Cost-effectiveness of colonoscopy in screening for colorectal cancer; cost-effectiveness of screening colorectal cancer in the general population.
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Colonoscopy↗
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Risk and surveillance of individuals with heritable factors for colorectal cancer. WHO Collaborating Centre for the Prevention of Colorectal Cancer.
Heritable and genetic factors pertinent to colon cancer can be divided into three categories: inherited syndromes, genetic epidemiology, and molecular genetics. Familial adenomatous polyposis (FAP) and Gardner syndrome (GS) are rare dominantly inherited syndromes characterized by hundreds to thousands of colonic adenomatous polyps. Colon cancer occurs at a young age in both diseases unless the colon is removed. Peutz-Jeghers syndrome and familial juvenile polyposis are inherited hamartomatous polyposis conditions with a less dramatic, but definite, increased risk for colon cancer. These four polyposis syndromes together account for less than 1% of cases of colon malignancy. Hereditary nonpolyposis colorectal cancer is a dominantly inherited form of colon cancer characterized by an early age of onset and a predilection for proximal colonic tumours. Multiple primary malignancies are frequently observed and one or several adenomatous polyps are often present in affected individuals; 4-6% of colon cancer cases occur in relationship to this syndrome. Genetic epidemiological studies have consistently shown that first-degree relatives of persons with colon cancer have a twofold to threefold increased risk of having colon malignancy. More recent studies have found a similar risk among relatives of those with adenomatous polyps. Studies of colon cancer and adenomatous polyps in pedigrees have further demonstrated that this familial clustering probably occurs on the basis of partially penetrant inherited susceptibilities. These inherited susceptibilities probably interact with environmental factors to give rise to polyp growth and finally colon cancer. Molecular studies have begun to elucidate the genetic mechanisms of colon cancer at the DNA level. The germinal mutation of FAP and GS has been localized to the long arm of chromosome 5. Tissue samples from "random" adenomatous polyps and colon cancers have shown frequent and specific acquired DNA sequence deletions on chromosomes 5, 17, and 18. Mutations and over-expression of the ras oncogene likewise have been observed in such tissues. The chromosome 5 defect in polyp and cancer tissues is probably at the same locus as the germinal mutation of FAP. There is evidence that this locus normally regulates expression of the c-myc oncogene, which in turn probably has a regulatory function in DNA replication. The chromosome 17 deletion is a mutation of the gene for the transformation-associated protein, p53. Appropriate screening starting at a relatively young age is necessary to prevent cancer in the inherited syndromes. Screening is also indicated in close relatives of those with nonsyndromic or common colon cancer in view of the moderately increased risk for colon cancer in this group.(ABSTRACT TRUNCATED AT 400 WORDS)
Colorectal Neoplasms↗
The epidemiology of endometrial cancer in hereditary nonpolyposis colorectal cancer.
Family members from hereditary nonpolyposis colorectal cancer (HNPCC) families are at an increased risk of developing endometrial cancer. The present study was performed to investigate the epidemiology of endometrial cancer associated with HNPCC. Data on 125 cases of endometrial cancer from HNPCC families were collected from seven countries. The mean age at diagnosis was 48 years (range: 27-72 years). Fifty-seven percent of the cases were diagnosed under 50 years of age and 98 percent under 65 years. The mean ages at diagnosis of endometrial cancer were not significantly different between the countries. At the time of the investigation, 58 of the 125 cases had died (mean age at death: 59 years; range: 32-88 years). Fifteen of the 125 (12%) patients died from endometrial cancer. In 75 of the 113 (61%) endometrial cancer cases, a second primary cancer occurred. Most of these cancers (54 out of 75) were colorectal cancers. In 18 (15%) of the cases of endometrial cancers, more than two primary cancers occurred. In conclusion, endometrial cancer in HNPCC develops at a significant earlier age than in the general population. More than half of the cases had a second primary tumor. Endometrial cancer is an infrequent cause of death in the HNPCC families. A prospective study is warranted to assess the value of surveillance for endometrial cancer in these families.
Adult↗
Strategy for colorectal cancer screening.
Colorectal cancer is a leading cause of cancer death in Israel. Our current understanding of the colorectal adenoma-carcinoma sequence has led to the use of screening for timely detection of polyps and cancer. Digital examination of the rectum is a test that can be performed by all doctors. Fecal occult blood testing, flexible sigmoidoscopy and colonoscopy are the standard screening techniques for patients. Computerized tomography colonography is now entering this field. This review discusses the merits and uncertainties of these strategies as related to the risk of colorectal cancer in selected populations.
