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PubMed1991

Metachronous colorectal cancer in young patients: expression of the hereditary nonpolyposis colorectal cancer syndrome?

The cumulative incidence rate of metachronous colorectal cancer in patients younger than 40 years of age at diagnosis of the primary cancer has been shown to be 30 percent. Metachronous colorectal cancer is predominantly located in the right colon with a decreasing frequency toward the rectum. The risk of developing a metachronous colorectal cancer was found to be 16-29 times increased when compared with the risk of having a primary colorectal cancer. Because of the resemblance between characteristics of metachronous colorectal cancer and the features of hereditary nonpolyposis colorectal cancer (HNPCC), it is proposed that young colorectal cancer patients developing metachronous colorectal cancer could in fact be HNPCC patients.

Adolescent↗
PubMed2001

Racial and ethnic colorectal cancer patterns affect the cost-effectiveness of colorectal cancer screening in the United States.

BACKGROUND & AIMS: Colorectal cancer screening beginning at age 50 is recommended for all Americans considered at "average" risk for the development of colorectal cancer. METHODS: We used 1988-1995 California Cancer Registry data to compare the cost-effectiveness of two 35-year colorectal cancer screening interventions among Asians, blacks, Latinos, and Whites. RESULTS: Average annual age-specific colorectal cancer incidence rates were highest in blacks and lowest in Latinos. Screening beginning at age 50 was most cost-effective in blacks and least cost-effective in Latinos (measured as dollars spent per year of life saved), using annual fecal occult blood testing (FOBT) combined with flexible sigmoidoscopy every 5 years and using colonoscopy every 10 years. A 35-year screening program beginning in blacks at age 42, whites at age 44, or Asians at age 46 was more cost-effective than screening Latinos beginning at age 50. CONCLUSIONS: Colorectal cancer screening programs beginning at age 50, using either FOBT and flexible sigmoidoscopy or colonoscopy in each racial or ethnic group, are within the $40,000-$60,000 per year of life saved upper cost limit considered acceptable for preventive strategies. Screening is most cost-effective in blacks because of high age-specific colorectal cancer incidence rates.

Adult↗
PubMed2001

Colorectal cancer screening.

Colorectal cancer causes significant morbidity and mortality in the United States. The incidence of colorectal cancer increases at age 50, approximately. Risk factors that have been identified include a personal history of colorectal cancer or adenomas, a family history of colon cancer or adenomas, inherited colorectal cancer syndromes, and long standing inflammatory bowel disease. Several screening tests have been developed for colorectal cancer prevention. Surveillance strategy is based on an individual's colorectal cancer risk. This article reviews fecal occult blood testing, flexible sigmoidoscopy, colonoscopy, barium enema, and genetic testing.

Barium Sulfate↗
PubMed2003

Early-age-at-onset colorectal cancer and microsatellite instability as markers of hereditary nonpolyposis colorectal cancer.

PURPOSE: Early-age-at-onset colorectal cancer and microsatellite instability are characteristic features of hereditary nonpolyposis colorectal cancer. Our aim was therefore to investigate whether these features might be useful markers in screening for hereditary nonpolyposis colorectal cancer and mismatch repair gene mutations. METHODS: From 1,132 consecutive patients who underwent surgery for colorectal cancer at our department between 1980 and 1999, we selected all patients 40 years of age or younger (study group, n = 59) and a subset of patients 40 years of age or older (control group, n = 60) who were matched for gender and pathologic TNM stage. Patients for whom a complete family cancer history or microsatellite status was unavailable were excluded from the study. Family cancer histories, retrieved from archival charts, were reassessed. Microsatellite status was investigated with the five microsatellites from the Bethesda recommended panel (BAT-26, BAT-25, D2S123, D5S346, and D17S250). On the basis of the number of altered microsatellites (> or = 2, 1, or 0), tumors were considered as having high or low instability or microsatellite stability, respectively. Mutation analysis for MLH1 and MSH2 genes was performed only in cases of high instability. DNA was investigated for mutations by single-strand conformational polymorphism and sequencing analysis. RESULTS: Data from 95 patients (study group: n = 37, 18 males, mean age 35 years; control group: n = 58, 29 males, mean age 62 years) were available for analysis. Four patients (study group, n = 3; control group, n = 1) fulfilled the Amsterdam II criteria for hereditary nonpolyposis colorectal cancer. Of the 37 study group tumors, 12 (32.4 percent) showed high-frequency microsatellite instability, and 25 had microsatellite stability, whereas among the 58 control group tumors, 4 (7 percent) showed high-frequency microsatellite instability, and 54 had microsatellite stability (P < 0.002). Mismatch repair gene mutation analysis was performed in 12 cases (study group, n = 7; control group, n = 5). We found four mutations (MSH2 119delG, MLH1 ex9 684insT, MSH2 Gln239Stop, and MLH1 del0.8 Kb) in the study group patients and none in the control group. Of four hereditary nonpolyposis colorectal cancer patients who underwent mismatch repair gene mutation analysis, one had a mutation. CONCLUSIONS: Early-age-at-onset colorectal cancer is significantly correlated with high-frequency microsatellite instability tumor status and is a useful criterion to identify hereditary nonpolyposis colorectal cancer patients. Moreover, when used in association with high-frequency microsatellite instability status, it is effective in selecting patients for mismatch repair gene mutation analysis.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Surveillance improves survival of colorectal cancer in patients with hereditary nonpolyposis colorectal cancer.

