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Biomedical subjects

A Laplanche

Publications and source records attributed to A Laplanche.

At least 37 records · Page 2Linked to original sources

Benefit of surgery after chemoradiotherapy in stage IIIB (T4 and/or N3) non-small cell lung cancer.

OBJECTIVE: The purpose of this study was to evaluate postchemoradiotherapy surgery in stage IIIB non-small cell lung cancer. METHODS: Forty patients with stage IIIB non-small cell lung cancer were included in this phase II study. A preoperative diagnosis of stage IIIB cancer was based on mediastinoscopy or a thoracotomy in all patients. Induction treatment included two cycles of cisplatin (100 mg/m(2), day 1), 5-fluorouracil (1 g/m(2), days 1-3), and vinblastine (4 mg/m(2), day 1) combined with 42 Gy of hyperfractionated radiotherapy delivering 21 Gy in two sessions. Patients with a clinical response were offered surgery. RESULTS: The minimum follow-up for survivors was 48 months. Thirty patients had a T4 lesion and 18 had N3 disease. Twenty-nine patients (73%) had a clinical objective tumor response after induction treatment. These 29 patients underwent thoracotomy, and a complete resection was performed in 23 (58%). Two postoperative deaths occurred (7%). Four patients had a pathologic complete response at the time of surgery (10%). The 5-year survival is 19% for the overall population. When only patients who had persistent viable tumor cells at surgery are considered (n = 25), the 5-year survival is 28%. The 5-year survival is 42% for patients having no mediastinal lymph node involvement at the time of surgery and being treated with complete resection. CONCLUSION: This study shows that surgery, when feasible, is associated with a 28% long-term survival for patients in whom chemoradiotherapy alone fails to control disease.

Adult↗

Kinetics of oxidation of odorous sulfur compounds in aqueous alkaline solution with H2O2.

Sulfur species oxidation is a crucial issue wastewater treatment. The production of sulfur compounds like H2S,CH3SH, C2H5SH, disulfides and dimethyle sulfide generates odorous nuisances for the neighborhood. The oxidation of these species by H2O2 in alkaline solution has been investigated. The results showed that thiols CH3SH and C2H5SH react with H202 only in their dissociated form RS- with rate constants respectively k = 8.81 +/- 0.48 M-1s-1 and 8.37 +/- 0.63 M-1.s-1. Mercaptans oxidation produces 100 % of dimethyldisulfide or diethyldisulfide. The oxidation of disulfides shows a difference of reactivity between H2O2 and HO2- towards sulfur species. Increasing the pH accelerates significantly the reactions in the case of CH3SSCH3. The oxidation rate can be described as: r = k[RSSR][H2O2][RSSR][H2O2] + k[RSSR][HO2-] [RSSR][HO2-] with k[RSSR][H2O2] = 1.2 x 10(-4) +/- 0.2 x 10(-4) M-1s-1 and k[RSSR][HO2-] = 3.4 x 10(-4) +/- 0.6 x 10(-4) M-1.s-1 for CH3SSCH3. Dimethyl sulfide presents a reactivity different from disulfides. The oxidation rate can also be described as: r = k[CH3SCH3][H2O21][CH3SCH3][H2O2] + k[CH3SCH3][HO-] [CH3SCH3][HO2-], however, oxidation rate decreases with pH increase. k[CH3SCH3][H2O2] = 12.8 x 10(-3) +/- 0.96 x 10(-3) M-1.s-1 and k[CH3SCH3][HO2-] = 4 x 10(-3) +/- 0.3 x 10(-3) M-1.s-1.

Hydrogen Peroxide↗

[Statistical analysis of a prognostic study].

Prognostic studies aim to stress and quantify the effect of some individual characteristics on the evolution of an illness. Statistically speaking, most of the time, a prognostic study relying on a censored endpoint can be summarized in building a Cox model. Even though they are often encountered in clinical research or in epidemiology, prognostic studies are rarely reliable and there is no real consensus on the way to perform them. The aim of this article is to give some directions regarding the analysis of such studies. For illustration purpose, this paper relies on commented results from a study in oncology.

Analysis of Variance↗

Accuracy of totally implanted ports, tunnelled, single- and multiple-lumen central venous catheters for measurement of central venous pressure.

