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Background: Epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of colorectal cancer (CRC). There are several potential strategies to target EGFR. However, monoclonal antibodies and low molecular weight tyrosine kinase inhibitors are the most advanced in clinical development. The majority of studies so far have merely required EGFRs to be expressed by CRC cells. The detection of EGFR expression is usually performed by immunohistochemistry (IHC) in the primary tumor. There are few data regarding the EGFR status in the corresponding distant metastases. Patients and methods: EGFR status was analyzed by IHC in 80 patients (31 male, 49 female) with CRC (70 colon, 10 rectum) and at least one distant metastatic lesion. Metastatic sites analyzed (n=80) were liver (79 patients) and lung (one patient). Results: EGFR reactivity was similar in the primary tumor and the related metastases. Among the 80 paired primary/metastatic tumors, only five (6.3%) showed discordance in EGFR status: two cases with EGFR expression in the primary tumor but not in the metastasis, and three samples with EGFR expression in the metastasis but not in the primary tumor. Conclusions: Between the paired primary tumors and distant metastatic lesions, 94% of samples had concordant EGFR status when analyzed by IHC.

Purpose. The efficacy and safety of single-agent, high-dose irinotecan (CPT-11, Campto) 500 mg/m2 every 3 weeks were investigated as first-line treatment for advanced colorectal cancer (CRC). Patients and methods. Patients were enrolled into the study to receive a first cycle of therapy with irinotecan at a dose of 350 mg/m2 every 3 weeks, which could be escalated to 500 mg/m2 for the second and subsequent cycles depending on toxicity. Efficacy, safety and pharmacokinetics were determined in the intent to treat (ITT) population and the high-dose population (i.e. patients who had received at least three cycles of irinotecan, the second and third at 500 mg/m2). Results. Of 49 patients enrolled into the study (ITT population), 31 (63%) received at least three cycles of treatment with cycles 2 and 3 at an irinotecan dose of 500 mg/m2 (the high-dose population). The response rates (RR) for the ITT and high-dose populations were 24.5% and 35.5%, respectively. The main grade 3/4 toxicities per cycle in the ITT and high-dose populations were neutropenia 22% and 17%, febrile neutropenia 5% and 3%, and diarrhoea 12% and 7%, respectively. The pharmacokinetics of irinotecan and its metabolite SN-38 were investigated in 31 patients in cycle 1 and 22 patients in cycle 2. Irinotecan clearance and SN-38 exposure were not sufficiently correlated with toxicity in cycle 1 to identify patients for dose increase in subsequent cycles. The exposure to irinotecan and SN-38 increased in proportion to dose from 350 to 500 mg/m2. Conclusion. These results suggest that high-dose irinotecan can be safely administered as first-line monotherapy to approximately two-thirds of patients who present with advanced CRC following a selective first cycle.

The study aim was to investigate predictive factors related to the results, in terms of survival and quality of life, of palliative surgery in cancer patients presenting with intestinal obstruction.A total of 109 patients already treated for a neoplasm were operated on for intestinal obstruction between 1990 and 2000. The investigated prognostic factors were age, sex, location of the primary tumour, extension of the cancer at the time of the operation and the surgical procedure carried out. The impact on the quality of life was assessed by the resumption of intestinal transit and the return home.The median survival rate was 64 days and the postoperative mortality rate 21%. The quality of life was improved in 65% of the patients. The only factors clearly correlated with survival and the success of the operation were the aetiological diagnosis of the intestinal obstruction and the type of procedure which was possible to carry out.Palliative surgery may improve the quality of life of a certain number of patients, but it was not possible to demonstrate predictive factors for the selection of patients who could have the larger benefits of such surgery.

Fibrate derivatives and HMG-CoA reductase inhibitors modify homeostasis of cholesterol. The aim of this study was to assess in an unselected population whether these hypolipidemic drugs are risk factors for cholelithiasis or, conversely, are protective agents. Both sexes, all socioeconomic categories, pregnant women, and cholecystectomized subjects were included. Clinical data collection and gallbladder ultrasonography were both carried out in a double-blind fashion. Fibrate derivatives were predominantly fenofibrate, HMG-CoA reductase inhibitors were simvastatin and pravastatin. On univariate analysis, age (50 years), sex, and use of fibrates were found to be significantly related to the presence of cholelithiasis. Age, sex, and fibrate treatment remained independently correlated with the presence of gallstones on multivariate analysis. With fibrates, the relative risk for lithiasis was 1.7 (P = 0.04). The HMG-CoA reductase inhibitors were not associated with a protective effect on univariate analysis. Of the lipid-lowering drugs, only fibrate derivatives were found to increase the risk of gallstone formation.

The authors describe the discovery of ascending colonic variceal veins via celiomesenteric diagnostic angiography following a bout of melena in a 44-year-old woman. Magnetic resonance imaging, including phase-contrast MR venography, allowed visualization of the portal and systemic veins immediately after the initial angiograms. The hemorrhagic episode did not resolve until after transjugular intrahepatic shunt insertion and selective variceal embolization through the shunt. At 1 week-, 3 months-, and 6 months post treatment, follow-up MR venography no longer revealed the presence of colonic varices. Colonoscopy at 6 months was normal and the patient did not have any further episodes of bleeding until a liver transplantation was performed after 9 months.

