[Management of medulloblastoma in children: the experience of a single institution in Liege from 1991 to 2005]. / Prise en charge du médulloblastome de l'enfant.

We present the experience of the Citadelle Hospital (Liege, B) in the diagnosis, treatment and follow-up of medulloblastoma in children. A retrospective study of 10 cases of medulloblastoma was performed. Five years after diagnosis, the event-free survival was 77%.

[Clinical evaluation of 23 children with neuroblastoma. The experience of a single institution]. / Les neuroblastomes de l'enfant. A propos de 23 cas.

In this retrospective study, we analyse epidemiology, clinical symptoms and therapeutic results in a group of 23 children with neuroblastoma. Half of them were less than 2 years of age; in 19 of 23, the primitive tumour was abdominal; 35% of them were initially metastatic. The overall survival was 83% at 5 years and the event free survival, 75% at 5 years. Pronostic factors are age, extension of the disease at diagnosis, biologic parameters and genetic study of the neuroblast cells (amplification of N-myc oncogen). Our study shows the deleterious effect of bone lesions.

[Retrospective study of childhood lymphomas. Report of 27 children treated at a single institution]. / Etude rétrospective des lymphomes de l'enfant. A propos de 27 cas traités dans une même institution.

Childhood lymphomas represent a heterogeneous group of disorders that are quite different from adult lymphomas. Over the past three decades, empirical chemotherapeutic management has transformed survival figures, and more recently greater understanding of the biology is offering hope for improved management of resistant disease. We present here the experience of a single institution in the management of 27 childhood lymphomas; epidemiological and clinical characteristics are described as well as survival rates. The median follow up of the patients is 4 years 7 months. The five-year overall survival for the entire group is more than 95 %; the 5-year disease free survival is 91,6 % for Hodgkin's lymphomas, 92,8% for non Hodgkin's lymphomas and 100% for Burkitt diseases. Two relapses have occurred and all of them appeared within the 18 months of the diagnosis. No toxic death has been reported.

Socio-economic differences in psychiatric in-patient care.

OBJECTIVE: We seek to investigate socio-economic differences in psychiatric in-patient care regarding admission, treatment and outcome. METHOD: This study is undertaken on a comprehensive and exhaustive psychiatric case register of all psychiatric in-patient care carried out in Belgium in 1997 and 1998 (n=144 754). RESULTS: Lower socio-economic groups were more likely to be compulsorily admitted, to be cared for in a non-teaching or psychiatric hospital, to be admitted in a hospital with unexpectedly long average length of stay and to be admitted to a ward with a more severe case-mix. They were less likely to receive antidepressants and psychotherapies. The improvements in functioning and in symptoms were also less favourable for these groups. The lowest group had a higher risk of dying in the hospital. CONCLUSION: Psychiatric in-patient care is associated with moderate socio-economic differences in access, treatment and outcome. Further research is needed to clarify the causes of such disparities.

[Clinical study of the month. Adjuvant radio-chemotherapy and chemotherapy following curative resection of pancreatic cancer: results of the randomized trial ESPAC-1]. / Etude clinique du mois. Radio-chimiothérapie et chimiothérapie adjuvante après résection à visée curative du cancer du pancréas: résultats de l'étude randomisée ESPAC-1.

The prognosis of pancreatic adenocarcinoma remains poor, with a 5-year survival rate lower than 5%. Resection, the gold standard treatment, can be performed in less than 15% of patients. Following surgery, the median survival is 12 months for the most favourable cancer patients. Adjuvant treatment have attempted to improve results. However, chemotherapy, radiotherapy and multimodal treatments don't have demonstrated a clear advantage in controlled trials. We will discuss results of the current trials in this topic. The randomised trial of the European Study Group for Pancreatic Cancer (ESPAC) recently published in the Lancet revealed a potential benefit of adjuvant chemotherapy. A critical analysis of the publication showed, however, that definitive conclusions of this trial must be interpreted with caution.

Are the WOSCOPS clinical and economic findings generalizable to other populations? A case study for Belgium. The WOSCOPS Economic Analysis Group. West of Scotland Coronary Prevention Study.

AIMS: As the West of Scotland Coronary Prevention Study (WOSCOPS) was conducted in Scotland, a country well-known for its high cardiovascular risk, the generalizability of its findings on pravastatin's clinical and economic effects has been questioned. This study examines the legitimacy of this concern, using Belgium as a case study. METHODS AND RESULTS: Local information on the prevalence and clustering of risk factors in individual patients was used in a risk equation to estimate the reference risk in Belgium. In contrast to prevailing beliefs, this risk was shown to coincide with the trial population's risk. As the relative risk reduction documented in a trial should apply across populations, the health benefits observed in WOSCOPS can clearly be extrapolated. This information in combination with local costs was then used to assess the economic efficiency of primary prevention with pravastatin in Belgium by means of a previously developed model. In parallel with the original estimates for the United Kingdom, the cost-effectiveness ratios remain well within the range of what is considered strong to moderate evidence for adoption and appropriate utilization, over a wide range of input values. CONCLUSION: This study demonstrates that the clinical and economic findings from WOSCOPS can indeed be generalized to other populations.

