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Colorectal Cancer Patients (colorectal + cancer_patient)

Distribution by Scientific Domains

Medical Sciences	88%
3 Other Domains	12%

Selected Abstracts

The Prevalence of Erectile Dysfunction in Post-Treatment Colorectal Cancer Patients and Their Interests in Seeking Treatment: A Cross-Sectional Survey in the West-Midlands

THE JOURNAL OF SEXUAL MEDICINE, Issue 4pt1 2010
Richard Ellis MBChB
ABSTRACT Introduction., Erectile dysfunction (ED) is a recognized complication of colorectal cancer treatment, particularly if surgery is below the recto-sigmoid junction (RSJ), and is an important quality-of-life issue. Previous studies have generated inconsistent prevalence estimates. Aim., We aimed to establish the prevalence of ED in postsurgery colorectal cancer patients and to establish what proportion wished to seek treatment. Main Outcome Measures., Questionnaire: sociodemographics, treatment methods, International Index of Erectile Function (IIEF)-5 questionnaire (validated tool to assess erectile function): score of <21 being used to define ED. Methods., Cross-sectional survey. Inclusion criteria: adult male colorectal cancer patients diagnosed in 2000,2007, treated with curative intent in one teaching hospital. Statistical analysis: logistic regression analysis to determine predictors of ED. Results., The response rate was 46% (229/499). Respondents were aged 28 to 95 years; the majority were white (93.9%), more than half (57.1%) were in a sexual relationship, only a third reported having sex in the past 6 months (33.3%). The vast majority (75.1%; 172/229) of responders had ED as defined by the IIEF-5. ED was significantly associated with increasing age (P < 0.0005), having a malignancy below the RSJ (P = 0.002), having previous radiotherapy (P = 0.007), and having a stoma (P = 0.014). Those with ED were less likely to be in a sexual relationship (P = 0.002) and less likely to have had sex in the last 6 months (P < 0.0005). Only 29% of those with ED were not interested in treatment for their condition. Conclusions., These data suggest a prevalence rate of ED of 75% in colorectal cancer survivors; this may be functional or psychological in origin. Quality of life may be improved if follow-up clinics for cancer survivors not only concentrated on the detection of recurrence but also offered assessment of erectile function and referral for patients who desire treatment. Ellis R, Smith A, Wilson S, Warmington S, and Ismail T. The prevalence of erectile dysfunction in post-treatment colorectal cancer patients and their interests in seeking treatment: A cross-sectional survey in the west-midlands. J Sex Med 2010;7:1488,1496. [source]

Stability of preferences with regard to adjuvant chemotherapy: impact of treatment decision, experience and the passing of time

EUROPEAN JOURNAL OF CANCER CARE, Issue 1 2008
S.J.T. JANSEN phd
Research has shown that patients' preferences for adjuvant chemotherapy do not change as a result of experience. However, the preferences of experienced patients are usually more favourable than those of inexperienced patients. These results indicate a shift in preferences after the decision to proceed with adjuvant chemotherapy has been made, but before actual experience. We tested this assumption in early-stage breast and colorectal cancer patients. We asked patients to provide their preferences for chemotherapy before surgery and thus before they knew whether chemotherapy would be advised (T1), after surgery but before the start of chemotherapy (T2) and about 1 month after chemotherapy (T3). Patients who did not undergo chemotherapy co-operated at similar points in time. Preferences were measured on a nine-point scale, ranging from (1) ,very strong preference for no chemotherapy' to (9) ,very strong preference for chemotherapy'. As hypothesized, the preferences of patients who would be treated with chemotherapy became more favourable after the treatment decision had been made (n = 7, P = 0.06). The preferences of patients for whom chemotherapy was not part of the treatment plan showed the opposite effect (n = 38, P = 0.03). We did not find any effect of experiencing treatment (n = 22, P = 0.62) or the passing of time (n = 81, P = 0.25) on the stability of preferences. We conclude that the frequently observed discrepancy in treatment preferences between experienced and inexperienced patients seems to be an effect of the treatment decision and not of experience of the treatment. [source]

Genome-wide scan identifies a copy number variable region at 3q26 that regulates PPM1L in APC mutation-negative familial colorectal cancer patients

GENES, CHROMOSOMES AND CANCER, Issue 2 2010
L. F. Thean
Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited form of colorectal cancer (CRC) caused by mutation in the adenomatous polyposis coli (APC) gene. However, APC mutations are not detected in 10,50% of FAP patients. We searched for a new cancer gene by performing genome-wide genotyping on members of an APC mutation-negative FAP variant family and ethnicity-matched healthy controls. No common copy number change was found in all affected members using the unaffected members and healthy controls as baseline. A 111 kb copy number variable (CNV) region at 3q26.1 was shown to have copy number loss in all eight polyps compared to matched lymphocytes of two affected members. A common region of loss in all polyps, which are precursors to CRC, is likely to harbor disease-causing gene in accordance to Knudsen's "two-hit" hypothesis. There is, however, no gene within the deleted region. A 2-Mb scan of the genomic region encompassing the deleted region identified PPM1L, coding for a novel serine-threonine phosphatase in the TGF-, and BMP signaling pathways. Real-time PCR analyses indicate that the 3,UTR of PPM1L transcript was down-regulated more than two-folds in all six polyps and tumors compared to matched mucosa of the affected member. This down-regulation was not observed in APC mutation-positive FAP patients. Our results suggest that the CNV region at 3q26 harbors an element that regulates the expression of an upstream candidate tumor suppressor, PPM1L, thus providing a novel mechanism for colorectal tumorigenesis in APC mutation-negative familial CRC patients. © 2009 Wiley-Liss, Inc. [source]

