Search PubMed⌕ Search

Biomedical subjects

F Demard

Publications and source records attributed to F Demard.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Percutaneous endoscopic gastrostomy: cost/benefit analysis in patients with carcinoma of the upper aero-digestive tract].

The aim of this retrospective study was to evaluate the cost and benefit of percutaneous fluoroscopic gastrostomy feeding (PFG) in 70 cancer patients with advanced stage disease of the upper-aero digestive tract; we retrospectively analyzed the consequences in terms of nutritional status (evaluated by weight and body mass index), the possibility to lead a treatment by high dose chemo-radiotherapy to the end of the therapeutic schedule, the feasibility, complications and cost ratios. Three weeks after the procedure, no major complication was observed, the initial nutritional threshold was conserved. PFG is a safe and effective technique; the additional cost is low (2%) compared with the total cost of hospitalization.

Adult↗
PubMed2000

[Parathyroid carcinoma: diagnosis and treatment].

Pre operative and per-operative suspicion, and recognition of parathyroid carcinoma are essential in the effective approach and the prognosis of this type of tumor. On the basis of our experience over 20 years, helped by the literature we review our 179 cases of primary hyperparathyroidism out of which 5 were malignant tumors and the 174 others were benign (adenomas and hyperplasias). We conclude that patients with primary hyperparathyroidism, reflected by high levels of serum calcium (75%) and elevated levels of parathormone (100%) are suspect of carrying a parathyroid malignancy particularly when these levels are profoundly abnormal. Furthermore, a severe clinical presentation featuring, palpable cervical mass, renal symptoms in 30% to 60% of all, bone disease in 90%, is suspect of malignancy. The operative findings such as important size of tumour, local seeding, local invasion are also significant features of malignancy. All this data gathered by comparing carcinomas to adenomas suggest and confirm what many reviews on the subject have reported, early recognition of the parathyroid carcinoma is of primal importance, because aggressive initial surgical management should be applied, as total extirpation of the malignancy is the only treatment allowing maximal survival rates.

Aged↗
PubMed1999

Low-energy He/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer.

Use of the low-energy helium-neon laser (LEL) appears to be a simple atraumatic technique for the prevention and treatment of mucositis of various origins. Preliminary findings, and significant results obtained for chemotherapy-induced mucositis in a previous phase III study, prompted a randomized multicenter double-blind trial to evaluate LEL in the prevention of acute radiation-induced stomatitis. Irradiation by LEL corresponds to local application of a high-photon-density monochromatic light source. Activation of epithelial healing for LEL-treated surfaces, the most commonly recognized effect, has been confirmed by numerous in vitro studies. The mechanism of action at a molecular and enzymatic level is presently being studied. From September 1994 to March 1998, 30 patients were randomized. Technical specification: 60 mW (25 mW at Reims, 1 patient), He-Ne, wavelength 632.8 nm. The trial was open to patients with carcinoma of the oropharynx, hypopharynx and oral cavity, treated by radiotherapy alone (65 Gy at a rate of 2 Gy/fraction, 5 fractions per week) without prior surgery or concomitant chemotherapy. The malignant tumor had to be located outside the tested laser application areas (9 points): posterior third of the internal surfaces of the cheeks, soft palate and anterior tonsillar pillars. Patients were randomized to LEL or placebo light treatment, starting on the first day of radiotherapy and before each session. The treatment time (t) for each application point was given by the equation : t(s)= energy (J/cm2) x surface (cm2)/Power (W). Objective assessment of the degree of mucositis was recorded weekly by a physician blinded to the type of treatment, using the WHO scale for grading of mucositis and a segmented visual analogue scale for pain evaluation. Protocol feasibility and compliance were excellent. Grade 3 mucositis occured with a frequency of 35.2% without LEL and of 7.6% with LEL (P<0.01). The frequency of "severe pain" (grade 3) was 23.8% without LEL, falling to 1.9% with LEL (P<0.05). Pain relief was significantly reduced throughout the treatment period (weeks 2-7). LEL therapy is capable of reducing the severity and duration of oral mucositis associated with radiation therapy. In addition, there is a tremendous potential for using LEL in combined treatment protocols utilizing concomitant chemotherapy and radiotherapy.

Adult↗
PubMed1999

A multifactorial approach including tumoural epidermal growth factor receptor, p53, thymidylate synthase and dihydropyrimidine dehydrogenase to predict treatment outcome in head and neck cancer patients receiving 5-fluorouracil.