OBJECTIVE: To verify the accuracy of totally implanted ports, tunnelled central venous catheters (CVC), widely used in cancer patients, and multi-lumen catheters, used in intensive care units (ICUs), in measuring central venous pressure (CVP), using right atrial pressure (RAP) measured in a Swan-Ganz catheter as the reference standard. DESIGN: A prospective study, over a 10-month period. SETTING: A medical-surgical ICU in a comprehensive cancer centre. PATIENTS AND PARTICIPANTS: Patients who had both (1) a Swan-Ganz catheter and (2) either a tunnelled catheter, a single or a multi-lumen catheter, or a totally implanted port. INTERVENTIONS: RAP and CVP were measured simultaneously in each patient. MEASUREMENTS AND RESULTS: Fifty-six pairs of RAP-CVP measurements were performed in 35 patients: 6 tunnelled catheters, 6 non-tunnelled single-lumen catheters, 26 multiple-lumen catheters and 18 totally implanted ports were studied. RAP measured in the Swan-Ganz catheter and CVP measured in the CVC were strongly correlated (r = 0.94, p < 0.01), whatever the type of catheter studied. The mean difference between RAP and CVP was -0.39 +/- 1.73 (SD) mmHg. In 51 cases (91%), the difference was within the limits of agreement (-3.78 to 3.00 mmHg, Bland and Altman method). For the five cases with a difference of 4 mmHg (three totally implanted ports, one double- and one triple-lumen catheter), CVP was greater than RAP. CONCLUSIONS: CVP can be accurately measured in totally implanted ports, tunnelled or non-tunnelled single-lumen and multiple-lumen catheters. When the difference exceeds the limit of agreement, the discrepancy between the two measurements has limited significance in most cases.

Aged↗

Polyadenylic-polyuridylic acid plus locoregional radiotherapy versus chemotherapy with CMF in operable breast cancer: a 14 year follow-up analysis of a randomized trial of the Fédération Nationale des Centres de Lutte contre le Cancer (FNCLCC).

With a median follow-up of 14 years, the combination of polyadenylic-polyuridylic acid plus locoregional radiotherapy (257 patients) has significantly improved disease-free survival (p = 0.03) and significantly reduced the incidence of metastases (p = 0.04) when compared to CMF alone (260 patients), in women with operable breast cancer. The trial does not, however, permit an appreciation of the respective role of radiotherapy and PolyAU in these results.

Adjuvants, Immunologic↗

Ex vivo expanded mobilized peripheral blood CD34+ cells accelerate haematological recovery in a baboon model of autologous transplantation.

To address the value of ex vivo expanded haematopoietic cells for shortening cytopenia in autologous haematopoietic transplantation, we designed an ex vivo expansion protocol based on a cocktail of early acting cytokines and short-term culture and tested it in a baboon model. Expansion involved enriched CD34+ peripheral blood haematopoietic cells cultured for 6 d with a combination of FLT3-L, stem cell factor (SCF), thrombopoietin (TPO) and interleukin (IL)-3 (50 ng/ml each); CD34+ cells, granulocyte-macrophage colony-forming units (GM-CFU) and megakaryocytic colony-forming units (MK-CFU) were amplified, respectively, 10.5-, 20.5- and 17.9-fold. Baboons were submitted to a myeloablative regimen consisting of cyclophosphamide plus total body irradiation (TBI; 6 Gy) and were then grafted with either 2 x 106/kg unmanipulated CD34+ cells (control group, n = 4) or cells cultured from 2 x 106/kg CD34+ cells (expansion group, n = 4). No cytokines were administered after transplantation. All the animals engrafted. The mean times to white blood cell (WBC), granulocyte and platelet recovery were significantly shorter in the expansion group than in the control group: WBC (> 1 x 109/l) and neutrophil (> 0.5 x 109/l) recovery occurred on days 8 (range 6-9) and 9 (range 6-11), respectively, compared with days 12 (range 10-15) and 14 (range 11-16); platelets recovered (> 20 x 109/l) on day 9 (range 7-12) compared with day 13 (range 11-15) in the control group (P < 0.05). No toxicity was observed after reinfusion. No secondary hypoplasia was observed during more than 12 months of follow-up. Functions of both neutrophils and platelets produced from expanded cells were normal in terms of oxidative metabolism, chemotaxis and the bleeding time. This study shows that in comparison with unmanipulated cells peripheral blood haematopoietic cells expanded from similar doses of CD34+ cells, under the conditions defined here, accelerated both neutrophil and platelet recovery without impairing long-term haematopoiesis.

