SEARCH · PubMed Health

Results for “Colorectal Cancer”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources

PubMed1999

Microsatellite instability: impact on cancer progression in proximal and distal colorectal cancers.

Whilst individual planning of treatment and follow-up in every colorectal cancer case is an increasing demand, prognostic markers are needed for predicting cancer progression in the primary phase. We studied the effect of replication error (RER)-positivity on colorectal cancer progression by analysing 255 colorectal cancer specimens by polymerase chain reaction (PCR) and fragment analysis and correlating the results with the clinical and histological features of the tumour and with patient outcome. RER-positivity was detected in 12% (28/235) of cases. It was associated with proximal location of the tumour (P < 0.001), poor differentiation (P = 0.001) and large tumour size (P = 0.009). The 5-year cumulative survival rate of the patients with RER-positive cancer of the proximal colon was markedly better (100%) than that of those with RER-negative proximal cancer (74%), whilst in cases of cancer of the distal colon or rectum, RER-positivity (21%) indicated poorer survival than RER-negativity (57%). Thus, it is suggested that RER-positivity has an opposite impact on cancer progression in cases of proximal and distal cancers. RER-positivity appears to indicate improved prognosis only in cases of proximally located cancer, in which it could accordingly be useful as a prognostic marker.

Adolescent↗

PubMed2006

Genetics of colorectal cancer.

Approximately 6% of colorectal cancers can be attributed to recognizable heritable germline mutations. Familial adenomatous polyposis is an autosomal dominant syndrome classically presenting with hundreds to thousands of adenomatous colorectal polyps that are caused by mutations in the APC gene. Adenomas typically develop in the midteens in these patients, and colorectal cancer is a virtual certainty if this condition is untreated. A low-penetrance susceptibility allele that is common in Jews from Eastern Europe, APC 11307K, confers a two-fold increased risk of colorectal cancer without the full expression of familial adenomatous polyposis. Biallelic mutations in the MYH gene are associated with an attenuated familial adenomatous polyposis phenotype. Lynch syndrome (hereditary nonpolyposis colorectal cancer) is an autosomal dominant disorder characterized by early onset of colorectal cancer with microsatellite instability. Mutations in mismatch repair genes lead to a lifetime colon cancer risk of 85% in these patients; carcinomas of the endometrium, ovary, and other organs also occur with increased frequency. Although adenomas are not characteristic of the hamartomatous polyp syndromes such as juvenile polyposis and Peutz-Jeghers syndrome, individuals with these diseases have a markedly increased risk of colorectal cancer relative to the general population. In this review, we will describe the phenotypes, genotypes, diagnosis, and management of hereditary colon cancer syndromes.

Alleles↗

PubMedDate not supplied

Using the Cancer Rehabilitation Questionnaire in patients with colorectal cancer.

This article describes the development and testing of the Cancer Rehabilitation Questionnaire (CRQ) in patients with colorectal cancer. A descriptive, correlational survey was conducted in a sample of patients with colon or rectal cancer who received care at an outpatient cancer clinic at a large, northeastern U.S. academic medical center. Patients were identified from the Tumor Registry (N = 327) and received a mailed questionnaire. One hundred and three patients with colorectal cancer completed the demographic questionnaire, the CRQ developed by the investigators, and the Quality of Life Index (QLI). Significant differences were found between individuals with colon cancer and individuals with rectal cancer on the total CRQ (p < .005) and the physical, future orientation, and role-relationship subscales. For the QLI, significantly lower scores were reported on the family subscale for patients with rectal cancer in comparison with those with colon cancer. More attention to rehabilitation issues and quality of life is required across the trajectory of the cancer experience. With the increasing incidence of colorectal cancer, nurses in rehabilitation practice must address the issues affecting patients with this disease as they progress from diagnosis to treatment and rehabilitation.

Adult↗

PubMed2001

Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful?