The prognostic value of tumoural epidermal growth factor receptor (EGFR), p53, thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) was analysed on 82 advanced head and neck cancer patients (71 men, 11 women; mean age 59). Induction treatment was cisplatin-5-FU +/- folinic acid (61 patients, Chem group) or concomitant cisplatin-5-FU-radiotherapy (21 patients, RChem group). EGFR (binding assay), p53 protein (Sangtec immunoluminometric assay), TS and DPD activities (radioenzymatic assays) were measured on biopsies obtained at time of diagnosis. Significant positive correlation was demonstrated between p53 and EGFR. In the RChem group, p53 was higher in non-complete responders (median 1.03 ng mg(-1)) than in complete responders (median 0.08 ng mg(-1)) (P = 0.057). Univariate Cox analyses stratified on treatment group showed that specific survival (33 events) was significantly related to T staging, p53 taken as continuous or categorial (below vs over 0.80 ng mg(-1)) variable, and EGFR (below vs over 220 fmol mg(-1)); survival increased when EGFR and p53 were below thresholds. Multivariate stepwise analysis including T staging, EGFR and p53 revealed that T staging and EGFR were independent predictors of survival; relative risks were 3.68 for T staging and 2.65 for EGFR. Overall, EGFR remained an independent prognostic factor when response to treatment and T staging were considered in the multivariate analysis.

Adult↗
PubMed1999

[Chronic sinusitis in patients infected by HIV: therapeutic strategies].

Chronic sinus pathology is a frequently encountered disease in HIV infected patients. The responsible bacterial agents and management are yet to be settled. The authors report the results of a retrospective study led in the unit of Head and Neck Surgery of the University Hospital of Nice. 25 patients where HIV holders and had a sinus pathology which had lasted more than 6 weeks, despite one or several antimicrobial drug administrations. Clinical and CT scan data are detailed as well as pathology results of the samples harvested during sinus surgery (bacteria free 32%, Pseudomonas aeruginosa 32%, Streptococcus pneumoniae 16%, Staphylococcus aureus 16%, Hemophilus influenzae 16%, anaerobic agents 16% and Toxoplasma gondii 4%). All patients underwent surgery (antral puncture with maxillary sinus drainage 17, functional endoscopic sinus surgery 8). Results where gathered at 4 months with 76% of relapse (100% in patients with less than 200/mm3 CD4 cells). In conclusion empiric antimicrobial drug therapy will be expected to be also effective on Pseudomonas aeruginosa, the surgical management being most often deceiving and leading to relapse especially when considering the frequency of bilateral morbidity and the level of CD4 cell below 200/mm3.

Adult↗
PubMed1999

[Standards, options and recommendations (SOR) for clinical care of squamous cell carcinoma of the oropharynx. Groupe de travail SOR].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature systematic review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the management of squamous carcinoma of the oropharynx. METHODS: Data have been identified by literature search using Medline (1991-1998) and the expert groups personal reference lists. Once the guidelines were defined, the document was submitted for review to national and international independent reviewers and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for squamous cell carcinoma of the oropharynx management are that: 1) diagnosis and initial assessment should be based on appropriate clinical and radiological findings; 2) the therapeutic strategy is based on surgery, radiotherapy, bradytherapy and chemotherapy; 3) in limited tumours, the recommended strategy involved the use of one of these modality; 4) a multimodality approach is recommended for the treatment of extended resectable tumours. Following results of recent meta-analyses, use of neo-adjuvant chemotherapy is not recommended. The same studies have shown that association of chemotherapy and radiotherapy either in sequence or in combination significantly improve survival of extended curable tumours. These associations are recommended within the framework of clinical trials; 5) follow-up of squamous carcinoma of the oropharynx should involve physical examination of the upper aerodigestive tract and the lymph nodes areas every three months during the first year, every six months during the second year and then every year. An annual chest x-ray is recommended. Other investigations should be performed as indicated by symptoms and clinical manifestations.

Carcinoma, Squamous Cell↗
PubMed1998

Concomitant b.i.d. radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in unresectable squamous-cell carcinoma of the pharynx: clinical and pharmacological data of a French multicenter phase II study.