Colonography, Computed Tomographic↗
[Schistosomiasis and its prognostic significance in patients with colorectal cancer. National Cooperative Group on Pathology and Prognosis of Colorectal Cancer].
This paper analyses 430 cases of colorectal cancer complicated with schistosomiasis. The 5 year survival rate was 45.6%, lower than that without schistosomiasis. The lowered 5 year survival rate may have been associated with higher percentage of negative immune response in the regional lymph nodes and higher percentage of infiltrating growth pattern of the tumor. The infection of schistosome should be considered as one of the important factors in prognosis.
Adenocarcinoma↗
Radiation exposure and familial aggregation of cancers as risk factors for colorectal cancer after radioiodine treatment for thyroid carcinoma.
PURPOSE: In thyroid cancer patients, radioiodine treatment has been shown to be associated with an increased risk of colon carcinoma. The aim of this study in thyroid cancer patients was to evaluate the role of familial factors in the risk of colorectal cancer and their potential interaction with radioiodine exposure. METHODS AND MATERIALS: We performed a case-control study on 15 colorectal cancer patients and 76 matched control subjects, nested in a cohort of 3708 thyroid cancer patients treated between 1933 and 1998. For each patient, the radiation dose delivered to the colon by radioiodine was estimated by use of standard tables. In those who received external radiation therapy, the average radiation doses delivered to the colon and rectum were estimated by use of DOS_Eg software. A complete familial history was obtained by face-to-face interviews, and a familial index was defined to evaluate the degree of familial aggregation. RESULTS: The risk of colorectal cancer increased with familial aggregation of colorectal cancer (p = 0.02). After adjustment for the radiation dose delivered to the colon and rectum, the risk of colorectal cancer was 2.8-fold higher (95% CI, 1.0-8.0) for patients with at least one relative affected by colorectal cancer than for patients without such a family history (p = 0.05). The radiation dose delivered to the colon and rectum by (131)I and external radiation therapy was associated with an increase of risk near the significance threshold (p = 0.1). No significant interaction was found between radiation dose and having an affected relative (p = 0.9). CONCLUSIONS: The role of familial background in the risk of colorectal cancer following a differentiated thyroid carcinoma appears to increase with the radiation dose delivered to the colon and rectum. However, the study population was small and no interaction was found between these two factors.
Algorithms↗
Development of quality indicators for patients undergoing colorectal cancer surgery.
BACKGROUND: Colorectal cancer is the second most common cancer type among new cancer diagnoses in the United States. Attention to the quality of surgical care for colorectal cancer is of particular importance given the increasing numbers of colorectal cancer resections performed in the aging population. A National Cancer Institute-sponsored consensus panel produced guidelines for colorectal cancer surgery in 2000. We have updated and extended that work by using a formal process to identify and rate quality indicators as valid for care during the preoperative, intraoperative, and postoperative periods. METHODS: Using a modification of the RAND/UCLA Appropriateness Methodology, we carried out structured interviews with leaders in the field of colorectal cancer surgery and systematic reviews of the literature to identify candidate quality indicators addressing perioperative care for patients undergoing surgery for colorectal cancer. A panel of 14 colorectal surgeons, general surgeons, and surgical oncologists then evaluated and formally rated the indicators using the modified Delphi method to identify valid indicators. RESULTS: A total of 142 candidate indicators were identified in six broad domains: privileging (which addresses surgical credentials), preoperative evaluation, patient-provider discussions, medication use, intraoperative care, and postoperative management. The expert panel rated 92 indicators as valid. These indicators address all domains of perioperative care for patients undergoing surgery for colorectal cancer. CONCLUSIONS: The RAND/UCLA Appropriateness Methodology can be used to identify and rate indicators of high-quality perioperative care for patients undergoing surgery for colorectal cancer. The indicators can be used as quality performance measures and for quality-improvement programs.
Colectomy↗
Extracolonic cancers associated with hereditary nonpolyposis colorectal cancer in the Utah Population Database.