BACKGROUND: Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers worldwide. Its main application is mostly in gastrointestinal cancers, especially in colorectal malignancy. Although in use for almost 30 years, the clinical value of CEA in colorectal cancer is still not clear. METHODS: The literature relevant to the clinical value of CEA in colorectal cancer was reviewed. Particular attention was paid to studies involving metaanalyses and guidelines issued by Expert Panels. RESULTS: Although of little use in detecting early colorectal cancer, high preoperative concentrations of CEA correlate with adverse prognosis. Serial CEA measurements can detect recurrent colorectal cancer with a sensitivity of approximately 80%, a specificity of approximately 70%, and can provide a lead time of approximately 5 months. CEA is the most frequent indicator of recurrence in asymptomatic patients and currently is the most cost-effective test for the preclinical detection of resectable disease. CEA is most useful for the early detection of liver metastasis in patients with diagnosed colorectal cancer. Overall, however, little evidence is available that monitoring of all patients with diagnosed colorectal cancer leads to enhanced patient outcome or quality of life. CONCLUSIONS: Currently, the most useful application of CEA is in the detection of liver metastasis from colorectal cancers. Because of the relative success of surgery in resecting hepatic metastases, serial determinations of the marker are recommended for detecting cancer spread to the liver. In the future, preoperative concentrations of CEA may be included with the standard staging procedures for assessing prognosis.

Antineoplastic Agents↗

PubMed2005

Prognostic significance of DCC and p27Kip1 in colorectal cancer.

The progression of colorectal cancer is a multistage process associated with specific molecular alterations. The stepwise accumulation of these multiple genetic mutations progressively results in the acquisition of neoplastic cell behavior. The genetic abnormalities associated with the expression of metastatic phenotype, therefore, may be of prognostic significance in the clinical treatment of colorectal cancer patients. In this study, the immunohistochemical expression of the deleted in colorectal cancer gene (DCC) and p27Kip1 was assessed in 168 paraffin-embedded, formalin-fixed tumors of patients with stage II and III colorectal cancer. Kaplan-Meier survival curves and log-rank statistics were used to analyze survival times after curative primary tumor resection, and Cox proportional hazards models were used to adjust the assessment of demographic and clinical covariates. Loss of DCC or p27Kip1 expression had no influence on survival in patients with stage II or III colorectal cancer. The 5-year survival rates of DCC-positive and DCC-negative tumors were 51.8% and 35.7% (P=0.40), respectively. The 5-year survival rate of patients with p27Kip1-positive tumors was 47.9%, whereas the rate for patients with p27Kip1-negative tumors was 38.8% (P=0.68). After adjustment for all evaluated variables, neither DCC or p27Kip1 was found to be a predictor of survival (risk ratio for DCC, 0.98; 95% confidence interval, 0.66-1.56; P=0.92; risk ratio for p27Kip1, 0.87; 95% confidence interval, 0.58-1.29; P=0.49). The present study demonstrated that the expression of neither DCC nor p27Kip1 was predictive in poor survival outcome in patients with stage II or III colorectal cancer.

Biomarkers, Tumor↗

PubMed2005

Guanylyl cyclase C: a molecular marker for staging and postoperative surveillance of patients with colorectal cancer.

Staging patients with colorectal cancer defines their prognosis and therapeutic management. Unfortunately, histopathology, the current standard for staging, is relatively insensitive for detecting occult micrometastases and a significant fraction of patients are understaged and, consequently, undertreated. Similarly, current approaches to postoperative surveillance of patients with colorectal cancer detect disease recurrence at a point when interventions have little impact on survival. The detection of rare cells in tissue, for accurately staging patients, and in blood, for detecting disease recurrence, could be facilitated by employing sensitive and specific markers of disease. Guanylyl cyclase C (GCC), the receptor for the diarrheagenic bacterial heat-stable enterotoxin, is expressed selectively by cells derived from intestinal mucosa, including normal intestinal cells and colorectal tumor cells, but not by extragastrointestinal tissues and tumors. The nearly uniform expression of relatively high levels by metastatic colorectal tumors suggests that GCC may be a sensitive and specific molecular marker for metastatic colorectal cancer cells. Employing GCC reverse transcriptase PCR, occult colorectal cancer micrometastases were detected in lymph nodes that escaped detection by histopathology. Moreover, marker expression correlated with the risk of disease recurrence. Similarly, GCC reverse transcriptase PCR revealed the presence of tumor cells in blood of all patients examined with metastatic colorectal cancer and, in some studies, was associated with an increased risk of disease recurrence and mortality. These observations suggest that GCC reverse transcriptase PCR is a sensitive and specific technique for identifying tumor cells in extraintestinal sites and may be useful for staging and postoperative surveillance of patients with colorectal cancer.

