Walhain-Saint-Paul, Belgium
Walhain-Saint-Paul, Belgium

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Tanguy-Schmidt A.,French Institute of Health and Medical Research | Chalandon Y.,University of Geneva | Cayuela J.-M.,University Paris Diderot | Hayette S.,University of Lyon | And 9 more authors.
Biology of Blood and Marrow Transplantation | Year: 2013

We report here the results of the GRAAPH-2003 trial with long-term follow-up in 45 patients with de novo Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Imatinib-based strategy improved the 4-year overall survival (OS) up to 52% versus 20% in the pre-imatinib LALA-94 trial (P = .0001). Despite the selection in patients who actually underwent transplantation, these results suggest that allogeneic or autologous stem cell transplants (SCTs) still have a place in overcoming the poor prognosis of Ph+ ALL in the era of imatinib therapy. OS was 50% after allogeneic SCT (24 patients), 33% in patients without a transplantation (9 patients), and 80% after autologous SCT (10 patients without allogeneic donor or >55 years, including 7 patients in complete molecular response). © 2013 American Society for Blood and Marrow Transplantation.


Delannoy A.,Hopital de Jolimont
Drugs and Aging | Year: 2011

The main characteristic of acute lymphoblastic leukaemia (ALL) in the elderly is its dismal prognosis. However, other than a lower incidence of T-cell ALL and a greater likelihood of unfavourable chromosomal abnormalities, the clinical and biological characteristics of Philadelphia chromosome-negative (Ph-) ALL in the elderly at diagnosis are no different from those observed in younger adults, and do not account, per se, for its poor prognosis. Rather, the latter is explained to a large extent by a high rate of treatment-induced mortality andor by the use of less toxic but comparatively less effective drug regimens. Ph- ALL patients are offered treatments ranging from palliative care to intensive chemotherapy, but the survival of patients given palliative or minimally active chemotherapy is extremely poor. However, a valid comparison with patients given more intensive chemotherapy is lacking, as, in most cases, minimally active chemotherapy is used in patients with poor performance status at diagnosis. When more intensive chemotherapy is used, unacceptably high early mortality rates (up to 50) have been reported, with complete-response rates ranging from 40 to 80 and 5-year survival consistently below 20. Clearly, the results of therapy are unsatisfactory in Ph- ALL patients, which should encourage the development of innovative approaches, such as the use of new monoclonal antibodies. On the other hand, the availability of imatinib and second-generation tyrosine kinase inhibitors (TKIs) has improved the prognosis of Philadelphia-positive (Ph) ALL in older patients. Impressive response rates have been reported, even in patients given imatinib and corticosteroids without additional chemotherapy, at the cost of manageable toxicity. Paradoxically, in the imatinib era, elderly patients with Ph leukaemia (which is clearly associated with an adverse prognosis in younger adults) seem to survive longer than Ph- elderly patients, although long-term survivors still remain relatively few. Whether new TKIs, such as dasatinib or nilotinib, will improve the prognosis of Ph ALL in the elderly is being prospectively assessed in several countries. © 2011 Adis Data Information BV. All rights reserved.


Chapman M.J.,French Institute of Health and Medical Research | Ginsberg H.N.,Columbia University | Amarenco P.,Bichat University Hospital | Andreotti F.,Catholic University Medical School | And 15 more authors.
European Heart Journal | Year: 2011

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (<1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal. © 2011 The Author.


Nordestgaard B.G.,Copenhagen University | Chapman M.J.,French Institute of Health and Medical Research | Ray K.,St George's, University of London | Boren J.,Gothenburg University | And 15 more authors.
European Heart Journal | Year: 2010

AimsThe aims of the study were, first, to critically evaluate lipoprotein(a) [Lp(a)] as a cardiovascular risk factor and, second, to advise on screening for elevated plasma Lp(a), on desirable levels, and on therapeutic strategies. Methods and resultsThe robust and specific association between elevated Lp(a) levels and increased cardiovascular disease (CVD)/coronary heart disease (CHD) risk, together with recent genetic findings, indicates that elevated Lp(a), like elevated LDL-cholesterol, is causally related to premature CVD/CHD. The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels. Mechanistically, elevated Lp(a) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a) resembles both plasminogen and plasmin but has no fibrinolytic activity, or may accelerate atherosclerosis because, like LDL, the Lp(a) particle is cholesterol-rich, or both. We advise that Lp(a) be measured once, using an isoform-insensitive assay, in subjects at intermediate or high CVD/CHD risk with premature CVD, familial hypercholesterolaemia, a family history of premature CVD and/or elevated Lp(a), recurrent CVD despite statin treatment, ≥3 10-year risk of fatal CVD according to European guidelines, and/or ≥10 10-year risk of fatal + non-fatal CHD according to US guidelines. As a secondary priority after LDL-cholesterol reduction, we recommend a desirable level for Lp(a) <80th percentile (less than ∼50 mg/dL). Treatment should primarily be niacin 1-3 g/day, as a meta-analysis of randomized, controlled intervention trials demonstrates reduced CVD by niacin treatment. In extreme cases, LDL-apheresis is efficacious in removing Lp(a). ConclusionWe recommend screening for elevated Lp(a) in those at intermediate or high CVD/CHD risk, a desirable level <50 mg/dL as a function of global cardiovascular risk, and use of niacin for Lp(a) and CVD/CHD risk reduction. © 2010 The European Society of Cardiology . All rights reserved.


