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PubMed2007

Update on colorectal cancer imaging.

Colorectal cancer remains a leading cancer killer worldwide. The disease is both curable and preventable, and yet the importance of widespread screening is only now starting to be appreciated. This article reviews the variety of diagnostic tests, imaging procedures and endoscopic examinations available to detect colorectal cancer and polyps in their early stage and also presents details on various screening options. The critical role of the radiologist is elaborated on including accurate assessment of the tumor extent within the bowel wall and beyond and the detection of lymph node and distant metastases. Staging with CT, MR imaging, endorectal ultrasound, and positron emission tomography are of paramount importance in determining the most appropriate therapy and the risk of tumor recurrence and overall prognosis.

Adolescent↗
PubMed2004

Deleted in colorectal cancer protein expression as a possible predictor of response to adjuvant chemotherapy in colorectal cancer patients.

PURPOSE: The deleted in colorectal cancer (DCC) gene predicts a poor outcome for patients with colorectal carcinoma. This study was designed to investigate whether the expression of the DCC protein also can predict response to adjuvant chemotherapy. METHODS: The expression of DCC was evaluated immunohistochemically in 74 paraffin-embedded tumor samples from patients with Stage II (n = 41) and Stage III (n = 33) colorectal carcinomas. Follow-up time was at least 60 (median, 64) months. Follow-up was at least five years for all patients who are alive. End points of the study were recurrence of disease and death. Forty-eight patients received adjuvant therapy of 5-fluorouracil + levamisole; 28 were not treated. RESULTS: Fifty percent of tumors were deleted in colorectal cancer-positive (DCC+). Proportion of survival and disease-free survival were higher in the DCC+ patients (83 percent) than in deleted in colorectal cancer-negative (DCC-; 54 percent). In the DCC+ group, adjuvant treatment was a strong positive predictive factor for survival and disease-free survival. All DCC+ patients who received adjuvant chemotherapy (CHEMO+) are alive with no evidence of disease, whereas without chemotherapy (CHEMO-) only 54 percent are alive ( P = 0.0001). When stratification was performed by stage, patients in Stage II who were DCC+/CHEMO+ had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO- survival rate was 75 percent and disease-free survival rate 62 percent ( P = 0.042). Patients in Stage III who were DCC+/ CHEMO+ had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO- both dropped to zero ( P = 0.0002). On the other hand, in the DCC- tumors, there was no statistical significant relationship between chemotherapy and survival or disease-free survival (DCC-/CHEMO- had 57 percent survival; DCC-/CHEMO+ had 52 percent survival). CONCLUSIONS: DCC is a prognostic factor for colorectal cancer. Positive expression of DCC identifies a subgroup of patients who respond favorably to adjuvant chemotherapy, which resulted in our cases, in 100 percent survival and disease-free survival rates. Without treatment, the survival rate of DCC+ patients dropped significantly. We suggest that DCC immunostaining should be performed routinely. All DCC+ patients should receive adjuvant chemotherapy. For DCC- tumors, a larger cohort of patients should be studied before definitive conclusions can be drawn; however, clinical trials of new drug combinations should focus on DCC- patients.

Adjuvants, Immunologic↗
PubMedDate not supplied

Detection and clinical relevance of tumor cells in blood and bone marrow of patients with colorectal cancer.

In colorectal cancer, the predictive value of the currently used staging method is limited. Therefore, many parameters have been studied to improve the prediction of final clinical outcome, including several aspects of the primary tumor that are associated with its aggressiveness and the capacity of the host response. A more direct approach to predict the metastatic potential of a tumor may be the determination of limited disseminated disease at an early stage before it becomes clinically evident. Very sensitive techniques have been developed to detect single or very few tumor cells that have been disseminated into lymph nodes, blood, bone marrow and the peritoneal cavity. This review describes the advantages and disadvantages of the main detection techniques and discusses the current state of clinical relevance of disseminated tumor cells in patients with colorectal cancer.

