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Biomedical subjects

M Delforge

Publications and source records attributed to M Delforge.

At least 19 recordsLinked to original sources
PubMed2005

[Chronotherapy combining 5-fluorouracil, folinic acid and carboplatin as first line treatment in metastatic colorectal cancer. A phase 2 study].

Seventy-two patients suffering from a metastatic colorectal cancer received, as first line treatment, a combination chronotherapy with 5-FU and folinic acid (infused from 10 pm to 10 am with a peak at 4 am, respectively at doses of 700 and 300 mg/m2 per day) and carboplatin (infused at the dose of 40 mg/m2 per day from 10 am to 10 pm with a peak at 4 pm). The courses of four days were repeated every two weeks. A major tumoral response was observed in 60% cases (68% in those not previously treated with adjuvant chemotherapy). The median times to progression and overall survival established at 11 and 27 months. The clinical (grades 3-4 in maximum 5% cases) and hematological (grades 3-4 in maximum 10-29% cases) toxicities were quite limited. Our observations suggest the interest to incorporate carboplatin in the combined infusional treatment of colorectal cancer.

Adult↗
PubMed2005

CD34+ marrow progenitors from MDS patients with high levels of intramedullary apoptosis have reduced expression of alpha4beta1 and alpha5beta1 integrins.

Excessive intramedullary apoptosis is central in the pathogenesis of myelodysplastic syndromes (MDS). Growth-inhibiting cytokines, the Fas/FasLigand pathway, and autoreactive cytotoxic T-lymphocytes have been identified to be important proapoptotic factors in MDS. In normal hematopoiesis, alpha4beta1 and alpha5beta1 integrin-mediated interactions between progenitors and fibronectin are critical for progenitor cell survival. In this study, we have used flow cytometry to quantify the expression levels of members of the beta1 integrin family on CD34(+) marrow progenitors in 27 untreated patients with MDS, three with s-AML, and 25 control subjects. In MDS, we observed that nonapoptotic progenitors significantly downregulate cell surface expression levels of alpha4 and beta1 integrin chains compared with healthy controls. Downregulation of alpha4, beta1, and also alpha5 was present in MDS patients with > or =25% apoptotic progenitors, irrespective of their French, American, British subcategory. Reduced cell surface expression levels of alpha4, alpha5, and beta1 did also correlate with decreased in vitro adhesiveness to fibronectin fragments. Therefore, our observations suggest that downregulation of alpha4beta1 and alpha5beta1 integrins on CD34(+) progenitors could be a newly identified proapoptotic mechanism in MDS.

Aged↗
PubMed2004

Circulating myeloid and lymphoid precursor dendritic cells are clonally involved in myelodysplastic syndromes.

Circulating myeloid and lymphoid precursor dendritic cell (pDC) counts were determined in peripheral blood from 22 patients with myelodysplastic syndromes (MDS) by a single-platform flow cytometric protocol. The absolute count of myeloid and lymphoid pDC, as well as their relative number (as proportion of mononuclear cells or total leukocytes) was significantly lower in MDS (n=22) than in healthy controls (n=41). In 11 patients with chromosomal aberrations, purified pDC were examined by interphase fluorescence in situ hybridization. This revealed clonal involvement of myeloid as well as lymphoid pDC in all of them. These data therefore strongly suggest that myeloid and lymphoid pDC share a common precursor. Whether reduced peripheral blood counts of pDC contribute to the immunological abnormalities observed in MDS remains to be investigated.

Adult↗
PubMed2003

Early development of stricturing or penetrating pattern in Crohn's disease is influenced by disease location, number of flares, and smoking but not by NOD2/CARD15 genotype.

BACKGROUND: Crohn's disease is a heterogeneous entity. Disease behaviour, characterised as stricturing, penetrating, or non-stricturing non-penetrating, is a clinically important phenotype as it is associated with complications and need for surgery. It has recently been showed that the behaviour of Crohn's disease changes over the course of the disease. AIM: To assess the association between rapid development of a penetrating or stricturing pattern of Crohn's disease and demographic and clinical characteristics as well as NOD2/CARD15 genotype. PATIENTS AND METHODS: A total of 163 patients with a firm diagnosis of Crohn's disease and who had non-penetrating non-stricturing disease at diagnosis were studied. Various demographic and clinical characteristics as well as antisaccharomyces cerevisiae antibody status and NOD2/CARD15 genotype were documented in these patients. These characteristics were compared in subgroups of patients according to evolution of disease behaviour five years after diagnosis. RESULTS: Five years after diagnosis there were 110 (67.5%) patients with non- structuring non-penetrating disease, 18 (11%) with stricturing disease, and 35 (21.5%) with penetrating disease. In multivariate analysis, only disease location and number of flares per year were significantly discriminant between the three subgroups (p=0.0009 and 0.0001, respectively). Ileal location of the disease was associated with a stricturing pattern while a high number of flares was associated with a penetrating pattern. Active smoking was also associated with a penetrating pattern compared with a non-stricturing non-penetrating pattern only. CONCLUSIONS: Early development of stricturing or penetrating behaviour in Crohn's disease is influenced by disease location, clinical activity of the disease, and smoking habit, but not by NOD2/CARD15 genotype.

