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International audience; BackgroundChemotherapy combined with radiotherapy is the standard treatment of “limited-stage” small-cell lung cancer. However, controversy persists over the optimal timing of thoracic radiotherapy and chemotherapy.Material and methodsWe performed a meta-analysis of individual patient data in randomised trials comparing earlier versus later radiotherapy, or shorter vs. longer radiotherapy duration, as defined in each trial. We combined the results from trials using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival.ResultsTwelve trials with 2,668 patients were eligible. Data from nine trials comprising 2,305 patients were available for analysis. The median follow-up was 10 years. When all trials were analysed together, “earlier or shorter” vs. “later or longer” thoracic radiotherapy did not affect overall survival. However, the HR for overall survival was significantly in favour of “earlier or shorter” radiotherapy among trials with a similar proportion of patients who were compliant with chemotherapy (defined as having received 100% or more of the planned chemotherapy cycles) in both arms (HR 0.79, 95% CI 0.69–0.91) and in favour of “later or longer” radiotherapy among trials with different chemotherapy compliance (HR 1.19, 1.05–1.34, interaction test p

International audience; A prospective (2005-2007) hospital-based multicentre surveillance of EORTC/MSG-proven or probable invasive aspergillosis (IA) cases whatever the underlying diseases was implemented in 12 French academic hospitals. Admissions per hospital and transplantation procedures were obtained. Cox regression models were used to determine risk factors associated with the 12-week overall mortality. With 424 case-patients included, the median incidence/hospital was 0.271/10(3) admissions (range 0.072-0.910) without significant alteration of incidence and seasonality over time. Among the 393 adults (62% men, 56 years (16-84 years)), 15% had proven IA, 78% haematological conditions, and 92.9% had lung involvement. Acute leukaemia (34.6%) and allogeneic stem cell transplantation (21.4%) were major host factors, together with chronic lymphoproliferative disorders (21.6%), which emerged as a new high-risk group. The other risk host factors consisted of solid organ transplantation (8.7%), solid tumours (4.3%), systemic inflammatory diseases (4.6%) and chronic respiratory diseases (2.3%). Serum galactomannan tests were more often positive (≥69%) for acute leukaemia and allogeneic stem cell transplantation than for the others (

A multidisciplinary working group devoted to epidemiological surveillance of invasive aspergillosis (IA) was created in January 2000 in Grenoble University Hospital. This article presents the results of a three-year IA surveillance. The multidisciplinary working group surveyed all hospitalized patients, and the mycology laboratory detected most suspected IA cases. Cases were reviewed monthly by the Aspergillosis Committee, and were classified according to international consensus criteria. Possible nosocomial acquisition was determined. Among the 490 alerts, 74 IA cases were observed: six proven cases (8%), 36 (49%) probable cases and 32 (43%) possible cases. The incidence was 4.4 (95% CI 3.4-5.4) IA/100 000 patient-days. Among the proven and probable IA cases, we observed 10 nosocomial cases and six cases of undetermined origin. No cases were noted in the protected rooms in the haematology unit. Only one cluster of cases (three nosocomial cases) was detected in the haematology unit. Forty-three percent of cases (N=32) were hospitalized in the haematology unit, and all other cases were hospitalized elsewhere. This three-year survey found a high rate of non-nosocomial IA cases and a high frequency of IA cases hospitalized in units other than haematology. Thus, this study shows the importance of IA surveillance in haematology units and all high-risk units.

