Search

The aim of this study was to assess the impact of area deprivation and primary care facilities on colorectal adenoma detection and on colorectal cancer (CRC) incidence in a French well-defined population before mass screening implementation. The study population included all patients aged 20 years or more living in Côte d'Or (France) with either colorectal adenoma or invasive CRC first diagnosed between 1995 and 2002 and who were identified from the Burgundy Digestive Cancer Registry and the Côte d'Or Polyp Registry. Area deprivation was assessed using the European deprivation index on the basis of the smallest French area available (Ilots Regroupés pour l'Information Statistique). Healthcare access was assessed using medical density of general practitioners (GPs) and road distance to the nearest GP and gastroenterologist. Bayesian regression analyses were used to estimate influential covariates on adenoma detection and CRC incidence rates. The results were expressed as relative risks (RRs) with their 95% credibility interval. In total, 5399 patients were diagnosed with at least one colorectal adenoma and 2125 with invasive incident CRC during the study period. Remoteness from GP [RR=0.71 (0.61-0.83)] and area deprivation [RR=0.98 (0.96-1.00)] independently reduced the probability of adenoma detection. CRC incidence was only slightly affected by GP medical density [RR=1.05 (1.01-1.08)] without any area deprivation effect [RR=0.99 (0.96-1.02)]. Distance to gastroenterologist had no impact on the rates of adenoma detection or CRC incidence. This study highlighted the prominent role of access to GPs in the detection of both colorectal adenomas and overall cancers. Deprivation had an impact only on adenoma detection.

Background: Unlike experimental results, epidemiologic studies that used dietary questionnaires were not convincing as regards the relations between dietary fatty acids (FAs) and risk of colorectal cancer (CRC). The FA composition of adipose tissue, which is considered to be an indicator of dietary intake over 2-3 y because of the slow turnover rate, appears promising but has so far been rarely used to explore the relation between CRC and exogenous or endogenously produced FAs., Objective: In this case-control study, we aimed to investigate associations between risk of CRC and the FA composition of subcutaneous adipose tissue and product-to-precursor ratios as indexes of enzymatic activities., Design: From 2008 to 2011, we recruited 203 cases with newly diagnosed CRC and elective surgery with a curative intent and 223 control subjects with planned abdominal surgery for benign disease and no history of CRC or polyp resection. During surgery, abdominal subcutaneous adipose tissue samples were optimally collected, stored, and analyzed by using high-performance gas chromatography. Multivariate logistic regression was used to estimate ORs for CRC in relation to individual FAs divided into tertiles according to the FA distribution in controls., Results: After adjustment, significant positive associations with CRC risk were observed in highest compared with lowest tertiles of 16:1n-9 (OR: 1.75; 95% CI: 1.00, 3.06; P-trend = 0.045), 20:3n-6 (OR: 1.79; 95% CI: 1.01, 3.17; P-trend = 0.038), 22:5n-3 (OR: 1.82; 95% CI: 1.06, 3.12; P-trend = 0.023), and the ratio of 18:2n-6 to 18:3n-3 (OR: 2.34; 95% CI: 1.37, 3.98; P-trend = 0.001). Significant inverse associations were observed for 18:3n-3 (OR: 0.48; 95% CI: 0.29, 0.81; P-trend = 0.007). Several product-to-precursor ratios showed significant differences between cases and controls in particular ratios that reflected elongase 2/5 activity., Conclusions: CRC patients presented higher concentrations of some FAs but lower concentrations of α-linolenic acid in their subcutaneous adipose tissue than did controls. These results may reflect both dietary patterns and altered FA metabolism but require mechanistic explorations., (© 2015 American Society for Nutrition.)

Background: Chronic inflammation is a key feature of colorectal cancer (CRC), meaning that inflammatory biomarkers may be useful for its diagnosis. In particular, high neutrophil gelatinase-associated lipocalin (NGAL) expression has been reported in CRC. Thus, we investigated whether serum NGAL and NGAL/MMP-9 could be potential biomarkers for the early detection of CRC. Concurrently, we studied other inflammatory biomarkers such as soluble tumor necrosis factor receptor 1 and 2 (sTNFR-1, sTNFR-2), and C reactive protein (CRP)., Methods: The AGARIC multicenter case-control study was performed in eastern France and included patients admitted for elective surgery either for a priori non-metastatic incident CRC (n=224) or for benign causes (n=252). Pre-operative serum levels of NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were measured., Results: Median values of serum NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were significantly higher in CRC patients than in controls. Receiver Operating Characteristic analysis provided relatively poor values of area under the curve, ranging from 0.65 to 0.58. Except for NGAL/MMP-9, all biological parameters were strongly correlated in CRC cases and, less strongly in controls. Multivariate odds ratio (OR) of CRC comparing the extreme tertiles of serum NGAL was 2.76 (95% confidence interval (CI): 1.59-4.78; p<0.001),. Lower but significant multivariate associations were observed for sTNFR-1, and sTNFR-2: OR=2.44 (95% CI : 1.34-4.45, p=0.015) and 1.93 (95% : CI 1.12-3.31), respectively. No independent association was found between case-control status and NGAL/MMP-9. Among CRC cases, maximal tumor size was an independent determinant of serum NGAL (p=0.028) but this association was reduced after adjustment for CRP (p=0.11)., Conclusion: Despite a significant increase in serum NGAL and other inflammatory markers among CRC patients, our findings suggest that they may not be suitable biomarkers for the diagnosis and especially early detection of CRC.