Multiple serological biomarkers for colorectal cancer detection

INTERNATIONAL JOURNAL OF CANCER, Issue 7 2010
Chung-Chuan Chan
Abstract The aim of this study was to initiate a survey of human autoantibody responses to a panel of select colorectal tumor-associated antigens identified by previous serological analysis of a cDNA expression library and to subsequently identify multiple serological biomarkers for the detection of colorectal cancer. For screening of autoantibodies against colorectal tumor-associated antigens, sera from 94 colorectal cancer patients and 54 normal controls were analyzed by enzyme-linked immunosorbent assay using recombinant rCCCAP, rHDAC5, rP53, rNMDAR and rNY-CO-16 proteins as coating antigens. Seropositivity among colorectal cancer patients to the 5 individual coating antigens varied from 18.1% to 35.1%. Seropositivity to any of the 5 coating antigens was 58.5% and combining this analysis with evaluation of serum carcinoembryonic antigen (,5 ng/ml) significantly increased the seropositivity to 77.6%. Seropositivity of early-stage (Dukes' Stages A and B) colorectal cancer patients to CEA was 21.9%, and seropositivity to any of the 5 colorectal cancer-associated antigens was 53.7%, and the combination of these 2 measurements resulted in a higher diagnostic capacity (65.9%) than either marker alone. In conclusion, these results collectively indicated that combined detection of serum autoantibody profiles against our panel of colorectal tumor-associated antigens and the analysis of carcinoembryonic antigen provides a promising diagnostic biomarker for colorectal cancer, particularly among early-stage patients. [source]

Population-based detection of Lynch syndrome in young colorectal cancer patients using microsatellite instability as the initial test

INTERNATIONAL JOURNAL OF CANCER, Issue 5 2009
Lyn Schofield
Abstract Approximately 1,2% of colorectal cancers (CRC) arise because of germline mutations in DNA mismatch repair genes, referred to as Lynch syndrome. These tumours show microsatellite instability (MSI) and loss of expression of mismatch repair proteins. Pre-symptomatic identification of mutation carriers has been demonstrated to improve survival; however, there is concern that many are not being identified using current practices. We evaluated population-based MSI screening of CRC in young patients as a means of ascertaining mutation carriers. CRC diagnosed in patients aged <60 years were identified from pathology records. No prior information was available on family history of cancer. PCR techniques were used to determine MSI in the BAT-26 mononucleotide repeat and mutation in the BRAF oncogene. Loss of MLH1, MSH2, MSH6 and PMS2 protein expression was evaluated in MSI+ tumours by immunohistochemistry. MSI+ tumours were found in 105/1,344 (7.8%) patients, of which 7 were excluded as possible Lynch syndrome because of BRAF mutation. Of the 98 "red flag" cases that were followed up, 25 were already known as mutation carriers or members of mutation carrier families. Germline test results were obtained for 35 patients and revealed that 22 showed no apparent mutation, 11 showed likely pathogenic mutations and 2 had unclassified variants. The proportion of MSI+ cases in different age groups that were estimated to be mutation carriers was 89% (<30 years), 83% (30,39), 68% (40,49) and 17% (50,59). We recommend MSI as the initial test for population-based screening of Lynch syndrome in younger CRC patients, regardless of family history. © 2008 Wiley-Liss, Inc. [source]

Quantitative real-time RT-PCR for detection of disseminated tumor cells in peripheral blood of patients with colorectal cancer using different mRNA markers

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2004
Ronny Schuster
Abstract The detection of disseminated tumor cells in peripheral blood from colorectal cancer patients by RT-PCR could be an attractive method for selecting patients for adjuvant therapy. We here report on real-time RT-PCR assays (LightCycler) to quantitate potential mRNA markers. We investigated specimens from colon carcinoma and normal colon mucosa tissues, cell lines, blood samples from 129 patients with colorectal cancer (all stages) and 58 reference blood samples (healthy donors, persons suffering from inflammatory bowel or infectious diseases). The expression profile in tissues showed high values for CEA and CK20, whereas in cell lines ProtM was predominant. All markers were detected in reference and patient blood samples (ProtM, 22, 17%; CEA, 84, 86%; CK20, 85, 88%). After quantitative analysis, the definition of cutoff values for each marker and the combination of markers, 13% of patients were judged to have elevated marker concentrations in their blood, from which only 6 had values significantly differing from cutoff value. There were no differences between stages of disease. In the case of 19 patients, investigated prior to and 1 week after surgery, 2 samples revealed a significant postoperative increase in CEA or CK20 mRNA concentration. In spite of high expression levels in tissues and cell lines, we were not able to differentiate satisfyingly mRNA markers originating from tumor cells and those from illegitimate transcription in hematopoetic cells in blood. We conclude that either copy numbers of analyzed markers in circulating tumor cells are not sufficient for detection or, more probably, peripheral blood is not a suitable compartment for detection of tumor cells in colorectal cancer. © 2003 Wiley-Liss, Inc. [source]