Animals↗

Diagnosis of catheter-related bacteraemia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures.

BACKGROUND: A method of diagnosing catheter-related infection (CRI) without removing the catheter would be useful. An earlier positivity of central compared with peripheral venous-blood cultures may be associated with catheter-related bacteraemia. We evaluated prospectively the differential time to positivity (DTP) of paired blood cultures drawn simultaneously via the catheter hub and from a peripheral venous site. METHODS: Over a 14-month period in an intensive-care unit of a cancer referral centre, simultaneous hub-blood and peripheral-blood cultures (a mean of two per patient) were obtained from patients with a suspected CRI. According to clinical criteria and quantitative culture of the catheter tip, cases were classified as CRI or sepsis of other origin. At least one pair of hub-blood and peripheral-blood cultures was obtained within 48 h before catheter removal, and we recorded the DTP between hub-blood and peripheral-blood cultures with an automatic device for detection of blood culture positivity. FINDINGS: We analysed 93 catheters removed because of suspicion of CRI. In 28 episodes, the same micro-organisms were found in both hub-blood and peripheral-blood cultures. A diagnosis of definite bacteraemic CRI was made in 16 of the 17 patients in whom a positive hub-blood culture was detected at least 2 hours earlier than peripheral-blood culture. About half (9/17) of these episodes occurred in long-term (>30 days) devices. CRI was excluded in ten of the 11 patients with a DTP lower than 2 h. The DTP of paired blood cultures was significantly greater in patients with CRI than in others (p<10(-4)). A cut-off DTP value of 120 min had 91% specificity and 94% sensitivity for the diagnosis of CRI. Three of 17 episodes with only hub-blood culture positive were associated with CRI. INTERPRETATION: This prospective study suggests that measurement of the differential time to positivity between hub-blood and peripheral-blood cultures is a simple and reliable tool for in-situ diagnosis of catheter-related sepsis in cancer patients. Further studies are needed to confirm these data for short-term catheters.

Bacteremia↗

Radiosensitivity of human normal and tumoral thyroid cells using fluorescence in situ hybridization and clonogenic survival assay.

PURPOSE: By using cell survival as a reference, we evaluated the radiosensitivity of human normal and tumoral thyroid cells using of radiation-induced translocations. METHODS AND MATERIALS: Tissue samples were obtained from patients undergoing thyroidectomy. Cell cultures were established, irradiated with 60Co, and metaphases painted using commercial whole-chromosome 4 hybridization probe and pancentromeric probe. The clonogenic survival was assessed by conventional colony forming assay. RESULTS: After irradiation, normal cultured thyroid cells yielded a higher number of translocations than cultures derived from adenomas or thyroid carcinoma. The colony forming assay demonstrated, by way of the mean inactivation dose, a higher survival of thyroid carcinoma and adenoma cells than of normal thyroid cells. This difference between tumoral and nontumoral cells is significant in each method (p = 0.0001), and cannot be explained by apoptosis in irradiated malignant cells. Correlation of the results obtained by both methods is shown by comparing the survival fraction at 2 Gy (SF2) and the percentage of chromosome 4 translocations at 2 Gy. CONCLUSION: These results indicate that the yield of radiation-induced translocations serves as a good and rapid prediction of the intrinsic radiosensitivity of thyroid cells, and that this test could be applied to other tumors.

Adenoma↗

Cost-minimization analysis of prophylactic granulocyte colony-stimulating factor after induction chemotherapy in children with non-Hodgkin's lymphoma.