Animals↗

PubMed2005

O(6)-methylguanine methyltransferase in colorectal cancers: detection of mutations, loss of expression, and weak association with G:C>A:T transitions.

BACKGROUND AND AIMS: O(6)-methylguanine methyltransferase (MGMT) repairs inappropriately methylated guanine in DNA. MGMT mutations have not previously been reported in cancers, but in colorectal tumours MGMT promoter methylation is common and has been associated with increased G:C>A:T transitions, a high frequency of K-ras mutations, and low level microsatellite instability (MSI low). However, some have suggested that MGMT changes are background or secondary events, with little importance for tumorigenesis. METHODS: We have analysed fresh frozen colorectal cancers and colorectal cancer cell lines for MGMT changes: mutations, allelic loss, and protein expression. RESULTS: Six of 113 cancers harboured somatic missense MGMT mutations, at least three of which probably caused reduced MGMT function and were accompanied by silencing or loss of the wild-type allele. Cancers with pathogenic MGMT mutations tended to harbour G:C>A:T somatic mutations at other loci. Overall, MGMT expression was reduced or lost in more than half of the cancers. We found no association between MGMT expression and the somatic mutation spectrum at APC, beta-catenin, K-ras, or p53, but decreased MGMT expression was weakly associated with the presence of a G:C>A:T change at any one of these loci. Reduced MGMT expression was not however associated with an increased frequency of K-ras mutations or with MSI low. CONCLUSION: In summary, we found that mutation of MGMT contributes to decreased protein function. Our findings provide good evidence to show that MGMT changes, including methylation, are selected rather than background events, at least in some cases. Decreased MGMT expression or function probably has a weak or moderate effect on the mutation spectrum in colorectal cancers.

Cell Line, Tumor↗

PubMedDate not supplied

What is hereditary nonpolyposis colorectal cancer (HNPCC).

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited disease associated with a marked increase in cancer susceptibility, especially cancer of the colorectum. It is one of the most common cancer predisposing syndromes affecting as many as one in 400 individuals in the Western World. Two (mismatch repair) genes (hMSH2 on chromosome 2p and hMLH1 on chromosome 3p) have recently been identified which appear to be involved in the development of cancer in most of the HNPCC families. Colorectal cancer in HNPCC differs from sporadic colorectal cancer by an early age of onset, a proclivity for the proximal colon, and an excess of synchronous and metachronous colorectal cancers. A variety of extracolonic tumors may be encountered in HNPCC, including cancers of the endometrium, stomach, small bowel, urinary tract (renal pelvis and ureter), biliary system and ovary. The diagnosis HNPCC is currently based upon the combined patient and family data. Future identification of HNPCC will be facilitated by the introduction of genetic markers. Identification of HNPCC families is extremely important, because periodic examination may prevent development of disease and death from cancer.

Colorectal Neoplasms, Hereditary Nonpolyposis↗

PubMed2000

Pathogenesis of colorectal cancer.

