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PubMed2002

New strategies for colorectal cancer prevention and treatment.

Colorectal cancer (CRC) is the second most common fatal malignancy in the Western world, with more than 150,000 new cases accounting for 55,000 deaths in the United States every year. Surgical resection is an effective treatment for localized disease, achieving a 5-year survival rate of 90%; but chemotherapy and other novel treatments for metastatic disease remain ineffective. There have been significant efforts to identify risk factors associated with the development of CRC and to explore potential preventive therapies. Both genetic and epigenetic factors contribute to the development of colorectal cancer. Specific genetic changes in proto-oncogenes, tumor suppressor genes, and DNA mismatch repair genes have led to a genetic model of CRC. Cooperative genetic aberrations involving APC (adenomatous polyposis coli), beta-catenine, K-ras, and p53 are involved in the multistep adenoma-carcinoma sequence of CRC. Emerging data have implicated cyclooxygenase-2 (COX-2) and prostanoid production in the pathogenesis of colorectal carcinoma. Several reports indicate a close relation between the intake of nonsteroidal antiinflammatory drugs (NSAIDs) and a decreased risk for developing colorectal cancer. Epidemiologic studies indicate a 40% to 50% reduction in mortality due to colorectal cancer in individuals taking NSAIDs (e.g., aspirin). Epigenetic factors including age, diet, angiogenesis, and immune responses also appear to contribute to the development of CRC. Combining knowledge of the genetic and epigenetic events implicated in this disease may allow a broader understanding of the pathogenesis of CRC. These developments may yield benefits in earlier detection and in the design of better antitumor interventions.

Adenocarcinoma↗

PubMedDate not supplied

Hepatectomy for metastases from breast cancer offers the survival benefit similar to that in hepatic metastases from colorectal cancer.

BACKGROUND/AIMS: There have been no reports comparing surgical results of hepatectomy for metastases between breast cancer origin and colorectal cancer origin. The aim of the present study was to compare the both and to clarify the survival benefit brought by hepatectomy for metastases from breast cancer. METHODOLOGY: Between 1990 and 1999, 6 patients with hepatic metastases from breast cancer and 94 patients with those from colorectal cancer underwent hepatectomy with curative intent. All patients in the breast-cancer-origin group received adjuvant chemotherapy following hepatectomy, however, fewer patients (55% of the 94 patients) did in the colorectal-cancer-origin group (P = 0.034). RESULTS: Morbidity and mortality rates after hepatectomy in patients with hepatic metastases from breast cancer were 0% and 0%, respectively, and those in patients with metastases from colorectal cancer were 12% and 1%, respectively. Postoperative survival curves in the both groups were similar. Three- and five-year survival rates in the breast-cancer-origin group were 60% and 40%, respectively, and those in the colorectal-cancer-origin group were 54% and 42%, respectively. CONCLUSIONS: When appropriate adjuvant chemotherapy is performed, hepatectomy for metastases from breast cancer offers the survival benefit similar to that in hepatic metastases from colorectal cancer.

Adult↗

PubMed1998

Epirubicin has modest single-agent activity in head and neck cancer but limited activity in metastatic melanoma and colorectal cancer: phase II studies by the Eastern Cooperative Oncology Group.

Epirubicin (4'-epidoxorubicin), a diastereoisomer of doxorubicin, has established activity in the treatment of many cancer types sensitive to doxorubicin. Its activity in other tumor targets such as melanoma, head and neck cancer, and recurrent colorectal cancer has been less well defined. Three concurrent phase II studies examined the efficacy and toxicity of epirubicin (90 mg/m2 given intravenously at 3-week intervals) in the treatment of 71 patients with the aforementioned cancers. Of 66 eligible patients who were assessable for response, one patient (with colorectal cancer) achieved a complete response and three patients (with head and neck cancer) achieved partial responses. The response rate in patients with head and neck cancer was 18% (95% confidence interval, 4-43%). Myelosuppression, alopecia, and nausea were the most frequent toxicities. Two patients died of neutropenic sepsis and grade IV leukopenia occurred in six patients (8%). Grade III toxicities were as follows: leukopenia (17%), anemia (10%), alopecia (8%), fever (1%), thrombocytopenia (1%). Grade I or II cardiac toxicity was noted in four patients at cumulative doses ranging between 375 mg/m2 to 1,283 mg/m2. Epirubicin is ineffective as a single agent at this dose and schedule in the treatment of patients with melanoma and colorectal cancer. In head and neck cancer, a modest response rate encourages further exploration of epirubicin and related anthracyclines in combination regimens.