Some patients with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome develop carcinoma despite surveillance. The aim of this study was to determine whether survival was greater in colorectal cancer (CRC) cases detected by surveillance than in patients who had disease diagnosed on the basis of symptoms. All 150 CRC cases detected in 57 HNPCC families over the last 15 years were divided into two groups depending on whether they had been included in the surveillance program (n = 35) or not (n = 115). The stage distribution of the tumors in the group that underwent surveillance (Dukes' A, 50%; B, 35%; C, 15%; D, 0%) was significantly more favorable (P < .001) than in the group without surveillance (Dukes' A, 17%; B, 50%; C, 16%; D, 17%). CRC-specific 10-year survival was 93% in the surveillance group, significantly better than the 68% in the nonsurveillance group (P < .02). The overall survival did not differ significantly between the two groups despite a tendency in favor of the surveillance group. Colonoscopic surveillance enables early detection of CRC in HNPCC and reduces CRC mortality.

Adult↗
PubMed2006

A cost-effective algorithm for hereditary nonpolyposis colorectal cancer detection.

Colorectal cancer with microsatellite instability (MSI) may occur sporadically or be inherited in cases of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. However, there is no consensus as to which patients must be tested and how to test MSI. In this study, MSI was tested by immunohistochemical analysis and by polymerase chain reaction in 148 cases of colorectal cancer, and methylation of the hMLH1 promoter was examined. MSI status was correlated with tumor phenotype. We found that localization, tumor infiltrating lymphocytes, and mucinous differentiation were predictive of high-frequency MSI (MSI-H) colorectal cancer and might be used to select cases for MSI analysis. Immunohistochemical analysis detected most MSI-H colorectal cancer and might constitute the first step in MSI detection. Absence of hMLH1 promoter methylation in MSI-H colorectal cancer could be predictive of hereditary colorectal cancer, and, hence, methylation analysis might constitute the second step in the identification of patients with HNPCC.

Adaptor Proteins, Signal Transducing↗
PubMed2006

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

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.

Adaptation, Psychological↗
PubMedDate not supplied

CA19-9 as the most significant prognostic indicator of metastatic colorectal cancer.

BACKGROUND/AIMS: Colorectal cancer is the third leading cause of cancer-related mortality in Taiwan. We became interested in searching for the factors predictive of survival. Serum CA19-9 (carbohydrate antigen 19-9) level has been reported as a factor predictive of survival in patients with colorectal cancer. A few articles have reported that patients with metastatic colorectal cancer who have normal (< or = 37 U/mL) serum CA19-9 levels survived significantly longer than those with higher serum CA19-9 levels. However, these reports are contradictory and lack definite conclusions. This study was carried out in an effort to evaluate the prognostic significance of serum CA19-9 levels in patients with metastatic colorectal cancer in Taiwan. METHODOLOGY: Between 1991 and 1994, a total of 128 patients with histologically confirmed metastatic colorectal cancers were evaluated retrospectively at Veterans General Hospital-Taipei. All patients had measurable metastatic lesions and life expectancies of more than 3 months. 5-Fluorouracil-based chemotherapy, either in a weekly bolus regimen or a monthly 5-day bolus schedule, were administered to all of them. Data on age, sex, performance status, location of primary tumor, extent of metastases, site of metastases, histological differentiation, serum CEA (carcinoembryonic antigen) and CA19-9 levels were analyzed before chemotherapy to determine their association with survival. Blood samples for CEA and CA19-9 measurement were analyzed using the radioimmunoassay method. Multivariate analysis by the Cox's proportional hazards regression model was performed to determine independent prognostic factors among all of the possible variables. RESULTS: By univariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.022) were identified as prognostic factors, while age, sex, location of primary tumor, site of metastasis, histological differentiation, and pre-treatment serum CEA levels were not considered significant. By multivariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.014) were still found as independent prognostic factors of these patients. CONCLUSIONS: The data from our study indicate that serum CA19-9 level is the most significant prognostic indicator of patients with metastatic colorectal cancer. It is recommended that stratification for further clinical trials for patients with metastatic colorectal cancer should be carried out according to serum CA19-9 levels.