The development of colorectal cancer has been viewed as an ordered process in which three main phases can be identified: initiation, promotion and progression. There is definite proof that stable alterations of the structure or sequence of DNA (mutations) represent the initiating event; these are followed by an uncontrolled expansion of the neoplastic clones which characterizes tumoural growth. Several classes of genes have been identified foncogenes, tumour suppressor genes and "mutator" genes) the alterations of which are important in the initiation as well as in the promotion and progression of tumours. Colorectal cancer, therefore, results from a series of genetic changes which lead to the progressive and irreversible loss of normal control of cell growth and differentiation. Available evidence is consistent with the hypothesis that there are several molecular pathways underlying the passage from normal mucosa to colorectal carcinoma, thus explaining the existence of intestinal tumours with a different biological nature, which may represent specific targets for prevention and cure. Well-defined molecular pathways have been identified for: A) sporadic colorectal cancer ("Loss of heterozygosity pathway"); B) familial adenomatous polyposis and related polyposis syndromes; C) hereditary non-polyposis colorectal cancer ("mutator genes/microsatellite instability pathway"); D) cancer developing in inflammatory bowel diseases; E) familial colorectal cancer. Thus, there is consistent and considerable evidence suggesting the existence of several biological pathways leading to the same phenotypical expression (i.e., colorectal cancer), and it is likely that additional pathways will be clarified in the future. From a practical point of view, tumours with a diverse biology might offer different and more effective preventive and curative approaches.

Colorectal Neoplasms↗

PubMed2005

Effect of pre-operative short course famotidine on tumor infiltrating lymphocytes in colorectal cancer: a double blind, placebo controlled, prospective randomized study.

BACKGROUND: Pilot studies have shown that histamine H2 receptor antagonists augment the natural immunity against cancer in colorectal and gastric cancer by enhancing lymphocytic infiltration in the tumors. However, a study of adjuvant ranitidine failed to show a significant benefit in colorectal cancer, possibly because of the immunosuppression exerted by blood transfusion and post-operative infections. The pre-operative use of H2 receptor antagonists may therefore be of greater benefit. Except for a pilot study using cimetidine, there are no trials that have evaluated the effect of pre-operative H2 receptor antagonists on tumor infiltrating lymphocytes in colorectal cancer. OBJECTIVE: To evaluate the efficacy of famotidine in augmenting tumor infiltrating lymphocytes in colorectal cancer. STUDY DESIGN: Double blind, placebo controlled, prospective randomized study. METHODS: Twenty-three patients with resectable colorectal cancer were randomized to receive famotidine (n = 11) or placebo (n = 12). Famotidine was given for 1 week pre-operatively in a dose of 40 mg per day p.o. After resection, the specimens were analyzed histologically for lymphocytic infiltration by a pathologist blinded to the two groups. Lymphocytic infiltration more than 50 cells per high power field, involving more than 50% of the tumor-normal tissue interface was considered significant. RESULTS: The two groups were comparable for age, gender, pre-operative carcino embryonic antigen (CEA) levels and pathological stage. Significant lymphocytic infiltration was seen in 63.6% (7 of 11) patients in the study group compared to only 8.5% (1 of 12) patients in the placebo group (P = 0.005). Despite fewer recurrences and a longer survival in the study group, the difference was not significant. CONCLUSION: This study shows that pre-operative famotidine may significantly enhance lymphocytic infiltration in colorectal cancer and may have potential for use as an anticancer agent in colorectal cancer.

Adult↗

PubMed1990

The influence of patient age on the diagnosis and treatment of lung and colorectal cancer.

We examined the relationship between patient age and medical care received by patients diagnosed with the following two common cancers: non-small-cell lung cancer and colorectal cancer. Controlling for the influence of sex, marital status, presence of comorbid disease, and socioeconomic status, we found that age was not related to the diagnostic tests ordered for either cancer type. However, lung cancer patients with local disease who were older than age 74 years underwent definitive surgical treatment less often than did younger patients. Few patients at any age (less than 9%) with colorectal cancer did not undergo definitive surgical treatment. Patients with regional colorectal disease who were older than 74 years of age underwent radiation therapy to the abdomen less often than did younger patients. These results add to the growing body of literature suggesting that older cancer patients are less likely to undergo the same type of care received by younger patients.

Age Factors↗

PubMedDate not supplied

Qualitative comparison of dietary choices and dietary supplement use among older adults with and without a history of colorectal cancer.