Penninckx F.,UZ Gasthuisberg | Fieuws S.,Hasselt University | Beirens K.,Belgian Cancer Registry | Demetter P.,Erasme University Hospital | And 6 more authors.
Gut | Year: 2013

Objective: The abdominoperineal excision (APE) rate, a quality of care indicator in rectal cancer surgery, has been criticised if not adjusted for confounding factors. This study evaluates variability in APE rate between centres participating in PROCARE, a Belgian improvement initiative, before and after risk adjustment. It also explores the effect of merging the Hartmann resections (HR) rate with that of APE on benchmarking. Design: Data of 3197 patients who underwent elective radical resection for invasive rectal adenocarcinoma up to 15 cm were registered between January 2006 and March 2011 by 59 centres, each with at least 10 patients in the registry. Variability of APE or merged APE/HR rates between centres was analysed before and after adjustment for gender, age, ASA score (3 or more), tumour level (rectal third), depth of tumour invasion (cT4) and preoperative incontinence. Results: The overall APE rate was 21.1% (95% CI 19.7 to 22.5%). Significant variation of the APE rate was observed before and after risk adjustment (p<0.0001). For cancers in the lower rectal third, the overall APE rate increased to 45.8% (95% CI 43.1 to 48.5%). Also, variation between centres increased. Risk adjustment influenced the identification of outliers. HR was performed in only 2.6% of patients. However, merging of risk adjusted APE and HR rates identified other centres with outlying definitive colostomy rates than APE rate alone. Conclusion: Significant variation of the APE rate was observed. Adjustment for confounding factors as well as merging HR with APE rates were found to be important for the assessment of performances.


S. Descamps O.,Hopital de Jolimont | De Sutter J.,Ghent University | Guillaume M.,ISPPC Site de Vesale | Missault L.,Sint Jan Hospital
Atherosclerosis | Year: 2011

The evidence of the different concepts underlying the interplay between cholesterol absorption and synthesis in the context of statin and ezetimibe treatment were reviewed in the light of the eight major trials where cholesterol absorption and synthesis were analyzed on a large scale using the plasma levels of precursors of cholesterol and plant sterols. The only concept supported in all studies is a significant and consistent increase of cholesterol absorption with statin (correlated with the inhibition of synthesis) and of cholesterol synthesis with ezetimibe, whereas in combination, statin and ezetimibe reduce both cholesterol synthesis and absorption. In contrast, most of the other concepts failed to be clearly proven. At baseline, the inverse relationship between cholesterol absorption and synthesis (only examined in two studies) was found to be weak. On statin treatment, four studies showed that the changes in cholesterol synthesis and absorption, contributed less than 9% to the variability in cholesterol response to statin therapy. It has not been consistently demonstrated that good absorbers/bad synthesizers are bad responders to statin (6 studies) and good responders for ezetimibe (3 studies). There is also no clear inverse correlation between LDL reduction on statin treatment and that on ezetimibe treatment. Finally, the original idea from the first pioneer study of Miettinen et al. that, the higher the baseline intestinal ability to absorb cholesterol, the lower the benefit on the clinical cardiovascular outcomes was not reproduced in the PROSPER study. In conclusion, with the exception of a reverse effect of statin and ezetimibe on absorption and synthesis, most ideas supporting the interplay between cholesterol absorption and synthesis lacked consistency between studies. At present, the use of the plasma levels of plant sterols and cholesterol precursors as markers of cholesterol absorption and synthesis is far too limited to definitively solve these questions. © 2011 Elsevier Ireland Ltd.


