[Infection and cancer: general information and specific questions]. / Infection et cancer: notions générales et questions actuelles.

The main risk factors of infectious complications in cancer patients result from immune deficiency more or less related to cancer. Prognosis is related to the type and grade of the underlying disease. Prospective studies should be conducted to update data on the frequency of infections, morbidity and mortality (expert agreement). Prospective studies are needed to follow the epidemiology in cancer patients, particularly in neutropenic patients (expert agreement). Prospective studies should be conducted to determine prognosis factors allowing precise recognition of "low-risk" neutropenic patients with fever who could benefit from home care (expert agreement). When infection is suspected, the first criterion determining the therapeutic attitude concern signs of gravity requiring emergency care (septic shock). Beyond this situation, the first criterion determining the therapeutic attitude is the severity of the neutropenia. Microbial diagnosis is essential for initiating and later adapting anti-infectious treatment as well as for assessing efficacy.

[Standards, options and recommendations for good practice in hemoculture in cancerology]. / Standards, Options et Recommandations pour une bonne pratique des hémocultures en cancérologie.

Excepting emergency and aplasia: two to three blood samples should be draw for culture an hour apart within a 24 period (standard). For emergency or aplasia: two to three blood samples should be drawn for culture before initiating early antibiotic therapy. The delay between samples drawn from different sites should be less than one hour (standard). For patients on antibiotics: four to six blood samples should be drawn for culture within 48 hours, outside ongoing antibiotic administration. If the patient is given corticosteroids, it is recommended to draw two or three blood samples in case of deterioration (agreement of the experts). Rigorous aseptic techniques must be used (standard). Culture media are chosen according to the institution's microbial ecology (standard). The volume of blood drawn should be adapted to the system used (standard). Culture positivity is determined at 24 to 48 hours.

Intravenous access: related problems in oncology.

This article reviews the latest developments in the literature concerning two types of catheter widely used in oncology: Hickman central venous catheters (CVCs) and totally implanted venous ports. It now seems possible to diagnose catheter-related bloodstream infections (CRBI) without removing the device; recent studies showed that paired quantitative blood cultures are the most reliable and convenient method for diagnosis of CRBI. Can CRBI be cured and treated without device removal? A decision-tree/flow-chart resulting from analysis of international data by French International Experts is presented. Futures trends are reviewed: new techniques for prevention, including catheters impregnated with antimicrobials and, antiseptic hubs; flushing and antibiotic lock techniques that can be used both for prevention and treatment.

[Standards, Options and Recommendations (SOR) for the surveillance and the prevention of cross infections in oncology. Fédération Nationale des Centres de Lutte Contre le Cancer]. / Standards, Options et Recommandations (SOR) pour la surveillance et la prévention des infections nosocomiales en cancérologie.

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 the prevention and the surveillance of cross infection in oncology. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 106 independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: 1) Criteria of infection status and nosocomiality defined by the Centers for Infectious Diseases (CDC) and Prevention and the Superior Council of Public Hygiene (CSHPF) are not adapted and have to be redefined in oncology. 2) The epidemiology of nosocomial infections in oncology is not well known but their incidence seems to be higher. Numerous risk factors of cross infections coexist in cancer patients, among which the duration and depth of neutropenia. 3) Surveillance and prevention of cross infection are compulsory and were taken into account in the accreditation of hospitals. Obligation is expressed in terms of means and results. 4) The objectives of the cross infection surveillance are to detect major problems and critic situations, to guide probabilistic antibiotic therapy and to assess the effectiveness of the infections control. The surveillance means consist in prevalence and incidence survey, punctually and continuously conducted. 5) The three specific behaviors to be adopted to prevent cross infections are to control: all the patients, infected patients carrying multiresistant bacteria, immunodepressed patients. 6) Standards of care have to be applied to a/l patients with cancer. 7) It is necessary to add particular septic cares for the patients infected with micro-organisms indicated on reference lists or carrying multiresistant bacteria. 8) The only objective of the protective isolation of immunodepressed cancer patients is to reduce the cross infection. There is no standard behavior for the indications and the modalities of protective isolation. The prevention behaviors to be taken are defined by expert agreements.

