Diagnostic yield of a one sample immunochemical test at different cut-off values in an organised screening programme for colorectal cancer.

BACKGROUND: Quantitative immunochemical faecal occult blood tests have become the recommended tests for colorectal cancer screening. The aim of this study was to complete our knowledge on the performance of one of the quantitative immunochemical tests available, FOB-Gold, and to propose a possible strategy for an organised screening programme. PATIENTS AND METHODS: Within the French organised screening programme, 23,231 average-risk individuals, aged 50-74 performed both a 3-day Hemoccult test and a 1-day FOB-Gold test. Performances of the immunochemical test were evaluated at different cut-off levels. RESULTS: The positivity rate for the Hemoccult was 2.1% and for the FOB-Gold varied between 4.6% (cut-off value of 100 ng/mL, the lowest studied cut-off) and 2.1% (cut-off value of 352 ng/mL). The number of colonoscopies decreased with increasing cut-off values by 21.5% (150 ng/mL), 35.4% (200 ng/mL) and 53.3% (352 ng/mL). The corresponding miss rate for CRC was respectively 6.4%, 11.1% and 22.2%, and for advanced adenoma respectively 16.3%, 29.2% and 43.6%. Compared with the reference cut-off for the FOB-Gold (100 ng/mL) the miss rate for Hemoccult was 53% for CRC and 77% for advanced adenoma. CONCLUSION: The study suggests that in countries with colonoscopy facilities compatible with a screening test positivity rate of up to 5%, use of a 1-day test with a cut-off value between 100 and 150 ng/mL could be the recommended strategy. Further increasing the cut-off value up to the same positivity rate as Hemoccult could be used in areas with limited access to colonoscopy.

Comparison between a guaiac and three immunochemical faecal occult blood tests in screening for colorectal cancer.

BACKGROUND: The aim of this study was to compare the performance of the guaiac-based faecal occult blood test (G-FOBT), with that of three immunochemical faecal occult blood tests (I-FOBT) which allow automatic interpretation. PATIENTS AND METHODS: Under the French organised screening programme, 85,149 average-risk individuals aged 50-74 participating in the third screening round, performed both the G-FOBT (Hemoccult-II test) and one of the I-FOBTs: FOB-Gold, Magstream and OC-Sensor. RESULTS: Given the chosen threshold, the positivity ratio between the different I-FOBTs and the G-FOBT was 2.4 for FOB-Gold, 2.0 for Magstream and 2.2 for OC-Sensor (P=0.17). The three I-FOBTs were superior to the G-FOBT for colorectal cancer (CRC) detection. The ratios for detection rates were 1.6 (FOB-Gold), 1.7 (Magstream) and 2.1 (OC-Sensor) (P=0.74). For non-invasive CRC they were, respectively, 2.5, 3.0 and 4.0 (P=0.83) and for advanced adenomas 3.6, 3.1 and 4.0 (P=0.39). CONCLUSIONS: This study provides further evidence that I-FOBT is superior to G-FOBT. None of the three I-FOBTs studied appeared to be significantly better than the others.

Incidence and patterns of recurrence after resection for cure of colonic cancer in a well defined population.

BACKGROUND: The aim of this study was to determine the incidence and patterns of failure following potentially curative surgery of colonic cancer. METHODS: Data were obtained from the cancer registry of the Côte-d'Or (France). Data on 2657 patients who had resection for cure of colonic cancer between 1976 and 2000 were analysed. Local and distant failure rates were calculated using the actuarial method and multivariable analysis was performed using a Cox model. RESULTS: The 5-year cumulative rate was 12.8 percent for local recurrence and 25.6 percent for distant metastases. Five-year cumulative local recurrence rates were 4.9 percent for stage I, 11.0 percent for stage II and 23.5 percent for stage III tumours (P<0.001). The corresponding rates for distant metastases were 6.4, 21.4 and 48.0 percent (P<0.001). The 5-year cumulative rates for distant metastases were 31.7 percent for the period 1976-1980 and 21.1 percent for 1996-2000, and the local recurrence rates were 17.6 and 9.0 percent respectively. The decreases in rates of local recurrence and distant metastases were significant in multivariable analysis. Cancer extension and presenting features were related to patterns of failure. Tumour location was significantly associated with risk of local recurrence, whereas age and gross features were associated with risk of distant metastasis. CONCLUSION: Recurrence following resection of colonic cancer remains a substantial problem. Follow-up is of particular importance in the 3 years after surgery.

Modeling recurrence in colorectal cancer.

OBJECTIVE: To assess the role of recurrence in prognosis of colon cancer, we investigated several methodologic issues, including application of classic survival analysis and Markov model. STUDY DESIGN AND SETTING: The data were recorded by the Registry of Digestive Tumors of Côte d'Or, France, for 874 patients who had been treated by surgery between 1976 and 1984 and followed for up to 11 years. Survival analyses included the Cox proportional hazards model and its two generalizations that allow recurrence to be taken into account as a time-dependent covariate or as a competing outcome. The Markov model was used to analyze simultaneously recurrence and death. RESULTS: The competing risks approach is not appropriate because censoring is indisputably informative. The Markov model and the Cox model, with recurrence as a time-dependent covariate, provided similar results, demonstrating the impact of age and gender on recurrence and revealing a reduction in the effect of site and stage on mortality. CONCLUSION: A Markov multistate model seems to give new insights about the course of digestive cancer progression and into the role of recurrence in this process.

