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Biomedical subjects

B Raynard

Publications and source records attributed to B Raynard.

At least 19 recordsLinked to original sources

Heated intra-operative intraperitoneal oxaliplatin alone and in combination with intraperitoneal irinotecan: Pharmacologic studies.

The results of four prospective clinical trials testing intraperitoneal chemohyperthermia (IPCH) are reported. The first one aimed at determining the appropriate dose of heated (42 degrees C) intraperitoneal oxaliplatin following complete resection of peritoneal carcinomatosis (PC) by studying its pharmacokinetics. The recommended dosage was set at 460 mg/m2 in 2 l/m2 of peritoneal instillation. The second trial is a phase 2 study on 24 patients with colorectal PC treated with the preceding regimen: the 2-year survival rate was 74% after a minimal follow-up of 18 months. A second pharmacokinetic study using intraperitoneal oxaliplatin at the same dose but in hypotonic solutions did not show any survival advantage and was associated with an increase in complications. A third pharmacokinetic study was to determine the appropriate dose of intraperitoneal oxaliplatin combined with intraperitoneal irinotecan: the recommended dosage was 360 mg/m2 for each of the chemotherapy agents.

Animals↗

Heated intra-operative intraperitoneal oxaliplatin plus irinotecan after complete resection of peritoneal carcinomatosis: pharmacokinetics, tissue distribution and tolerance.

BACKGROUND: The purpose of this study was to report the pharmacokinetics (PK) and tolerance profile of intraoperative intraperitoneal chemo-hyperthermia (IPCH) with oxaliplatin and irinotecan. PATIENTS AND METHODS: Thirty-nine patients with peritoneal carcinomatosis (PC) of either gastrointestinal or peritoneal origin underwent complete cytoreductive surgery followed by IPCH with a stable dose of oxaliplatin (460 mg/m(2)), plus one among seven escalating doses of irinotecan (from 300 to 700 mg/m(2)). IPCH was carried out with the abdomen open, for 30 min at 43 degrees C, with 2 l/m(2) of a 5% dextrose instillation in a closed continuous circuit. Patients received intravenous leucovorin (20 mg/m(2)) and 5-fluorouracil (400 mg/m(2)) just before IPCH to maximize the effect of oxaliplatin and irinotecan. RESULTS: Irinotecan concentration in tumoral tissue increased until 400 mg/m(2) and then remained stable despite dose escalations. It was 16-23 times higher than in non-bathed tissues. Increasing doses of intraperitoneal irinotecan did not modify the PK of intraperitoneal oxaliplatin, and the drug concentration ratio was 17.8 higher in tumoral tissue (bathed) than in non-bathed tissues. The hospital mortality rate was 2.5% and the non-hematological complication rate was 25%. However, grade 3-4 hematological toxicity rate was 58%. CONCLUSION: Intraperitoneal heated oxaliplatin (460 mg/m(2)) plus irinotecan (400 mg/m(2)) presented an advantageous PK profile and was tolerated by patients, despite a high hematological toxicity rate.

Adult↗

Acute respiratory distress syndrome after chemotherapy for lung metastases from non-seminomatous germ-cell tumors.

GOALS: To describe an acute respiratory distress syndrome (ARDS) occurring after chemotherapy for non-seminomatous germ-cell tumors (NSGCT) with diffuse lung metastases, we conducted a retrospective study in a 15-bed intensive care unit (ICU) in a comprehensive cancer center. PATIENTS AND METHODS: During a 10-year period, 16 consecutive patients with diffuse lung metastases from a NSGCT were admitted to the ICU for respiratory distress and high-risk chemotherapy. MAIN RESULTS: Nine patients developed acute respiratory failure requiring mechanical ventilation (MV) within 3 days of the initiation of chemotherapy, while the respiratory status of the seven other patients improved. The evolution was independent of tumor marker levels and the type of chemotherapy regimen. The SAPS II score did not accurately describe the severity of this population. The only predictor of intubation was the initial PaO2/FiO2 ratio upon admission to the ICU. Six out of seven patients who did not require MV were discharged alive from the hospital, whereas all but one patient requiring MV died. Refractory hypoxemia and ventilator-associated pneumonia were the leading causes of death. CONCLUSIONS: Acute respiratory distress in patients with lung metastases from NSGCT is a rare cause of ARDS. Chemotherapy could be responsible for triggering the respiratory worsening. Patients with severe respiratory insufficiency (PaO2 <70 mmHg on room air) on admission to hospital should be promptly transferred to the ICU for the first chemotherapy course.