Prognostic value of serum angiogenic activity in colorectal cancer patients

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2007
Francisco-Jesus Gonzalez
Abstract Angiogenesis, resulting from an imbalance between angiogenic activator factors and inhibitors, is required for tumour growth and metastasis. The determination of the circulating concentration of all angiogenic factors (activators and inhibitors) is not feasible at present. We have evaluated diagnostic and prognostic values of the measurement of serum angiogenic activity in colorectal carcinoma (CRC) patients. Serum proliferative activity (PA) on human umbilical vein endothelial cells (HUVEC) in vitro, and serum vascular endothelial growth factor (VEGF) levels were determined by ELISA in 53 patients with primary CRC, 16 subjects with non-neoplastic gastrointestinal disease (SC) and 34 healthy individuals. Data were compared with clinical outcome of the patients. Although serum from CRC patients significantly increased the PA of HUVEC, compared to culture control (HUVEC in medium + 10% foetal bovine serum (FBS); P < 0.001); our results indicate that serum PA in CRC patients was similar to that of SC or healthy individuals. There was no correlation between serum PA and circulating VEGF concentrations. Surgery produced a decrease of PA at 8 hrs after tumour resection in CRC patients compared to pre-surgery values (186 ± 47 versus 213 ± 41, P < 0.001). However, an increase in serum VEGF values was observed after surgery (280 [176,450] versus 251 [160,357] pg/ml, P = 0.004). Patients with lower PA values after surgery showed a worse outcome that those with higher PA values. Therefore, this study does not support a diagnostic value for serum angiogenic activity measured by proliferative activity on HUVEC but suggests it could have a prognostic value in CRC patients. [source]

Nutritional status of preoperative colorectal cancer patients

JOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 4 2010
S. T. Burden
Abstract Background:, The present study aimed to determine the extent of malnutrition in preoperative colorectal cancer patients. Malnutrition has been shown to affect post-operative outcome, so it would be beneficial to identify those who are malnourished or who are at risk of becoming so preoperatively. We examine whether weight loss is related to the length of stay or changes in fat free mass. Methods:, Patients were enrolled consecutively from outpatients 2,4 weeks prior to surgery. Assessments included body mass index, percentage weight loss, dynamometry, Malnutrition Universal Screening Tool, Subjective Global Assessment and bioelectrical impedance. Cancer staging and hospital length of stay were recorded. Results:, One hundred and thirty-two patients were eligible and 87 enrolled. Sixty-seven patients were weight losing and 20% had lost >10% of their usual body weight. Handgrip strength was lower in malnourished patients compared to those who had not lost weight (mean 19.4 and 27.3 kg, respectively, P = 0.013). Mean (SD) fat free mass in patients with a weight loss >10% was 39.7 (13.5) kg and, in those with <10% weight loss, was 51.9 (12.0) kg (P = 0.001). This difference was not demonstrated for fat. Conclusions:, Over half of these patients had lost weight prior to surgery and one in five were malnourished. Body composition measurements demonstrated that malnourished patients had significantly less fat free mass compared to patients who were not clinically malnourished. Nutritional screening would be beneficial in this group preoperatively to identify weight-losing patients at an early stage in the care pathway when they initially enter the secondary care system. [source]

Phase I study on sentinel lymph node mapping in colon cancer: A preliminary report,

JOURNAL OF SURGICAL ONCOLOGY, Issue 2 2002
Yves Bendavid
Abstract Background and Objectives Lymph node (LN) metastasis is one of the most significant prognostic factor in colorectal cancer. In fact, therapeutic decisions are based on LN status. However, multiple studies have reported on the limitations of the conventional pathological LN examination techniques, and therefore, the actual number of patients with LN positive colorectal cancer is probably underestimated. We assume that lymphatic tumor dissemination follows an orderly sequential route. We report here a simple and harmless coloration technique that was recently elaborated, and that allows us to identify the sentinel LN(s) (SLN) or first relay LNs in colorectal cancer patients. The main endpoint of this clinical trial is the feasibility of the technique. Methods Twenty patients treated by surgery for a colic cancer were admitted in this protocol. A subserosal peritumoral injection of lymphazurin 1% was performed 10 min before completing the colic resection. A pathologist immediately examined the specimens, harvested the colored SLN, and examined them by serial cuts (200 ,m) with H&E staining, followed by immunohistochemical staining (AE1-AE3 cytokeratin markers), when serial sections were classified as cancer free. Results The preoperative identification of the SLN was impossible in at least 50 of the cases, however, SLNs were identified by the pathologist in 90% of cases. In two patients (10%) SLN was never identified. The average number of SLN was 3.9. Immunohistochemical analysis of the SLN has potentially changed the initial staging (from Dukes B to Dukes C) for 5 of the 20 patients (25%). On the other hand, there was one patient (5%) with hepatic metastasis from adenocarcinoma for whom SLN pathology was negative for metastasis (skip metastasis). Conclusions SLN biopsy is readily feasible with identification of SLN in at least 90% of patients with colorectal cancers. Our results indicate that 45% of patients initially staged as Dukes B had tumor cells identified in their SLN when these were subjected to our protocol. This represented a 25% upgrading rate when our complete study population is considered. However, controversy persist about the clinical significance and metastatic potential of these often very small clusters of tumor cells. J. Surg. Oncol. 2002;79:81,84. © 2002 Wiley-Liss, Inc. [source]