Bone Marrow↗
PubMed2001

Integrating the oral fluoropyrimidines into the management of advanced colorectal cancer.

In colorectal cancer, leucovorin-modulated 5-fluorouracil (5-FU) has been the mainstay of both adjuvant treatment and treatment of metastatic disease for many years. In advanced disease, response rates of 10-43% are reported; efforts to improve efficacy through schedule modification, including prolonged infusions, have led to limited success. New agents with improved efficacy, tolerability and ease of administration are required. Among the newer drugs, irinotecan and oxaliplatin are becoming established as first- and second-line treatment for advanced disease. Their novel mechanisms of action have proven to be of value in 5-FU-resistant patients. In tandem with these developments, thymidylate synthase inhibition has remained an important objective and oral fluoropyrimidines such as capecitabine and UFT (uracil plus tegafur)/leucovorin have been developed with this goal in mind. Two large, phase III studies of capecitabine in metastatic disease demonstrated objective response rates of 26.6 and 24.8%. UFT/leucovorin has also been evaluated in phase III trials, with an 11.7% response rate reported. Both agents are being evaluated in combination with oxaliplatin and irinotecan, and ultimately oral fluoropyrimidines as monotherapy or combination therapy may replace intravenous (i.v.) 5-FU as first-line treatment for metastatic colorectal cancer.

Administration, Oral↗
PubMed2004

First-line treatment strategies to improve survival in patients with advanced colorectal cancer.

Advanced colorectal cancer is a significant cause of worldwide cancer-related mortality. For the majority of patients, palliative chemotherapy can yield substantial improvements in survival. Fluorouracil has been the mainstay of treatment in this setting for the past few decades. The relatively recent availability of new combinations with active agents such as irinotecan and oxaliplatin makes this a promising and hopeful time for the treatment of metastatic colorectal cancer, with median survivals now approaching 18-21 months. For patients presenting with resectable metastases, the goal of therapy is surgery with a curative intent. There exists the potential for this approach to be extended also to a greater proportion of patients whose cancer may be rendered resectable following effective neoadjuvant chemotherapy. In addition, an improved understanding of molecular predictors for treatment response and toxicity may facilitate the future selection of individualised treatments for a given tumour profile. Further improvements in the management of advanced disease will continue to be pursued through the ongoing development of multimodality approaches and the incorporation of novel targeted agents with innovative chemotherapy combinations.

Antineoplastic Agents↗
PubMed2002

Epidermal growth factor receptor-targeted therapy in colorectal cancer.

Advanced colorectal carcinoma is a major cause of morbidity and mortality in the United States and other developed countries. Thus, new therapeutic strategies are urgently needed. The expression of various growth factors, growth inhibitors, and their receptors contributes to the development of colorectal cancer as well as to the proliferation and survival of malignant cells. Approximately 65% to 70% of human colon carcinomas have been shown to express the epidermal growth factor receptor (EGFR). Several investigators have reported that EGFR expression correlates with more aggressive disease and a poorer prognosis. Epidermal growth factor receptor plays a crucial role in initiating signal transduction; thus, strategies directed towards interruption of this signaling pathway have been shown to impair tumor cell proliferation. These include anti-EGFR monoclonal antibodies, immunotoxin conjugates, and EGFR tyrosine kinase inhibitors. Preclinical and clinical trials using these new therapeutic modalities appear promising in the treatment of colorectal cancer and are reviewed in this article.

Animals↗
PubMed2001

Proliferation, apoptosis, and survival in high-level microsatellite instability sporadic colorectal cancer.