Adenocarcinoma↗
PubMed2005

Differences in attitudes between patients with primary colorectal cancer and patients with secondary colorectal cancer: is it reflected in their willingness to participate in drug trials?

Recruitment of patients into drug trials is essential in order to evaluate new treatments. Knowing why patients enter drug trials and their fears regarding them can be used in future research to ensure good recruitment and provide a supportive atmosphere for patients. Forty patients with colorectal cancer and 30 patients with colorectal liver metastases were asked to participate in a drug trial involving the oral consumption of a diet-derived agent of unknown therapeutic action. All patients agreeing or refusing to participate were asked to complete a short questionnaire with a series of options detailing the reasons behind their decision. Patients with colorectal hepatic metastases were motivated by altruism in entering the trial (e.g. helping others, helping the investigator) and displayed a realistic expectation that the drug would give little direct benefit to them. Patients with primary colorectal tumours were motivated by more 'selfish' reasons such as helping themselves and displayed an unrealistic expectation concerning any therapeutic benefit from the trial drug. Over 90% of all patients polled stated that their decision was made after reading the patient information leaflet. Patients with different stages of the same disease have very different fears and anticipations of drug trials, which need to be addressed specifically. The importance of the initial contact is demonstrated. Unrealistic expectations regarding the trial drug are common despite clear information to the contrary.

Administration, Oral↗
PubMed1996

Cytogenetic findings in colorectal cancer mirror multistep evolution of colorectal cancer.

Successful cytogenetic analysis was performed on tumor material from 26 patients with resectable colorectal cancer. 9 women and 17 men, aged 43 to 92 years, median 67 years. Clonal anomalies were found in twenty patients; five tumors showed mainly slight numerical changes such as trisomy 7 and loss of Y (2 cases). The remaining 15 tumors had highly complex karyotypes. The mainline was near diploid in six cases (5/6 tumors of the proximal colon), near triploid in four and near tetraploid in five tumors. Loss of chromosomes was most frequently observed with chromosomes 2, 5, 18, 20, and Y, the most frequently gained chromosomes were 7, 8, 13, 15, and X. Structural aberrations affected all chromosomes, except Y. The most frequently rearranged bands were 5q21, 7p15, 9p21, 13q11, 16p12, 17p13, 18q21, 21q11. Anomalies of chromosomes 5, 17, and 18 occurred concomitantly in 9/20 patients. All patients with deletions of 17p (n = 6) had near tetraploid karyotypes with high cell to cell variability and a median of nine structural aberrations (p < 0.007); four of them presented with parenchymal metastases at the time of surgery. Tumors of the proximal part of colon were with one exception diploid or near diploid, but no specific pattern of aberrations was detectable. However, it appears noteworthy that of the six patients with tumors of the ascending colon, three tumors had deletions at 16p12 and the affected patients had a short duration of survival. The tumor karyotypes of patients with parenchymal metastases revealed a trend to greater complexity of numerical and structural aberrations. Changes involving 8p22 or loss of chromosomes 8 were found in tumors of all parts of the colon and potentially associated with an unfavorable prognosis (4/7 decreased patients showed such changes).

Adult↗
PubMed2004

Minnesota Colorectal Cancer Initiative: successful development and implementation of a community-based colorectal cancer registry.