Background: Several randomized trials have shown a reduction of colorectal cancer mortality by screening using guaiac-based faecal occult blood tests. However, little is known on the long-term effect of screening at the population level in everyday practice., Methods: Small-sized geographic areas including a total of 91,199 individuals were allocated to either biennal screening using the Hemoccult-II test or no screening. The expected mortality and incidence in the cohort invited to screening was determined using mortality and incidence in the non-screened population., Results: Colorectal cancer mortality was significantly lower in the population invited to screening than in the non-screened population after 11 screening rounds (standardized mortality ratio: 0.87; 0.80-0.94). The standardized mortality ratio remained significant whatever the duration of follow-up. This reduction in colorectal cancer mortality was more pronounced in those who participated in the first screening campaign, who were regular participants in screening rounds (standardized mortality ratio: 0.67; 0.59-0.76). In contrast, colorectal cancer incidence was not different between the screened and non-screened populations (standardized incidence ratio: 1.01; 0.96-1.06)., Conclusion: Our findings confirm, in the long term, that screening with Hemoccult can reduce colorectal cancer mortality. The data also highlight the benefit of regular participation in screening and the absence of effect of screening on colorectal cancer incidence., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: We investigated the impact of municipality of residence on colonoscopic surveillance and colorectal cancer risk after adenoma resection in a French well-defined administrative area., Methods: This registry-based study included all patients residing in Côte d'Or (n=5769) first diagnosed with colorectal adenomas between January 1, 1990, and December 31, 1999. Information about colonoscopic surveillance and colorectal cancer incidence was collected until December 31, 2003., Results: A rural place of residence reduced the probability of colonoscopic surveillance in men [HR=0.89 (95%CI: 0.79-0.99), p=0.041] and in patients without family history of colorectal cancer [HR=0.91(0.82-0.99), p=0.044]. After a median follow-up of 7.7 years, 87 patients developed invasive colorectal cancer. After advanced adenoma removal, the standardized incidence ratio for colorectal cancer was 3.03 (95%CI: 1.92-4.54) for rural patients and 1.87 (95%CI: 1.26-2.66) for urban patients compared with the general population. The risk of colorectal cancer was higher in rural patients than in urban ones only after removal of the initial advanced adenoma [HR=1.73 (95%CI: 1.01-3.00, p=0.048)]. Further adjustment for surveillance colonoscopy, physician location, and other confounders had little impact on these results., Conclusion: The increased risk of subsequent colorectal cancer after advanced adenoma removal in French rural patients was not explained by a lower rate of colonoscopic surveillance. The role of socio-economic and environmental factors requires further exploration., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Previous studies examining the incidence of colorectal cancer after polypectomy have provided discordant findings. The aim of this study was to compare the risk of colorectal cancer after adenoma removal in routine clinical practice with the risk in the general population., Design: Cohort study based on detailed data from a population-based registry that has collected all cases of both colorectal cancers and adenomas diagnosed in a clearly-defined population since 1976., Setting: French administrative area of Côte-d'Or (Burgundy)., Methods: Residents of the area diagnosed for the first time with colorectal adenoma between 1990 and 1999 were included (n=5779). Initial and follow-up data until December 2003 were used to calculate the colorectal cancer standardised incidence ratio (SIR) and cumulative probabilities after adenoma removal., Results: After a median follow-up of 7.7 years, 87 invasive colorectal cancers were diagnosed whereas 69 cases were expected. Compared with the general population, the overall SIR was 1.26 (95% CI 1.01 to 1.56). The risk of colorectal cancer depended on the characteristics of the initial adenoma (SIR 2.23 (95% CI 1.67 to 2.92) for advanced adenomas and 0.68 (95% CI 0.44 to 0.99) for non-advanced adenomas). In cases of advanced adenomas, the SIR was 1.10 (95% CI 0.62 to 1.82) in patients with colonoscopic follow-up and 4.26 (95% CI 2.89 to 6.04) in those without. The 10-year cumulative probabilities of colorectal cancer were, respectively, 2.05% (95% CI 1.14% to 3.64%) and 6.22% (95% CI 4.26% to 9.02%)., Conclusions: In routine practice, the risk of colorectal cancer after adenoma removal remains high and depends both on initial adenoma features and on colonoscopy surveillance practices. Gastroenterologists should encourage patients to comply with long-term colonoscopic surveillance.