Purpose: To report a retrospective study concerning the impact of fused 18F-fluoro-deoxy- d -glucose (FDG)-hybrid positron emission tomography (PET) and CT images on three-dimensional conformal radiotherapy planning for patients with non–small-cell lung cancer. Methods and Materials: A total of 101 patients consecutively treated for Stage I–III non–small-cell lung cancer were studied. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same treatment position. Images were coregistered using five fiducial markers. Target volume delineation was initially performed on the CT images, and the corresponding FDG-PET data were subsequently used as an overlay to the CT data to define the target volume. Results: 18F-fluoro-deoxy- d -glucose-PET identified previously undetected distant metastatic disease in 8 patients, making them ineligible for curative conformal radiotherapy (1 patient presented with some positive uptake corresponding to concomitant pulmonary tuberculosis). Another patient was ineligible for curative treatment because the fused PET-CT images demonstrated excessively extensive intrathoracic disease. The gross tumor volume (GTV) was decreased by CT-PET image fusion in 21 patients (23%) and was increased in 24 patients (26%). The GTV reduction was ≥25% in 7 patients because CT-PET image fusion reduced the pulmonary GTV in 6 patients (3 patients with atelectasis) and the mediastinal nodal GTV in 1 patient. The GTV increase was ≥25% in 14 patients owing to an increase in the pulmonary GTV in 11 patients (4 patients with atelectasis) and detection of occult mediastinal lymph node involvement in 3 patients. Of 81 patients receiving a total dose of ≥60 Gy at the International Commission on Radiation Units and Measurements point, after CT-PET image fusion, the percentage of total lung volume receiving >20 Gy increased in 15 cases and decreased in 22. The percentage of total heart volume receiving >36 Gy increased in 8 patients and decreased in 14. The spinal cord volume receiving at least 45 Gy (2 patients) decreased. Multivariate analysis showed that tumor with atelectasis was the single independent factor that resulted in a significant effect on the modification of the size of the GTV by FDG-PET: tumor with atelectasis (with vs. without atelectasis, p = 0.0001). Conclusion: The results of our study have confirmed that integrated hybrid PET/CT in the treatment position and coregistered images have an impact on treatment planning and management of non–small-cell lung cancer. However, FDG images using dedicated PET scanners and respiration-gated acquisition protocols could improve the PET-CT image coregistration. Furthermore, the impact on treatment outcome remains to be demonstrated.

Aspergillus fumigatus infection in hospitalized immunocompromised patients often raises suspicion regarding the potential for hospital acquisition. Hospital staff have an important responsibility in implementing preventive measures, especially since the advent of current legislation concerning hospital-acquired infections. There have been high expectations that molecular typing methods might determine the source of Aspergillus fumigatus, a ubiquitous mould. The aim of the present epidemiological study, was therefore, to identify the origin(s) of Aspergillus infection in six well-documented patients. All the clinical strains (N=33), and those from hospital (N=14) and home environments (N=34) were isolated according to a standardized protocol and typed by sequence-specific DNA primer analysis. The results confirmed the huge biodiversity of the A. fumigatus population, and consequently the difficulty in ascertaining a hospital source of the infection, as opposed to infections due to other Aspergillus species less frequently encountered.

To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non-small-cell lung cancer (NSCLC).A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m(2), day 1), ifosfamide (1.5 g/m(2), days 1 to 3) and cisplatin (30 mg/m(2), days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy.Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P =.38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P =.15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P =.027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P =.044). Disease-free survival time was significantly longer in the PCT arm (P =.033).Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease.

The gold standard laboratory tests used to diagnose invasive Candida infection (ICI) are based on the in vitro culture of blood or samples from other sterile sites. However, these tests have limited sensitivity (Se) and are generally not diagnostic until late in the infectious process. The Serion Candida mannan kit was evaluated for the diagnosis of ICI at Grenoble University Hospital (France) between 2007 and 2011. The results were then compared with worldwide data published between 1997 and 2011. This retrospective study was based on follow-up from the investigation of 162 patients of whom 91 had proven ICI; 13 had Candida colonization index (CCI) scores ≥0.42, positive mannan tests, with nonconcomitant infections; and 58 had no evidence of Candida infection. Candida albicans, C. glabrata, C. tropicalis, and C. parapsilosis were the etiologic agents in 104 patients. For patients with or without ICI, the 12-week mortality rates were 35/104 (33.7%) and 6/58 (10.3%), respectively. The mannan diagnostic specificity was 51% and Se was 77%. However, in the meta-analysis (n = 1,536), values were 86% and 62%, respectively. Positive mannan test results may appear early (median 6 days) in the development of candidemia and have moderate diagnostic value for ICI, with a negative predictive value of 83%. In patients at risk of ICI with negative candidemia, the combination of Candida mannan test data with a CCI score ≥0.42 may improve the diagnosis of probable ICI.

