Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy.

The predictive value of KRAS mutation in metastatic colorectal cancer (MCRC) patients treated with cetuximab plus chemotherapy has recently been suggested. In our study, 59 patients with a chemotherapy-refractory MCRC treated with cetuximab plus chemotherapy were included and clinical response was evaluated according to response evaluation criteria in solid tumours (RECIST). Tumours were screened for KRAS mutations using first direct sequencing, then two sensitive methods based on SNaPshot and PCR-ligase chain reaction (LCR) assays. Clinical response was evaluated according to gene mutations using the Fisher exact test. Times to progression (TTP) were calculated using the Kaplan-Meier method and compared with log-rank test. A KRAS mutation was detected in 22 out of 59 tumours and, in six cases, was missed by sequencing analysis but detected using the SNaPshot and PCR-LCR assays. Remarkably, no KRAS mutation was found in the 12 patients with clinical response. KRAS mutation was associated with disease progression (P=0.0005) and TTP was significantly decreased in mutated KRAS patients (3 vs 5.5 months, P=0.015). Our study confirms that KRAS mutation is highly predictive of a non-response to cetuximab plus chemotherapy in MCRC and highlights the need to use sensitive molecular methods, such as SNaPshot or PCR-LCR assays, to ensure an efficient mutation detection.

Incidence of rectosigmoid adenomatous polyps in subjects without prior colorectal adenoma or cancer: a prospective cohort study.

BACKGROUND: Subjects without known colorectal adenomas or cancer constitute a large majority of the population where 85% of all cases of colorectal cancer are thought to occur. Consequently these people should be considered for screening to decrease mortality from colorectal cancer in the general population. AIMS: To estimate the incidence rate of rectosigmoid adenomas in these subjects. METHODS: Subjects without adenomas or cancer at a previous examination which had visualised the rectosigmoid underwent a fibre endoscopy every three years. Endoscopic data and population characteristics were collected prospectively. RESULTS: A total of 450 subjects fulfilled the selection criteria; 287 (64%) underwent at least two examinations, and 163 had three or more. At the second examination, with a mean delay of 39 months, the incidence rate of rectosigmoïd adenomas was 1.50% per patient year. The rate was 1.75% per patient year (95% CI 0.80-3.33) at the third endoscopy with an additional mean delay of 38 months. The cumulative incidence rate at six years was 7.3% (95% CI 4.3-10.3), representing a mean of 1.2% per patient year. This rate increased with age and was higher for men than for women after age adjustment (p< 0.03). CONCLUSIONS: The incidence rates are very low compared with those of patients with prior adenomas. These results should be considered in establishing rectosigmoid adenoma screening strategies.

[Controlled study of propranolol in the prevention of recurrent hemorrhage in cirrhotic patients]. / Etude contrôlée du propranolol dans la prévention des récidives hémorragiques chez les patients cirrhotiques.

The aim of this study was to assess, by a pragmatic controlled trial, the value of propranolol in the prevention of recurrent bleeding in patients with cirrhosis. From January 1982 to December 1984, 368 cirrhotic patients were admitted for bleeding episode due to portal hypertension. Ninety-nine patients were included in the trial 24 h after cessation of bleeding (5 days on the average after hospital admission) and were randomly assigned to 2 groups: 51 patients receiving propranolol at doses that reduced the resting heart rate by 25 p. 100 and 48 receiving neither treatment nor placebo. Ninety-one per cent presented a rupture of varices, and 9 p. 100 acute gastric erosions: 94 p. 100 had an alcoholic cirrhosis. The distribution according to Child Turcotte's classification was grade A: 45.5 p. 100, B: 45.5 p. 100, C: 100 p. 100. The two groups were not significantly different excepted for previous bleeding episodes. The cumulative percentages of recurrent bleeding were not significantly different: between the treated and untreated groups (60 p. 100 vs. 68 p. 100 at 18 months); between the compliant patients (n = 39) and untreated and not compliant patients altogether; between the treated and untreated patients of Child's grade A on the one hand, and patients grades B and C on the other hand. The curves of cumulative survival were not significantly different between treated and untreated patients (66 p. 100 vs. 78 p. 100 at 18 months).(ABSTRACT TRUNCATED AT 250 WORDS)