Systematic percutaneous fluoroscopic gastrostomy for concomitant radiochemotherapy of advanced head and neck cancer: optimization of therapy.

Wasting is a major complication of advanced head and neck cancer. Concomitant chemotherapy and twice-daily continuous radiotherapy with no acceleration represents a promising treatment modality for these tumors, but increases the risk of mucositis. This report describes the results achieved with percutaneous fluoroscopic gastrostomy (PFG) and its impact on the quality of life of patients with head and neck cancer in terms of their nutritional status. A total of 50 stage IV tumors of the oropharynx and hypopharynx recorded in a prospective database were reviewed retrospectively. All patients were managed by PFG, which was found to be a safe and effective technique with no technical failures. PFG feeding resulted in a mean increase in body weight of 2.5 kg within 3 weeks. The body mass index (BMI) was maintained at 3 and 6 weeks. Minor complications occurred, but no major complications were noted. The overall procedure-related mortality rate was nil. Further prospective investigations are necessary to determine whether treatment of wasting improves patient survival.

Variation in antimicrobial utilization for febrile neutropenia in cancer patients. The CEMIC Study Group. Club d'Etudes des Maladies Infectieuses en Cancer.

BACKGROUND: No previous study has compared hospitals with respect to the variation of antimicrobial utilization (AU) for cancer patients with febrile neutropenia (FNE). PATIENTS AND METHODS: We conducted an observational cohort study, carried out in 18 tertiary care centers across nine countries, in order to describe AU patterns for cancer patients with FNE and to evaluate whether prescription was appropriate. RESULTS: A total of 148 patients was exposed to 483 antimicrobial agents and 318 therapeutic courses, corresponding to 1,766 antimicrobial exposure-days. The most frequently used initial treatment consisted of a combination of a broad-spectrum beta-lactam agent and an aminoglycoside (50%). The extent of initial monotherapy varied between 5% in German and 30% in French centers. Glycopeptides, fluconazole and acyclovir were incorporated into initial empiric therapy in 21,13, and nine instances, respectively. The French centers prescribed the largest number of antimicrobial courses per FNE (mean 2.5 +/-1.5), whereas the center with the highest antimicrobial exposure density was observed in the USA (2.8 exposure-days per 1 FNE-day). AU was judged to be inappropriate by at least one criterion in 59 patients (40%). CONCLUSION: This pilot study revealed important variation in AU intensity and prescription preferences in FNE patients and may help to develop appropriate strategies to improve antimicrobial therapy for this patient population.

Resource implications of febrile neutropenia in cancer patients. An international collaborative study.

No previous study has compared countries with respect to differences in clinical practice and resource use of cancer patients with febrile neutropenic episodes (FNE). The purpose of this international, cross-sectional pilot study conducted in tertiary care centers across Europe, Brazil and Australia was to evaluate the resource use attributable to febrile neutropenia in different countries. A total of 17 centers from eight countries provided 128 patients. The leading malignant disorders were hematological malignancies (n = 47), lymphomas (n = 27), and breast cancer (n = 26). The median length of duration of FNE was 4 days (interquartile range, 3-8). The incidence density of antimicrobial exposure was 4.691 days of antimicrobial therapy per 1,000 days of FNE. There were 23 patients who received a total of 280 days of G-CSF therapy. On average, 5 (+/-5.4) blood samples per patient were drawn and cultured. The most common diagnostic radiographic test was the chest X-ray, with a total of 224 such examinations performed in 82 patients. We conducted an international cross-sectional study on resource implications of febrile neutropenia in cancer patients. The records of the febrile neutropenic patients included in this study reflect clinical practice in a heterogeneous, international patient population, treated with modern supportive care and early empiric antibiotics by clinicians at different levels of expertise.

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.

Cefepime versus imipenem-cilastatin as empirical monotherapy in 400 febrile patients with short duration neutropenia. CEMIC (Study Group of Infectious Diseases in Cancer).