Background: Because few data are available on this topic, we investigated the influence of geographical determinants on colorectal adenoma detection and cancer incidence rates., Methods: Between 1990 and 1999, 6220 Côte d'Or inhabitants (France) were first-diagnosed with a colorectal adenoma, and 2389 with an invasive adenocarcinoma. The impact of the rural-urban place of residence and of a physician location in municipalities on adenoma and cancer detection rates was studied using Poisson regression., Results: World-standardized adenoma detection rate was significantly higher in urban areas (102 [95% CI: 97-107]) than in rural areas (78 [95% CI: 72-84]). The impact of the absence of physicians in municipalities was only found in rural areas. The detection rate ratio associated with the absence of a primary care physician was 0.70 [95% CI: 0.61-0.81], and the detection rate ratio associated with the absence of a gastroenterologist was 0.75 [95% CI: 0.64-0.89]. Colorectal cancer incidence rates were similar in urban and rural areas with only marginal variations related to physician location., Conclusions: These results suggested a differential impact of geographical variables on the detection rates of colorectal adenomas and cancers in the population. Further studies are needed to examine socio-economic factors likely to be involved in these disparities., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to compare the cost and the effectiveness of two biennial fecal occult blood screening tests for colorectal cancer: a guaiac nonrehydrated test (G-FOBT) and an immunochemical test (I-FOBT) with the absence of screening., Methods: A Markov model was developed to compare these strategies in a general population of subjects aged 50 to 74 over a 20-year period., Results: Compared with the absence of screening, G-FOBT and I-FOBT were associated with a decrease in colorectal cancer mortality of 17.4 percent and 25.2 percent, respectively. With regard to cost-effectiveness, expressed as cost per life-year gained, I-FOBT was the most effective and most costly alternative. Compared with no screening, G-FOBT and I-FOBT presented similar discounted incremental cost-effectiveness ratios: 2,739 euros and 2,819 euros respectively per life-year gained. When compared with G-FOBT, I-FOBT presented an incremental cost-effectiveness ratio of 2,988 euros per life-year gained. Sensitivity analyses showed the strong influence of the I-FOBT lead time, of the participation rate to screening for I-FOBT, and of the purchase price of the I-FOBT on the discounted incremental cost-effectiveness ratios., Conclusions: Compared with the absence of screening and with G-FOBT, the biennial two-stool immunochemical test can be considered a promising method for mass screening for colorectal cancer.

Little is known about costs related to the surveillance of patients that have undergone curative resection of colorectal cancer. The aim of this study was to calculate the observed surveillance costs for 385 patients followed-up over a 3-year period, to estimate surveillance costs if French guidelines are respected, and to identify the determinants related to surveillance costs to derive a global estimation for France, using a linear mixed model. The observed mean surveillance cost was 713. If French recommendations were strictly applied, the estimated mean cost would vary between 680 and 1,069 according to the frequency of abdominal ultrasound. The predicted determinants of cost were: age, recurrence, duration of surveillance since diagnosis, and adjuvant treatments. For France, the surveillance cost represented 4.4% of the cost of colorectal cancer management. The cost of surveillance should now be balanced with its effectiveness and compared with surveillance alternatives.

Somatic mutations of the D310 sequence of the mitochondrial DNA are reported in human cancers, including colorectal cancers (CRC). The presence of these mutations at early or late steps of colorectal carcinogenesis is unknown. Their prevalence increased significantly with the number of cytosines in the D310 sequence of the matched normal tissue (D310 polymorphism), suggesting that this polymorphism could be a risk factor for CRC. The aim of this study was (i) to investigate the prevalence of D310 mutations in 64 colorectal adenomas and 36 liver metastases from 15 CRC patients, (ii) to assess the relation between D310 polymorphism and the risk of colorectal adenoma in a case-control study including 613 cases with colorectal adenoma and 572 polyp-free (PF) controls. D310 mutations were found in colorectal adenomas and liver metastases from CRC patients in 27 and 33%, respectively and so are an early genetic event in colorectal carcinogenesis. The frequency of the mutations increased significantly with the number of cytosines in the matched normal tissue D310 sequence (p < 0.001) but the distribution of D310 polymorphisms was not significantly different between adenoma cases (large (>9 mm) and small (<5 mm) adenomas) and PF controls (C(4)-C(7)TC(6): 47, 52 and 49%; C(8)TC(6): 44, 39 and 41%; C(9)-C(10)TC(6): 9, 9 and 10%, respectively; p > 0.05), suggesting that germline D310 polymorphism is not a risk factor for colorectal adenomas. Considering their high frequency in colorectal adenomas, mitochondrial D310 mutations could represent a biomarker for early detection of CRC although their causative role in colorectal carcinogenesis remains uncertain., ((c) 2008 Wiley-Liss, Inc.)

Background: Little is known about the descriptive epidemiology of colorectal adenomas diagnosed in the population., Aim: To describe time trends in the rate of first diagnosis of colorectal adenomas and estimate the proportion of adenoma-bearing individuals detected over a 24-year period., Methods: A total of 11,027 patients were first-diagnosed with colorectal adenomas among Côte-d'Or residents (France) between 1976 and 1999. Annual percentage changes were estimated using a Poisson regression model. The proportion of diagnosed adenoma-bearing individuals was estimated using the prevalence of adenomas in an autopsy study performed in the area., Results: Standardized diagnosis rates were 89.6/100,000 men and 50.3/100,000 women. During the period 1976-1993, diagnosis rates significantly increased with annual percentage changes in men and women of respectively +17.1% and +22.3% for proximal adenomas, +7.5% and +9.1% for distal adenomas and +7.2% and +8.0% for advanced adenomas. Changes were less marked during the period 1994-1999. The estimated proportion of adenoma-bearing individuals diagnosed during the 24-year period was 20.0% in men and 16.0% in women., Conclusion: Despite a marked increase in the rate of first adenoma diagnosis, the proportion of diagnosed adenoma-bearing individuals seems too low to induce a significant decrease in colorectal cancer incidence.

