - DICMI - Sezione di Semeiotica Chirurgica I, University of Genoa School of Medicine, Genoa, Italy.
AIMS: This paper aims to evaluate the diagnostic efficacy and costs of follow-up tailored according to risk of recurrence compared with minimal surveillance. METHODS: A total of 358 patients treated by surgery alone for colorectal cancer were prospectively divided into two groups of 200 and 158 patients considered at high and low risk of recurrence respectively, according to prognostic factors. They were further randomized into two subgroups: group 1, 192 patients undergoing risk-adapted follow-up, intensive and low-intensity; group 2, 145 patients undergoing minimal surveillance. Twenty-one cases dropped out. Median follow-up was 61.5 months and 42 months for cases at high risk (intensive follow-up) and at low risk (low-intensity follow-up) respectively. RESULTS: At the end of the study, 52.6% of patients undergoing risk-adapted follow-up and 57.2% undergoing minimal follow-up had developed recurrence. In patients at high risk, a significant difference in the incidence of curative re-operations was observed between the subgroups undergoing risk-adapted follow-up and subgroups undergoing minimal surveillance (P<0.05). The actuarial 5 year survival of patients at high and at low risk of recurrence undergoing risk-adapted follow-up is significantly better than that of cases undergoing minimal follow-up. The economic costs for 34 patients in the intensive follow-up group and for the 57 patients in the low-intensity follow-up group who were free from disease after primary surgery was very similar. CONCLUSIONS: Risk-adapted follow-up has significantly improved the targeting of curative re-operations and overall survival of patients independently of risk of recurrence and has allowed a reduction in the costs of following up of disease-free patients.
UI - 12105829
AU - Harewood GC; Wiersema MJ; Nelson H; Maccarty RL; Olson JE; Clain JE;
TI - Ahlquist DA; Jondal ML A prospective, blinded assessment of the impact of preoperative staging on the management of rectal cancer.
SO - Gastroenterology 2002 Jul;123(1):24-32
AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA.
BACKGROUND & AIMS: The influence of preoperative staging of rectal carcinoma on therapeutic decisions is uncertain. The use of fine-needle aspiration (FNA) of perirectal nodes in this setting has not been evaluated. The aim of this prospective, blinded study of patients with rectal cancer was to assess the impact of preoperative staging on treatment decisions and compare the tumor (T), nodal (N) staging performance characteristics of pelvic computed tomography (CT), rectal endoscopic ultrasonography (EUS), and EUS FNA. METHODS: Eighty consecutive patients with newly diagnosed rectal cancer were prospectively evaluated. Therapy decisions were recorded after sequential disclosure of staging information to the patient's surgeon. RESULTS: In 31% of patients (95% confidence interval, 21%-42%), EUS staging information changed the surgeon's original treatment plan based on CT alone. The further addition of FNA changed therapy in one patient. T staging accuracy was 71% (CT) and 91% (EUS) (P = 0.02); N staging accuracy was 76% (CT), 82% (EUS), and 76% (EUS FNA) (P = NS). CONCLUSIONS: Preoperative staging with EUS results in more frequent use of preoperative neoadjuvant therapy than if staging was performed with CT alone. The addition of FNA only changed the management of one patient, whereas FNA did not significantly improve N staging accuracy over EUS alone. FNA seems to offer the most potential for impacting management in those patients with early T stage disease, and its use should be confined to this subgroup of patients. EUS is more accurate than CT for determining T stage of rectal carcinoma.
UI - 12110792
AU - Watanabe T; Tsurita G; Muto T; Sawada T; Sunouchi K; Higuchi Y; Komuro
TI - Y; Kanazawa T; Iijima T; Miyaki M; Nagawa H Extended lymphadenectomy and preoperative radiotherapy for lower rectal cancers.
SO - Surgery 2002 Jul;132(1):27-33
AD - Department of Surgery, University of Tokyo Hospital, the Cancer Institute Hospital, Japan.
BACKGROUND: Extended lymphadenectomy including lateral node dissection (EXT-L) contributes to a low incidence of local recurrence of lower rectal cancer. However, EXT-L is frequently associated with impairment of sexual and urinary function. We therefore compared the effectiveness of preoperative radiotherapy with that of EXT-L. METHODS: One hundred fifteen patients were studied. Seventy-eight patients underwent preoperative radiotherapy with a total dose of 50 Gy (Rad[+] group), and 37 did not (Rad[-] group). Seventy-five patients received EXT-L (EXT-L[+] group), and 40 did not (EXT-L[-] group). Patients wer