Cholelithiasis leads to 80,000 cholecystectomies being performed every year in France, but its prevalence is still unknown. The aim of this study was to assess the prevalence and risk factors of cholelithiasis in a random population of 1027 women and 727 men over the age of 30 in a small town in the southeast of France. Detailed clinical history, dietary investigation, and gallbladder ultrasound were collected for each subject and assessed by univariate analysis. A regression model was used in the multivariate analysis to detect the relative risk of cholelithiasis. Cholelithiasis was found in 130 individuals (global prevalence 13.9%). The relative risk for lithiasis was higher in women compared to men (1.89). Age (P0.0001) and body mass index (BMI)25 (P = 0.013) were also significant risk factors. Neither pregnancy nor oral contraceptive use proved to be risk factors. Typical biliary colic pain was the only symptom significantly associated with cholelithiasis (P0.0001). These results show that the prevalence of gallstones in France is similar to that in Denmark and Italy.

The role of a large gallbladder volume with regard to a predisposition for gallstones is unknown. It is possible that an increase in gallbladder volume could result in impaired gallbladder motility and bile stasis. We looked for factors affecting gallbladder volume in a random population in the southeast of France.To assess the relationship between gallbladder volume and gallstones, 528 subjects over the age of 30 were studied (72 with lithiasis). Age, sex, body mass index, body surface area and gallbladder volume were collected for each subject. A linear regression analysis was performed to look for significant variables.The overall adjusted prevalence of cholelithiasis was 13.9% in our population. On linear regression analysis, two variables (age and surface area) were found to be independently correlated with gallbladder volume. Gallbladder volume was significantly increased in subjects over 50 years (p0.001). There was a positive correlation between gallbladder volume and body surface area (r = 0. 33, p0.001). In this study, the presence or absence of gallstones did not significantly affect the gallbladder volume.We report that there is dilatation of the gallbladder with age and with an increase in body surface area. Whether this could represent risk factors for the occurrence of gallstone remains uncertain.

Dietary risk factors have been implicated in the development of cholelithiasis. The aim of this study was to determine in a homogeneous French population whether a particular type of diet may be lithogenic. Seventy-six subjects over 30 years of age (26 men, 50 women) with cholelithiasis detected by ultrasound were selected from a population sample of 830 subjects by drawing lots using the polling list. These were matched by 76 control subjects without cholelithiasis randomly selected from the same population. Univariate analysis was significant for a high calorie diet2500 kcal/day (OR = 3.62, P = 0.0065), a diet rich in carbohydrates with a consumptionor = 55 g/day (OR = 2.98, P = 0.0067), and a diet rich in total lipids (OR = 4.97, P = 0.023) or saturated fatty acids (OR = 3.06, P = 0.0146). An alcohol consumption equivalent to 20-40 g/day was protective (P = 0.018). Multivariate analysis confirmed these results. Our study suggests that a change in dietary habits by limiting excess calories, saturated fats and carbohydrates could reduce the incidence of cholelithiasis.

The aim of this work was to specify the time course of response to interferon (IFN) of hepatitis G virus (HGV) and hepatitis C virus (HCV) in coinfected individuals. A group of 33 patients, undergoing 12 months of IFN therapy for chronic hepatitis C, was screened for the presence of both HGV and HCV RNAs to select seven coinfected patients. Spontaneous recovery from HGV infection was excluded through the detection of antibodies to the envelope-2 protein of HGV and HCV isolates were genotyped. Within three months of treatment, we found that HGV RNA was transiently cleared in 6/7 patients, but the rate of long-term favorable response was very low (1/7). In addition, considering the same individuals separately, it was shown that HGV and HCV responded to IFN with different kinetics in 5/7 patients. Taken together, these results underscore the importance of the virological basis of the resistance to IFN treatment.

The gallbladder seems to play an important role in lithogenesis. Moreover, the morphology and the implantation of the cystic duct may also influence this process. Our purpose was to evaluate if the length and the implantation of the cystic duct may affect the formation of gallstones. Between April 1992 and March 1994, 270 patients who underwent endoscopic retrograde cholangiopancreatography were included in the study, and the radiological length of the cystic duct was carefully recorded. Patients were divided into two groups: I, absence of lithiasis: 113 patients (65 men, 48 women); and II, gallbladder lithiasis or lithiasis in the common bile duct with or without gallbladder lithiasis: 157 patients (73 men, 84 women). A statistically significant difference was observed among the two groups regarding the insertion of the cystic duct: implantation on the left side of the common bile duct represented a risk factor of lithiasis. The length of the cystic duct was not directly implicated. Hypokinesis of the gallbladder is currently recognized as being a major factor in the initial steps of lithogenesis, but the implantation of the cystic duct can play an important role by increasing cystic duct resistance and causing a reduced washout effect of the gallbladder contents, including cholesterol crystals.