OBJECTIVE: To explore colorectal cancer survivors' beliefs about diet, dietary supplements, health, and cancer in relation to beliefs of a similar group without colorectal cancer. DESIGN: In-depth, semistructured, open-ended interviews were used to examine perceptions. PARTICIPANTS: Twenty-two participants (10 colorectal cancer survivors and 12 from a comparison group) from the North Carolina Strategies for Improving Diet, Exercise, and Screening Study. ANALYSIS: Verbatim interview transcripts were coded and analyzed. Comparisons were made between colorectal cancer survivors and the comparison group. RESULTS: Three main themes emerged: the influence of significant life events on dietary change, concerns about contaminants in the food supply, and a lack of physician guidance in dietary supplement selection. CONCLUSION AND IMPLICATIONS: The experience of colorectal cancer is significant and may lead to dietary change among some survivors, but these findings do not suggest that it is necessarily more influential than other life events. Participants sought to control diet (for coping or survival) and also felt that diet cannot be controlled (due to the contamination of the food supply). Although many lacked guidance from physicians about dietary supplements, they were comfortable making their own decisions to self-treat. Enhanced understanding of the themes that guide selection of diet and dietary supplements can provide a context for dietitians in practice and researchers conducting behavioral interventions.

Aged↗

PubMed2003

Molecular pharmacology of cancer therapy in human colorectal cancer by gene expression profiling.

Global gene expression profiling has potential for elucidating the complex cellular effects and mechanisms of action of novel targeted anticancer agents or existing chemotherapeutics for which the precise molecular mechanism of action may be unclear. In this study, decreased expression of genes required for RNA and protein synthesis, and for metabolism were detected in rectal cancer biopsies taken from patients during a 5-fluorouracil infusion. Our observations demonstrate that this approach is feasible and can detect responses that may have otherwise been missed by conventional methods. The results suggested new mechanism-based combination treatments for colorectal cancer and demonstrated that expression profiling could provide valuable information on the molecular pharmacology of established and novel drugs.

Adult↗

PubMed2000

NCCN Practice Guidelines for Colorectal Cancer.

The NCCN Colorectal Cancer Guidelines panel believes that a multidisciplinary approach is necessary for the management of the patient with colorectal cancer. The panel endorses the concept that treatment of patients in a clinical trial has priority over standard or accepted therapy. The recommended surgical procedure for resectable colon cancer is an en bloc resection; laparoscopic surgery should be done only in the context of a clinical trial. For patients with stage III disease, 5-FU-based adjuvant therapy is recommended. A patient who has metastatic disease in the liver or lung should be considered for surgical resection if he or she is a candidate for surgery and if surgery can extend survival. Surgery should be followed by adjuvant chemotherapy. The panel advocates a conservative post-treatment surveillance program for colon and rectal carcinoma patients. Serial CEA determinations are appropriate if the patient is a candidate for aggressive surgical resection, should recurrence be detected. Abdominal and pelvic CT scans should be utilized only when there are clinical indications of possible recurrence. Patients whose disease progresses during 5-FU-based therapy should be treated with irinotecan or encouraged to participate in a phase I or phase II clinical trial.

Colorectal Neoplasms↗

PubMed2004

Expression of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-12 in gastric and colonic cancer cell lines and in human colorectal cancer.

OBJECTIVE: The expression of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-12 (pp-GalNAc-T12) was studied in 3 normal human tissues (stomach, small intestine and colon), 3 stomach and 6 colon cancer cell lines, as well as in the resected cancer tissues and normal tissues (control) from 19 patients with colorectal cancer. METHODS: Marathon Ready cDNAs were used as the templates of normal tissues. mRNA was extracted from the cell lines and resected tissues, and reverse-transcribed to cDNA. The expression of pp-GalNAc-T12 was determined with a real-time polymerase chain reaction (PCR). RESULTS: It was found that the expression of pp-GalNAc-T12 was strong in 3 normal tissues, weak or negligible in 9 cancer cell lines, and down-regulated in all of the colorectal cancer tissues as compared with normal control samples. Moreover, the expression of pp-GalNAc-T12 tended to inversely correlate with the TNM stage, and statistically was much lower in the samples with metastasis than in those without. However, the expression in the tissues did not correlate with the concentration of serum CA 19-9 routinely applied in the diagnosis and assessment of prognosis in patients with colonic cancers. CONCLUSION: the expression of pp-GalNAc-T12 seems to be a negative marker especially of metastatic gastric and colorectal cancer.