Dimensions of quality of life and psychosocial variables most salient to colorectal cancer patients

PSYCHO-ONCOLOGY, Issue 1 2006
Jeff Dunn
Abstract Colorectal cancer is one of the most common invasive cancers, and is responsible for considerable physical and psychosocial morbidity. Understanding the quality of life experienced by colorectal cancer patients is essential for evaluating the full impact of the disease on individuals, their families and their communities. Patient perspective is essential in establishing a proper understanding of the quality of life of colorectal cancer patients. Despite this, few studies have employed a qualitative methodology to explore quality of life issues for colorectal cancer patients. A review of the literature identified only seven qualitative studies pertaining to quality of life issues for colorectal cancer patients, a surprising finding given the prevalence of this cancer. Accordingly, this study sought to build on the findings of previous qualitative research by providing descriptive data on the quality of life and psychosocial variables most salient to colorectal cancer patients. Six core themes emerged from interview and focus group data: Satisfaction with diagnosis and treatment; support (including information provision); quality of life; benefits of diagnosis; making sense of the cancer experience; and coping strategies. The information derived from this study will help inform the development of supportive care services to address the needs of the increasing number of people diagnosed with colorectal cancer. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Development of a disease specific questionnaire to supplement a generic tool for QoL in colorectal cancer

PSYCHO-ONCOLOGY, Issue 7 2003
J. Davidson-Homewood
The need for disease-specific quality of life measures is highlighted in the literature. The psychometric properties of a supplementary disease-specific quality of life questionnaire developed for use with a generic Quality of Life tool in colorectal cancer patients are explored. Originally developed and tested in a German sample, the English translation was tested on a cohort of UK colorectal cancer patients. Relevance and acceptability was previously established in Germany. A rigorous factor analysis ascertained the underlying structure of two factors with a number of single items that were retained as clinically important symptom indicators. In considering validity, four conditions were assessed: Reliability using Cronbach's alpha; Construct validity by comparing patient subgroups; Clinical Validity, by testing the hypothesis that some patient subgroups experience worse quality of life; Construct Reliability using second order factor analysis with the EORTC QOLQ-C30 scales, confirming that the factors retained provide an excellent measure of physical discomfort and a good measure of physical well being. Two other such questionnaires were developed in parallel with this one and reported in the literature (FACT-C and QOLQ-CR38). However, this questionnaire provides a useful alternative tool for use in clinical trials of colorectal cancer treatments alongside a core QoL questionnaire especially when brevity is an important consideration. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Mass spectrometry study of hemoglobin-oxaliplatin complexes in colorectal cancer patients and potential association with chemotherapeutic responses

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2006
Rupasri Mandal
Oxaliplatin is the most active platinum (Pt)-containing anticancer drug for the treatment of advanced colorectal cancer. We report here the study of potential association of the levels of oxaliplatin-protein complexes in 19 cancer patients with treatment efficacy using size-exclusion high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC/ICPMS) and nanoelectrospray ionization mass spectrometry (nanoESI-MS) techniques. Blood samples from 19 colorectal cancer patients were collected at 1 and 48,h after the first infusion of oxaliplatin. HPLC/ICPMS quantification of the oxaliplatin-protein complexes showed that the levels of Pt-protein complexes in plasma samples at 48,h were reduced by approximately 50% compared to those at 1,h, whereas those in hemolysates did not change significantly. The concentrations of hemoglobin (Hb)-oxaliplatin complexes determined by HPLC/ICPMS ranged from 3.1 to 8.7,µM. NanoESI-MS analysis of the patient hemolysates showed three distinct mass spectral profiles of the Hb-oxaliplatin complexes: (1) 1:1, (2) 1:1 with 1:2, and (3) multiple complexes of 1:1, 1:2, 1:3, and 1:4, corresponding to the Hb-oxaliplatin complex concentrations determined by HPLC/ICPMS. Potential association of variables including Hb-oxaliplatin complex concentrations with time to progress as the treatment efficacy indicator was analyzed using the Cox model. Multivariate analysis of the potential predictors showed that the statistically significant variables were Hb-oxaliplatin complex concentration (p,=,0.02), performance status (p,=,0.02), baseline neutrophil count (p,=,0.05), and the site of the primary cancer (colon vs. rectal, p,=,0.01). The hazard ratio for the concentration of the Hb-oxaliplatin complexes was 2.4, suggesting that the risk of cancer progression significantly increased with increasing of Hb-oxaliplatin complexes in patients. These results demonstrate that the level of the Hb-oxaliplatin complexes in erythrocytes is a potential biomarker for indicating inter-patient variations in oxaliplatin treatment efficacy. Copyright © 2006 John Wiley & Sons, Ltd. [source]

The Prevalence of Erectile Dysfunction in Post-Treatment Colorectal Cancer Patients and Their Interests in Seeking Treatment: A Cross-Sectional Survey in the West-Midlands

Inducible nitric oxide synthase expression and its prognostic significance in colorectal cancer