Sporadic colorectal cancer (CRC) characterized by high-level DNA microsatellite instability (MSI-H) has a favorable prognosis. The reason for this MSI-H survival advantage is not known. The aim of this study was to correlate proliferation, apoptosis, and prognosis in CRC stratified by MSI status. The proliferative index (PI) was measured by immunohistochemical staining with the Ki-67 antibody in a selected series of 100 sporadic colorectal cancers classified according to the level of MSI as 31 MSI-H, 29 MSI-Low (MSI-L), and 40 microsatellite stable (MSS). The Ki-67 index was significantly higher in MSI-H cancers (P < 0.0001) in which the PI was 90.1 +/- 1.2% (mean +/- SE) compared with 69.5 +/- 3.1% and 69.5 +/- 2.3% in MSI-L and MSS subgroups, respectively. There was a positive linear correlation between the apoptotic index (AI) and PI (r = 0.51; P < 0.001), with MSI-H cancers demonstrating an increased AI:PI ratio indicative of a lower index of cell production. A high PI showed a trend toward predicting improved survival within MSI-H cancers (P = 0.09) but did not predict survival in MSI-L or MSS cancers. The AI was not associated with survival in any MSI subgroup. In conclusion, this is the first study to show that sporadic MSI-H cancers are characterized by a higher AI:PI ratio and increased proliferative activity compared with MSI-L and MSS cancers, and that an elevated PI may confer a survival advantage within the MSI-H subset.

Aged↗
PubMed2005

Beyond 5-fluorouracil: new horizons in systemic therapy for advanced colorectal cancer.

Worldwide, colorectal cancer is a common cancer and a major cause of morbidity and mortality. Patients frequently present with, or later develop, metastatic disease. Median survival with supportive care alone is approximately 6 - 8 months. However, a number of recent developments have greatly increased the range of therapeutic options, improving median survival to > 20 months. Cytotoxic agents such as capecitabine, irinotecan and oxaliplatin are now established treatment strategies. In parallel, an improved understanding of tumour biology has led to the development of non-cytotoxic targeted therapies. Examples include bevacizumab (targeting tumour angiogenesis) and cetuximab (targeting the epidermal growth factor receptor). These agents have recently been incorporated into standard management. This paper reviews these and other advances in the care of patients with advanced colorectal cancer and discusses a number of agents that are currently under development.

Animals↗
PubMed2001

Chemotherapy in elderly patients with colorectal cancer.

BACKGROUND: Colorectal cancer is usually diagnosed in patients around 70 years of age. With a continuous increase in life expectancy we may expect a higher number of elderly patients in the future. Because patients above 70 or 75 years are often excluded there is uncertainty as to what extent systemic adjuvant and palliative treatment should be offered to elderly patients. METHODS: We reviewed the available literature on adjuvant and metastatic colorectal cancer in order to identify reports on elderly patients treated within chemotherapy trials. RESULTS: Only about 20% of patients entering clinical trials belong to the age group of over 70 years and represent the minority of the very fit patients. Compared to their younger counterparts 5-FU-based treatment appears to be equally effective and more toxic according to some reports. Data regarding raltitrexed, oral fluoropyrimidines, topoisomerase I inhibitors or DACH-platin derivates are limited but suggest no age-specific differences in activity or toxicity. CONCLUSIONS: Elderly patients should not be excluded from clinical trials and studies in unfit elderly patients are warranted. Elderly patients need more attention regarding their functional, social and mental status. Fit elderly patients should be offered adjuvant or palliative chemotherapy.

Aged↗
PubMed1999

beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer.

Most colorectal cancers have loss of function mutations in the adenomatosis polyposis coli (APC) tumor suppressor gene. This leads to accumulation of beta-catenin, which together with the DNA binding protein TCF-4 functions as a transcriptional activator. Recently defined target genes are c-myc and cyclin D1, linking the APC gene defect to the capacity for autonomous proliferation of colon tumors. Here we report the identification of the matrix metalloproteinase MMP-7 as another target gene of beta-catenin/TCF-4. MMP-7 is overexpressed in 80% of human colorectal cancers and known to be an important factor for early tumor growth, with a potential function also for later progression steps, like invasion and metastasis. Our results explain the high percentage of MMP-7 overexpression in colon tumors. Moreover they indicate that defects in the APC tumor suppressor gene may also have an influence on later steps of colon tumor progression.

Biomarkers, Tumor↗
PubMed1997

Comparison between endoscopic and surgical sampling for the measurement of potential doubling time in colorectal cancer.