Adult↗

PubMedDate not supplied

An overview of adjuvant therapy for colorectal cancer.

Adjuvant therapy of colorectal cancer is one of the most active areas of clinical oncology research. Although the data for the benefits from early trials of adjuvant therapy were inconclusive, these trials suffered from inadequate sample sizes, poor staging, potentially suboptimal treatment regimens and ill-defined prognostic subgroups. More recently, larger trials of higher scientific quality have demonstrated that regimens of fluorouracil plus levamisole in stage III colon cancer and fluorouracil with postoperative radiation in stages II and III rectal cancer can reduce mortality. Such regimens have now become standard practice in settings in which treatment is believed to be both efficacious and tolerable, and when the overall impact of therapy is considered to be clinically relevant. More recent advances in adjuvant treatment of colorectal cancer further support the role of fluorouracil-based regimens. Peri-operative portal vein infusions of fluorouracil demonstrate improved relapse-free and overall survival, and infusional fluorouracil administered with radiation for rectal primaries appears superior to less intensive bolus fluorouracil regimens. Completed trials of fluorouracil plus leucovorin combinations are awaiting maturation, with expectations for superior adjuvant activity based on demonstrated improved response rates for biochemically modulated fluorouracil in advanced metastatic colorectal cancer. New systemic agents are also entering large-scale adjuvant trials, including monoclonal antibody 17-1a, given alone and in conjunction with standard fluorouracil regimens. Additional cytotoxic drugs, including CPT-11 and Tomudex, offer new opportunities for alternative adjuvant regimens for the large, heterogeneous population of patients with resected colorectal cancer.

Antimetabolites, Antineoplastic↗

PubMed2005

Unfavourable expression of pharmacologic markers in mucinous colorectal cancer.

Patients with mucinous colorectal cancer generally have worse prognoses than those with the nonmucinous variety. The reason for this disparity is unclear, but may result from a differential response to adjuvant chemotherapy. We examined known molecular markers for response to common chemotherapy in these two histological subtypes. In all, 21 patients with mucinous and 30 with nonmucinous Dukes C colorectal cancer were reviewed for demographic data and outcome. Total RNA from the tumours and adjacent normal mucosa was isolated and reverse transcribed. Quantitative expression levels of drug pathway genes were determined using TaqMan RT-PCR (5-fluorouracil (5-FU): TYMS, DPYD, ECGF1; oxaliplatin: GSTP1 (glutathione S-transferase pi), ERCC1 and 2; irinotecan: ABCB1, ABCG2, CYP3A4, UGT1A1, CES2, TOP1). Mucinous tumours significantly overexpressed both TYMS and GSTP1 relative to nonmucinous tumours and patient-matched normal mucosa. No significant differences in expression of the remaining markers were found. Mean follow-up was 20 months; 17 patients had recurrent disease. Among patients receiving 5-FU, those with mucinous tumours experienced shorter disease-free survival (DFS) than those with nonmucinous tumours (median DFS 13.8 vs 46.5 months, P=0.053). Mucinous colorectal cancer overexpresses markers of resistance to 5-FU and oxaliplatin. Likewise, DFS may be decreased in patients with mucinous tumours who receive 5-FU. The presence of mucin should be carefully evaluated in developmental trials of new agents for treating colorectal cancer.

Adenocarcinoma, Mucinous↗

PubMed2000

[Significance of cancer cell growth and apoptosis in morphogenesis of colorectal cancer].