APMIS, Issue 2 2010
KYRIAKOS ZAFIRELLIS
Zafirellis K, Zachaki A, Agrogiannis G, Gravani K. Inducible nitric oxide synthase expression and its prognostic significance in colorectal cancer. APMIS 2010; 118: 115,24. Nitric oxide synthases (NOS) are expressed in colorectal cancer. The aim of this study was to examine the inducible NOS (iNOS) expression in colorectal cancer and to investigate its prognostic relevance. Tissue sections of primary tumors from 132 patients undergoing curative resection for colorectal cancer were immunohistochemically examined for iNOS expression. The expression pattern of iNOS was correlated with various clinicopathological characteristics and survival. iNOS immunoreactivity was observed in the cytoplasm of tumor epithelial cells in 60 patients (45.5%) and positively correlated with lymph node involvement (p = 0.019). No significant correlation was found between iNOS expression and various clinicopathological characteristics, including age, gender, tumor location, tumor size, tumor grade, T stage, and Union International Contra la Cancrum (UICC) stage. Survival analysis showed a significant correlation between iNOS-positive tumors and poor disease-specific survival (p < 0.0001), with independent prognostic significance in multivariate analysis (HR = 4.42; p < 0.0001). Patients with stage II disease and iNOS-positive tumors had significantly worse disease-specific survival than those with iNOS-negative tumors (p < 0.0001). In addition, patients with stage III disease and iNOS-positive tumors had significantly worse disease-specific survival than those with iNOS-negative tumors (p = 0.001). The ability of iNOS to predict outcome in colorectal cancer patients may be independent of other known prognostic factors, providing a new molecular marker with significant potential for clinical utility. [source]

Decrease in intrahepatic CD56+ lymphocytes in gastric and colorectal cancer patients with liver metastases

APMIS, Issue 12 2009
MAYA GULUBOVA
The aim of the study was to examine the main intrahepatic lymphocyte subpopulations, namely CD3+ lymphocytes, natural killer (NK)-like T lymphocytes (NKT) expressing the CD3+ CD56+ phenotype, CD56+ NK cells, CD4+, and CD8+ T cells in livers of patients with gastric and colorectal cancer with and without hepatic metastases. The proportion of each lymphocyte subset was determined in 34 patients with gastric or colorectal cancer (18 with and 16 without liver metastasis) by two-color flow cytometry after extraction of hepatic mononuclear cell fraction. The distribution of lymphocyte subpopulations in selected areas of liver metastases and adjacent liver tissue was evaluated using immunohistochemistry for CD4, CD8, and CD56. Flow cytometry analysis revealed a significant decrease in the proportion of CD3+ CD56+ cells in metastatic livers, but not in nonmetastatic livers (11.9 ± 10.3 vs 24.2 ± 13.6%, p = 0.02). The percentage of intrahepatic CD3,CD56+ cells was also decreased in patients with metastases compared to those without (10.1 ± 11.6 vs 16.6 ± 8.9%, p = 0.039). Immunohistochemically, three types of lymphocytes (CD4+, CD8+, and CD56+) were present in the metastatic tissue, although the number of CD56+ cells was almost twice lower. We found a low prevalence of tumor-infiltrating CD4+, CD8+, and CD56+ cells in livers with multiple metastases, whereas in cases with solitary metastasis a higher degree of lymphocyte infiltration was observed. The number of CD3,CD56+ and CD3+ CD56+ cells was decreased in metastatic livers compared to those unaffected by metastases. Therefore the prevalence of tumor-infiltrating lymphocytes seems to be related to the progression of metastatic liver disease. Depletion of hepatic innate lymphocytes may reveal susceptibility to metastatic liver disease and could be a reason for the escape of metastatic cells from the mechanisms of liver immune control. [source]

Combining Information from Cancer Registry and Medical Records Data to Improve Analyses of Adjuvant Cancer Therapies

BIOMETRICS, Issue 3 2009
Yulei He
Summary Cancer registry records contain valuable data on provision of adjuvant therapies for cancer patients. Previous studies, however, have shown that these therapies are underreported in registry systems. Hence direct use of the registry data may lead to invalid analysis results. We propose first to impute correct treatment status, borrowing information from an additional source such as medical records data collected in a validation sample, and then to analyze the multiply imputed data, as in Yucel and Zaslavsky (2005,,Journal of the American Statistical Association,100, 1123,1132). We extend their models to multiple therapies using multivariate probit models with random effects. Our model takes into account the associations among different therapies in both administration and probability of reporting, as well as the multilevel structure (patients clustered within hospitals) of registry data. We use Gibbs sampling to estimate model parameters and impute treatment status. The proposed methodology is applied to the data from the Quality of Cancer Care project, in which stage II or III colorectal cancer patients were eligible to receive adjuvant chemotherapy and radiation therapy. [source]

Absence of large intragenic rearrangements in the DPYD gene in a large cohort of colorectal cancer patients treated with 5-FU-based chemotherapy