Epidemiological studies have provided inconsistent data about the role of dietary fatty acids in colorectal cancer, and few studies have addressed their role in colorectal adenoma. The aim of the study was to assess the risk of overall adenoma recurrence associated with dietary consumption of total fat, subtypes of fat, and specific fatty acids (oleic acid, linoleic acid, alpha-linolenic acid). The study sample was composed of 523 patients with confirmed adenomas at the index colonoscopy, 35 to 75 yr old, who completed the European fiber-calcium intervention trial and had an initial dietary assessment using a qualitative and quantitative food questionnaire. The overall 3-yr recurrence rate was 22.6% (118 out of 523 patients). There were no significant associations between overall adenoma recurrence and either total fat, subtypes of fat, or specific fatty acids. However, polyunsaturated fatty acids and linoleic acid were both moderately but significantly associated with distal and multiple recurrence. No significant associations were observed with recurrence of proximal or advanced adenomas. Our findings do not support the hypothesis of strong associations between dietary fatty acids and recurrence of colorectal adenomas. The hypothesis of a differential role of specific fatty acids according to colorectal subsites deserves further investigation.

The aim of the study was to assess the contribution of general practitioners in the surveillance of colorectal cancer, and to examine characteristics and survival of patients with routine general practitioner follow-up. This French registry-based study included 389 patients diagnosed with first colorectal cancer in 1998 and free of disease at least 6 months after curative surgery. For each physician involved, medical records were thoroughly reviewed to collect information about the clinical examinations and follow-up tests prescribed within 3 years after surgery or until death or detection of recurrence. Five-year vital status was obtained through registry records. The proportion of routine clinical examinations performed by general practitioners increased from 35% in the first year to 65% in the third year. Patients having undergone regular general practitioner routine examinations (> or =one examination every 6-month period) had significantly less advanced disease (odds ratio: 0.45; 95% confidence interval: 0.21-0.96), preoperative complications (odds ratio: 0.28; 95% confidence interval: 0.08-0.91) and routine examinations by gastroenterologists/oncologists (odds ratio: 0.37; 95% confidence interval: 0.14-0.98) compared with those without general practitioner examinations. Routine general practitioner follow-up had no influence on 3 and 5-year survival. General practitioners detected significantly more recurrences than specialists in patients over 75 and in those presenting symptoms. French general practitioners are widely involved in the surveillance of patients with early-stage colorectal cancer, without any unfavourable impact on the patient's survival. Some suggestions exist that continuing education in oncology may increase the implication of general practitioners in colorectal cancer surveillance.

Objectives: To assess the contribution of gastroenterologists (GEs) to the surveillance of colorectal cancer after curative surgery., Patients and Methods: This registry-based study included 407 patients residing in two French administrative areas diagnosed with newly diagnosed colorectal cancer in 1998 and free of disease six months after curative surgery. All surveillance examinations performed either in the three years after surgery or until death or recurrence were collected retrospectively., Results: One hundred nine patients (27%) had a regular clinical check-up with a GE at least once a year. Factors independently associated with GE follow-up were young age (P=0.004), use of adjuvant chemotherapy (P=0.013), and surgeon follow-up (P=0.068). GEs ordered 84% of colonoscopies, 44% of abdominal ultrasound examinations and 52% of abdominal CT scans. They detected 35% of recurrences. A significant proportion of patients (20%) had no regular follow-up, irrespective of the physicians involved., Conclusions: GEs play a modest role in the routine follow-up of patients with colorectal cancer, but are largely involved in ordering surveillance tests. They might play an important role in the surveillance of patients who presently have poor access to health care.

Background & Aims: The risk of developing colorectal neoplasia is not well established among family members of individuals with large adenomas, and screening strategies remain under debate in this population. This study aimed at quantifying the risk of colorectal adenomas and cancers using colonoscopic screening in first-degree relatives of patients with large adenomas., Methods: This case-control study was performed in 18 endoscopic units of French nonuniversity hospitals. A colonoscopy was offered to first-degree relatives of 306 index cases with adenomas > or =10 mm if they were alive, aged 40-75 years, and could be contacted by the index case. Among them, 168 were examined and matched for age, sex, and geographical area with 2 controls (n = 307). Controls were randomly selected from 1362 consecutive patients aged 40-75 years having undergone a colonoscopy for minor symptoms., Results: The prevalence of large adenomas and cancers was 8.4% and 4.2%, in relatives and controls, respectively. Odds ratios (ORs) associated with a history of large adenomas in relatives were 2.27 (95% confidence interval [CI], 1.01-5.09) for cancers or large adenomas, 1.21 (95% CI, 0.68-2.15) for small adenomas, and 1.56 (95% CI, 0.96-2.53) for all colorectal neoplasia. The risk of large adenomas and cancers was higher in relatives of index cases younger than 60 years (OR, 3.82; 95% CI, 0.92-15.87) and when the index case had large distal adenomas (OR, 3.14; 95% CI, 1.27-7.73)., Conclusions: First-degree relatives of patients with large adenomas are at increased risk of developing colorectal cancers or large adenomas. This result has implications for screening in this high-risk population.