BACKGROUND: Colony-stimulating factors promote the proliferation of certain bone marrow cell populations. The primary objective of treating patients with these factors prophylactically following chemotherapy is to reduce the risk of infection, thereby minimizing the need for hospitalization and parenteral antibiotics. The use of colony-stimulating factors in children is widespread, despite the absence of conclusive supportive data and the high cost of these drugs. Consequently, the cost-benefit ratio of using prophylactic colony-stimulating factors is an important issue in cancer therapy. METHODS: During the period from January 1994 through June 1996, 149 afebrile children with newly diagnosed non-Hodgkin's lymphoma were randomly assigned either to receive granulocyte colony-stimulating factor (G-CSF) (lenograstim; 5 microg/kg body weight per day subcutaneously) or not to receive it (the control) at the end of the first two courses of induction chemotherapy with cyclophosphamide, vincristine, prednisone, doxorubicin, and methotrexate. A cost-minimization analysis was performed to assess the cost of chemotherapy in each group and to quantify how much could be economized by prescribing G-CSF. RESULTS: The total cost for induction chemotherapy was $29,765 in the G-CSF-treated group and $30,774 in the control group, indicating that the treatment strategy with G-CSF was slightly less expensive than the strategy without G-CSF (mean difference = $1009; 95% confidence interval = -$1474 to $3492). CONCLUSION: Treatment with G-CSF following chemotherapy in children with non-Hodgkin's lymphoma--previously shown to be of limited clinical benefit--also does not appear to reduce the costs of chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Controlled clinical trial of prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission.

We conducted a randomised clinical trial on 211 patients with small-cell lung cancer in complete remission (CR). The aim of this trial was to evaluate the effect of prophylactic cranial irradiation (PCI) on overall survival. Eligible patients were randomly assigned to receive either PCI (100 patients) or no PCI (111 patients). Each centre was allowed to use its own PCI protocol as long as the total dose was within the range of 24-30 Gy and delivered in less than 3 weeks with fractions of 3 Gy or less. The mean follow-up is 5 years. The survival curves do not differ significantly (P = 0.25) between the two groups. The 4-year overall survival rate (95% confidence interval) is 22% [15-32%] in the PCI group versus 16% [10-25%] in the control group. The relative risk of death in the PCI group compared to the control group is 0.84 (95% CI = [0.62-1.13]). The incidence of brain metastasis is lower in the PCI group, but the difference is not statistically significant (P = 0.14). The 4-year cumulative rate of brain metastasis is 44% [32-57%] in the PCI group compared to 51% [38-63%] in the control group. In conclusion, in this study, which had to be closed prematurely, no significant difference was found in terms of the incidence of brain metastases nor in survival.

Adult↗

Earlier positivity of central-venous- versus peripheral-blood cultures is highly predictive of catheter-related sepsis.

To diagnose catheter-related sepsis without removing the catheter, we evaluated the differential positivity times of cultures of blood drawn simultaneously from central venous catheter and peripheral sites. In a 450-bed cancer reference center, simultaneous central- and peripheral-blood cultures were prospectively performed for patients with suspicion of catheter-related sepsis over an 18-month period. Data for 64 patients for whom the same microorganisms were found when central- and peripheral-blood samples were cultured were retrospectively reviewed by two independent physicians blinded to the differential positivity time values in order to establish or refute the diagnosis of catheter-related sepsis. The diagnosis was established in 28 cases, refuted in 14, and indeterminate in the remaining 22. The differential positivity time was significantly greater for patients with catheter-related sepsis (P < 10(-4)). A cutoff limit of +120 min had 100% specificity and 96.4% sensitivity for the diagnosis of catheter-related sepsis. These results strongly suggest that measurement of the differential positivity time might be a reliable tool facilitating the diagnosis of catheter-related sepsis in patients with an indwelling catheter.

Catheterization, Central Venous↗

Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer.

PURPOSE: The administration of fluorouracil (5-FU) by continuous intravenous infusion (CI) is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancer. Although more than 1,200 patients have been enrolled onto randomized trials that compared these two treatment modalities, there is still no definitive evidence of an advantage of 5-FU CI, and the magnitude of this advantage, if any, is also controversial. A meta-analysis was performed to assess this benefit in terms of tumor response and survival, and to compare the toxicity profiles of these two modalities of administration of 5-FU. DESIGN: Individual data of 1,219 patients included in six randomized trials served as the basis for this meta-analysis, which was conducted by an independent secretariat in close collaboration with the investigators. RESULTS: Tumor response rate was significantly higher in patients assigned to 5-FU CI than in patients assigned to 5-FU bolus (22% v 14%; overall response odds ratio, 0.55; 95% confidence interval [95% CI], 0.41 to 0.75; P = .0002). Overall survival was also significantly higher in patients assigned to 5-FU CI (overall hazards ratio [HR], 0.88; 95% CI, 0.78 to 0.99; P = .04), although the median survival times were close. Multivariate analyses showed that randomized treatment and performance status were the only two significant predictors of tumor response, whereas the same plus primary tumor site were independent significant predictors of survival (patients with rectal cancer did somewhat better). Grade 3 or 4 hematologic toxicity was more frequent in patients assigned to 5-FU bolus (31% v 4%; P < 10(-16)), whereas hand-foot syndrome was more frequent in the 5-FU CI group (34% v 13%; P < 10(-7)). CONCLUSION: 5-FU CI is superior to 5-FU bolus in terms of tumor response and achieves a slight increase of overall survival. The hematologic toxicity is much less important in patients who receive 5-FU CI, but hand-foot syndrome is frequent in this group of patients.