Costs induced by hip fractures: a prospective controlled study in Belgium. Belgian Hip Fracture Study Group.

The economic burden of hip fractures is thought to be important, but the excess medical costs they induce remain largely unknown. We assessed the direct medical costs induced by hip fractures during and after hospitalization. Hospital costs of 170 consecutive Belgian women with hip fracture were gathered. During the year following discharge, all medical costs were collected for the 159 hip fracture women who survived the acute hospitalization stay. A similar collection of data was performed on a comparison group of 159 age-and residence-matched women without a history of hip fracture. The mean cost of the acute hospital stay was 8,667 Belgian francs and the mean 1-year hip-fracture-related extra costs after hospitalization was 6,636 Belgian francs. During the year following the acute hospital stay, 19% of the hip fracture women and 4% of the comparison women were newly admitted to nursing homes (p<0.001). Although health care costs increased with age, hip-fracture-related extra costs after hospitalization seemed similar in those below or above 81 years old. These extra costs amounted to 7,710 Belgian francs in women not living in nursing homes at the time of fracture, and to 3,479 Belgian francs in women who lived in nursing homes. Health or mental status before hip fracture seemed not to affect extra costs. Taking into account the higher mortality of women with hip fracture, the extra costs during the acute hospital stay and during the 1-year follow-up amounted to a mean 15,151 Belgian francs. In conclusion, both acute hospital stays and subsequent medical care contribute significantly to medical costs induced by hip fractures.

[Chronopharmacologic approach to the administration of anticancer agents in pancreatic adenocarcinoma. Pilot experience]. / Approche chronopharmacologique de l'administration des agents anticancéreux dans l'adénocarcinome pancréatique. Expérience pilote.

The authors first analyzed the potential interest of the delivery of anticancer agents according to chronobiological concepts for human pancreatic cancer. They report their experience on 41 patients treated in adjuvant (12 cases) or palliative (29 cases) situations. The excellent therapeutic index observed warrants further evaluations of this concept in randomized trials.

Comparison of drugs use according to surgical procedures as instrument for budgeting and improvement of prescription efficiency.

Making an effort to control health expenditure's escalation, especially in hospital, the Belgian government is planning and experimenting with prospective budgeting. A research financed by the Ministry of Public Health allows us to point out the structure of the pathologies treated as well as other variables included in the medical MBDS like urgency, number of diseased systems, ... and explains a high percentage of the variance (62%) in drugs expenditures of the surgical cases. These variables have to be used in order to calibrate hospital drugs budgets. The Interdisciplinary Centre in Health Economics has developed tools to compare drugs prescriptions by type of surgical procedures in order to help hospitals to evaluate their performance should such drugs budgets be progressively introduced.

Treatment with a nonanthracycline regimen in advanced breast cancer: vinorelbine, cyclophosphamide, and 5-fluorouracil with folinic acid.

The efficacy of combination therapy with vinorelbine, cyclophosphamide, and 5-fluorouracil was assessed in women who had received no prior therapy for locally advanced or metastatic breast cancer. Sixty patients with metastatic breast cancer who had finished any adjuvant therapy at least 6 months previously and who had not received treatment for advanced disease were entered onto the study. The schedule consisted of vinorelbine (Navelbine, Pierre Fabre Medicament) 25 mg/m2 on days 1 and 8, cyclophosphamide 500 mg/m2 on day 1, and 5-fluorouracil 500 mg/m2 followed by folinic acid 200 mg/m2 on days 1 and 8. Treatment was repeated every 21 days up to a maximum of 8 cycles. Objective responses were observed in 27 of 60 patients (45%; CI95 32.4-57.6) including 4 complete responses (6.7%; CI95 0-13) and 23 partial responses (38.3%; CI95 22.5-54.1). The responses were achieved in both visceral and nonvisceral sites and at the same rate for patients with multiple sites of disease. Neutropenia was dose limiting, with 40% of patients affected at grade 3 or 4, while other hematologic and nonhematologic toxicity was very mild. This schedule achieves good levels of response without the use of an anthracycline, so it is suitable either for patients who have been extensively exposed to anthracyclines during adjuvant therapy or for those who have other contraindications to their use.