The present study was carried out to elucidate the relationship between cancer cell growth and apoptosis in morphogenesis of colorectal cancer, and the role of p53 expression, one of apoptosis-related genes, in apoptosis. Specimens from 82 cases of colorectal cancer, all surgically resected, were divided into intramucosal polypoid growth (PG) and nonpolypoid growth (NPG) types according to Shimoda's classification. Expressions of proliferating cell nuclear antigen (PCNA) and p53 protein were assessed by immunohistochemical staining, and apoptosis by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. Immunohistological detection of p53 protein was performed by the use of Pab1801. In the assessment of PCNA and apoptosis the numbers of positive cells per 1000 tumor cells were expressed as PCNA labeling index (L.I.) and apoptosis labeling index (Apo L.I.), respectively. In tumor invading muscularis propria (mp), the cancer tumor tissue was equally divided into three by the depth, top, middle, and bottom, and the number of apoptosis-positive cells per 500 tumor cells was calculated per each depth of invasion and compared between PG and NPG types. PCNA L.I. was 658.5 +/- 127.1 (mean +/- SD) in PG type. When determined according to depth of invasion, PCNA L.I. was 533.8 +/- 188.2 for tumor invading submucosa (sm), 741.8 +/- 62.2 for mp, and 679.2 +/- 94.3 for tumor invading subserosa or penetrating the serosa (ss-a). The corresponding values in the NPG type were 651.9 +/- 176.2, 482.2 +/- 227.1, 766.2 +/- 90.7, and 690.9 +/- 84.3, respectively. There was no significant difference in the relationship of PCNA L.I. with the depth of invasion in both growth types. Apo L.I. was 19.9 +/- 9.8 in PG type. When determined according to depth of invasion, Apo L.I. was 29.2 +/- 9.7 for sm, 21.7 +/- 9.0 for mp, and 15.4 +/- 7.0 for ss-a. The corresponding values in the NPG type were 52.8 +/- 25.1, 67.5 +/- 25.6, 37.2 +/- 9.4, and 52.6 +/- 26.3, respectively. Apo L.I. of NPG type was significantly higher than that of PG type in each depth of invasion (p < 0.01). In mp tumor the numbers of apoptosis-positive cells in the top, middle, and bottom of the PG type were 8.0 +/- 4.8, 11.8 +/- 3.9, and 12.9 +/- 5.9, and the corresponding values of the NPG type were 26.6 +/- 7.6, 17.3 +/- 5.3, and 11.8 +/- 4.3, respectively. The number of apoptosis in the top and middle of the lesion of NPG tumors was significantly higher than that of PG tumors. There was no difference in the number of apoptosis in the bottom of the lesion between the NPG and the PG types. There was no significant difference in the Apo L.I. between p53 positive cancers and negative cancers. These results indicate that colorectal cancers show a pattern of PG if apoptosis is low, and a pattern of NPG if apoptosis is high, and that apoptosis of colorectal cancer cell is not regulated by p53.

Apoptosis↗

PubMed2004

Immunohistochemistry and microsatellite instability testing for selecting MLH1, MSH2 and MSH6 mutation carriers in hereditary non-polyposis colorectal cancer.

Hereditary non-polyposis colorectal cancer (HNPCC) represents 1-3% of all colorectal cancers. HNPCC is caused by a constitutional defect in a mismatch repair (MMR) gene, most commonly affecting the genes MLH1, MSH2 and MSH6. The MMR defect results in an increased cancer risk, with the greatest lifetime risk for colorectal cancer and other cancers associated to HNPCC. The HNPCC-associated tumor phenotype is generally characterized by microsatellite instability (MSI) and immunohistochemical loss of expression of the affected MMR protein. The aim of this study was to determine the sensitivity of IHC for MLH1, MSH2 and MSH6, and MSI analysis in tumors from known MMR gene mutation carriers. Fifty-eight paired normal and tumor samples from HNPCC families enrolled in our high-risk colorectal cancer registry were studied for the presence of germline mutations in MLH1, MSH2 and MSH6 by DGGE and direct sequencing. MSI analysis and immunostaining for MLH1, MSH2 and MSH6 were evaluated. Of the 28 patients with a real pathogenic mutation, loss of immunohistochemical expression for at least 1 of these MMR proteins was found, and all except 1 have MSI-H. Sensitivity by MSI analysis was 96%. IHC analysis had a sensitivity of 100% in detecting MMR deficiency in carriers of a pathogenic MMR mutation, and can be used to predict which gene is expected to harbor the mutation for MLH1, MSH2 and MSH6. This study suggests that both analyses are useful for selecting high-risk patients because most MLH1, MSH2 and MSH6 gene carriers will be detected by this 2-step approach. This practical method should have immediate application in the clinical work of patients with inherited colorectal cancer syndromes.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Overexpression of keratinocyte growth factor in cancer cells and enterochromaffin cells in human colorectal cancer.