Antimetabolites, Antineoplastic↗

Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors.

PURPOSE: Fluorouracil (5-FU) continuous infusion is superior to 5-FU bolus in patients with advanced colorectal cancer, but the survival difference between the two treatments is small and, therefore, the difference in toxicity profile is crucial in choosing a treatment for individual patients. MATERIALS AND METHODS: We conducted a meta-analysis of all randomized trials that compared 5-FU bolus with 5-FU CI, based on individual data from 1,219 patients, to compare the toxicity of the two schedules of 5-FU administration and to identify predictive factors for toxicity. The toxicities considered were World Health Organization (WHO) grade 3 to 4 anemia, thrombopenia, leukopenia, neutropenia, nausea/vomiting, diarrhea, mucositis, and hand-foot syndrome. RESULTS: Hematologic toxicity, mainly neutropenia, was more frequent with 5-FU bolus than with 5-FU CI (31% and 4%, respectively; P < .0001). Hand-foot syndrome was less frequent with 5-FU bolus than with 5-FU CI (13% and 34%, respectively; P < .0001). There was no difference between the two treatment groups in terms of other nonhematologic toxicities. Independent prognostic factors were age, sex, and performance status for nonhematologic toxicities, performance status, and treatment for hematologic toxicities, and age, sex, and treatment for hand-foot syndrome. CONCLUSION: Based on a large data set, this study confirmed and quantified the toxicity profile of the two schedules of administration of 5-FU and allowed the identification of clinical predictors of toxicity.

Colorectal Neoplasms↗

[Quality of death certificates in cases of cancer death in France].

International mortality statistics are based on death certificates on which the causes of death are coded using the World Health Organization's International Classification of Diseases. Most of these statistics are based on the underlying cause of death and do not use the contributory causes of death. We studied the validity of death certificates in a sample of 1,194 French patients known to have died of cancer, comparing the cause of death reported on the death certificate with the cause of death found in the medical record. Death certificates correctly identify cancer as the cause of death in 95% of the cases and with the exact site in 86% of the cases.

Cause of Death↗

[Statistics of mortality in 1994 and predictions of death caused by cancer 1997].

The latest mortality statistics available in France, for 1994, are presented and show that the first cause of death was cardiovascular disease (32%) followed by cancer (27%). Previsional estimations for 1997 reveal that in men, there will be an expected 85,000 deaths from cancer, the first cause of mortality in men, the first three localizations being lung cancer (24%), prostate cancer (11%) and colorectal cancer (10%). In women, there will be an estimated 55,000 deaths due to cardiovascular disease, the primary cause of mortality. Breast cancer is expected to be the number one cause of death by cancer (20%) followed by colorectal cancer (14%) and lung cancer (7%).

Adolescent↗

Cancer mortality around French nuclear sites.

This study was designed to investigate cancer mortality in the population aged 0 to 64 years residing around the 13 main French nuclear sites in operation before 1985. Five hundred and three communes located within 16 km of the installation were identified and their populations were followed from 1968 to 1989. A total of 8,970,000 person-years of observation was accumulated. The number of cancer deaths and the number of deaths for cancers possibly related to radiation observed in these communes were compared to national mortality rates. There was no difference in overall cancer mortality or in the risk of mortality by cancer site except for breast cancer, for which a deficit was observed in the vicinity of nuclear sites. After correction for the multiplicity of tests, this difference was not significant. Our study showed no excess cancer mortality in the population aged 0 to 64 years residing around French nuclear sites.

Adolescent↗