In a surveillance study of candidemia in cancer patients that was conducted by the European Organization for Research and Treatment of Cancer, 249 episodes were noted; Candida albicans was isolated in 70% (63) of the 90 cases involving patients with solid tumors (tumor patients) and in 36% (58) of the 159 involving those with hematologic disease (hematology patients). Neutropenia in tumor patients and acute leukemia and antifungal prophylaxis in hematology patients were significantly associated with non-albicans candidemia in a multivariate analysis. Overall 30-day mortality was 39% (97 of 249). In a univariate analysis, Candida glabrata was associated with the highest mortality rate (odds ratio, 2.66). Two multivariate analyses showed that mortality was associated with older age and severity of the underlying disease. Among hematology patients, additional factors associated with mortality were allogeneic bone marrow transplantation, septic shock, and lack of antifungal prophylaxis.

Surmmary A possible relationship between the ability of Aspergillus fumigatus strains to invade tissues and genetic polymorphism was studied by random amplified polymorphic DNA (RAPD) analysis. One hundred randomly designed oligonucleotide decamers were examined with DNA of three reference strains, eight environmental isolates and 21 isolates from two distinct clinical situations: Non-invasive aspergillosis (predominantly aspergilloma) and invasive aspergillosis. One primer (OPQ 6) was found to generate a reproducible amplification product that enabled distinction between the two groups according to the presence or absence of a 0.95-kb fragment that correlated with the nature of the infection (non-invasive or invasive) and immune status of the patient. The results indicated that the pathogenicity of A. fumigatus was related not only to the host's immune status but also to the virulence of the strain of A. fumigatus.

The effectiveness of galactomannan detection with the Platelia test was evaluated in a prospective study of 3,327 sera from 807 patients. The specificity was 99.6% (748 of 751 cases). For the groups of patients with proven and probable invasive aspergillosis, the sensitivity was 50.0% (17 of 34 cases). The disappointing sensitivity associated with the presence of rare false-positive cases underlines the limits of this test.

International audience; OBJECTIVES: This study aims at describing the evolution of the epidemiology of invasive aspergillosis (IA) in a French University Hospital focussing on nosocomial cases, in order to assess the efficiency of the environmental preventive measures which were implemented. METHODS: From 2003 to 2009, IA cases were reviewed monthly and classified according to the EORTC/MSG criteria and the origin of contamination. RESULTS: Five proven and 65 probable IA cases were diagnosed. Most of the cases (74.3%) occurred in patients with haematological malignancies. Incidences of IA and nosocomial IA (NIA) were 0.106 and 0.032 cases per 1000 admissions, respectively. All the 21 NIA cases occurred in the absence of air treatment (laminar air flow facilities or Plasmair decontamination units) and/or during construction works. The 3-month and 1-year overall survival rates were 50.6% [38.2-61.7] and 31.1% [20-42.9] respectively, and did not differ according to the origin of contamination. CONCLUSION: Nosocomial IA still accounted for a third of all IA cases diagnosed from 2003 to 2009 and mainly occurred in the absence of environmental protective measures, which were confirmed to be effective when applied. Our results show that extension and/or reinforcement of these measures is needed, especially in the haematology unit and during construction works.