Keratinocyte growth factor (KGF) is a mitogenic polypeptide that is mainly synthesized by mesenchymal cells. Its actions are dependent on its binding to a specific cell-surface KGF receptor (KGFR), which is localized in epithelial cells. In the present study, the expression level of KGF and KGFR messenger RNA (mRNA), and the localization of these mRNA and proteins in tumor specimens obtained from 12 human colorectal cancer cases were estimated. Competitive reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the expression of KGF and KGFR mRNA in both colorectal cancer and normal colorectal tissues. In specimens from 10 of the 12 cancer cases, the KGF mRNA level was higher in the specimens obtained from the cancerous portions than in those obtained from non-cancerous tissues of the same cases. KGFR mRNA was higher in cancerous tissues in eight of 12 cases. To localize the KGF protein in normal and cancerous human colorectal tissues, immunohistochemistry was employed. In normal colorectal tissue, faint KGF immunoreactivity was present in a few fibroblasts. In contrast, strong KGF immunoreactivity was present in many of the neuroendocrine cells present in close proximity to cancer cells, and moderate immunoreactivity was recognized in the cancer cells themselves and adjacent fibroblasts. KGF-positive neuroendocrine cells also showed serotonin immunoreactivity, indicating that they were enterochromaffin cells. By in situ hybridization, both KGF and KGFR mRNA were co-overexpressed in these colorectal cancer cells, and KGF mRNA was recognized in neuroendocrine cells lying in close proximity to the cancer cells. These findings indicate the possibility that KGF acts in both a paracrine and autocrine manner to induce colorectal cancer cell growth in vivo.

Aged↗

PubMed1996

Association of rectal prolapse with colorectal cancer.

BACKGROUND: Although screening for colorectal cancer facilitates earlier detection and improves survival, cost-effective screening requires identification of patients at high risk for colorectal cancer. Rectal prolapse has not been clearly linked to colorectal carcinoma. Whether patients with rectal prolapse should be screened for colorectal cancer is therefore unclear. METHODS: We retrospectively identified 70 consecutive patients treated for rectal prolapse at a community hospital during a period of 16 years and monitored for an average of 4.4 +/- 2.7 years and 350 patients of similar age treated for chronic unrelated conditions in the same institution during a similar period. We determined their incidence of colorectal cancer and sought demographic correlates. RESULTS: The prevalence of rectosigmoid carcinoma among patients with prolapse was 5.7% during the study. Only 1.4% of the comparative group had colorectal cancer. Thus patients with rectal prolapse exhibited a 4.2-fold (95% confidence interval, 1.1 to 16.0) relative risk for colorectal cancer over the comparative group (p < 0.02). CONCLUSIONS: To the extent to which these patients represent the population of patients with rectal prolapse, routine initial screening of patients with symptomatic rectal prolapse by use of flexible sigmoidoscopy may be appropriate.

Aged↗

PubMed2006

[Chances and risks of prevention in elderly people for the three major cancers: breast-, prostate- and colorectal cancers].