Adult↗
PubMed2002

[Barrett's esophagus: overview].

Barrett's oesophagus (BE) is a segment of columnar lined epithelium in the distal oesophagus, above the gastrooesophageal junction. So it is important to localize this junction endoscopically; the proximal margin of the gastric folds is the anatomic landmark. Another important feature of BE is the specialized intestinal metaplasia. In the aetiology of this condition, acid reflux is a primary event but there is evidence that other factors are causal. As BE is a well known premalignant condition, detection of dysplastic epithelium and its severity is the crucial element. Practical guidelines are presented for endoscopic surveillance program. The purpose is the early detection of high grade dysplasia and carcinoma to advise oesophagectomy or endoscopic ablation therapy for patients unfit to undergo surgery.

Algorithms↗
PubMed2002

[Evaluation criteria for acute pancreatitis. Recent data from the literature].

This paper related to the diagnosis and etiological factors of acute pancreatitis (AP). 20% of all cases of AP will develop local and/or systemic complications; infections of the lesions play an important role. To predict severity and outcome, the value of clinical examination, current biological parameters, new markers and computed tomography is discussed.

Biomarkers↗
PubMed2001

Genotypically nonidentical related donors for transplantation of patients with myelodysplastic syndromes: comparison with unrelated donor transplantation and autologous stem cell transplantation.

Transplantation with histocompatible identical siblings is a curative treatment for patients with myelodysplastic syndromes (MDS). Alternative treatments, such as transplantation with other family donors, are an option for patients without HLA-identical siblings. This study evaluated transplantation with genotypically nonidentical family donors and compared the results to those obtained with unrelated donors and autologous stem cell transplantation. Overall 3-year survival was 35% for the 79 patients transplanted using genotypically nonidentical donors, DFS was 31%, relapse risk 16%, and the treatment-related mortality (TRM) 62%. Patients transplanted using phenotypically identical family donors had a significantly superior survival and a lower TRM than patients transplanted with mismatched family donors. Age had no influence on the outcome of transplantation. The DFS of patients transplanted in early stage of the disease was 42% compared to 28% in patients transplanted with more advanced disease (P = 0.03). The results of transplantation with mismatched family donors were comparable to those obtained with unrelated donor transplantation. This suggests that nonidentical family donors may be considered if a fully matched unrelated donor is not available. The TRM of patients transplanted with nonidentical family donors is significantly higher than the TRM of patients transplanted with autologous stem cells. The disease-free survival of ASCT is not inferior to allogeneic transplantation using nonidentical family donors, and the intensity of the treatment is much lower. The choice of ASCT or alternative donor transplantation must be influenced by the age of the patient and the risk of relapse. For patients under the age of 20 years the treatment of choice may indeed be an alternative donor transplantation.

Adolescent↗
PubMed2001

[Prevalence and treatment of Helicobacter pylori in gastro-duodenal ulcers. An experience in Liege].

Between April 1998 and July 1999, we prospectively investigated 152 patients with gastric or duodenal ulcer and we observed concomitant H. pylori infection in 72.8% and 78.5% respectively. We proposed to the GPs of these patients the recommended triple therapy (omeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg (OAC) twice daily for 7 or 10 days). H. pylori eradication was tested using the C13-urea breath test. Our results showed a modest overall eradication rate of about 70%. We have to persuade the patients and the GPs of the benefit of antibiotics and of the importance of the correct dosages. We have to continue to follow the resistance against antibiotics.

Adult↗
PubMed2001

[Value of MRCP for detection of choledocholithiasis in symptomatic patients: one-year experience with a standardized high resolution breath-hold technique].

In our institution, MRCP is actually replacing diagnostic ERCP. This study is addressing its accuracy in the diagnosis of symptomatic choledocholithiasis. 137 MRCP were performed in patients with upper abdominal pain and biological anomalies (n = 48), pain with cholelithiasis at sonography (n = 69) or non-alcoholic acute pancreatitis (n = 20) on a 1.5 T system with high gradients using a standardized combination of breath-hold HASTE and RARE sequences. We included in our study 74 patients who underwent as second test ERCP (n = 36), peroperative cholangiography (n = 13), or extensive follow-up with laboratory tests and/or sonography (n = 25). All examinations were judged as diagnostic, discrepancies between direct cholangiography and MRCP being noted in 4 patients (5.4%). Lithiasis was misinterpreted on MRCP as bubbles in 2 patients after sphincterotomy or surgery. We had two false positive diagnoses on MRCP: in one patient peroperative cholangiography was negative and in the other one ERCP was negative. With a sensitivity and PPV of 92%, a specificity and NPV of 96% MRCP in our experience is shown as an accurate diagnostic tool for the detection of stone in the common bile duct replacing ERCP.

