Evolution of colorectal cancer epidemiology in a setting of opportunistic screening. A 20 year national survey in Luxembourg.

UNLABELLED: Invasive colorectal cancer (CRC) is the second leading cause of cancer death in Luxembourg. There is no organized screening programme in Luxembourg. This study aims to obtain a precise epidemiological description of the evolution of invasive CRC and high grade intraepithelial neoplasia (HGIEN) from 1990 to 2009, extracted from the database of the Morphologic Tumor Registry. Tumor stages and observed survival rates were also recorded. They were compared to the change in use of colonoscopic procedures. During the 20-year period, 4810 invasive CRC cases and 1180 HGIEN were recorded. Incidence rose from 1990 to 2005 and declined thereafter, especially in women. A sharp rise in HGIEN was noted from 2004 onwards, paralleling the rates of colonoscopies. 76% of CRC cases were found in advanced stages pT3 and pT4. The pT stage distribution did not change over the observation period. Observed survival rates improved during the study period. CONCLUSION: Under opportunistic screening conditions, mainly through colonoscopy, the incidence of CRC was declinig in recent years, whereas HGIEN incidence is rising in Luxembourg. Tumor pT staging remained unchanged whereas survival rates improved. We conclude that opportunistic screening is of little benefit for CRC prevention. A national organized screening programme is warranted.

Everolimus in patients with rheumatoid arthritis receiving concomitant methotrexate: a 3-month, double-blind, randomised, placebo-controlled, parallel-group, proof-of-concept study.

OBJECTIVES: Everolimus, a proliferation signal inhibitor with disease-modifying properties, may be useful in treating rheumatoid arthritis (RA). This proof-of-concept study assessed efficacy and safety of everolimus in combination with methotrexate (MTX) in patients with refractory RA. METHODS: A multi-centre, randomised, double-blind, placebo-controlled trial was performed in 121 patients with active RA receiving MTX. Patients were randomised to receive everolimus (6 mg/day) or placebo. The primary endpoint was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR20) at 12 weeks. RESULTS: There was a rapid onset of action and at 12 weeks the ACR20 response rate was significantly higher in the everolimus group (36.1%) than in the placebo group (16.7%; p = 0.022). Improvements from baseline in tender and swollen joint counts, patient's assessment of pain, and patient's and physician's global assessment of disease activity were significantly greater after treatment with everolimus. The most common adverse events (AEs) in the everolimus group were gastrointestinal (52.5% vs 31.7% in the placebo group), skin (29.5% vs 8.3%), and nervous system disorders (21.3% vs 10.0%); AEs leading to treatment discontinuation were reported for 16.4% and 10.0% of patients, respectively. Changes in haematological parameters, liver function tests, and lipid levels occurred more frequently with everolimus compared to placebo, but were mild and reversible. CONCLUSIONS: The study indicates that everolimus plus MTX provides clinical benefit with an acceptable safety and tolerability profile. It may offer a new treatment option in RA patients with inadequate response to MTX.

Efficacy and safety of oral cyclosporin A (CyA; Sandimmun) for long-term treatment of chronic severe plaque psoriasis.

The value of oral cyclosporin A (CyA; Sandimmun) in the treatment of chronic severe plaque psoriasis has already been established. Many controlled studies have addressed the issues of efficacy and safety, mostly in studies of several months duration. Patients treated for up to several years have been reported, but never in multicentre controlled studies. Guidelines have established the maximum dose permissible to reduce the risk of side-effects. However, the efficacy and safety of therapy of longer duration remain under investigation. The results of a multicentre prospective randomized clinical study (251 patients) to evaluate the efficacy, safety and tolerability of two dose levels of CyA (2.5 or 5 mg/kg/day) for inducing remission, and for use in long-term maintenance therapy for up to 21 months, are presented. An assessment of relapse as the dose was tapered (during the last 3 months of treatment), and the reversibility of CyA-induced side-effects, is also presented (follow-up phase of 3 months). Efficacy was evaluated by means of the psoriasis area and severity index (PASI). Safety was assessed by using the results of vital signs, physical examination, laboratory tests and physician and patient evaluation of adverse events. During the induction of remission phase of therapy, a total of 184 patients (73%) were treated successfully. The percentage of patients classified as successes at the end-point was significantly higher in the group on 5.0 mg/kg/day (92%) than in that on 2.5 mg/kg/day (52%; P < 0.001). A total of 215 (86%) patients reported at least one adverse event during the study. In 136 patients (54%) the reported adverse event was judged by the investigator as being related to CyA. Nineteen patients (8%) reported events that were judged as severe, and related to treatment with CyA. A total of 45 patients (18%) discontinued treatment due to adverse events. Hypertension was one of the reasons, or the reason, for discontinuation in 16 patients (6%). The occurrence of hypertension appeared unrelated to CyA dose. One hundred and sixteen patients (46%) experienced a maximum increase in serum creatinine > 30% above baseline values on at least one occasion. This increase in serum creatinine was often transient, and was one of the reasons, or the reason, for discontinuation in 24 patients (10%). An increase in serum creatinine > 30% above baseline was dose-related. The results of this study show that 5.0 mg/kg/day of CyA is significantly more effective than 2.5 mg/kg/day in the treatment of chronic plaque psoriasis.(ABSTRACT TRUNCATED AT 400 WORDS)

Risk factors for the development of chronic cyclosporine-nephrotoxicity.

Ninety CSA-treated kidney transplants recipients entered the study. The patients were allocated to three groups based on serum creatinine at 12 months and kidney biopsy findings: control group (serum creatinine less than 177 mumol/l), rejection group (verified by biopsy, serum creatinine greater than 177 mumol/l), nephrotoxicity group (verified by biopsy, serum creatinine greater than 177 mumol/l). Thirty variables were systematically evaluated. The following parameters had a predictive value for the development of chronic CSA-nephrotoxicity: number of CSA-induced episodes of acute deterioration of renal function, CSA trough level (day 0-30, day 31-90), number of unexplained episodes of acute deterioration of renal function, number of nephrotoxic drugs, number of rejection treatments, number of rejection episodes and primary poor renal function. The results indicate that all factors leading to acute renal failure, favor the development of CSA-nephrotoxicity.

A computer program package for relative survival analysis.

A computer program package has been constructed for use in patient survival analyses for chronic diseases based on aggregated data. The central concept of the analyses--the relative survival rate--is the ratio of the observed survival rate of the patients to the survival rate expected in a group in the general population similar to the group of patients at the beginning of the follow-up (interval), with respect to age, sex and calendar time. This quantity is used to measure patient survival adjusted for the effect of mortality attributable to the competing risks of death without employing information on causes of death of individual patients. The package contains three alternative methods of estimating the relative survival rates, two different ways of estimating the expectation of life for the patients, and five methods of testing the relative survival patterns using information on the whole follow-up period. Conventional survival and competing risk analysis can also be performed with the package. It is hoped that the package will facilitate standardization of statistical methodology and terminology in long-term survival studies for chronic diseases.