Cost-effectiveness of pravastatin in secondary prevention of coronary heart disease: comparison between Belgium and the United States of a projected risk model.

Methodological differences and variations in health care regulations among countries often preclude direct comparisons of cost-effectiveness studies. A projected risk model was applied, designed to determine the economic value in the United States of pravastatin in the secondary prevention of coronary heart disease (CHD), to Belgium using local health care costs. A Markov process was used to model the effectiveness of treatment for 3 years with pravastatin versus placebo in 1000 male CHD patients aged 60 years and clinically similar to those in the pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I) and pravastatin, lipids and atherosclerosis in the carotid arteries (PLAC II) studies. The PLAC I and II trials have shown that pravastatin treatment for 3 years at a weighted mean dose of 36.64 mg daily significantly reduced the incidence of non-fatal myocardial infarction in patients with CHD. Framingham data were used to project the risk of mortality 10 years post-myocardial infarction. The incremental cost per life year gained (LYG), after discounting costs and benefits by 5% annually, in the setting of Belgian health care regulations, was Belgian francs (BEF) 720794 (US$ 24359) for CHD patients with one additional risk factor; BEF 526464 (US$ 17792) for those with two additional risk factors; and BEF 392765 (US$ 13274) for those with three or more additional risk factors. The cost per LYG in Belgium appeared to be more sensitive to drug acquisition cost than to costs of medical interventions. The cost-effectiveness ratios of pravastatin monotherapy for 3 years in secondary prevention of CHD, obtained with the same projected risk model, are from 86 to 92% higher in Belgium than in the United States, due to differences in medical patterns of practice and in intervention costs.

[Treatment of epithelial ovarian cancer]. / Le traitement du cancer épithélial de l'ovaire.

Cancer of the ovary is much less frequent than breast cancer. Nevertheless, it hits 12 women out of 1,000,000 every year. The majority of patients are diagnosed with the disease in their fifties. The usual prognosis for ovarian cancer is back. Indeed, in 70 percent of all cases, it is, unfortunately, discovered at an advanced stage. This article will discuss the medical therapeutic approaches to ovary cancer, while stressing that major surgery is the basic treatment. If hormonotherapy and immunotherapy have not so far proven their efficacy, chemotherapy treatment has shown its ability to combat this affliction.

Is antiviral treatment (IFN alpha and/or ribavirin) justified in cirrhosis related to hepatitis C virus? Société Royale Belge de Gastro-entérologie.

AIM: To assess the benefit risk ratio of interferon and ribavirin in the treatment of patients with post hepatitis C cirrhosis we summarize the spontaneous over mortality of this disease, and made an overview of the randomized trials and of other controlled studies. RESULTS: In comparison to controls, patients with post hepatitis C cirrhosis have a 17 fold increase risk of dying from a liver disease that a control population, and a 6 fold increase from primary liver cancer. In France the hepatitis C epidemic which start in the sixties explains now the observed dramatic increase in mortality by primary liver cancer, both in men and women. Meta-analysis of randomized trials and controlled retrospective studies showed that interferon treatment is associated with a significant increase in ALT response at the end of the treatment, with a decrease in hepatocellular incidence as well as a decrease in mortality in comparison with controls. Very few data are published concerning ribavirin alone or in combination with interferon in patients with cirrhosis. Preliminary data suggest that this combination during 48 weeks permit to obtain in patients with compensated cirrhosis 20% of sustained virological response. The safety was acceptable but patients with low initial blood cells count must be carefully followed. In conclusion this overview clearly demonstrates a benefit-risk ratio in favor of treatment in patients with post hepatitis C cirrhosis by interferon.

Drug use in relation to clinical activities as an instrument for prospective drug budgeting. The Belgian experience.