PURPOSE: The aim of this phase II study conducted on unresectable squamous cell carcinoma (USCC) of the oro- and hypopharynx was to associate twice-a-day (b.i.d.) continuous nonaccelerated radiotherapy with concomitant cisplatin (CP)-5-fluorouracil (5-FU) chemotherapy, both given at full dose. Feasibility, efficacy, survival, and pharmacokinetic-pharmacodynamic relationships were analyzed. METHODS AND MATERIALS: Fifty-four consecutive patients with strictly USCC of oro- and/or hypopharynx received continuous b.i.d. radiotherapy (RT) (2 daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total RT dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Three chemotherapy (CT) courses of CP-5-FU were given during RT at 21-day intervals (third not delivered after the end of RT). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (day 2-day 6: 750 mg/m2/day cycle 1, 750 mg total dose/day cycle 2 and 3). Pharmacokinetics was performed for 5-FU (105 h follow-up) and CP (single sample at 16 h). Special attention was paid to supportive care. RESULTS: Good feasibility of RT was observed (85.2% of patients with total dose > 75 Gy). Five patients received 1 CT cycle, 34: 2 cycles, and 15: 3 cycles. The most frequent and severe acute toxicities were mucositis with grade 3-4 occurring in 28% at cycle 1 and 86% at cycle 2, as well as neutropenia (43% at cycle 2). Locoregional control at 6 months was observed in 66.7% of patients. No late toxicity above grade 2 RTOG was noticed. CP dose and 5-FU AUC(0-105h) were significantly linked to grade 3-4 neutropenia (cycle 2). Cumulative total platinum (Pt) concentration and Karnofsky index were the only independent predictors of locoregional control at 6 months. Finally, total RT dose and total Pt concentration were the only independent predictors of specific survival. CONCLUSION: This protocol showed good locoregional response with an acceptable toxicity profile. Pharmacokinetic survey is probably an effective approach to further reduce toxicity and improve efficacy. A multicentric randomized phase III study, now underway, should confirm these encouraging results.

Adult↗
PubMed1998

Complications of the myocutaneous platysma flap in intraoral reconstruction.

BACKGROUND: Pedicled myocutaneous flaps remain important tools in head and neck reconstruction. Evaluation of their complications are necessary to judge their merits. METHODS: From 1985 to 1995, 44 patients underwent a myocutaneous platysma flap reconstruction of the oral cavity or oropharynx. The following potential risk factors for complications were analyzed: age, sex, site of primary tumor, TNM stage, previous treatment, neoadjuvant chemotherapy, and type of operation. RESULTS: Flap-related complications occurred in 18 patients. Only one patient required reoperation for flap failure. Nineteen minor complications occurred in 17 patients. A significant increase in complications was seen in patients in which neoadjuvant chemotherapy was given. CONCLUSIONS: One flap failure was observed in our series. As the platysma flap has several advantages, it should be considered in the reconstruction of small intraoral defects. Contraindications are previous radiotherapy and surgery in the head and neck, neoadjuvant chemotherapy, nodal disease, and large defects.

Adult↗
PubMed1997

Tumoral-reduced folates and clinical resistance to fluorouracil-based treatment in head and neck cancer patients.

PURPOSE: To describe the distribution of tumoral-reduced folates in cancer patients and to analyze the link between this parameter and antitumor efficacy of fluorouracil (FU)-based induction chemotherapy. PATIENTS AND METHODS: Ninety-five patients with head and neck squamous cell carcinoma were included in the present study and 41 received induction treatment with FU-based chemotherapy (35 men and six women; mean age, 59 years; range, 40 to 76). Thymidylate synthase (TS) activity was measured according to the tritium-release assay. Reduced folates (5-10 methylenetetrahydrofolate [CH2FH4] plus tetrahydrofolate) were measured according to the entrapment assay. RESULTS: Among the whole group of patients, reduced folates ranged from nondetectable (< 0.3) to 17.7 pmol/mg protein; CH2FH4 ranged from nondetectable (< 0.3) to 8.2 pmol/mg protein. There was no significant link between tumoral levels of reduced folates and the severity of disease stage. Among 41 treated patients, there were 12 (29%) complete responses (CRs), 18 (44%) partial responses (PRs), and 11 patients (27%) with no response (NR). No statistically significant relationship was observable between TS activity and response. The distribution of CH2FH4 in tumors was significantly higher for complete responders in comparison to patients with a PR or NR. CONCLUSION: The present clinical data demonstrate the importance of basal tumoral-reduced folates for the achievement of optimal efficacy of FU-based treatment. They may have implications for the identification of patients resistant to FU chemotherapy and for a better understanding and management of FU modulation by folinic acid (FA).

Adult↗
PubMed1997

[Malignant nasosinusal melanomas. Review of the literature apropos of 12 cases].