The big three, breast cancer (BC), prostate cancer (PC) and colorectal carcinoma are the most frequent malignancies world wide and also typical tumors of advanced age. Therefore the question to screen and how to screen for these tumors in the elderly is the main question for reduction of the total cancer burden and mortality in all western countries. BREAST CANCER (BC): The age related risk of BC increases from 1 : 2,500 at age 30+ to > 1 : 10 at age 80. Nevertheless, most of the national BC-Screening-Programs stop at age 60 or earlier. Therefore the majority of all advanced i. e. T (4) stages of BC are found in women age > 60. Frequently it is suggested that age related comorbidity should eliminate the benefit of treatment. Recently two longitudinal studies have clearly shown that correct standard treatment is as effective in elderly as in younger individuals. Mammography (MG) has been shown to reduce mortality of BC significantly with best results for specificity and sensitivity at age 70+. PROSTATE CANCER (PC): The screening situation of PC is quite different to BC, because risk profiles are poorly defined and the benefit of radical prostatectomy is not clearly demonstrated in the early non symptomatic stages of PC. At the other side watchful waiting leads to an elevated frequency of incontinence and enuresis as well. Two studies are now under progress and may possibly change the situation; but the final results are expected 2005-2008 at the earliest. Therefore an assisted individual decision making is the only recommendation at this time. COLORECTAL CANCER (CC): Risk groups are clearly defined. Risk of the elderly (> 60) is the average risk. The incidence increases from < 50/10 (5) to more than 500 at age 75+(male) and 500 (female). When to start and when to stop screening? Experts give the advice to begin at age 50 and to end at age 80; but this is not really evidence based. There are several unanswered questions and open problems: we are not exactly informed about complication rates of colonoscopy during the screening programs. There is a lack of data according accuracy of barium enema, virtual colonoscopy and genetic stool test in comparison to colonoscopy in combination with fecal occult blood test (FOBT). And adherence to screening is not well documented among informed patients. However, effectiveness of CC-screening (FOBT alone or in combination with colonoscopy) has been documented in three high randomised trials which have shown a disease specific mortality reduction of 15-33 % over a period of 8-13 years. But it must be clear that the economic resources must be mobilised individually or by insurance: offering the testing of only FOBT for ten years to one thousand persons can save one life.

Adult↗

PubMed1996

[Recent advance in chemotherapy for advanced colorectal cancer].

Chemotherapy for advanced colorectal cancer is reviewed stressing the historical development of combination chemotherapy and the application of a new idea called biochemical modulation based upon a preclinical biochemical and molecular pharmacological rationale. While 5-fluorouracil (5-FU) is a key drug for more than three decades, many a combination chemotherapy with 5-FU and other drugs such as methyl-CCNU, vincristine, streptozocin, mitomycin C and so on has been studied extensively only to show no significant improvement compared with monotherapy with 5-FU. Recently, the mechanisms of 5-FU action have been recognized more in detail biochemically, and it enabled us to try the drug in a more optimal way. For example, bolus i.v. infusion of 5-FU can produce a response rate of around 10% to 15% at most for advanced colorectal cancer. On the other hand, a more continuous mode of i.v. infusion, typically known as protracted i.v. infusion lasting up to 6 weeks or more, can produce the response rate of up to 40%. The difference underlying the mechanisms of action in these typical two administrative methods is that the main target can be RNA-directed cytotoxicity in the bolus type infusion and it can be shifted toward DNA-directed cytotoxicity in the continuous type infusion through the inhibition of thymidylate synthase (TS) enzyme activity which is relevant to DNA de novo synthesis. More importantly, investigations using clinical materials imply that DNA-directed cytotoxicity may be more relevant in a clinical setting, showing consistent findings between bench-top experiments and the clinical outcome. Given a precise knowledge about the mechanisms of 5-FU action, we could have developed a new type combination chemotherapy called biochemical modulation which manipulates non-cytotoxic agents or cytotoxic agents in non-cytotoxic level as modulators enhancing cytotoxicity of 5-FU biochemically. Among modulators, leucovorin (LV) has been shown to have a pivotal role in this field. Although no optimal combination dose schedule of LV is well known, randomized studies have shown improved activity of 5-FU modulation by LV over 5-FU alone for advanced colorectal cancer doubled the response rate by monotherapy (20-25%) vs 10-15%). New drugs are also promising with the response rate of 25% approximately obtained with a new camptothecin derivative CPT-11, and a pure TS inhibitor, Tomudex in phase II trials. It is also necessary to explore the clinical activity of the combination of low-dose cisplatin and 5-FU, chronotherapy, new dihydropyrimidine dehydrogenase inhibitors and new TS inhibitors. We are facing a new era with a new treatment concept of biochemical modulation or an understanding of optimal administrative methods with the key drug, 5-FU. Obviously, we still seek new agents or new laboratory rationales which enable us to extend the survival of patients with advanced colorectal cancer.