This open, comparative, randomized, multicentre equivalence study compared cefepime 2 g bd and imipenem-cilastatin 1 g tds (50 mg/kg/day) as empirical monotherapy for febrile episodes in a homogeneous cohort of cancer patients with short duration neutropenia following chemotherapy for solid tumour, lymphoma or myeloma. The study was conducted in 17 French anti-cancer centres in 1995 and 1996. Response to monotherapy was assessed 7 days after treatment and was based on resolution of fever and signs and symptoms, eradication of pathogens, absence of new infection, relapse, and death of infectious origin, without addition of other antibiotics. Patients were treated for a minimum of 4 days. Of the 400 episodes randomized, 344 (86%) were evaluable for efficacy. Patient characteristics were comparable between treatment groups. Success of monotherapy was observed in 79% of episodes with cefepime and 72% with imipenem-cilastatin (equivalence, P <0.0001). The response rate for microbiologically documented infections was 66% with cefepime and 61% with imipenem-cilastatin (bacteraemic episodes: 63% for cefepime; 44% for imipenem-cilastatin). A second antibiotic (usually a glycopeptide) was added in 20% and 21% of the cases, respectively. Overall, the response to therapy, with or without an additional antibiotic, was 95% (cefepime) and 90% (imipenem-cilastatin). Survival was similar in both groups (95% and 98%, respectively). Cefepime treatment was better tolerated, with 9% of the patients experiencing related intercurrent events compared with 19% in the imipenem-cilastatin group (P = 0.003). Nausea/vomiting was significantly more frequent in the imipenem-cilastatin group (15%) than in the cefepime group (5%; P = 0.001). Cefepime monotherapy was as effective as, and better tolerated than, imipenem-cilastatin in the empirical treatment of fever during short duration neutropenia.

[Standards, Options, and Recommendations for the management of brief neutropenias. Fedération Nationale des Centres de Lutte Contre le Cancer]. / Standards, Options et Recommandations pour la prise en charge des neutropénies courtes.

CONTEXT: The "Standards, Options and Recommendations" (SOR), initiated in 1993, is a collaborative project 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 outcomes for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary experts group, with feedback from specialists in cancer care delivery. OBJECTIVE: To develop a clinical practice guideline for the management of neutropenic cancer patients (excluding prolonged neutropenia). METHODS: Data have been identified by literature search using Medline and Current Contents (up to February 1997) and personal reference lists. The main end points considered were mortality, morbidity, risk factors, fever, source of infection, microbiological documentation, incidence and length of hospital stays, quality of life, efficacy of treatment, safety and costs. Once the guideline was defined, the document was submitted to 48 reviewers for peer review and to the medical committees of the 20 French Cancer Centres for review and agreement. RESULTS: The key recommendations are: 1) before receiving cytotoxic chemotherapy, patients must be informed of potential risks and precautions to observe; 2) non-febrile neutropenic patients can be followed at home (except specific context); antibiotic prophylaxis is not recommended; 3) initial empirical antibiotic therapy for febrile patients is mandatory, whether associated beta-lactam and aminoglycoside, or monotherapy with a broad-spectrum beta-lactam (except in case of septic shock or pneumopathy). A glycopeptide can be added in case of overt catheter-related or cutaneous infection, in case of microbiologically documented infection with a oxacillin-resistant Gram positive bacteria, or in case of persistent fever in a clinically deteriorating patient; 4) at the present time, there is insufficient evidence to recommend the management of febrile neutropenic patients at home. We recommend participation in studies to identify predicting factors of low-risk patients and to assess the feasibility and safety of early discharge and home therapy.

Influence of strain, biomaterial, proteins, and oncostatic chemotherapy on Staphylococcus epidermidis adhesion to intravascular catheters in vitro.