Malignant melanoma with primary onset in the nasal cavity and paranasal sinuses remains a scarcely encountered malignancy and we report 12 cases of our own experience from 1991. These mucosal melanomas occur mainly in the elderly and present most commonly as a one sided airway obstructive syndrome with often bleeding in the nasal cavity. No sex or race ratio is found. Histological examination of the surgical specimen has been made easier since the use of immunohistochemical studies. The original site of onset is commonly located at the inferior part of the nasal cavity but in many cases, it is noted several sites of tumor localization. Despite well conducted treatment the prognosis remains quite deceiving and significantly poor. In our study, the 4-year actuarial survival was 26%. The 5-year survival rate ranges in the literature from 10% to 40%. Short and long term follow-up show an important rate of recurrence (local and lymph node metastases as well as distant metastases). The insidious evolution of the malignancy usually happens during the first year. Computed tomography and MRI are essential in the evaluation of tumor extension. The treatment is based on the combination of surgery and radiotherapy: Surgery is practised first and must ensure sufficient excision of the tumor without minimal functional or aesthetic damage in this complex region. This surgery is based on surgical approaches to the midface known as Lateral rhinotomy and midfacial degloving. When there is cervical lymph node involvement at the time of diagnosis it is suitable to treat it, even in case of recurrence. Complementary high dose radiation is required to treat tumors which could not undergo surgery and also as adjuvant therapy after removal of the mass.

Aged↗
PubMed1997

Analysis of retinoic acid receptor beta expression in normal and malignant laryngeal mucosa by a sensitive and routine applicable reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay method.

Retinoic acid receptor beta (RAR-beta) seems to be a useful intermediate marker in trials of retinoids, and the aim of this work was to describe a fast, sensitive, and routine applicable method to measure RAR-beta expression in tumor biopsies. We developed a new technique combining reverse transcription-PCR with a colorimetric ELISA detection of amplification products. The principle of this nonradioactive method is based on digoxigenin labeling of PCR products during amplification. Amplified DNA is hybridized with a biotinylated capture probe. The generated hybrid is immobilized on a streptavidin-coated microtiter plate, and detection is performed with the use of an antidigoxigenin peroxidase conjugate. We applied this method to quantify the expression of RAR-beta and an internal control (beta2 microglobulin) in laryngeal tumors. We found a detection threshold at 50 pg of PCR products, which represents a 100-fold improvement when compared to the detection limit of ethidium bromide detection. The method was reproducible (intra- and interassay reproducibilities at 7 and 5%, respectively). We used this technique for determining RAR-beta expression in 20 patients with laryngeal carcinoma and in 20 patients without cancer. The data show that the value of the RAR-beta:beta2 microglobulin ratio is decreased in tumoral versus nontumoral specimens (P = 0.0012), which is consistent with previously published results.

Adult↗
PubMed1996

Boron neutron capture irradiation: setting up a clinical programme in Nice.

Neutron capture irradiation aims to selectively destroy tumor cells using 10B(n,alpha)7Li nuclear reactions produced within themselves. Following the capture reaction, an alpha particle and a, 7Li ion are emitted. Carrying an energy of 2.79 MeV, they destroy all molecular structures along their path close to 10 microns. These captures, used exclusively with a 'slow' neutron irradiation, provide a neutron capture therapy (BNCT). If they are used in addition to a fast neutron beam irradiation, they provide a neutron capture potentiation (NCP). The Centre Antoine-Lacassagne in Nice is actively involved in the European Demonstration Project for BNCT of grade IV glioblastomas (GBM) after surgical excision and BSH administration. Taking into account the preliminary results obtained in Japan, work on an 'epithermal' neutron target compatible with various cyclotron beams is in progress to facilitate further developments of this technique. For NCP, thermalized neutron yield has been measured in phantoms irradiated in the fast neutron beam of the biomedical cyclotron in Nice. A thermal peak appears after 5 cm depth in the tissues, delayed after the fast neutron peak at 1.8 cm depth. Thus, a physical overdosage of 10% may be obtained if 100 ppm of 10B are assumed in the tissues. Our results using CAL 58 GBM cell line demonstrate a dose modification factor (DMF) of 1.19 when 100 ppm of boric acid are added to the growth medium. Thus for the particles, issued from neutron capture, a biological efficiency at least twice that of fast neutrons can be derived. These results, compared with historical data on fast neutron irradiation of glioblastoma, suggest that a therapeutic window may be obtained for GBM.

Boron Neutron Capture Therapy↗
PubMed1996

[New strategies in the surgery of primary hyperparathyroidism].