Antimetabolites, Antineoplastic↗

PubMedDate not supplied

Expression of multidrug resistance gene (mdr-1) mRNA in gastric and colorectal cancers.

Fresh surgical specimens of 52 gastric cancers and 25 colorectal cancers were analyzed for the expression of multidrug resistance (mdr-1) gene mRNA with non-isotopic in situ hybridization (ISH) using a biotin-labeled oligonucleotide probe. The mdr-1 mRNA was expressed in 15.4% in cancerous portions and 1.9% in non-cancerous portions of gastric cancers (p < 0.02). In colorectal cancers, the mdr-1 mRNA was positive in 36% in cancerous portions and 28% in non-cancerous portions. In gastric cancers, the well-differentiated type showed a significantly higher positive rate than the poorly differentiated type (p < 0.01). These results suggest that the mdr-1 mRNA expression in gastric and colorectal cancers is related to the degree of cellular differentiation.

Adenocarcinoma↗

PubMed2002

[Colorectal exfoliated cell in stool and its nuclear DNA quantitative analysis for diagnosis of colorectal cancer].

BACKGROUND AND OBJECTIVES: Detection of colorectal exfoliated epithelial cells and their nuclear DNA content may provide another non-invasive way of screening and early diagnosis of colorectal cancer. This study was designed to analyze the roles of exfoliated cells in stool and its nuclear DNA content in diagnosis of colorectal cancer. METHODS: 1. One hundred and seventy nine individuals were selected, forty-six of them had pathological confirmation of colorectal carcinoma. The other 133 persons had no colonoscopic evidence of colorectal malignancy and therefore served as control. Exfoliated cells in the stool were isolated by elutriation, and the elutriation means was modified Iyengar's method. All individuals in the study had stool specimens for occult blood test(FOBT). 2. Nuclear DNA content and morphometric quantitative analysis in the exfoliated cells was performed on the 33 patients with colorectal cancer and 30 individuals served as control. The parameters selected in this study were DNA content, nuclear area, nuclear irregular index, and percent of > or = 5C cells. RESULTS: 1 Exfoliative cytology and FOBT: In 35 of 46 cases of colorectal malignancy(76.09%), cytology was positive: 5 cases demonstrated dysplastic cells, 4 cases indicated suspected carcinoma cells, 26 cases showed carcinoma cells. The positive rate of exfoliated cells had no significant relation to locations, sizes, histomorphologies, histological differentiations, Dukes stages, and lymph node metastases of the lesion(P > 0.05). Exfoliative cytology had a 98.50% (131/133) specificity for colorectal cancer in the study. The sensitivity for colorectal cancer was no significant difference between the two methods of exfoliative cytology and FOBT (76.09% vs 84.78%, P > 0.05), but the specificity for colorectal cancer, exfoliative cytology was significant higher than FOBT(98.50% vs 73.68%, P < 0.05). 2. DNA analysis of exfoliated cells nuclear, DNA content, nuclear area, nuclear irregular index and percent of > or = 5C cells in the stool were significant higher in colorectal cancer than in control group(P < 0.05). The percentage of > or = 5C cells were significantly associated with histological grade (P < 0.05). CONCLUSIONS: 1. Detection of exfoliated cells in stool plays an important role in diagnosis of colorectal cancer. Testing of FOBT and exfoliated cells sequentially hopes to be a new useful non-invasive test for screening of colorectal cancer. 2. DNA analysis of exfoliated cell in stool may provide an objective method of determining malignant grades and diagnosis of colorectal cancer.