Background: Matrix metalloproteinases (MMP) have been shown to play a role in colorectal cancer (CRC). More recently, MMP1, MMP3 and MMP7 functional gene promoter polymorphisms have been found to be associated with CRC occurrence and prognosis. To document the role of MMP polymorphisms in the early step of colorectal carcinogenesis, we investigated their association with colorectal adenoma risk in a case-control study comprising 295 patients with large adenomas (LA), 302 patients with small adenomas (SA) and 568 polyp-free (PF) controls., Methods: Patients were genotyped using automated fragment analysis for MMP1 -1607 ins/del G and MMP3 -1612 ins/delA (MMP3.1) polymorphisms and allelic discrimination assay for MMP3 -709 A/G (MMP3.2) and MMP7 -181 A/G polymorphisms. Association between MMP genotypes and colorectal adenomas was first tested for each polymorphism separately and then for combined genotypes using the combination test. Adjustment on relevant variables and estimation of odds ratios were performed using unconditional logistic regression., Results: No association was observed between the polymorphisms and LA when compared to PF or SA. When comparing SA to PF controls, analysis revealed a significant association between MMP3 -1612 ins/delA polymorphism and SA with an increased risk associated with the 6A/6A genotype (OR = 1.67, 95% CI: 1.20-2.34). Using the combination test, the best association was found for MMP3.1-MMP1 (p = 0.001) with an OR of 1.88 (95% CI: 1.08-3.28) for the combined genotype 2G/2G-6A/6A estimated by logistic regression., Conclusion: These data show a relation between MMP1 -1607 ins/del G and MMP3 -1612 ins/delA combined polymorphisms and risk of SA, suggesting their potential role in the early steps of colorectal carcinogenesis.

Background: Little is known about compliance with colonoscopy as a screening method in first-degree relatives of patients with large adenomas. Aims To evaluate the compliance with screening colonoscopy among this population, and its determinants., Methods: Data were obtained from the family part of the GEADE study, a study on genetic factors of colorectal adenomas. Index cases were 306 patients with adenomas > or = 10 mm. All living first-degree relatives aged 40-75 who could be contacted by the index case were asked to undergo a colonoscopy, unless they had had one in the previous 5 years., Results: Among 674 eligible relatives, 56 had had a colonoscopy within the preceding 5 years and 114 underwent a screening colonoscopy resulting in a compliance with screening colonoscopy of 18%. This was not related to most characteristics of index cases. Compliance was significantly lower when the index case lived in the Greater Paris area than when he/she lived in other areas (12% vs. 21%). It was higher in siblings (18%) and offspring (23%) than in parents (9%) and in relatives under 55 years old (22%) than in relatives aged 55 and over (15%)., Conclusions: Compliance with colonoscopy was low in first-degree relatives of patients with large adenomas. The reasons for this should be determined and appropriate strategies developed to increase compliance.

Purpose: Despite controversies, postoperative surveillance of colorectal cancer is generally recommended. This registry-based study was designed to assess the adherence of surveillance practices to French guidelines and identify three-year surveillance patterns and their demographic and clinical determinants., Methods: All patients (N = 409) diagnosed with first colorectal cancer in 1998 and alive without recurrence at least six months after curative surgery were identified from a population-based registry. Medical charts from multiple sources were reviewed to collect exhaustive information on follow-up procedures used during a three-year period. Multiple correspondence and cluster analyses were used to identify surveillance patterns., Results: The proportion of patients with a lower surveillance than that recommended was 35 percent for clinical examination, 65 percent for abdominal ultrasound, 52 percent for chest x-ray, and 20 percent for colonoscopy. Cluster analysis identified three patterns called minimal, moderate, and intensive surveillance patterns, which included 47, 24, and 29 percent of the patients respectively. The main independent predictors of both moderate and intensive surveillance patterns vs. minimal pattern were advanced tumor stage, chemotherapy, and radiation therapy. Younger age also was strongly associated with the intensive surveillance pattern, and the presence of symptoms with the moderate surveillance pattern., Conclusions: Adherence of surveillance practices to French guidelines seems relatively poor. Surveillance patterns are mainly explained by patient age, tumor stage, and treatment modalities.

Background: Little is known about the management of recurrences from colorectal cancer at a population level., Materials and Methods: Data was obtained from the population-based cancer registry of Cote d'Or (Burgundy, France) over a 28-year period. Univariate and multivariate analyses were performed to analyse trends in treatment and survival for local recurrence and distant metastases., Results: The proportion of patients resected for cure increased from 6.7% (1976-1984) to 23.7% (1994-2003; P <0.001) for distant metastases and from 15.9% to 58.1% (P <0.001) for local recurrence. Age and period of diagnosis were independent factors associated with a resection for cure. Rectal cancer local recurrence was less often resected for cure than colon cancer local recurrence (P=0.05). Long-term survival was observed only after resection for cure: 5-year relative survival rates were 36.1% for local recurrence and 24.0% for distant metastases. In the multivariate analysis, survival decreased with age and increased over time but significantly only over the last study period. Surgical resection and palliative chemotherapy were other determinants of prognosis for distant metastases whereas surgical resection and palliative radiotherapy did influence the prognosis for local recurrence., Conclusion: Substantial advances in the management of recurrences have been achieved over time. More effective treatments and mass screening represent promising approaches to decrease this problem.