Initial adhesion of four phenotypically different strains of Staphylococcus epidermidis to 16 silicone, polyurethane, or hydrophilic polyurethane catheters was assessed in vitro by a bacterial radiolabeling method. The effect of catheter exposure to plasma proteins, to an anticancer polychemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide), or to both of them was determined. Bacterial adhesion on native catheters was dependent on the hydrophobicity of both bacteria and catheters. The four strains tested adhered preferentially to silicone catheters (p < 0.05); adhesion was moderate to polyurethane surfaces, whereas the least adhesion was obtained for hydrophilic polyurethane catheters. Adsorption of plasma proteins on the surface produced a marked decrease in adhesion on silicone (-66.2%; p < 0.001) and polyurethane (-32.8%; p < 0.01) catheters and a marked increase in adhesion on hydrophilic surfaces (+91.7%; p < 0.05). Chemotherapeutic treatment of the catheter produced a slight but not significant decrease in adhesion on silicone (-17.4%) and polyurethane (-19.8%) catheters and a marked increase in adhesion on hydrophilic polyurethanes (+148.2%; p < 0.001). The in vitro simulation of catheter use suggested that oncostatic drugs and plasma proteins play an important role in S. epidermidis adhesion to intravascular catheters. Overall, bacterial adhesion is lowest on hydrophilic polyurethane catheters before and after simulation of catheter use.

Prospective multicentric study of the etiology of 1051 bacteremic episodes in 782 cancer patients. CEMIC (French-Belgian Study Club of Infectious Diseases in Cancer).

A total of 1051 bacteremic episodes (782 patients) were prospectively recorded in 10 cancer centers (9 French, 1 Belgian), with: patient's age (mean 53, range 1-89 years), underlying cancer, neutropenia (< 1000 neutrophils/microliters; 233), signs and symptoms, type of i.v. line (percutaneous central: 534; peripheral: 228; central implanted: 304), treatment, blood culture system, number of positive blood culture bottles/total obtained, time to growth. Of all episodes, 23.2% occurred within 48 h of admission. The patients were receiving systemic antibiotics at sampling (on AB) in 34.6% of cases. The 1147 pathogens isolated (86 polymicrobial) were: E. coli (10.7%), Klebsiella-Enterobacter-Serratia (6.1%), other enterobacteriaceae (2.2%), Pseudomonas aeruginosa (4.8%), other nonfermenters (4.7%), coagulase-negative staphylococci (CNS, 40.8%), Staphylococcus aureus (9.9%), streptococci (5.4%), enterococci (2.2%), anaerobes (3.4%), yeasts (3.5%), and other bacteria (6.9%). The CDC (Centers for Disease Control) criteria (1988) were used to assess significance: group 1: pathogenic species (616 episodes; 59%); group 2: clinical signs and isolation of a "contaminant" species (47; 4.5%); group 3: as in group 2 with an i.v. line and empiric antibiotic treatment (181 episodes including 176 CNS; 17%); group 4: non-significant (207 episodes including 203 CNS; 20%). Groups 1-3, in which the episodes were considered to be significant (844 episodes; 80%) were compared with non-significant episodes (Fisher). Significant differences (P < or = 0.05) were seen in time to growth (median growth within 24 h vs 48 h), fever (86% vs 54%), chills (40% vs 3%), hypotension (10% vs 2%), septic shock (9% vs 1%), polymicrobial etiology (10% vs 0.5%), and initiation of empiric antibiotic treatment (71% vs 4%). Bacteremic episodes of CDC groups 1, 3 and 4 were further studied in episodes with a single isolate as a doubtful clinical significance (482 episodes) and episodes with > or = 2 bottles positive of probable clinical significance (569 episodes; 54%). In group 1 (218 doubtful, 398 probably significant episodes) significant differences were seen in chills (36% vs 52%), shock (7% vs 13%), polymicrobial (8% vs 17%), initiation of empiric antibiotic treatment (60% vs 72%); in group 3 (87 doubtful, 94 probably significant) in time to growth delay; in group 4 (177 doubtful, 30 probably significant) in proportion with implanted catheter (26% vs 52%), fever (62% vs 10%), and time to growth. This study confirms the predominant role of Gram-positive cocci in bacteremia occurring in cancer patients.

Value of urinary hydroxyproline and bone isoenzyme of alkaline phosphatase in the early detection and follow-up of bone metastasis in breast cancer patients.