In colorectal cancer, tumoral kinetic parameters could influence the therapeutic strategy. The aim of this study was to test the validity of a preoperative assessment of tumoral kinetics on biopsies obtained from endoscopic sampling. After infusion of 250 mg of bromodeoxyuridine (BrdUrd), tumor samples were taken. The following kinetic parameters were evaluated by Begg's method: labeling index (LI) of BrdUrd, duration of the S phase (Ts), and potential doubling time (Tpot). We compared the findings in preoperative endoscopic samples (t1), endoscopic samples (t2), and macrobiopsies of the tumor after surgical resection (t3) to test the effect of time, surgical procedures, and sampling mode on results. Eight diploid and 11 aneuploid colorectal cancers were studied. In diploid tumors, no difference in Tpot, Ts, or LI values was found among the three time intervals. In aneuploid tumors, Tpot value at t1 was lower than t3: 2.9 +/- 1.2 versus 4.5 +/- 1.4 days (P = 0.02). This difference seemed to be independent of sampling type but related instead to the time interval between BrdUrd infusion and biopsy and to the changes due to the surgical condition. On the other hand, LI seemed to be the most stable kinetic parameter. With a cutoff value of 4 days for Tpot and of 10% for LI to differentiate slow and fast growing tumors, the positive predictive values of LI were 90% at t1, 80% at t2, and 50% at t3 in aneuploid tumors.

Aneuploidy↗
PubMed1994

[p21ras expression, DNA ploidy and prognosis in colorectal cancer].

83 colorectal cancer patients who underwent radical surgery were studied. Serial sections were carried out for detection of p21ras expression level by means of immunohistochemical assay combined with image analysis technique, measurement of DNA ploidy by flow cytometry and re-confirmation of diagnosis. We found that the high level of p21ras expression indicated a group of tumors with more aggressive behavior and worse prognosis. The five-year survival rate was only 26.83% in patients with p21D > or = 0.24 tumor, compared with 78.57% in those with p21D < 0.24 tumor. Five-year survivors tended to display diploid and had lower p21D. Detection of p21ras expression level (p21D) and DNA index in tumors may be helpful in predicting the outcome of colorectal cancer patients.

Adult↗
PubMed1992

[Intra-arterial chemotherapy of local recurrence and non-curative case of colorectal cancer].

Twelve colorectal cancer patients, including 9 with local recurrent cancer and 3 with remnant cancer after surgery, were treated with intraarterial chemotherapy. Three cases were treated with MMC injection alone, 1 case with MMC combined with irradiation (MMC-R) and 8 cases with ADM combined with irradiation (ADM-R). In 7 evaluable patients, the response rate was 28.6% with 1 CR case, 1 PR case and 5 NC cases. The 2 cases treated with ADM-R were successful. Six of 8 patients treated with ADM-R survived more than 1 year, while all 4 patients treated with MMC or MMC-R died within 8 months. The cumulative survival rate after ADM-R treatment was 44% at 24 months. It is suggested that the combination of intra-arterial chemotherapy and radiation therapy is an effective treatment for local recurrence and non-curative cases of colorectal cancer.

Chemotherapy, Adjuvant↗
PubMed1994

Are women with breast cancer more likely to develop colorectal cancer? Critical review and meta-analysis.

Breast cancer has been reported to confer greater risk for colorectal cancer. In order to estimate the magnitude of this risk, we critically reviewed all studies evaluating the association of breast and colorectal cancer and performed a meta-analysis. The combined results from seven cohort studies demonstrated a weak association between breast cancer and the subsequent risk of colorectal cancer [pooled relative risk (RR) = 1.15; 95% confidence interval (CI) = 0.99-1.31]. Pooled results from five cohort studies showed that the risk of breast cancer after colorectal cancer was similar (pooled RR = 1.10; 95% CI = 1.03-1.17). The combined results from five cross-sectional/case-control studies revealed a positive association between breast cancer and colorectal adenomas (pooled RR = 1.74; 95% CI = 1.27-2.21). Population-based cohort studies, the strongest research design, show essentially no increase in risk of colorectal cancer in women with previous breast cancer. Based upon this evaluation, there appears little justification for special colorectal surveillance of women with previous breast cancer.