Adult↗

PubMed2026

How advances in machine learning drive early detection and risk prediction of early-onset colorectal cancer.

Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before age 50, is rising across high- and middle-income settings whilst organised screening stays anchored to older age thresholds. Blood-based liquid biopsy, combined with machine learning, is the most plausible route to early detection in this group because it does not depend on bowel preparation, endoscopy capacity, or adherence to stool-based testing. The gap is structural: incidence climbs fastest in the population below the age at which any guideline-endorsed modality is offered. The analytical challenge is that early-stage tumour-derived signals in plasma are low in abundance and distributed across heterogeneous molecular layers: circulating tumour DNA mutations, aberrant methylation, cfDNA fragmentomics, and small non-coding RNA. Machine learning converts these into a single calibrated probability. This review examines where artificial intelligence (AI)-driven liquid biopsy genuinely adds diagnostic value in EOCRC, distinguishes components in which learned models are decorative from those in which they are mechanistically necessary, and identifies the validation deficit separating research cohorts from deployable clinical tools. It summarises the first-generation tools used clinically for early detection and post-treatment monitoring, then considers analytes from exosome-bound microRNAs to long-read whole-genome sequencing of circulating plasma DNA, which reads cytosine modification natively, resolves methylation and fragmentation on single molecules, and characterises structural events short reads cannot anchor. Any analyte can feed a learned model, but more diverse input yields better discrimination. The central argument is that approved, guideline-included blood tests were validated in populations aged 45 and above, and their performance in younger patients cannot be assumed.

cfDNA fragmentomics↗

PubMed2005

Patient priorities in colorectal cancer screening decisions.

BACKGROUND: Colorectal cancer screening guidelines in the United States recommend that decisions about screening should incorporate patient preferences, but little is known about how patients make the trade-offs inherent in choosing one of the five currently recommended screening programmes. STUDY POPULATION: Forty-eight primary care patients at average risk for colorectal cancer who completed an experimental shared decision-making intervention based on a multicriteria decision analysis. METHODS: Descriptive analysis of priorities assigned to decision criteria describing the advantages and disadvantages of the five currently recommended colorectal screening programmes in the United States. Criteria were divided into four major criteria - avoid cancer, avoid screening side-effects, avoid false positive test results and the combined importance of other considerations - and three subcriteria: the number of screening tests, test preparation and the test itself. Cluster analysis was used to identify common combinations of priorities within each set of criteria. RESULTS: Patients assigned widely variable priorities to both the criteria and subcriteria: the average range of priorities was 46 on a 100 point priority scale. Cluster analysis identified six different combinations of priorities for the major criteria and four for the subcriteria. The differences in priorities assigned to both the criteria and subcriteria in the clusters were statistically significant with P < 0.0001. CONCLUSIONS: Even within a small group of patients, preferences vary widely regarding trade-offs involved in choosing among the currently recommended colorectal cancer screening programmes in the United States. These results provide empiric support for recommendations to utilize a shared decision-making process when making colorectal cancer screening decisions and highlight the need for additional research into how average risk patients view the trade-offs inherent in choosing a colorectal cancer screening programme.

Aged↗

PubMed2002

Microsatellite instability of cancers and concomitant adenomas in synchronous multiple colorectal cancer patients.

The precise role of microsatellite instability (MSI) in the development of multiple colorectal cancers has not been elucidated. In the present study, the authors examined MSI and the clinicopathological features of both cancers and concomitant adenomas in nonfamilial multiple synchronous colorectal cancer (multiple CC) patients. Fifty adenomas and 108 cancers were obtained from the surgically resected specimens of 51 multiple CC patients. Nine microsatellite markers were used to determine MSI by polymerase chain reaction (PCR). The frequency of MSI-H adenomas in multiple CC patients was higher than that in single CC patients, while MSI-H frequency of cancers was similar to that in single CC patients. There was a tendency that, in multiple CC patients, when a patient has an MSI-H adenoma, he/she also has MSI-H cancer. The clinicopathological features of multiple CC were similar to those of single CC except the ratio of mucinous cancer and concomitant adenomas. According to this study, in some multiple CC patients, genetic instability seems to play an important role in the development of cancers as well as adenomas. We regard MSI testing for multiple CC patients is useful to distinguish "MSI-related" multiple CC from "MSI-unrelated" multiple CC, and MSI-related multiple CC should be followed up carefully as hereditary nonpolyposis colorectal cancer (HNPCC) patients.