The relations between individual foods and nutrients to colorectal tumours are conflicting. Few studies have taken into account the interdependence between individual components of diet and their possible interactions. The aim of the study was to examine the associations between dietary patterns and the risk of colorectal adenoma recurrence in the European fibre-calcium intervention trial. Among the 640 patients with confirmed adenomas at the index colonoscopy, 592 had an initial dietary assessment using a diet history questionnaire. The present analysis was restricted to 277 men and 165 women without history of adenoma prior to the index colonoscopy and who completed the study. The main end point was the 3-year recurrence of adenomas. Principal component analysis was used to identify dietary patterns from 50 food groups. Ninety-two patients presented new colorectal adenomas at the 3-year colonoscopy (65 men and 27 women). In men, three meaningful dietary patterns emerged from analysis, explaining 21.3% of variability. They were called 'Mediterranean', 'Sweets and snacks' and 'High fat and proteins' patterns. None of them were significantly related to the overall recurrence of colorectal adenomas either in univariate or multivariate analyses. Among women, the 'Mediterranean', the 'Western' and the 'Snacks' patterns explained 21.9% of variability. The 'Mediterranean' pattern characterized by a high consumption of olive oil, vegetables, fruit, fish and lean meat significantly reduced adenoma recurrence [second tertile: adjusted odds ratio (OR)=0.50, 95% confidence interval (CI)=0.18-1.42; third tertile: adjusted OR=0.30, 95% CI=0.09-0.98; P for linear trend=0.04]. The 'Western' and 'Snacks' patterns were not associated with recurrence among women. In conclusion, this study suggests that the Mediterranean dietary pattern may reduce the recurrence of colorectal adenomas, at least in women. These exploratory results need to be confirmed by larger studies.

Objectives: Clinical trials have demonstrated that fecal occult blood screening for colorectal cancer can significantly reduce mortality. However, to be deemed a priority from a public health policy perspective, any new program must prove itself to be cost-effective. The objective of this study was to assess the cost-effectiveness of screening for colorectal cancer using a fecal occult blood screening test, the Hemoccult-II, in a cohort of 100,000 asymptomatic individuals 50-74 years of age., Methods: A decision analysis model using a Markov approach simulates the trajectory of the cohort allocated either to screening or no screening over a 20-year period through several health states. Clinical and economic data used in the model came from the Burgundy trial, French population-based studies, and Registry data., Results: Modeling biennial screening versus the absence of screening over a 20-year period resulted in a 17.7 percent mortality reduction and a discounted incremental cost-effectiveness ratio of 3357 Euro per life-year gained among individuals 50-74 years of age. Sensitivity analyses performed on epidemiological and economic data showed the strong impact on the results of colonoscopy cost, of compliance to screening, and of specificity of the screening test., Conclusions: Cost-effectiveness estimates and sensitivity analyses suggest that biennial screening for colorectal cancer with fecal occult blood test could be recommended from the age of 50 until 74. Our findings support the attempts to introduce large-scale population screening programs.

Background & Aims: Several randomized population-based studies have shown that screening for colorectal cancer (CRC) by fecal occult blood tests (FOBTs) can reduce CRC mortality. The aim of this French population-based study was to assess whether a similar benefit could be obtained in countries characterized by high performances in the diagnosis and management of CRC., Methods: Small-sized geographic areas, including 91,199 individuals aged 45-74 years, were allocated to either FOBT screening or no screening. Six screening rounds were performed. The FOBT was performed without diet restriction and was sent to a central analysis center and processed without rehydration. Screening group participants who had a positive test result were offered a full colonoscopy. The entire population was followed up for 11 years after study entry., Results: Acceptability of the test was 52.8% at the first screening round and varied between 53.8% and 58.3% in the successive rounds. Positivity rates were 2.1% initially and 1.4% on average in the successive rounds. CRC mortality was significantly lower in the screening population compared with the control population (mortality ratio, 0.84; 95% confidence interval, 0.71-0.99). The reduction in CRC mortality was more pronounced in those who participated at least once (mortality ratio, 0.67; 95% confidence interval, 0.56-0.81)., Conclusions: Our findings, together with the results of other trials, suggest that biennial screening by FOBTs can reduce CRC mortality regardless of the quality of the health system and support attempts to introduce large-scale screening programs into the general population.