Adult↗

PubMed2005

Molecular pathogenesis of colorectal cancer: implications for molecular diagnosis.

Colorectal cancer is the third leading cause of cancer-related death in both men and woman in industrialized countries. Major advances have been made in our understanding of molecular events leading to formation of adenomatous polyps and cancer. Most colorectal cancers are sporadic, but a significant proportion (5-6%) has a clear genetic background. It is now widely accepted that colorectal carcinogenesis is a multistep process involving the inactivation of a variety of tumor-suppressor and DNA-repair genes and simultaneous activation of certain oncogenes. In addition, epigenetic alterations through aberrant promoter methylation and histone modification have been found to play a major role in the evolution and progression of a large proportion of sporadic colon cancers. Consequently, it is now apparent that individual colorectal cancers may evolve through diverse molecular pathways. In this article, the authors have summarized the current knowledge of molecular pathogenesis in common hereditary syndromes and sporadic forms of colorectal cancer. Novel molecular diagnostic tools for the early diagnosis and prevention of colorectal cancer that have emerged from these insights are discussed.

Colorectal Neoplasms↗

PubMed1999

[Present and future of home anti-cancer chemotherapy for unresectable recurrence of colorectal cancer].

Continuous hepatic arterial infusion chemotherapy (HAI) was performed for 100 colorectal cancer patients with unresectable liver metastases in our outpatient clinic. The administration schedule was 5-FU 250 mg/day for 7 days every other week. In this study, 93 cases were evaluable. The average dose of 5-FU was 24 g (3.0-66.5 g). The response rate was 59.1% (CR: 4 cases, PR: 51 cases, NC: 12 cases and PD: 26 cases). The prognostic outcome was significantly prolonged in the effective cases (50% survival duration was as follows: CR: 764 days, PR: 620 days, NC: 255 days and PD: 152 days). The complication rate with HAI was 15.1%, but nobody died from these complications. Hepatectomy after HAI was performed in 19 cases (20.4%) because of the effect of HAI. The three-year survival rate was 35.3% for HAI with hepatectomy and 3.8% for only HAI. There was statistically significant difference (p < 0.0001) between these two groups. Hepatectomy after HAI is a new strategy for unresectable liver metastasis of colorectal cancer. Recently, we performed home systemic chemotherapy using 5-FU for 3 recurrent patients of colorectal cancer and were able to continue this therapy safely for more than 2 months.

Aged↗

PubMed2000

Optimising methods for determining RER status in colorectal cancers.

Approximately 13% of colorectal cancers display microsatellite instability (MSI), a form of replication error repair. Colorectal cancers developing in individuals with constitutional defects in the mismatch repair (MMR) genes hMLH1, hMSH2, hPMS1 and hPMS2 consistently show evidence of this phenomenon. Since MSI is indicative of MMR deficiency, testing colorectal cancers for MSI provides a method of refining the identification of carriers of germline MMR mutations. To assess which microsatellites represent the best reporters of replication error (RER) status we have examined 116 early onset colorectal cancers for MSI. MSI was assessed using eight dinucleotide- and two mononucleotide-repeat fluorescently labelled polymerase chain reaction (PCR) markers. The two mononucleotide repeat markers (BAT25 and BAT26) were highly sensitive and typing of either represents an efficient strategy for defining RER status of colorectal cancers and obviates the requirement of typing numerous microsatellite markers.

Base Pair Mismatch↗