Adenoma↗

PubMed2003

Colorectal cancer screening: scientific review.

CONTEXT: Screening for colorectal cancer clearly reduces colorectal cancer mortality, yet many eligible adults remain unscreened. Several screening tests are available, and various professional organizations have differing recommendations on which screening test to use. Clinicians are challenged to ensure that eligible patients undergo colorectal cancer screening and to guide patients in choosing what tests to receive. OBJECTIVE: To critically assess the evidence for use of the available colorectal cancer screening tests, including fecal occult blood tests, sigmoidoscopy, colonoscopy, double-contrast barium enema, and newer tests, such as virtual colonoscopy and stool-based molecular screening. DATA SOURCES: All relevant English-language articles were identified using PubMed (January 1966-August 2002), published meta-analyses, reference lists of key articles, and expert consultation. DATA EXTRACTION: Studies that evaluated colorectal cancer screening in healthy individuals and assessed clinical outcomes were included. Evidence from randomized controlled trials was considered to be of highest quality, followed by observational evidence. Diagnostic accuracy studies were evaluated when randomized controlled trials and observational studies were not available or did not provide adequate evidence. Studies were excluded if they did not evaluate colorectal screening tests and if they did not evaluate average-risk individuals. DATA SYNTHESIS: Randomized controlled trials have shown that fecal occult blood testing can reduce colorectal cancer incidence and mortality. Case-control studies have shown that sigmoidoscopy is associated with a reduction in mortality, and observational studies suggest colonoscopy is effective as well. Combining fecal occult blood testing and sigmoidoscopy may decrease mortality and can increase diagnostic yield. CONCLUSION: The recommendation that all men and women aged 50 years or older undergo screening for colorectal cancer is supported by a large body of direct and indirect evidence. At present, the available evidence does not currently support choosing one test over another.

Aged↗

PubMed2006

Systemic treatment of patients who have colorectal cancer and inflammatory bowel disease.

Colorectal cancer is the most common malignant complication in patients who have IBD. The disease is difficult to diagnose because there is an overlap in symptoms in patients who have colon cancer and those who have IBD. Much has been learned about the incidence of colorectal cancer in patients who have IBD and its correlation with disease activity, duration, and anatomic location; however, almost no data are available regarding specific therapeutic considerations during adjuvant or palliative chemotherapy for these patients with respect to their underlying disease. Patients who have IBD who develop colorectal cancer are at higher risk for developing severe diarrhea during chemotherapy that may be due to the toxic effects of cytotoxic drugs or a flare of the IBD. Continuous infusional 5-FU alone, in combination with leucovorin, or in combination with oxaliplatin (FOLFOX) seems to be tolerated best. Bolus infusions of 5-FU (Roswell Park or Mayo regimens) and combination therapy of irinotecan with 5-FU should be avoided because of severe diarrhea and the possibility of sepsis. When diarrhea develops or worsens, empiric aminosalicylates may be given. Although it is theoretically possible that anti-EGFR therapies could affect IBD activity adversely, clinical experience with cetuximab in patients who have colorectal cancer has not shown any significant gastrointestinal side effects. Therefore, it seems reasonable to use it in patients who have colorectal cancer and IBD. The administration of bevacizumab has been associated with rare episodes of intestinal perforation; it should be used with great care in patients who have IBD. More studies and an integrative, multidisciplinary approach from oncologists and gastroenterologists are needed to provide optimal care for patients who have IBD during chemotherapy for colorectal cancer

Antineoplastic Agents↗