Hompes D.,University Hospitals Gasthuisberg | D'Hoore A.,University Hospitals Gasthuisberg | Van Cutsem E.,University Hospitals Gasthuisberg | Fieuws S.,Hasselt University | And 6 more authors.
Annals of Surgical Oncology | Year: 2012

Background. Up to 25% of patients with metastatic colorectal cancer (CRC) present with peritoneal carcinomatosis (PC) as the only site of metastases. Complete cytoreductive surgery (CCRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) aims for locoregional disease control and long-term survival. Oxaliplatin is effective for treating advanced CRC. This study assesses the safety and efficacy of CCRS with HIPEC with oxaliplatin for patients with PC of CRC. Methods. A Belgian prospective multicenter registry was performed to monitor perioperative morbidity and assess mortality, disease-free survival (DFS), and overall survival (OS). Results. Forty-eight consecutive patients underwent CCRS (R0/1) with HIPEC (male/female ratio 17/31, median age 60 years, range 24-76 years). Median PC index was 11 (range 1-22). Median operation time was 460 (range 125-840) min, with a median blood loss of 475 (range 2-6,000) ml. Thirty-day mortality was 0%. Complication rate (any grade) was 52.1%. Anastomotic leakage occurred in 10.4% of patients, bleeding in 6.3%, and bowel perforation in 2.1%. Median hospital stay was 20 (range 5-65) days. At median follow-up of 22.7 (range 3.2-55.7) months, OS was 97.9% [95% confidence interval (CI) 86.1-99.7] at 1 year and 88.7% (95% CI 73.6-95.4) at 2 years. DFS at 1 year was 65.8% (95% CI 52.3-76.2) and 45.5% (95% CI 34.3-55.9) at 2 years. Median time until recurrence was 19.8 months (95% CI 12-upper limit not defined). Only after dichotomizing PC index was a significant difference in OS found between low and high PC index. Conclusions. CCRS followed by HIPEC with oxaliplatin for PC from CRC can be implemented with acceptable morbidity. Long-term DFS and OS can be achieved in selected patients. © 2012 Society of Surgical Oncology.


Dierickx D.,University Hospitals Leuven | Kentos A.,Hopital de Jolimont | Delannoy A.,Hopital de Jolimont
Blood | Year: 2015

Warm antibody hemolytic anemia is the most common form of autoimmune hemolytic anemia. When therapy is needed, corticosteroids remain the cornerstone of initial treatment but are able to cure only a minority of patients (<20%). Splenectomy is usually proposed when a second-line therapy is needed. This classical approach is now challenged by the use of rituximab both as second-line and as first-line therapy. Second-line treatment with rituximab leads to response rates similar to splenectomy (∼70%), but rituximab-induced responses seem less sustained. However, additional courses of rituximab are most often followed by responses, at the price of reasonable toxicity. In some major European centers, rituximab is now the preferred second-line therapy of warm antibody hemolytic anemia in adults, although no prospective study convincingly supports this attitude. A recent randomized study strongly suggests that in first-line treatment, rituximab combined with steroids is superior to monotherapy with steroids. If this finding is confirmed, rituximab will emerge as a major component of the management of warm antibody hemolytic anemia not only after relapse but as soon as treatment is needed. © 2015 by The American Society of Hematology.


Seront E.,Hopital de Jolimont | Seront E.,Catholic University of Louvain | Machiels J.-P.,Catholic University of Louvain
Cancer Treatment Reviews | Year: 2015

Metastatic urothelial cancer (UC) is associated with poor prognosis. In the first-line setting, platinum-based chemotherapy is the standard of care but resistance rapidly occurs. With no validated treatment proven to increase survival after platinum failure, there is an urgent unmet medical need to develop new and efficacious cytotoxic agents.A better understanding of the molecular signaling pathways regulating UC has led to the development of new and innovative therapeutic strategies. Despite this, many recent drugs show only modest activity as single agents, and combining them with standard chemotherapy does not seem to enhance efficacy. Ongoing research is producing, however, a generation of new drugs that are showing promising results in clinical trials.This paper aims to review the most important mechanisms in bladder cancer tumorigenesis and describe the new therapeutic options currently undergoing evaluation in clinical trials. © 2015 Elsevier Ltd.


Ben Yahyaten O.,Hopital de Jolimont
Revue Medicale de Bruxelles | Year: 2014

Schizophrenia is a psychiatric disorder that causes severe cognitive, behavioral and social dysfunction, responsible for a shortening of the life expectancy of patients, with an increased risk of suicide, cardiovascular disease and cancer. The management of patient with schizophrenia is global and atypical antipsychotics, antagonizing dopamine pathway, are the first line pharmacological treatment. Clozapine, the first atypical antipsychotic discovered, is currently still the most effective molecule against schizophrenia, while causing less extrapyramidal side effects. Its particular pharmacological behavior towards serotonergic, muscarinic and NMDA receptors, seems essential to its action. However, clozapine is responsible for immunological and metabolic lethal adverse events, preventing its wider use. Clozapine is therefore reserved for resistant schizophrenia cases. Monitoring patients with different scales such as the Brief Psychiatric Rating Scale and the Positive And Negative Syndrome Scale showed that there were forms of ultra-resistant schizophrenia. The treatment in this case, must be customized to the patient's symptomatology, but the combination of clozapine with other pharmacological or non-pharmacological treatments, shows yet only small improvements.

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