Adolescent↗
PubMed2000

[Epidemiological aspects, risk factors, and detection of pancreatic cancer].

The incidence of pancreatic cancer (PC) is increasing in developing countries. Smoking, reduced consumption of fruits and vegetables, chronic pancreatitis appear to be the best established risk factors. PC is often diagnosed at a late stage. We have to look for it when dyspepsia with weight loss, pancreatic pain or impaired glucose tolerance occurs. Tumor markers are briefly exposed and we discuss the place of endoscopic retrograde cholangiopancreatography (ERCP) after non invasive imaging techniques.

Biomarkers, Tumor↗
PubMed2000

[Endoscopic ultrasonography in the diagnosis and staging of pancreatic and ampullary cancer: influence on patient management].

Accurate preoperative staging is now more prerequisite in the management of cancer of the pancreas and ampulla in order to orientate the patient toward the best selected treatment: either a curative or a palliative surgery associated or not with a pre- or postoperative multimodal therapy, or an endoscopic palliative technique which does not require surgery. Endoscopic ultrasonography (EUS) appears to be a highly accurate diagnostic procedure in the assessment of local resectability because it enables detailed visualization of the pancreatic gland, the depth of infiltration into the surrounding tissue and organs and visualisation of regional lymph nodes involvement. EUS-guided fine needle aspiration for cytology will provide a tissue diagnosis. The likelihood of successful resection for palliative or cure can be predicted before surgery. The following overview will point out the clinical impact of EUS on diagnosis, staging and management of these tumors.

Ampulla of Vater↗
PubMed2000

[Chronopharmacologic approach to the administration of anticancer agents in pancreatic adenocarcinoma. Pilot experience].

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.

Adenocarcinoma↗
PubMed1999

BCR/ABL- CD34(+)HLA-DR- progenitor cells in early chronic phase, but not in more advanced phases, of chronic myelogenous leukemia are polyclonal.

Chronic myelogenous leukemia (CML) is characterized by the Philadelphia (Ph) translocation and BCR/ABL gene rearrangement which occur in a pluripotent hematopoietic progenitor cell. Ph-negative (Ph-) hematopoiesis can be restored in vivo after treatment with -interferon or intensive chemotherapy, suggesting that normal stem and progenitor cells coexist with the Ph+ clone. We have previously shown that Ph- progenitors are highly enriched in the CD34(+)HLA-DR- fraction from early chronic phase (ECP) CML patients. Previous studies have suggested that the Ph-translocation represents a secondary clonal hit occurring in an already clonally mutated Ph- progenitor or stem cells, leaving the unanswered question whether Ph- CD34(+)HLA-DR- progenitors are normal. To show the clonal nature of Ph- CD34(+)HLA-DR- CML progenitors, we have compared the expression of BCR/ABL mRNA with X-chromosome inactivation patterns (HUMARA) in mononuclear cells and in CD34(+)HLA-DR+ and CD34(+)HLA-DR- progenitors in marrow and blood obtained from 11 female CML patients (8 in chronic phase and 3 in accelerated phase [AP] disease). Steady-state marrow-derived BCR/ABL mRNA-, CD34(+)HLA-DR- progenitors had polyclonal X-chromosome inactivation patterns in 2 of 2 patients. The same polyclonal pattern was found in the progeny of CD34(+)HLA-DR- derived long-term culture-initiating cells. Mobilization with intensive chemotherapy induced a Ph-, BCR/ABL mRNA- and polyclonal state in the CD34(+)HLA-DR- and CD34(+)HLA-DR+ progenitors from 2 ECP patients. In a third ECP patient, polyclonal CD34(+) cells could only be found in the first peripheral blood collection. In contrast to ECP CML, steady-state marrow progenitors in late chronic phase and AP disease were mostly Ph+, BCR/ABL mRNA+, and clonal. Further, in the majority of these patients, a Ph-, polyclonal state could not be restored despite mobilization with intensive chemotherapy. We conclude from these studies that CD34(+)HLA-DR- cells that are Ph- and BCR/ABL mRNA- are polyclonal and therefore benign. This population is suitable for autografting in CML.

Adult↗
PubMed1998

Patients with high-risk myelodysplastic syndrome can have polyclonal or clonal haemopoiesis in complete haematological remission.