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2010
Laia Paré
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Dihydropyrimidine dehydrogenase (DPD) is the enzyme responsible for the elimination of approximately 80% of the administered dose of 5-fluorouracil (5-FU). , Mutations in the DPD-coding gene have been shown to increase the risk of severe toxicity in 5-FU treated patients. , The IVS14+1G>A is the most common DPYD mutation. WHAT THIS STUDY ADDS , The intragenic rearrangements of DPYD using multiplex ligation-dependent probe amplification (MLPA) were studied for the first time in a large series of 234 colorectal cancer patients treated with 5-FU-containing chemotherapy. , No deletions or duplications of one or more DPYD exons were detected. The presence of the IVS14+1G>A mutation was also excluded. , These data show that neither the large genomic rearrangements in the DPYD gene nor the IVS14+1G>A mutation are responsible for the serious toxicity associated with a 5-FU containing regimen in this cohort of Spanish patients. AIMS To study the relationship between the toxicity associated with a 5-FU-based therapy and the presence of (i) the large intragenic rearrangements in the DPYD gene and (ii) the IVS14+1G>A mutation. METHODS We used the multiplex ligation-dependent probe amplification technique (MLPA) to study genomic DNA from 234 colorectal cancer patients treated with 5-FU-based chemotherapy. RESULTS We did not detect any deletion/duplication in the DPYD gene. The presence of the IVS14+1G>A mutation was also excluded. CONCLUSIONS Neither the large genomic rearrangements in the DPYD gene nor the IVS14+1G>A mutation play a significant role in the development of serious toxicity associated with a 5-FU containing regimen. [source]

Increased exposure to bacterial antigen RpL7/L12 in early stage colorectal cancer patients

CANCER, Issue 17 2010
Annemarie Boleij MSc
Abstract BACKGROUND: Intestinal bacteria have long been implicated in colorectal cancer pathology, and many reports point to a close linkage between Streptococcus bovis biotype I (recently renamed Streptococcus gallolyticus) infections and tumors of the human colon. This work aims to investigate the humoral immune response to this bacterium during different stages of colorectal cancer. METHODS: The presence of serum antibodies against S. bovis antigen RpL7/L12, previously assigned as a potential diagnostic antigen, was evaluated in Dutch (n = 209) and American (n = 112) populations using a newly developed enzyme-linked immunosorbent assay. RESULTS: The analyses consistently showed that an immune response against this bacterial antigen was increased in polyp patients and stage I/II colorectal cancer patients as compared with asymptomatic individuals. This was not paralleled by increased antibody production to endotoxin, an intrinsic cell wall component of the majority of intestinal bacteria, which implies that the humoral immune response against RpL7/L12 is not a general phenomenon induced by the loss of colonic barrier function. Notably, increased anti-RpL7/L12 levels were not or were only mildly detected in late stage colorectal cancer patients having lymph node or distant metastasis. CONCLUSIONS: These findings are indicative of an increased exposure to antigen RpL7/L12 during early stages of colon carcinogenesis and suggest that intestinal bacteria such as S. bovis constitute a risk factor for the progression of premalignant lesions into early stage carcinomas. Clearly, the current findings emphasize the necessity for further studies on the possible etiologic relationship between intestinal bacteria and human colorectal cancer. Cancer 2010. © 2010 American Cancer Society. [source]

Clinical trial enrollment, patient characteristics, and survival differences in prospectively registered metastatic colorectal cancer patients

CANCER, Issue 20 2009
Halfdan Sorbye MD
Abstract BACKGROUND: Trial accrual patterns were examined to determine whether metastatic colorectal cancer (mCRC) patients enrolled in trials are representative of a general cancer population concerning patient characteristics and survival. METHODS: A total of 760 mCRC patients referred for their first oncological consideration at 3 hospitals in Scandinavia covering defined populations were registered consecutively during 2003 to 2006. Clinical trial enrollment, patient characteristics, and treatment were recorded prospectively, and the follow-up was complete. RESULTS: Palliative chemotherapy was initiated in 61% of the patients. Approximately one,third (36%) of patients receiving chemotherapy were included in a trial. The main reason for nonparticipation was failed eligibility criteria (69%). The median survival after chemotherapy was 15.8 months for all patients, and 18 months after combination chemotherapy. Trial patients had better prognostic characteristics and significantly longer survival than nontrial patients: 21.3 months versus 15.2 months when receiving combination chemotherapy. Poor performance status was the main reason for giving best supportive care only, and the median survival was then only 2.1 months. The median survival for all 760 nonresectable mCRC patients was 10.7 months. CONCLUSIONS: mCRC patients enrolled into clinical trials differ in characteristics from patients receiving chemotherapy outside protocol and have better survival, even when given the same treatment. Although trial patients have a median survival close to 2 years, survival is lower for all patients receiving chemotherapy and much lower for all patients diagnosed with mCRC. Studies that better accept the heterogeneity of the population with mCRC are needed. Cancer 2009. © 2009 American Cancer Society. [source]