A simulation model for evaluating the medical and economic outcomes of screening strategies for colorectal cancer.

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.

Colon cancer in France: evidence for improvement in management and survival.

BACKGROUND: Cancer registries recording all cases diagnosed in a well defined population represent the only way to assess real changes in the management of colon cancer at the population level. AIMS: To determine trends over a 23 year period in treatment, stage at diagnosis, and prognosis of colon cancer in the Côte-d'Or region, France. PATIENTS: A total of 3389 patients with colon cancer diagnosed between 1976 and 1998. METHODS: Time trends in clinical presentation, surgical treatment, chemotherapy treatment, stage at diagnosis, postoperative mortality, and survival were studied. A non-conditional logistic regression was performed to obtain an odds ratio for each period adjusted for the other variables. To estimate the independent effect of the period on prognosis, a relative survival analysis was performed. RESULTS: Between 1976 and 1991, the resection rate increased from 69.3% to 91.9% and then remained stable. This increase was particularly marked in the older age group (56.4% to 90.5%). The proportion of stage III patients treated with adjuvant chemotherapy rose from 4.1% for the 1989-1990 period to 45.7% for the 1997-1998 period. Over the 23 years of the study the proportion of stage I and II patients increased from 39.6% to 56.6%, associated with a corresponding decrease in the proportion of patients with advanced stages. Postoperative mortality decreased from 19.5% to 7.3%. This led to an improvement in five year relative survival (from 33.0% for the 1976-1979 period to 55.3% for the 1992-1995 period). CONCLUSIONS: Advances in the management of colon cancer have resulted in improving the prognosis of this disease. However, progress is still possible, particularly in the older age group.

[Endoscopic monitoring after polypectomy. What efficacy? What rhythm?]. / La surveillance endoscopique après polypectomie. Quelle efficacité? Quel rythme?

IN THE ABSENCE OF ENDOSCOPIC MONITORING: The risk of colorectal cancer is higher than in the general population in patients presenting an adenoma with a diameter of more than 1 cm, and/or comprising villous structures and/or severe dysplasia. The risk is not increased in the presence of one or two tubular adenomas measuring less than 1 cm and without severe dysplasia. It has been demonstrated that endoscopic monitoring decreases the incidence and mortality of colorectal cancers in these patients. MONITORING MODALITIES: A control colonoscopy, 3 years after polypectomy is sufficient in most cases. Colonoscopy is recommended within the 3 months following exeresis of a transformed sessile adenoma, in order to check that the polypectomy was complete. A control colonoscopy can be performed 1 year later in the rare cases presenting more than 3 adenomas, with one measuring more than 1 cm. When the control colonoscopy is normal, one can wait at least five years before conducting a further control.

Estimation of screening test (Hemoccult) sensitivity in colorectal cancer mass screening.

3 controlled cohorts of mass-screening for colorectal cancer using a biennial faecal occult blood (HemoccultII test on well-defined European populations have demonstrated a 14% to 18% reduction in specific mortality. We aimed to estimate the sensitivity (S) of this HemoccultII test and and also mean sojourn time (MST) from French colorectal mass-screening programme data. 6 biennial screening rounds were performed from 1988 to 1998 in 45 603 individuals aged 45-74 years in Saône-et-Loire (Burgundy, France). The prevalent/incidence ratio was calculated in order to obtain a direct estimate of the product S.MST. The analysis of the proportional incidence and its modelling was used to derive an indirect estimate of S and MST. The product S.MST was higher for males than females and higher for left colon than either the right colon or rectum. The analysis of the proportional incidence confirmed the result for subsites but no other significant differences were found. The sensitivity was estimated at 0.57 and the MST at 2.56 years. This study confirms that the sensitivity of the Hemoccult test is relatively low and that the relatively short sojourn time is in favour of annual screening.

Atherogen lipid profile in HIV-1-infected patients with lipodystrophy syndrome.

Background: Cases of lipodystrophy syndrome and metabolic disorders have been described since the onset of highly active antiretroviral therapy in HIV-infected patients. The aim of our study was to estimate the prevalence of lipodystrophy (LD) and to define the associated lipid profile of these patients. Methods: The following were determined for each patient: lipid profile (cholesterol and its subfractions, atherogenicity ratios, and triglycerides), blood glucose, and immunovirological markers (CD4(+) cell count and plasma viral load). Patients were classified into two groups on the basis of whether or not they presented with clinical signs of LD. Results: Among 233 HIV-infected patients included in the study, 61 cases (26.1%) of lipodystrophy (LD) were noted. Compared with non-LD patients (NLD), LD patients were older men (P<10(-4)) with a lower CD4(+) lymphocyte cell count (P<0.007) and more often at the AIDS stage (P<10(-3)) (OR=3.2 (95% CI: 1.47-6.2)). Multivariate analysis showed a correlation between LD cases and age (10 years older) (OR=1.78 (95% CI: 1.23-2.57), P<0.002) and the decrease in CD4(+) cell count (100 CD4(+)/mm(3) lower) (OR=1.31 (95% CI: 1.09-1.58), P<0.004). An analysis of lipid subfractions and atherogenicity ratios clearly indicated a proatherogenic lipid profile for the LD patients. Conclusions: The underlying physiopathological mechanism of LD is still unknown. However, the lipid profile of HIV-1-infected patients with a LD syndrome appears to place these patients at an increased risk of progression of atherosclerosis.