The clonality of mature peripheral blood-derived myeloid and lymphoid cells and bone marrow haemopoietic progenitors from 18 females with myelodysplasia (MDS) (five refractory anaemia, RA; one RA with ringed sideroblasts, RARS; three chronic myelomonocytic leukaemia, CMML; four RA with excess of blasts, RAEB; five RAEB in transformation, RAEB-t) was studied by X-chromosome inactivation analysis. Using the human androgen-receptor (HUMARA) assay, we analysed the clonal patterns of highly purified immature CD34+ 38- and committed CD34+ 38+ marrow-derived progenitors, and CD16+ 14- granulocytes, CD14+ monocytes, CD3+ T and CD19+ B lymphocytes from peripheral blood. In high-risk patients (RAEB, RAEB-t), clonality analysis was performed before and after intensive remission-induction treatment. All patients, except one with RA, had predominance of a single clone in their granulocytes and monocytes. The same clonal pattern was found in CD34+ progenitor cells. In contrast, CD3+ T lymphocytes were polyclonal or oligoclonal in 14/18 patients. X-chromosome inactivation patterns of CD19+ B cells were highly concordant with CD3+ T cells except for two patients (one RA, one CMML) with monoclonal B and polyclonal T lymphocytes, therefore suggesting a clonal mutation in a progenitor common to the myeloid and B-lymphoid lineages or the coexistence of MDS and a B-cell disorder in these particular patients. After high-dose non-myeloablative chemotherapy, polyclonal haemopoiesis was reinstalled in the mature myeloid cells and immature and committed marrow progenitors in three of four patients achieving complete haematological remission. Therefore we conclude that most haematological remissions in MDS are associated with restoration of polyclonal haemopoiesis.

Adult↗
PubMed1998

[Dysfunction of the sphincter of Oddi in cholecystectomy patients].

Sphincter of Oddi dysfunction (SOD) is an obstructive syndrome of the papilla not resulting from a stone. It may cause recurrent biliary type pain to cholecystectomized patients. SOD is caused by sphincter dyskinesia or benign stenosis. Diagnosis is usually based on symptoms, serum biochemistry, endoscopic retrograde cholangiopancreatography and Sphincter of Oddi manometry. The latter is the best means of evaluating Sphincter of Oddi dynamics. However, because of the many inconveniences of Sphincter of Oddi manometry and of its high morbidity rate, it is seldom used. Non invasive techniques, such as cholescintigraphy, have been developed to replace Sphincter of Oddi manometry in diagnosing SOD. Patients can be cured by sphincterotomy. Certain drugs could also be effective but few controlled studies have been carried out of date.

Biliary Tract Diseases↗
PubMed1998

Gastric endoluminal treatment of Dieulafoy's ulcer.

Dieulafoy's ulcer, accounting for approximately 5% of upper GI bleeding, is best managed by therapeutic endoscopy. Some patients, however, require surgical treatment. Presented here is a case in which the lesion was treated by combined endoscopy and endogastric surgery. To the authors' best knowledge, this is the first published report of such management. This relatively new technique may be offered in suitable cases but should be attempted only by well-trained laparoscopic surgeons.

Adult↗
PubMed1997

Pathophysiology of CML: do defects in integrin function contribute to the premature circulation and massive expansion of the BCR/ABL positive clone?

Hematopoiesis takes place in close contact with the marrow microenvironment. Normal progenitors adhere through a variety of receptors to stroma and extracellular matrix components, including fibronectin. Adhesion through beta1-integrin receptors to fibronectin not only anchor progenitors to the stroma but also result in direct adhesion-mediated signaling that inhibits progenitor proliferation. In contrast to normal hematopoiesis, chronic myelogenous leukemia (CML) is characterized not only by abnormal, premature circulation of primitive progenitors in the blood but also by continuous progenitor proliferation. Although CML progenitors express the same integrin receptors as normal progenitors, they fail to adhere to stroma and fibronectin, suggesting structural or functional abnormalities of these receptors. Furthermore, CML cells present in contact with stroma or fibronectin continue to proliferate, suggesting that failure to adhere through integrin receptors may also underlie the abnormal proliferation of CML progenitors. The observation that integrin-mediated adhesion and proliferation-inhibitory signaling can be restored through treatment with interferon-alpha or an activating anti-beta1-integrin antibody suggests a functional rather than structural defect that may be related to the presence of the BCR/ABL gene rearrangement in these cells. Insights into the role of integrins as adhesion molecules but also receptors that instruct hematopoietic progenitors to survive, proliferate, and possibly differentiate will not only further our understanding of the normal hematopoietic process but also provide insights into diseases characterized by deranged adhesion and proliferation that may lead to novel therapeutic approaches.

Animals↗