Radioimmunotherapy of small-volume disease of metastatic colorectal cancer

CANCER, Issue S4 2002
Results of a phase II trial with the iodine-13, carcinoembryonic antigen antibody hMN-1, labeled humanized anti
Abstract BACKGROUND Whereas radioimmunotherapy (RIT) has shown disappointing results in bulky, solid tumors, preclinical results in small-volume disease and in an adjuvant setting are promising. In a previous Phase I study, the authors had encouraging results with the iodine-131 (131I),labeled humanized anti,carcinoembryonic antigen (anti-CEA) antibody (MAb) hMN-14 in small-volume disease of colorectal cancer. The aim of this study was to evaluate, in a subsequent Phase II trial, the therapeutic efficacy of this 131I-labeled humanized anti-CEA antibody in colorectal cancer patients with small-volume disease or in an adjuvant setting. METHODS Thirty colorectal cancer patients, with small-volume metastatic disease (n = 21; all lesions , 3.0 cm, and chemorefractory to 5-fluorouracil and folinic acid) or in an adjuvant setting (n = 9), 4,6 weeks after surgical resection of liver metastases with curative intention, were studied. The patients were given a single injection of 131I-hMN-14 immunoglobulin G at a 60 mCi/m2 dose level, which was shown to be the maximum tolerated dose in the previous Phase I study. Follow-up was obtained at 3-month intervals for as long as 36 months. RESULTS At a mean blood-based red marrow dose of 1.8 ± 0.8 Gy, myelotoxicity was the only toxicity observed, but only 1 of 28 assessable patients developed transient Grade 4 thrombocytopenia. Of the 21 patients with radiologically documented lesions, 19 were assessable. Three experienced partial remission and eight showed minor responses up to 15 months in duration (corresponding to an objective response rate of 16% and an overall response rate of 58%; the mean duration of response was 9 months). At the time this article was written, seven of nine patients in the adjuvant setting had remained free of disease for up to 36 months (one patient relapsed after 6 months and another after 30 months), whereas the relapse rate in a historical control group receiving chemotherapy was 67% over the same time period. Five patients with radiologically documented lesions, having experienced at least disease stabilization as a consequence of RIT, were retreated at the same 60-mCi/m2 dose level at 8,16 months after the first therapy. No evidence of increased toxicity was observed (no hematologic toxicity was higher than Grade 3). Two of four assessable retreated patients experienced partial remissions; one of these four again experienced disease stabilization as a consequence of the second radioantibody therapy injection. CONCLUSIONS These data suggest that RIT is a safe and effective form of therapy for small-volume colorectal cancer and has potential as treatment for colorectal cancer in an adjuvant setting. Toxicity is restricted to mild and transient leuko- and thrombocytopenia. Retreatment seems to be a feasible option. A prospective randomized comparison with standard chemotherapy is indicated. Cancer 2002;94:1373,81. © 2002 American Cancer Society. DOI 10.1002/cncr.10308 [source]

Plasma concentrations of VCAM-1 and PAI-1: A predictive biomarker for post-operative recurrence in colorectal cancer

CANCER SCIENCE, Issue 8 2010
Yasuhide Yamada
This prospective study used antibody suspension bead arrays to identify biomarkers capable of predicting post-operative recurrence with distal metastasis in patients with colorectal cancer. One hundred colorectal cancer patients who underwent surgery were enrolled in this study. The median follow-up period was 3.9 years. The pre-operative plasma concentrations of 24 angiogenesis-related molecules were analyzed with regard to the TNM stage and the development of post-operative recurrence. The concentrations of half of the examined molecules (13/24) increased significantly according to the TNM stage (P < 0.05). Meanwhile, a multivariate logistic regression analysis revealed that the concentrations of vascular cell adhesion molecule 1 (VCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were significantly higher in the post-operative recurrence group. The VCAM-1 and PAI-1 model discriminated post-operative recurrence with an area under the curve of 0.82, a sensitivity of 0.75, and a specificity of 0.73. A leave-one-out cross-validation was applied to the model to assess the prediction performance, and the result indicated that the cross-validated error rate was 12.5% (12/96). In conclusion, our results demonstrate that antibody suspension bead arrays are a powerful tool to screen biomarkers in the clinical setting, and the plasma levels of VCAM-1 and PAI-1 together may be a promising biomarker for predicting post-operative recurrence in patients with colorectal cancer. (Cancer Sci 2010) [source]

Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients: Possible involvement of c-myc suppression by interferon-,in situ

CANCER SCIENCE, Issue 1 2006
Kazuyuki Matsushita
Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients, although the precise mechanism is controversial. From an immunological point of view, HLA-DR antigen, induced by interferon (IFN)-,, is required for tumor-associated antigen recognition by CD4+ T cells. For instance, as reported previously, the expression of HLA-DR antigen in normal colorectal epithelium immediately adjacent to cancer coincided significantly with the existence of IFN-, mRNA in the tissue. From another aspect, IFN-, has been revealed to suppress c-myc expression in vivo through a stat1-dependent mechanism, which is important for cell growth, cell cycle and chromosome instability. In the present study, strong HLA-DR-positive expression on cancer cells was significantly related to better prognosis for colorectal cancer patients. High IFN-, mRNA expression in situ indicated significantly less activation of c-myc mRNA expression. Further, HLA-DR antigen expression in cancer cells, as well as Dukes stages, was an independent factor for better long-term survival by multivariate analysis. Taken together, IFN-,, which induces HLA-DR antigens on the cell surface, also suppresses c-myc expression in situ, and is a possible non-immunological mechanism involved in the better long-term survival of colorectal cancer patients. (Cancer Sci 2006; 97: 57, 63) [source]

Frequency of constitutional MSH6 mutations in a consecutive series of families with clinical suspicion of HNPCC