BACKGROUND: The data describing the extracolonic cancers associated with hereditary nonpolyposis colorectal cancer (HNPCC) are variable. METHODS: We ascertained all Amsterdam I criteria-positive pedigrees (N = 18) in the Utah Population Database (UPDB). We identified the extracolonic cancers in the colorectal cancer cases (N = 65) in these pedigrees, and in their first- (N = 509) and second-degree (N = 1,611) relatives. Standardized morbidity ratios were estimated by comparing the observed rates of extracolonic cancer in defined sets of relatives of probands with population expected rates estimated internally from the UPDB. RESULTS: The extracolonic cancers observed in significant excess in the 65 Amsterdam I criteria-positive colorectal cancer (CRC) cases in the UPDB were uterine (N = 3, p = 0.003), lip (N = 2, p = 0.007), stomach (N = 2, p = 0.009), female genitalia (N = 1, p = 0.004) and larynx (N = 1, p = 0.05). Extracolonic cancers observed in significant excess in the 509 first-degree relatives of the 65 colorectal cancer (CRC) cases in these Amsterdam I criteria pedigrees included: thyroid (N = 5, p = 0.0002) and prostate (N = 19, p = 0.002). Thyroid cancer (N = 6, p = 0.003) was found in significant excess in the second-degree relatives of the Amsterdam I criteria-positive CRC cases. CONCLUSIONS: In this population-based examination of the extracolonic cancers at excess in classic HNPCC pedigrees (selected by Amsterdam I criteria) we not only observed many of the same cancers previously reported to be associated with HNPCC in both CRC probands and their relatives, but also identified several previously unreported associations. Although our sample size is small, this study is population based, lacks ascertainment and recall bias, and benefits from uniform, consistent diagnoses of all cancers in a statewide registry.
Colorectal Neoplasms, Hereditary Nonpolyposis↗
'Tomudex' (ZD1694): results of a randomised trial in advanced colorectal cancer demonstrate efficacy and reduced mucositis and leucopenia. The 'Tomudex' Colorectal Cancer Study Group.
'Tomudex' (ZD1694), a direct and specific thymidylate synthase (TS) inhibitor entered phase III studies in November 1993. We present here the first analysis of a randomised multicentre, international phase III study. 439 patients with previously untreated advanced colorectal cancer were randomised to Tomudex 3.0 mg/m2 given once every 3 weeks or 5-fluorouracil (5-FU) 425 mg/m2 and leucovorin (LV) 20 mg/m2 for 5 days (the Mayo regimen), given every 4-5 weeks. Patients were evaluated weekly for toxicity and every 12 weeks for objective response. The two groups were well matched in terms of demographic characteristics. The mean age of the patients was 61 years and most had either liver (78%) or lung (25-29%) metastases. Ninety seven per cent of patients allocated to Tomudex and 94% of those allocated to 5-FU plus LV had measurable disease. Response was assessed using WHO/UICC criteria; all response data were source validated; 19.8% of patients who received Tomudex and 12.7% of patients who received 5-FU plus LV had complete or partial responses (P = 0.059, odds ratio 1.7, 95% confidence limits 0.98-2.81). There were no statistically significant differences in time to progression or survival between the two groups. Patients who received Tomudex spent a substantially shorter time in hospital for dosing and had significantly lower rates of grade 3 and 4 toxicities such as leucopenia and mucositis. Patients who received Tomudex had a significantly higher incidence of reversible grade 3 or 4 increase in transaminases, which appear to be of limited clinical significance. Improvement in quality of life, weight gain and performance status was seen in both groups. Tomudex has benefits in terms of higher response rates, reduced toxicity and more frequent palliative benefits when compared with 5-FU plus LV in the management of advanced colorectal cancer, and has a more convenient administration schedule.
Adult↗
Tumour spectrum in hereditary non-polyposis colorectal cancer (HNPCC) and in families with "suspected HNPCC". A population-based study in northern Italy. Colorectal Cancer Study Group.
Hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) is characterized by the early onset of colorectal neoplasms, frequently localized in the right colon, increased occurrence of multiple primaries, vertical transmission and aggregation of tumours in families in accordance to a Mendelian dominant type of inheritance. The syndrome accounts for approximately 5% of all colorectal cancers. The purpose of the present study was to describe the tumour spectrum and the most relevant clinical features of 28 kindreds with HNPCC, classified according to the guidelines of the International Collaborative Study Group, and of 61 "suspected" HNPCC. These families were observed during a 6-year registration of colorectal neoplasms in a health-care district of Northern Italy. Colorectal cancer was by far the most frequent malignancy; gastric cancer was the second. Uterine carcinoma was only slightly more frequent than expected. Lung- and breast-tumour rates were lower than expected. Cancer distribution in the large bowel showed that about two fifths of the tumours developed in the right colon. The occurrence of cancer before the age of 50 to 60 was much more frequent in HNPCC. Multiple tumours developed in 25 patients with HNPCC and in 32 with "suspected" HNPCC. Pancolonoscopy remains the procedure of choice for surveillance; other examinations, such as gastroscopy, gynaecological investigations, urography and cholangiography, are suggested only to selected families. One of the main features of the study was the inclusion of 61 "suspected" HNPCC, a heterogeneous group of families which nonetheless deserves careful follow-up.