Adult↗

Meta-analysis: evaluation of adjuvant therapy after curative liver resection for hepatocellular carcinoma.

AIM: To evaluate adjuvant modalities after curative resection for hepatocellular carcinoma using a meta-analysis of randomized and non-randomized controlled trials. METHODS: In a first step, a meta-analysis of randomized controlled trials was carried out. Sensitivity analyses after inclusion of non-randomized controlled trials were performed. Four therapeutic modalities were evaluated: pre-operative transarterial chemotherapy, post-operative transarterial chemotherapy, systemic chemotherapy and a combination of systemic and transarterial chemotherapy. RESULTS: Only post-operative transarterial chemotherapy improved survival significantly at 2 years [difference, 22.8%; confidence interval (CI), 8.6-36.9%; P = 0.002] and 3 years (difference, 27.6%; CI, 8.2-47.1%; P = 0.005), and decreased the probability of no recurrence at 1 year (difference, 28.8%; CI, 16.7-40.8%; P < 0.001), 2 years (difference, 27.6%; CI, 8.2-47.1%; P = 0.005) and 3 years (difference, 28%; CI, 8.2-47.9%; P = 0.006). In a sensitivity analysis after inclusion of non-randomized controlled trials, post-operative transarterial chemotherapy still improved survival at 1 year (difference, 9.6%; CI, 0.8-18.3%; P = 0.03), 2 years (difference, 13.5%; CI, 0.9-26%, P = 0.04) and 3 years (difference, 18%; CI, 7-28.9%; P < 0.001), and decreased the probability of no recurrence at 1 year (difference, 20.3%; CI, 7.7-33%; P = 0.002), 2 years (difference, 35%; CI, 21.4-46.3%; P < 0.001) and 3 years (difference, 34.5%; CI, 18.7-50.3%; P < 0.001). CONCLUSION: Post-operative transarterial chemotherapy improved survival and decreased the cumulative probability of no recurrence. New randomized controlled trials evaluating this modality are required.

Antineoplastic Agents↗

[Resuscitation management of patients with primary bronchopulmonary cancer].

OBJECTIVE: There is little data in the literature on the management of patients presenting with a primary broncho-pulmonary cancer in a reanimation unit. The aim of our study was to describe and analyze the prognostic factors of such a population. METHOD: This was a retrospective study of all the patients exhibiting a broncho-pulmonary cancer and admitted to the reanimation unit in the Gustave-Roussy Institute over a period of three years. RESULTS: Out of 67 patients, one out of two was still alive following reanimation. The prognosis was not influenced by the type of broncho-pulmonary cancer or its stage of progression, but essentially depends on the age, severity on admission, presence of acute respiratory failure and the necessity of using mechanical ventilation. The prognosis does not appear poorer when admission to the reanimation unit was related to a tumoral complication rather than an intercurrent affection or therapeutic complication. CONCLUSION: The existence of a broncho-pulmonary cancer, even at an advanced stage, does not appear to stall the management of such patients in reanimation.

Adult↗

[Regenerative nodular hyperplasia: variable clinical aspects].

BACKGROUND: Regenerative nodular hyperplasia can take on very misleading aspects making diagnosis difficult. CASE REPORTS: We report three cases of regenerative nodular hyperplasia (RNH). In the first patient rupture of esophageal varices was associated with myelofibrosis. In the second, extensive portal thrombus formation was associated with consumption coagulopathy and essential thrombocytemia. The third patient had systemic sclerodermia, hepatic macronodules, refractory exsudative ascitis and chronic hepatic encephalopathy following surgery for a porto-cava anastomosis. DISCUSSION: The diagnosis of RNH should be suspected in a variety of clinical situations with search for associated diseases in all cases. The prognosis is related to the consequences of portal hypertension and the severity of the associated diseases.