Purpose: The identification of groups with a high risk of colorectal adenoma recurrence remains a controversial issue for clinicians. This study was designed to assess the predictive value of initial patient and adenoma characteristics of the three-year recurrence., Methods: The study population was composed of 552 patients with resected colorectal adenomas who completed the European Fiber-Calcium Intervention trial. At both baseline and three-year examinations, the characteristics of adenomas were recorded according to a standardized protocol. The main outcomes measured were the three-year overall recurrence, recurrence of multiple adenomas, recurrence of advanced adenomas (size > or = 1 cm or tubulovillous/villous architecture or moderate/severe dysplasia), and proximal and distal recurrence., Results: A three-year recurrence was observed in 122 patients (22.1 percent), and more than one-half of them had recurrent adenomas on the proximal colon. After adjustment for patient characteristics and treatment allocation, the number of adenomas and their proximal location at baseline were the main predictors of recurrence. In comparison with patients who had one or two adenomas on the distal colon, patients with three or more adenomas with at least one of them located on the proximal colon had a much higher risk of overall recurrence (5.3; 95 percent confidence interval, 2.7-10.3), proximal recurrence (8.5; 95 percent confidence interval, 4.1-18), and advanced adenoma recurrence (5.5; 95 percent confidence interval, 2.4-12.6)., Conclusions: Follow-up colonoscopies in patients with adenomas should include careful examination of the proximal colon. The time interval between follow-up examinations could probably be extended beyond three years in patients who have only one or two distal adenomas.

Aims: The aim of this study was to assess the independent value of pathological criteria in the diagnosis of mismatch repair (MMR)-defective sporadic colorectal cancers., Methods and Results: Resected colorectal adenocarcinomas (n = 273) were reviewed in order to identify a number of specific morphological features of MMR-defective carcinomas. Of the 273 cases, 35.2% were right-sided and 5.9% were poorly differentiated. Focal extracellular mucin secretion was seen in 5.1% of cases and a stromal follicular reaction in 4.6%. The expression of the two major MMR proteins hMLH1 and hMSH2 was studied by immunohistochemistry. Carcinomas were considered deficient in the MMR system when a loss of nuclear signal in neoplastic cells was observed for one of the proteins. Such an extinction was seen in 37 of the cases (13.6%). The hMLH1 protein was the one most frequently altered (86.5%). After multivariate analysis, three independent factors were significantly associated with MMR deficiency: proximal location [odds ratio (OR) = 9.30; 95% confidence interval (CI) 2.79, 30.98], the presence of a true stromal follicular reaction (OR = 13.60; 95% CI 2.98, 62.00) and poor differentiation (OR = 8.33; 95% CI 1.63, 40.32)., Conclusions: These results confirm that sporadic colorectal MMR-defective adenocarcinomas display certain specific morphological characteristics. However, these pathological features are not sufficiently predictive and immunohistochemistry is needed to identify such tumours accurately.

Mathematical models have been shown to be useful in predicting the cost-effectiveness of cancer screening programmes. We designed a computer macro-simulation model aimed at predicting the cost-effectiveness of alternative colorectal cancer screening strategies. This model was built to determine the cost-effectiveness of a biennial screening programme using the Hemoccult test in Burgundy (France). It was validated with data from the Danish randomized study. Estimates of our model showed an extremely close concordance with observed results in the Danish study. The observed mortality reduction was 18.0% and the estimated mortality reduction was 18.4%. Preliminary data from the Burgundy study predict a 14.6% colorectal cancer mortality reduction after 10 years. Sensitivity analyses were performed with different assumptions regarding the participation rates and the lead-time. This model can serve to assess the cost-effectiveness of a variety of screening modalities.

The Inhibitor of Apoptosis Protein (IAP) family includes several critical cell death inhibitors, the expression of which could be involved in colorectal carcinogenesis. Among them, c-IAP1 and c-IAP2 expression has never been investigated in colorectal cancer. The present study was designed to determine whether expression of both IAPs was related to pathological parameters and survival in sporadic colon carcinomas. Analysis of five human colon cancer cell lines by both western blotting of cell fractions and immunocytochemistry showed that the two IAPs could be expressed both in the nucleus and in the cytoplasm. Immunohistochemical analysis of a series of 46 sporadic colorectal adenocarcinomas demonstrated that c-IAP1 expression was more frequent in the nucleus (85%), and that c-IAP2 was more often expressed in the cytoplasm (82%). A significant association was identified between a strong lymphoid infiltrate in the stroma and the nuclear expression of c-IAP2 (p = 0.02). No other relationship was observed between IAP expression and pathological features. After adjusting by age and stage, the relative risk of death was lower for cytoplasmic c-IAP1, cytoplasmic c-IAP2, and nuclear c-IAP2 expression. It was higher for nuclear c-IAP1 expression. These associations were not statistically significant, but this work underlines the importance of taking into account the subcellular location of the IAP family members in the evaluation of their prognostic significance.

Knowledge of the descriptive epidemiology of colorectal cancer is essential to a better understanding of the aetiology of the disease and the development of screening strategies. Considerable research efforts have been launched over the last 15 years to evaluate the ability of screening tests to decrease the incidence and mortality of colorectal cancer. This chapter provides a worldwide update of the incidence of colorectal cancer and reviews the evidence for screening for colorectal cancer based on published studies., (Copyright 2002 Elsevier Science Ltd.)