CLINICAL GENETICS, Issue 3 2007
B Roncari
A large majority of constitutional mutations in hereditary non-polyposis colorectal cancer (HNPCC) are because of the MHL1 or MSH2 genes. In a lower fraction of cases, another gene of the mismatch repair (MMR) machinery, MSH6, may be responsible. Families with MSH6 mutations are difficult to recognize, as microsatellite instability (MSI) may not be detectable and immunohistochemistry (IHC) may give ambiguous results. In the present study, we proposed (i) to determine the frequency of MSH6 mutations in a selected population of colorectal cancer patients obtained from a tumor registry, (ii) to assess whether IHC is a suitable tool for selecting and identifying MSH6 mutation carriers. One hundred neoplasms of the large bowel from suspected HNPCC families were analyzed for MSI (BAT25 and BAT26 markers) and immunohistochemical expression of the MSH6 protein. We found on 12 tumors (from different families) showing instability or lack of MSH6 expression. Among these, four potentially pathogenic MSH6 mutations were detected (del A at 2984; del TT at 3119; del AGG cod 385; and del CGT cod 1242) by direct gene sequencing. These represented 12.9% of all families with constitutional mutations of the DNA MMR genes. Thus, some 5% of all HNPCC families are featured by constitutional mutation of the MSH6 gene. This appears, however, as a minimum estimate; routine use of IHC and the study of large numbers of individuals and families with little or no evidence of Lynch syndrome might reveal that mutation of this gene account for a large fraction of HNPCC. [source]

Noncolonic cancer stem cells in bone marrow of colorectal cancer patients

COLORECTAL DISEASE, Issue 3 2010
D. F. Altomare
Abstract Objective, To investigate whether preoperative noncolonic cancer stem cells in bone marrow (BM) of R0 colorectal cancer (CRC) patients are cancer cells and impact on liver metastases (LM) rates. Method, Prospective data on continuous CRC patients were collected from five centres. Bone marrow aspirates, taken at laparotomy, were sent to a single lab. Noncolonic cancer stem cells were defined according to UICC. A quantity of 3 × 106 BM cells per patient was processed with monoclonal antibodies against cytokeratin 20. APC or p53 gene mutation and microsatellite instability (MSI) were assessed in primary tumours (PT) by single-strand conformation polymorphism. Noncolonic cancer stem cells in BM of PT mutation or MSI-positive patients were isolated with immunobeads coated with magnetically labelled anti-human epithelial antigen antibody and DNA-screened for mutations. Results, Although 199 patients were enrolled, 162 patients were available for analysis. No patients were lost to follow-up. Twenty-five (2,170) noncolonic cancer stem cells were found in BM of 40 patients. Twenty-two patients developed LM at 36-month follow-up. Adenomatous polyposis coli (APC) or p53 gene mutation or MSI were identified in the PT of 78 patients. The same gene mutations or MSI were not found in noncolonic cancer stem cells of the BM of these patients. After adjustment, there was no significant effect of confounding factors. Noncolonic cancer stem cells in BM had no impact on LM rates, cancer-specific death rates, or all death rates. Conclusions, Preoperative noncolonic cancer stem cells in BM of R0 CRC patients were not cancer cells and had no impact on LM rates. [source]

Preoperative plasma MMP-2 expression is prognostic in colorectal cancer

COLORECTAL DISEASE, Issue 8 2006
M. G. Tutton
Introduction:, The gelatinases (MMP-2 and MMP-9) are important in colorectal cancer invasion and metastasis. Plasma concentrations of the gelatinases correlate with clinical stage in colorectal cancer; however, whether this gives prognostic information is unknown. Method:, Gelatinase mRNA and protein levels in tumour and plasma were determined respectively by RT-PCR, ELISA and gelatin zymography in a prospective study of 75 colorectal cancer patients. At follow-up, 40 patients were alive with a median survival of 75 months (range 72,80). Results:, Expression of the gelatinases was significantly increased within tumour relative to normal colon and within plasma of cancer patients (P < 0.01; Mann,Whitney U -test). Within plasma, total MMP-2 and MMP-9 expression (MMP plus MMP/TIMP complexes), determined by ELISA, and free MMP-2(72 kDa) determined by gelatin zymography, increased significantly with Dukes' stage (P < 0.001; Kruskal,Wallis test). As well as correlating with Dukes' stage, lymphatic and vascular invasion, Kaplan,Meier survival analysis showed that only elevated plasma MMP-2 was significantly associated with a worse prognosis: free MMP-2 (worse prognosis with increasing quartile; P < 0.05) and total MMP-2 (upper quartile cut-off limit; P = 0.04). Discussion:, In addition to being an indicator of colorectal cancer invasion, plasma MMP-2 levels may provide a simple, non-invasive preoperative test for prognosis in colorectal cancer. [source]

Use of the internet by colorectal cancer patients

COLORECTAL DISEASE, Issue 1 2006
S. M. Powell
Abstract Objective, To identify the frequency of Internet use by colorectal cancer patients. Materials and methods, Fifty patients interviews. Results, Only four patients (8%) had used the internet to access information about colorectal cancer though 36% would have used it if a site had been recommended. Conclusion, The Internet is a resource rarely used by patients but there is potential for its use as an adjunct to written and verbal information. [source]