Adult↗

Mechanisms and risk factors for infection of pulmonary artery catheters and introducer sheaths in cancer patients admitted to an intensive care unit.

Pulmonary artery catheters (PACs) are typically inserted for short periods, and the extra-luminal route is assumed to be the overriding source of contamination and/or infection. Our aim was to assess the incidence of PAC and introducer colonization in cancer patients, and to study the mechanisms and risk factors for infection. Patients with a Swan-Ganz catheter admitted to an intensive care unit were prospectively analyzed over 14 months. As soon they were no longer necessary, PACs and introducer sheaths were removed and cultured. We recorded the mean duration of placement, the number of times PACs were handled and the site of insertion. Seventy-nine catheters were inserted in 68 patients. The median (range) duration was three days (0-10) for PACs, and 3.6 days (0-18) for introducers. PAC and/or percutaneous introducer sheath colonization was diagnosed in seven patients (8.9%), but in only one case were both colonized. Colonization rates were 15.5 per 1000 days for PACs and 14.1 per 1000 days for introducers. Introducers were mainly colonized before the 5th day, while PACs were mainly colonized after the 5th day. No PAC or introducer-related local infection or bacteraemia was diagnosed. Colonization was more frequent on catheters inserted into the internal jugular vein. The colonization rate was 5% for PACs and introducers. Our findings suggest that contamination of introducers and PACs may be dissociated and could result from either extraluminal or endoluminal colonization. As three of four PAC colonizations occurred after 5 days, the duration of catheter placement should be considered important. There was little clinical impact of microbial colonization.

Bacteremia↗

Tumor necrosis factor soluble receptor p55 and lipid peroxidation in patients with acute alcoholic hepatitis.

OBJECTIVES: In experimental models, liver injury induced by ethanol, cytotoxic activity of tumor necrosis factor (TNF) -alpha is principally mediated by TNF receptor p55 (TNFRp55). Among the various mechanisms underlying the toxic effects of TNF-alpha, overproduction of reactive oxygen species seems to play a key role in mediating TNF-alpha-induced cytotoxicity. The aim of this study was to evaluate, in patients with alcoholic liver disease, whether alcohol TNFRp55-mediated hepatotoxicity could account for lipid peroxidation expressed by significant increase in serum thiobarbituric reactive acid substances (TBARS) content, and could be amplified by decrease in blood total glutathione content and decrease in plasma antioxidant protective capacity. METHODS: We studied 27 patients with histological alcoholic liver disease (five fibrosis, six acute alcoholic hepatitis (AAH) without cirrhosis, four cirrhosis without AAH, and 12 cirrhosis with AAH. TNFsRp55 and TNFsRp75 plasma levels were measured using ELISA assays. Plasma lipid peroxidation was evaluated by the content of TBARS. Total glutathione (tGSH) content in blood was determined by a kinetic assay. The sensitivity of erythrocytes to an oxidative stress and the plasma antioxidant protective capacity were simultaneously determined by a simple method. RESULTS: In the 18 patients with mild or severe AAH, the plasma levels of TNFsRp55 were negatively correlated with tGSH and were positively correlated with TBARS, with total bilirubin and with discriminant function. tGSH was positively correlated with plasma selenium. The plasma levels of TNFsRp75 were positively correlated with TBARS and with total bilirubin. There was no significant correlation with the mean inhibitory 50% plasma volume or with the percentage of hemolyzed erythrocytes. CONCLUSIONS: Our data support the notions that, in patients with AAH, TNFsRp55 probably mediates cytotoxicity of TNF-alpha, and that cytotoxic effect could be amplified by tGSH depletion in enhancing lipid peroxidation.