Background: Some epidemiological studies have suggested that high dietary intake of calcium and fibre reduces colorectal carcinogenesis. Available data are not sufficient to serve as a basis for firm dietary advice. We undertook a multicentre randomised trial to test the effect of diet supplementation with calcium and fibre on adenoma recurrence., Methods: We randomly assigned 665 patients with a history of colorectal adenomas to three treatment groups, in a parallel design: calcium gluconolactate and carbonate (2 g elemental calcium daily), fibre (3.5 g ispaghula husk), or placebo. Participants had colonoscopy after 3 years of follow-up. The primary endpoint was adenoma recurrence. Analyses were by intention to treat., Findings: 23 patients died, 15 were lost to follow-up, 45 refused repeat colonoscopy, and five developed severe contraindications to colonoscopy. Among the 552 participants who completed the follow-up examination, 94 stopped treatment early. At least one adenoma developed in 28 (15.9%) of 176 patients in the calcium group, 58 (29.3%) of 198 in the fibre group, and 36 (20.2%) of 178 in the placebo group. The adjusted odds ratio for recurrence was 0.66 (95% CI 0.38-1.17; p=0.16) for calcium treatment and 1.67 (1.01-2.76, p=0.042) for the fibre treatment. The odds ratio associated with the fibre treatment was significantly higher in participants with baseline dietary calcium intake above the median than in those with intake below the median (interaction test, p=0.028), Interpretation: Supplementation with fibre as ispaghula husk may have adverse effects on colorectal adenoma recurrence, especially in patients with high dietary calcium intake. Calcium supplementation was associated with a modest but not significant reduction in the risk of adenoma recurrence.

Objective: To estimate the lifetime risk of colorectal cancer in the general population and in first degree relatives of patients with sporadic colorectal cancer or adenoma., Main Outcomes Measures: The cumulative risk of colorectal cancer (0-74) in the general population combined with the relative risk of colorectal cancer and the prevalence of different groups of subjects with family history of colorectal tumour allows the calculation of cumulative risks in these groups., Results: The lifetime risk of colorectal cancer was 1 in 23 in men and 1 in 40 in women. In males, 0.5% in the 55-59 age group and 4.5% in the 70-74 age group will develop a colorectal cancer. The corresponding values in females were 0.4% and 2.5%. The cumulative risk at age 74 varied between 7.7% (one family member affected) and 25.6% (two affected) in males, and 4.3% and 14.3% respectively in females. The risk in the 40-44 year age group for individuals with one first degree relative affected before 45 years of age was 0.5%, similar to that of those aged 45-49 with one first degree relative affected with a colorectal cancer or a large adenoma (> 1 cm)., Conclusions: These results suggest that screening in the general population should start at 50 or 55. The lifetime risk is high enough (over 10%) among individuals with one affected first degree relative before age 45, or with at least two affected first degree relatives, to warrant colonoscopic screening. The data provide a basis for recommendations that relatives of these patients should enter screening programmes at age 40 to 44.

The knowledge of descriptive epidemiology of colorectal cancer is a prerequisite essential to a better understanding of the aetiology of the disease and the development of prevention strategies. This work provides an update of descriptive epidemiological data on colorectal cancer incidence in the world. In 1988-1992, incidence rates of colorectal cancer varied from 15- to 25-fold according to the geographical area. The highest rates were observed in Western countries, especially in North America, Australasia and, to a lesser extent, in northern and western Europe. The geographical distribution of colorectal cancer was similar in men and women. An examination of incidence data by subsites showed that the magnitude of geographical variations was more important for colon cancer than for rectal cancer. Contrasting with the male predominance for rectal cancer and, to a lesser degree, for left colon cancer, cancers of the right colon were found to be as frequent in women as in men. Examination of time trends during the last decades reveals a sharp increase in incidence of colorectal cancer in Japan and in eastern and southern Europe. On the other hand, incidence rates show some stagnation in North America and western Europe in recent years. In fact, there are some suggestions for differential time trends according to the anatomical subsite, with a recent proximal shift in the distribution of cancers of the large bowel in Western countries. In conclusion, descriptive epidemiological data support the notion that distinct pathogenic mechanisms may be involved in the carcinogenesis of the proximal and distal bowel.

Epidemiological studies have emphasised the major role of diet in the aetiology of large bowel cancer. Attempts to identify causative or protective factors in epidemiological and experimental studies have led to some discrepancies. The time has come to test the most important hypotheses within the frame-work of intervention studies. Among studies specifically devoted to colorectal carcinogenesis, eight have been completed and five are ongoing. They evaluate the effect of the intervention on adenoma recurrence and, in three studies, on adenoma growth. Five intervention trials considering cardiovascular diseases and different cancer sites will provide data on the effect of the intervention on colorectal cancer incidence. Vitamins and antioxidants, fibre or calcium supplementation, aspirin therapy and dietary modifications are evaluated. Most of the available data do not support the idea of a protective effect of vitamins and antioxidants against colorectal carcinogenesis. It is too early to draw any conclusions on the effects of fibre, calcium supplementation, aspirin therapy and dietary intervention. The results of ongoing studies will be available within 2 years. If one of the evaluated interventions proves efficient, the benefits of a simple, safe and inexpensive prophylaxis for a very common cancer will be clear.