A multiparametric biological study of 178 evaluable breast cancer patients was performed to evaluate the usefulness of individual parameters for the prediction, diagnosis and follow-up of bone metastasis (BM) as compared to physical tests. Serum and urinary calcium and phosphorus were of little discriminative value. The sensitivity and specificity for the urinary hydroxyproline/creatinine ratio (UHP/creat.) were respectively 75% and 81.4% versus 43.2% and 91.4% for the bone isoenzyme of alkaline phosphatase in serum (BIE). During an average follow-up of 14.3 months for 51 patients with bone metastasis, variations in UHP-creat. and BIE correlated with clinical and physical findings; the best correlation was given by UHP/creat. Twenty patients who were initially free of bone metastasis were followed-up for a mean metastasis-free interval of 14 months; UHP/creat. predicted the appearance of bone metastasis in 50% of cases with a lead time of 5.5 months versus 40% and 8.5 months for BIE. Combined use of UHP/creat. and BIE gave a prediction rate of 70% and a mean lead time of 7 months, and this combination of markers thus merits consideration in the management of breast cancer patients.

Reevaluation of alkaline phosphatase measurement during Hodgkin's disease by electrophoretic isoenzyme separation.

Electrophoretic isoenzyme separation provides much more precise information than measurement of alkaline phosphatases (AP). Use of this technique for 83 patients with Hodgkin's disease revealed that the presence of the alpha 1 fraction (alpha 1 AP) was very significantly correlated with the stage of disease extension (P less than 0.01) and above all with the presence of general symptoms (P less than 0.001). Repeat measurements performed during patient follow-up demonstrated a close association between presence of alpha 1 AP and existence of progressive disease. While the mechanism of appearance of this abnormal alpha 1 AP fraction is not linked to Hodgkin-specific liver lesions, this test provides much more interesting data than classical measurement of total alkaline phosphatases (TAP).

Alpha 1 isoenzyme of alkaline phosphatases. Clinical importance and value for the detection of liver metastases.

Measurement of the alpha 1 (fast liver) fraction of alkaline phosphatases in the serum for 217 cancer patients, 92 patients with nonmalignant hepatic affections and 131 controls, revealed that the alpha 1 fraction offers better global value (94%), sensitivity (96%), and specificity (93%) than gamma GT or total alkaline phosphatase determinations for the detection of liver metastases during cancer. Initial data from study of the time of appearance of the alpha 1 fraction reveals that this fraction shows up earlier than rises in the gamma GT or total alkaline phosphatases. Results of a multiparametric study conducted on the alpha 1 fraction and various hepatic enzymatic tests (SGOT, SGPT, GLDH, ALP, gamma GT) indicate that the alpha 1 fraction used alone is better than any other test or combination of tests for biological detection of liver metastases. As concerns the influence of chemotherapy on the appearance of the alpha 1 fraction, the majority of the drugs used for anticancer chemotherapy do not seem to affect measurement of the alpha 1 ALP fraction. The alpha 1 fast liver fraction of alkaline phosphatases, detected by electrophoresis on cellulose acetate, can be considered one of the best known tests for the detection of liver metastases.

Comparative study of gamma glutamyl transferase, alkaline phosphatase and its alpha 1 isoenzyme as biological indicators of liver metastases.

Biological detection of liver metastases represents an important factor in the surveillance of the course of cancerous affections. The authors present a report on a potential new indicator, the isoenzyme of alkaline phosphatase migrating to the alpha 1 region (alpha 1 ALP). In comparison to those tests considered the most sensitive at present-gamma glutamyl transferase and total alkaline phosphatase-this alpha 1 isoenzyme appears more sensitive and more specific, capable of detecting 97% of liver metastases with a specificity of 90%.

The value of serum alkaline phosphatase alpha 1 isoenzyme in the diagnosis of liver metastases. Preliminary results.

Serum alkaline phosphatase isoenzyme electrophoresis on cellulose acetate plates in a normal population of 91 controls and 255 cancer patients demonstrates the presence of an isoenzyme alpha 1 in 36 out of39 cases of confirmed liver metastases. In 188 cancer patients without apparent hepatic lesion and with a normal liver biology, the alpha 1 isoenzyme has been found in 45 cases, but 11 presented afterwards confirmed liver metastases. This isoenzyme remained negative in the normal population. Therefore, our results indicate that the alpha 1 alkaline phosphatase isoenzyme may be a useful marker for the biological diagnosis of liver metastases.