Acute Disease↗

[Standards, Options and Recommendations for home parenteral or enteral nutrition in adult cancer patients].

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 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 the Standards, Options and Recommendations project for home parenteral or enteral nutrition in adult cancer patients. METHODS: Data were identified by searching Medline, Cancerlit, web sites and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 72 independent reviewers. RESULTS: The main recommendations for home parenteral or enteral nutrition in adult cancer patients are: 1) Home parenteral or enteral nutrition concerns cancer patients with malnutrition or with inadequate/impossible oral intake, during therapy of because of therapeutic after-effects (standard). Same indications apply for home and hospital artificial nutrition (standard). 2) Patients need a multidisciplinary follow-up (oncologists, nutritionists, and pain specialists), and this follow-up will make treatment adaptations according to the nutritional status possible (recommendation, expert agreement). An active participation of patients and/or their family circle is very important (standard). 3) The benefit of home parenteral or enteral nutrition on the quality of life of terminally ill patients (vs. hydration) has not been demonstrated. When life expectancy is below 3 months, and the Karnofsky index below 50, the drawbacks of home artificial nutrition are more important than its advantages. In this case, home parenteral or enteral nutrition is not recommended (recommendation, expert agreement). 4) Prospective clinical trials are recommended to evaluate the impact of home nutrition on quality of life in cancer patients (expert agreement). 5) The use of educational booklets that mention the telephone number of a referent health care and what to do when a problem happens (e.g. fever on home parenteral nutrition) is recommended (expert agreement). In France, patients should be referred to authorized home parenteral nutrition centres (recommendation, expert agreement).

Enteral Nutrition↗

[Standards, options and recommendations: nutritional support in palliative or terminal care of adult patients with progressive cancer].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the National Federation of Comprehensive Cancer Centres (FNCLCC), the 20 French Cancer Centers 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 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 the Standards, Options and Recommendations project for nutritional support in adult patients with advanced or terminal cancer. METHODS: Data were identified by searching Medline, web sites and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 95 independent reviewers. RESULTS: The main recommendations for nutritional support in adult patients with advanced or terminal cancer are: 1) Palliative care has been defined in a consensual way and is governed by the law (standard). Nutritional support is a palliative care which aim is to maintain and restore the "well-being" of the patient (standard). 2) Digestive symptoms and nutritional troubles are frequently noted in patients with advanced or terminal cancer (standard, level of evidence B2). Karnofsky index (KPS) and performance status (PS) are functional scores with a prognostic value and have to be used (standard, level of evidence B2). 3) Anorexia has a bad predictive value in patients with advanced or terminal cancer (standard, level of evidence B2). 4) In France, patients with advanced or terminal cancer are referred to medical institutions, palliative care units or remained at home (standard). Patients need a multidisciplinary follow-up (standard). An active participation of patients and/or their family circle is very important and physicians have to pay attention for their opinions (standard). 5) Dietetic counseling can help patients to improve their alimentation and its drawbacks (standard). 6) Palliative nutritional care often includes medicinal treatments (standard). 7) Artificial nutrition can slow down nutritional degradation, avoid dehydration and improve quality of life in patients with advanced stage cancer (especially head and neck cancer for enteral nutrition and digestive occlusions for parenteral nutrition) and unable to eat adapted meals (standard, level of evidence C). 8) When life expectancy is below 3 months with a KPS 3/4 50% (or PS > 2), artificial nutrition is not recommended (recommendation, expert agreement). 9) The assessment of nutritional care in patients with advanced or terminal cancer has to include functional scores measurement, quality of life and satisfaction degree of the patient and/or their family (standard, expert agreement).

Adult↗

[Abdominal tuberculosis: deceptive and still encountered].