PURPOSE: The aim of the Minnesota Colorectal Cancer Initiative is to implement risk-specific interventions to decrease colorectal cancer morbidity and mortality by 1) assisting clinicians to identify and educate individuals and families at high and increased risk for colorectal cancer; 2) providing professional and community education; 3) maintaining a database to evaluate the effectiveness of preventive intervention strategies; and 4) facilitating colorectal cancer research. METHODS: Two physician groups and the University Cancer Center founded the Minnesota Colorectal Cancer Initiative as a not-for-profit organization. Health care organizations, pharmaceutical companies, a consulting firm, and other practice groups provide continuing financial and other support. A database registry, risk-assessment survey, and consent document were developed and then were approved by an institutional review board. A trial enrollment was conducted. Minnesota Colorectal Cancer Initiative services are available to the public. Participants are actively recruited through member organizations. Minnesota Colorectal Cancer Initiative assesses hereditary risk and will document family history in the medical record on request. A personally targeted reply letter reviews risk factors and recommends specific screening and surveillance strategies for participants and their family members, and when appropriate, provides information regarding genetic counseling and testing services. Minnesota Colorectal Cancer Initiative services are free to participants. RESULTS: Since 1999, Minnesota Colorectal Cancer Initiative has sent individually tailored reply letters providing risk-specific information about colorectal cancer to 717 participants and more than 3200 of their first-degree and second-degree relatives. More than 200 families, previously unidentified as having histories suggestive of hereditary colorectal cancer (attenuated familial polyposis and hereditary nonpolyposis colorectal cancer), have been identified; genetic services were explained and recommended. A formal program evaluation confirmed that Minnesota Colorectal Cancer Initiative provides useful information and materials and promotes intrafamilial communication about colon cancer risk and recommendations. CONCLUSIONS: Minnesota Colorectal Cancer Initiative is a model of effective collaboration between academic and community health care providers. A community-based registry is a unique way to identify and provide personal, risk-specific information to large numbers of people at increased or high risk for colorectal cancer.

Adult↗
PubMed2000

Expression of the SART1 tumor-rejection antigens in colorectal cancers.

PURPOSE: Colorectal cancer is one of the major causes of cancer death in the world, including in the United States and Japan. We recently identified the tumor-rejection antigen gene SART1, which encodes both the SART1(259) antigen expressed in the cytosol of epithelial cancers and the SART1(800) antigen expressed in the nucleus of the majority of proliferating cells. This study investigated the expression of these tumor antigens to explore a potential molecule for specific immunotherapy of colorectal cancer patients. METHODS: SART1 antigens were investigated by Western blotting in six colorectal cancer cell lines and in 33 colorectal cancer tissues. The cancer cell lines were tested for their ability to stimulate interferon-gamma production by the human-leukocyte-antigen-A24-restricted and SART1-specific cytotoxic T lymphocytes and were also tested for their susceptibility to the lysis by the cytotoxic T lymphocytes. RESULTS: The SART1(259) antigen was detected in the cytosol of four of six cancer cell lines, 13 of 33 (39 percent) cancer tissues, and 0 of 20 nontumorous colorectal tissues. The SART1(800) antigen was expressed in the nucleus of all the colorectal cancer cell lines, 18 of 33 (55 percent) cancer tissues, and 0 of 20 nontumorous tissues. The human-lymphocyte-antigen-A24-restricted and SART1-specific cytotoxic T lymphocytes killed the human-lymphocyte-antigen-A24+ SART1(259+) cancer cells. CONCLUSIONS: The SART1(259) antigen could be an appropriate target molecule for specific immunotherapy of approximately 40 percent of the human-lymphocyte-antigen-A24+ patients with colorectal cancer.

Adenocarcinoma↗
PubMed2001

Rectal cancer in hereditary nonpolyposis colorectal cancer.

BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) accounts for approximately 2% to 5% of all colorectal cancers. Rectal cancer in HNPCC is not well characterized. METHODS: A retrospective medical record review of HNPCC patients with colorectal cancer diagnosis from December 1948 to December 1999 was performed in an attempt to elucidate the natural history of rectal cancer in HNPCC. Group A consisted of patients diagnosed with rectal cancer as the index colorectal cancer. Group B consisted of patients diagnosed with rectal cancer as a metachronous colorectal cancer. RESULTS: Twenty-five of 104 patients developed rectal cancer in our HNPCC registry. There were 18 patients in group A with a median age at diagnosis of rectal cancer of 48 years (range 24 to 79) and 7 patients in group B diagnosed at a median age of 58 years (range 45 to 68). Three of 18 patients (17%) in group A developed metachronous colon cancers at a median of 203 months (range 27 to 373) from the index rectal cancer. Rectal cancer in group B was diagnosed at a median 245 months (range 51 to 564) from the index colorectal cancer diagnosis. CONCLUSIONS: Rectal cancer in HNPCC is not uncommon. The presentation of rectal carcinoma should not obviate the evaluation for HNPCC in suspected cases.

Adenocarcinoma↗