Adenoma↗
PubMed2002

Adjuvant treatment of colorectal cancer (current expert opinion derived from the Third International Conference: Perspectives in Colorectal Cancer, Dublin, 2001).

This article summarises the progress that has been made in the adjuvant treatment of colorectal cancer over the last decade. In view of the consequent improvements in recurrence rates and in overall survival, the development of effective adjuvant treatments for colorectal cancer is considered as one of the most important to be made in clinical oncology over the last decade. Treatment recommendations based on evidence-based data and on expert opinions are summarised in this manuscript. However, a consensus cannot be reached on all aspects of treatment because of data that is currently emerging that will influence clinical practice and because of the many ongoing clinical trials. Those involved in the treatment of colorectal cancer should therefore be encouraged to continue to provide optimal patient care and to participate in well designed clinical trials in order to increase the evidence upon which they can base their clinical judgements and in order to make further progress.

Antineoplastic Agents↗
PubMed2000

Lack of communication about familial colorectal cancer risk associated with colorectal adenomas (United States).

BACKGROUND: Sufficient evidence has accumulated to suggest that the first-degree relatives of patients diagnosed with colorectal adenomas before the age of 60 are at increased risk of colorectal cancer. The principal objective of this study was to assess the extent to which channels of communication exist between physicians, patients and their at-risk first-degree relatives regarding both familial risk and screening recommendations. METHODS: A telephone survey was conducted among 79 patients (age < or = 60 years) with newly diagnosed colorectal adenomas. Information regarding patient demographics, awareness of familial risk, physician recommendations, and extent of communication with family members about their risk status and need for screening was ascertained. RESULTS: Forty-four (56%) of the 79 eligible subjects completed the survey. Only 18 (41%) responders were aware that their first-degree relatives were at increased risk of colorectal cancer, and the majority claimed to have gained their awareness through sources other than their physicians. Only five (28%) of the 18 knowledgeable patients notified their at-risk relatives of their status, and only two (11%) communicated the need for screening. CONCLUSIONS: This survey demonstrates poor communication about familial colorectal cancer risk associated with colorectal adenomas, and highlights the need for novel strategies to both promote awareness and facilitate screening of at-risk relatives.

Adenoma↗
PubMed2005

Predictive testing for hereditary nonpolyposis colorectal cancer: subjective perception regarding colorectal and endometrial cancer, distress, and health-related behavior at one year post-test.

This study evaluated illness representations, distress, and health-related behavior one year after disclosure of a predictive genetic test result for hereditary nonpolyposis colorectal cancer (HNPCC) in 36 carriers and 36 noncarriers. Post-test, no significant differences between carriers and noncarriers were found in perceived risk and perceived seriousness of colorectal and endometrial cancer or in perceived control over endometrial cancer. Confidence in the controllability of colorectal cancer by means of medical examinations was higher for carriers than noncarriers post-test. Mean levels of distress (cancer-specific distress, state anxiety, psychoneuroticism) were within normal ranges and none of the participants had an overall pattern (on all scales) of clinically elevated levels of distress. Carriers had significantly higher cancer-related distress one year posttest than noncarriers. In both groups, colorectal cancer-related distress decreased. Noncarriers additionally showed decreased endometrial cancer-related distress and state anxiety. Within the year after testing, none of the noncarriers had a colonoscopy and all carriers where adherent to the recommendations regarding colorectal cancer screening. Although interview data delineated individually different problems specifically related to predictive testing (e.g., worry, difficulties in relation to other relatives, burden of regular follow-up), generally, predictive testing for HNPCC does not seem to induce major psychological problems. Moreover, the presented data are promising regarding the impact on health-related behavior.

Adolescent↗