Adult↗
[Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer].
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Adaptor Proteins, Signal Transducing↗
[Effect of peroral doxifluridine plus hepatic arterial infusion for synchronous liver metastasis of colorectal cancer--correlation with the expression of thymidine phosphorylase and dihydropyrimidine dehydrogenase in primary colorectal cancer lesions].
We investigated whether the efficacy of peroral doxifluridine and hepatic arterial 5-FU infusion on synchronous liver metastasis of colorectal cancer could be predicted based on the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in the primary colorectal lesions. Ten patients with synchronous liver metastasis of colorectal cancer were given doxifluridine (600-800 mg/body/day) orally and 5-FU (500 mg/body, once or twice a week) through the hepatic artery following resection of the primary lesions between June 1996 and July 2001. The levels of TP and DPD in the primary lesions were determined by an enzyme-linked immunosorbent assay. The level of TP, DPD, and the ratio of TP/DPD in patients with partial response (n = 4) were 89.8 +/- 30.0 U/mg protein, 23.5 +/- 25.7 U/mg protein, and 3.8 +/- 1.4, respectively, while those in patients with no response or progressive disease (n = 6) were 41.8 +/- 9.7 U/mg protein, 25.8 +/- 15.8 U/mg protein, and 2.2 +/- 1.6, showing significant difference (p < 0.01) in the level of TP between the groups. These results indicate that determining the level of TS in primary colorectal lesions may be useful for predicting the efficacy of this regimen for patients with synchronous liver metastasis of colorectal cancer.
Aged↗
Personality as a risk factor in large bowel cancer: data from the Melbourne Colorectal Cancer Study.
In a case control study which formed one arm of a large, population-based investigation of colorectal cancer incidence, aetiology and survival. 'The Melbourne Colorectal Cancer Study', among others, 22 psychosocially orientated questions were asked by personal interview of 637 histologically confirmed new cases of colorectal cancer and 714 age/sex frequency matched community controls, from Melbourne (population 2.81 million). Self-reported childhood or adult life 'unhappiness' was statistically significantly more common among the cancer cases, while 'unhappiness with retirement' was similarly distributed among cases and controls. Questions which were formulated to test a particular personality profile as a cancer risk, and which included the elements of denial and repression of anger and of other negative emotions, a commitment to prevailing social norms resulting in the external appearance of a 'nice' or 'good' person, a suppression of reactions which may offend others and the avoidance of conflict, showed a statistically significant discrimination between cases and controls. The risk of colorectal cancer with respect to this model was independent of the previously found risk factors of diet, beer intake, and family history of colorectal cancer, and was also independent of other potential confounding factors of socioeconomic level, marital status, religion and country of birth. Although the results must be interpreted with caution, the data are consistent with the hypothesis that this personality type may play a role in the clinical expression of colorectal cancer and merits further study.
Adenocarcinoma↗
The human leukocyte antigen region and colorectal cancer risk.
PURPOSE: Recently, we found a certain haplotype in the human leukocyte antigen Class III subregion to be associated with breast cancer. Epidemiologic studies have shown that breast cancer and colorectal cancer have several risk factors in common. In view of these studies and because polymorphisms located in the human leukocyte antigen III region have been found to be associated with colorectal cancer, we wondered whether the same region also is involved in colorectal cancer susceptibility. METHODS: The human leukocyte antigen region was genotyped with 14 microsatellite markers in germline DNA from 643 colorectal cancer patients and 841 family-based controls. Association analyses and the Haplotype Sharing Statistic were used to search for differences between patients and controls. Subgroup analyses were performed for gender, age at diagnosis, and localization of the tumor. RESULTS: The Haplotype Sharing Statistic analysis revealed neither a difference in mean haplotype sharing between all patients and controls, nor in any of the subgroups. The single allele, genotype, and two-locus association analyses for all patients and for the different subgroups did not show an association with colorectal cancer for the 14 microsatellite markers. Also, no association was observed between the tumor necrosis factor-beta polymorphism and colorectal cancer. CONCLUSIONS: No association was observed between commonly occurring haplotypes and alleles in the human leukocyte antigen region and colorectal cancer risk.
Adult↗
Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer.