Although a remarkable pathology in terms of morbidity and life expectancy, primary hyperparathyroidism remains nonetheless a poorly recognized state despite highly suggestive clinical polymorphism, reliable biological signs and performing imaging for localisation. Through a retrospective study of a series of 129 patients surgically treated for primary hyperparathyroidism over a period of 12 years, helped by a review of the literature, we are able to propose an adapted surgical strategy for every different clinical aspect of this pathology (adenoma, benign hyperplasia, carcinoma). This strategy is guided by specific pre-operative findings and the Sestamibi scintigraphy.

Adenoma↗
PubMed1995

Phase II trial of cisplatin, fluorouracil, and pure folinic acid for locally advanced head and neck cancer: a pharmacokinetic and clinical survey.

PURPOSE: To analyze clinical and pharmacokinetic data of cisplatin (CP)/fluorouracil (FU)/l folinic acid (l FA) chemotherapy administered as first-line treatment to locally advanced head and neck cancer patients. PATIENTS AND METHODS: Thirty-nine patients (35 men and four women; median age, 60 years; six stage III and 33 stage IV) received CP on day 1 (100 mg/m2) followed by l FA (200 mg/m2/d x 5) plus FU (500 mg/m2/d x 5) administered by continuous venous infusion (three cycles planned). Mean plasma concentrations of FU, l FA, and 5-methyltetrahydrofolate (5MTHF) over the cycle were computed. RESULTS: Clinical response was assessable for 33 patients. Response rates on the primary tumor site (n = 33) were 63.7% complete responses (CRs), 24.2% partial responses (PRs), and 12.1% treatment failures. Response rates on lymph nodes (n = 27) were 40.7% CRs, 37.1% PRs, and 22.2% treatment failures. The most frequent toxicity was mucositis (36.2% of cycles grade 3 to 4). Grade 3 to 4 nausea-vomiting, diarrhea, neutropenia, and thrombocytopenia occurred in 6.7%, 1.9%, 13.3%, and 1% of cycles, respectively. Pharmacokinetic analysis showed a wide interpatient variability for both FU (mean, 1.01 mumol/L; range, 0.16 to 2.09), l FA (mean, 1.89, mumol/L; range, 0.52 to 7.88) and 5MTHF plasma concentrations (mean, 3.85 mumol/L; range, 1.30 to 8.11). A significant correlation was demonstrated between FU concentration and hematologic toxicity grade, mucositis grade, and nausea-vomiting/diarrhea grade. Regarding tumor response, patients who failed to respond significantly exhibited lower FU and total folate concentrations than patients with a CR or PR. CONCLUSION: This study highlights the efficacy of CP/FU/l FA in head and neck carcinoma and establishes the clinical importance of coupled FU/FA pharmacokinetics to predict pharmacodynamic variability.

Adult↗
PubMed1995

Response to fluorouracil therapy in cancer patients: the role of tumoral dihydropyrimidine dehydrogenase activity.

PURPOSE: The aim of the present study was to analyze the role of thymidylate synthase (TS; main cellular target of fluorouracil [FU]) and dihydropyrimidine dehydrogenase (DPD; rate-limiting enzyme of FU catabolism) in tumoral biopsies with respect to FU responsiveness. PATIENTS AND METHODS: This prospective study was conducted on 62 head and neck cancer patients (six stage II, 16 stage III, and 40 stage IV). All received first-line chemotherapy with biomodulated FU (5-day continuous infusion). Before treatment, a tumor biopsy and control biopsy (symmetrical nontumoral area) were obtained. Cytosolic TS and DPD activities were measured using radioenzymatic assays. RESULTS: DPD activity was detectable in all samples, without a significant difference between tumoral (median, 60 pmol/min/mg protein; range, 13 to 193) and nontumoral samples (median, 68 pmol/min/mg protein; range, 12 to 150). Tumoral TS and tumoral DPD were not significantly influenced by tumor localization or tumor staging. Among 52 tumors assessable for clinical response, we observed 46% complete responses (CRs), 33% partial responses (PRs), and 21% no responses (NRs). No relationship was demonstrated between TS activity and response to FU therapy. The comparison of tumoral DPD between complete responders and partial or nonresponders showed a trend toward significance (P = .06). In an attempt to reduce variability, we analyzed the tumoral/nontumoral DPD activity ratio; complete responders exhibited a significantly lower normalized DPD than partial or nonresponding patients (median, 0.86, 1.18, and 1.42 for CR, PR, and NR, respectively; CR v PR plus NR, P = .03). CONCLUSION: Although resistance to FU is multifactorial, the present clinical study suggests that FU catabolism in target cells is probably a determinant factor for FU responsiveness in cancer patients and justifies the clinical use of specific DPD inhibitors as FU biomodulators.

Adult↗