BACKGROUND: Extrapulmonary manifestations of tuberculosis are increasing in incidence. Abdominal tuberculosis may mimic a variety of gastrointestinal disorders. The diagnosis of abdominal tuberculosis is still difficult to establish before surgery. CASE REPORTS: We report 3 cases of abdominal tuberculosis in immunocompetent individuals. One patient presented with an ileocecal mass mimicking cancer. The second one presented with fever, ileocecal mass and ascites leading to the diagnosis of appendiceal peritonitis. The last patient was admitted for ascites, ovarian mass and high CA 125 serum level simulating ovarian cancer with peritoneal carcinomatosis. COMMENTS: In cases of abdominal tuberculosis when standard investigations are unhelpful, a PCR should be performed. Estimation of adenosine deaminase in ascitic fluid is an easy and reliable method for diagnosing tuberculous ascites. With these non invasive diagnostic procedures, surgery should be reserved only to patients with complications.

Adenosine Deaminase↗

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↗

Nutritional support of the cancer patient: issues and dilemmas.

Malnutrition in cancer patients results from multifactorial events and is associated with an alteration of quality of life and a reduced survival. A simple nutritional assessment program and early counselling by a dietitian are essential to guide nutritional support and to alert the physician to the need for enteral (EN) or parenteral nutrition (PN). A daily intake of 20-35 kcal/kg, with a balanced contribution of glucose and lipids, and of 0.2-0.35 g nitrogen/kg is recommended both for EN and PN, with an adequate provision of electrolytes, trace elements and vitamins. EN, always preferable for patients with an intact digestive tract, and PN are both safe and effective methods of administering nutrients. The general results in clinical practice suggest no tumor growth during nutritional support. The indiscriminate use of conventional EN and PN is not indicated in well-nourished cancer patients or in patients with mild malnutrition. EN or PN is not clinically efficacious for patients treated with chemotherapy or radiotherapy, unless there are prolonged periods of GI toxicity, as in the case of bone marrow transplant patients. Severely malnourished cancer patients undergoing major visceral surgery may benefit from perioperative nutritional support, preferably via enteral access. Nutritional support in palliative care should be based on the potential risks and benefits of EN and PN, and on the patient's and family's wishes. Research is currently directed toward the impact of nutritional pharmacology on the clinical outcome of cancer patients. Glutamine-supplemented PN is probably beneficial in bone marrow transplant patients. Immune diets are likely to reduce the rate of infectious complications and the length of hospital stay after GI surgery. Further studies are needed to determine the efficacy of such novel approaches in specific populations of cancer patients, and should also address the question of the overall cost-benefit ratio of nutritional pharmacology, and the effect of nutritional support on length and quality of life.

Cachexia↗

Value of gram stain examination of lower respiratory tract secretions for early diagnosis of nosocomial pneumonia.

Except for bronchoalveolar lavage, the value of the Gram stain examination of respiratory tract samples for the diagnosis of hospital-acquired pneumonia (HAP) and their potential impact on empiric antibiotic treatment have rarely been assessed. During a 14-mo period, both plugged telescoping catheter (PTC) and endotracheal aspirate (EA) were performed when an HAP was suspected in mechanically ventilated patients. The results of Gram stain examinations and cultures and previous and subsequent antibiotic treatment were prospectively recorded. Two criteria for pneumonia were considered: (1) clinically diagnosed pneumonia, according to attending physicians, based on clinical and radiological evolution and the PTC culture results, and (2) microbiologically proven pneumonia (solely based on the result of quantitative PTC culture). Of 91 episodes of suspected HAP in 51 patients, 27 (30%) episodes were clinically diagnosed as pneumonia. When considering clinically diagnosed pneumonia, the sensitivity and specificity of Gram stain examination were similar (respectively, 89% and 62% for EA and 67% and 95% for PTC). When considering microbiologically proven pneumonia, the sensitivity and specificity of Gram stain examination were, respectively, 91% and 64% for EA and 70% and 96% for PTC. The negative predictive value of Gram stain examination of EA and the positive predictive value of Gram stain examination of PTC were high. Our results suggest that the combination of Gram stain examination of paired PTC and EA may contribute to the early diagnosis of HAP in about two-thirds of mechanically ventilated patients, and guide the empiric therapy when needed. In the remaining one-third of patients, the Gram stain examination is not helpful in predicting HAP.

Bacteria↗