BACKGROUND: Patients with early-onset colorectal cancer (CRC) or those with multiple tumours associated with hereditary non-polyposis colorectal cancer (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR) gene mutations. AIM: To analyse the value of family history, microsatellite instability (MSI) analysis and MMR protein staining in the tumour to predict the presence of an MMR gene mutation in such patients. METHODS: In 281 patients diagnosed with CRC before the age of 50 years or with CRC and at least one additional HNPCC-associated cancer, germline mutation analysis in MLH1, MSH2 and MSH6 was carried out with denaturing gradient gel electrophoresis and multiplex ligation-dependent probe amplification. MSI analysis with five consensus markers and MMR protein staining for MLH1, MSH2 and MSH6 were carried out in the tumours. RESULTS: 25 pathogenic mutations (8 in MLH1, 9 in MSH2 and 8 in MSH6) were found. MSI analysis missed three and immunohistochemistry (IHC) missed two mutation carriers. Sensitivities of family history, MSI analysis and IHC for the presence of a mutation were 76%, 82% and 88%, specificities were 64%, 70% and 84%, and positive predictive values were 19%, 23% and 38%, respectively. Multivariate analysis showed the highest odds ratio for IHC (38.3, 95% confidence interval 9.0 to 184). Prevalence of pathogenic germline MMR gene mutations in patients with CRC before the age of 50 years was 6% and in those with > or =2 HNPCC-associated tumours was 22%. In the second group, no mutation carriers were found among the 29 patients who were diagnosed with their first tumour after the age of 60 years. CONCLUSION: Family history, MSI analysis and IHC are indicative parameters to select patients with CRC for MMR gene mutation analysis. The data show that IHC is the best single selection criterion.
Adaptor Proteins, Signal Transducing↗
Practice parameters for the treatment of patients with dominantly inherited colorectal cancer (familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer).
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Adenomatous Polyposis Coli↗
New trends in the surgical treatment of colorectal cancer liver metastases.
Colorectal cancer is one of the most common solid tumors affecting people around the world. A significant proportion of patients with colorectal cancer will develop or will present with liver metastases. In some of these patients, the liver is the only site of metastatic disease. Thus, surgical treatment approaches are an appropriate and important treatment option in patients with liver-only colorectal cancer metastases. Resection of colorectal cancer liver metastases can produce long-term survival in selected patients, but the efficacy of liver resection as a solitary treatment is limited by two factors. First, a minority of patients with liver metastases have resectable disease. Second, the majority of patients who undergo successful liver resection for colorectal cancer metastases develop recurrent disease in the liver, extrahepatic sites, or both. In this paper, in addition to the results of liver resection for colorectal cancer metastases, we will review the results of cryoablation, heat ablation, and hepatic arterial chemotherapy using a surgically implanted pump. Each of these surgical treatment modalities can produce long-term survival in a subset of patients with liver-only colorectal cancer metastases, whereas systemic chemotherapy used alone rarely results in long-term survival in these patients. While surgical treatments provide the best chance for long-term survival or, in some cases, the best palliation in patients with colorectal cancer liver metastases, it is clear that further improvements in patient outcome will require multimodality therapy regimens.
Antineoplastic Agents↗
In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer.
BACKGROUND AND OBJECTIVES: Irinotecan hydrochloride (CPT-11) is one of the camptothecin analogues that has shown a broad spectrum of strong antitumor effectiveness against various cancers, including colorectal cancer. In order to promote the clinical response of chemotherapy for colorectal cancer using CPT-11, one of the most effective strategies is to use it in combination with other anticancer agents. In the present study, anticancer effects after combining CPT-11 and other antitumor agents were determined by a 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay of colorectal cancer cells, especially freshly isolated cancer cells. METHODS: Freshly isolated cancer cells from 20 patients with colorectal cancer and the established colon cancer cell lines were used in this study. The augmentation of the antitumor effectiveness of 7-ethyl-10-hydroxy-CPT (SN-38) was analyzed in combination with other anticancer agents. Furthermore, the antitumor effectiveness using lower concentrations of anticancer agents was measured to understand the mechanism of the augmentation. RESULTS: The percent inhibition of SN-38 in combination with cisplatin (CDDP) and mitomycin revealed a high anticancer effect compared with each anticancer agent alone for freshly isolated rectal cancer. CDDP also had a synergistic effect in combination with SN-38 according to the fractional product concept. At lower than plasma peak concentrations of SN-38, the anticancer effects were augmented in combination with lower concentrations of CDDP for freshly isolated colorectal cancer. This augmentation showed a strong synergistic effect. CONCLUSIONS: These results may be supportive to ongoing clinical studies of chemotherapy by using CPT-11 and CDDP for advanced colorectal cancer.
Adenocarcinoma↗