In an effort to control escalating health expenditures, especially in hospitals, many countries are planning or experimenting with prospective budgeting systems. Belgium is no exception and has recently introduced, with some success, limited fixed charges per hospital admission and/or per hospitalisation day for laboratory tests and radiographic investigations. More recently, the focus has shifted to hospital drug expenditures, which have shown high growth rates over the past few years. Until now, such expenditures have been reimbursed on a fee-for-service system, often with limited out-of-pocket charges for hospitalised patients. In order to curb the growth of drug expenditures, it is appropriate to investigate whether the financing of hospital drugs through a prospective budgeting system could be a feasible solution. Therefore, we constructed a database of over 270 000 admissions from a sample of 23 Belgian general and teaching (university) hospitals for the year 1991. Data were obtained from the official Minimum Basic Data Set or Résumé Clinique Minimum, which contains summarised clinical and administrative information, plus detailed expenditures (including medications) for each hospital stay. This information allowed us to categorize each stay into an appropriate diagnosis-related group (DRG). Our first descriptive analysis identified a number of major variables that influenced patients' drug expenditures: all-patient DRG (APDRG), age, disease severity, length of stay in an intensive care unit, emergency admission, death during hospitalisation, and hospital type (teaching or general). A covariance analysis was then performed on all hospital stays combined, and separately on surgical and medical stays. The results indicated that these variables taken together account for between 56.5 and 76.3% of drug expenditures in medical and surgical stays, respectively, with the major variance explained by differences in APDRG category. However, when the data were disaggregated according to major diagnosis category, a large degree of heterogeneity in the explained variance was observed. In patients with drug use- and alcohol-related disorders, 5.2% of drug billings/expenditures were attributable to the APDRG, and the corresponding figure in patients undergoing circulatory system surgery was 84%. This means that, if DRGs are used to define a global prospective drug budget for a hospital, using the hospital's historical case mix as a weighting factor, we should pay particular attention to the hospital profile because the predictive power of such a system could be relatively low in some hospitals. Consequently, we need to construct larger confidence intervals for hospitals in which historical drug expenditures have low predictive power, or search for additional explanatory variables for expenditures in these hospitals.

Combination chemotherapy with carboplatin, cyclophosphamide and fluorouracil in advanced breast cancer.

Single agent carboplatin has demonstrated antitumoral activity in patients with advanced breast cancer. Thirty patients with inoperable locally advanced and/or metastatic breast cancer were treated with carboplatin (300 mg/m2) in combination with cyclophosphamide (600 mg/m2) and 5-fluorouracil (500 mg/m2) given on day 1 in a 4-weekly schedule. Of 29 patients evaluable for response, 4 presented CR and 4 PR (28%). Seven out of 19 chemotherapy-naive patients achieved CR (4) or PR (3) (37%). In contrast, only one patient out of 10 achieved PR in the group with previous adjuvant chemotherapy (10%). Responses were observed in primary tumours as well as in metastatic sites, including lymph nodes, lung, liver and skin. Median duration of response was 7.5+ and 3.8 months in CR and PR patients respectively. Toxicity was generally mild. Only 2 patients presented with clinically relevant hematologic toxicity. No significant non-hematologic toxicity was observed. It appears that this regimen, at the dosage and schedule studied, possesses only modest activity in patients with breast cancer, while being relatively atoxic. Carboplatin merits further investigation in this disease, but dosing should be individualised using e.g. a pharmacokinetic formula.

Phase II trial of weekly intravenous vinorelbine in first-line advanced breast cancer chemotherapy.

PURPOSE: This study investigated the therapeutic effects of single-agent intravenous (IV) weekly Navelbine (vinorelbine or 5'-nor-anhydro-vinblastine; Pierre Fabre Médicament, Boulogne, France), a semisynthetic vinca alkaloid, in women who had received no prior chemotherapy for locally advanced or metastatic breast cancer. PATIENTS AND METHODS: One hundred fifty-seven patients with assessable advanced or metastatic breast cancer who had received no prior chemotherapy were entered onto the study. They were stratified into five groups according to the main assessable tumor target: lung, liver, lymph nodes, skin, and others. One hundred forty-five patients were assessable for toxicity and response using World Health Organization (WHO) criteria; the 12 patients who were not evaluated were excluded because they were found not to meet the eligibility criteria. Navelbine was administered as a weekly 30-mg/m2 short IV infusion, and treatment was continued until disease progression. RESULTS: The overall response rate (WHO criteria) was 41% (complete response [CR], 7%; partial response [PR], 34%; 95% confidence interval [CI], 33% to 49%). In addition, 30% of the patients had stable disease. The response rate according to target was lymph nodes (28 of 42), 67%; liver (nine of 39), 23%; lung (10 of 30), 33%; skin (21 of 30), 70%; primary tumor (10 of 16), 56%; and bone (three of 10), 30%. The median time to treatment failure was 6 months and the median survival was 18 months. A total of 1,673 cycles were given to 145 eligible patients. At least one episode of WHO grade 3 or 4 granulocytopenia was seen in 72% of the patients. Nausea and/or vomiting, anemia, and/or thrombocytopenia were seen in less than 1% of cycles. Other side effects were rare, and additional toxicities were documented in the following proportions of patients: grade 2 to 3 alopecia, 8%; infectious episodes, 6%; and peripheral neuropathy, 3%. CONCLUSION: Our data confirm that Navelbine has major single-agent antitumor activity as front-line therapy in advanced breast cancer. Given its excellent tolerance profile and low toxicity, it should be considered for inclusion in first-line combination chemotherapy regimens.