Summary. Itraconazole, a new triazole antifungal agent, has marked in vitro activity against filamentous fungi, particularly Aspergillus. We studied three groups of patients suffering from aspergillosis (16 cases): six affected with aspergilloma, three with allergic bronchopulmonary aspergillosis and seven with invasive aspergillosis. The survey consisted in clinical, radiological, mycological and serological evaluations with respect to drug plasma levels. Itraconazole was given at a dosage of 200–400 mg day-1 for periods ranging from 14 to 488 days. Out of the 16 patients, nine responded to therapy (recovery or improvement) and one failed to respond. Three patients improved but experienced relapses and three others could not be evaluated because of liver function disorders, so that treatment had to be stopped prematurely. Zusammenfassung. Itraconazol, ein neues antimykotisches Triazol hat eine in vitro nachgewiesene Wirkung gegen Fadenpilze, im besonderen Aspergillus. Wir untersuchten 3 Patientengruppen, die an Aspergillose litten (16 Falle); 6 davon waren von einem Aspergillom betroffen, 3 Falle mit allergischer bronchopulmonarer Aspergillose und 7 Falle mit invasiver Aspergillose. Die Uberwachung bestand aus klinischen, radiologischen, mykologischen und serologischen Untersuchungen mit Berucksichtigung der Medikamentenspiegel im Plasma. Itraconazol wurde in einer Dosis von 200–400 mg/Tag fur die Dauer von 14–488 Tagen gegeben. Von 16 Patienten reagierten 9 mit Heilung oder Besserung, 1 Patient reagierte nicht auf die Therapie. Der Zustand von 3 weiteren Patienten bessertc sich, sie erlitten jedoch Ruckfalle. Drei andere Falle konnten wegen Storungen der Leberfunktion nicht berucksichtigt werden, so das die Behandlung in diesen Fallen sofort beendet werden muste.

Whole-body (18)F-deoxyglucose positron emission tomography (FDG-PET) has the potential to improve the management of non-small-cell lung cancer (NSCLC). We prospectively evaluated the impact of combining FDG-PET with conventional staging methods, including computed tomography (CT), on the staging and management of patients with potentially resectable NSCLC.Ninety-four consecutive patients with newly diagnosed/suspected NSCLC were enrolled. Each patient was first staged by using conventional methods, and then by FDG-PET. FDG-PET results were forwarded in a sealed envelope and divulged at the weekly staff meeting on staging and treatment, only after "Decision 1", based on conventional staging, had been reached by consensus; reevaluation taking FDG-PET into account yielded "Decision 2". The validity of these latter decisions was analyzed retrospectively.Eighty-nine patients were eligible. Relative to standard imaging, FDG-PET led to clinical staging changes in 26 (29.2%) patients. The stage was lowered in eight cases (9%) and raised in 18 cases (20.2%). "Decision 2" differed from "Decision 1" in 19 patients, modifying the surgical procedure in four cases, indicating other investigations to confirm FDG-PET evidence of metastases in 12 cases, or modifying the medical treatment in three cases. These modifications were retrospectively justified in 9/19 cases, and consisted of 2/4 modifications of the surgical procedure (one hilar and one adrenal metastasis not confirmed histologically), 4/12 further investigations (axillary and liver biopsies, mediastinoscopy, occult colon cancer) and three indications for palliative treatment, in patients who all died within 3 months after FDG-PET.Based on FDG-PET, management was modified in 19/89 (21.3%) patients, but these changes were justified in only 9/89 patients (10.1%). FDG-PET can detect asymptomatic local and distant metastases and improves the preoperative assessment of NSCLC, thereby avoiding unnecessary surgery. However, histological verification is required because of the risk of false-positive results.

International audience; We describe 6 cases of severe filamentous fungal infections after widespread tissue damage due to traumatic injury in previously healthy people. Additionally, we report 69 cases from an exhaustive 20-y review of the literature to investigate the epidemiological and clinical features, the prognosis and the therapeutic management of these post-traumatic severe filamentous fungal infections. Traffic (41%) and farm accidents (25%) were the main causes of injury, which involved either the limbs only (41%) or multiple sites (41%). Necrosis was the main symptom (60%) and Mucorales (72%) and Aspergillus (11%) were the 2 most frequent fungi causing infection. These infections required substantial surgical debridement or amputation (96%) associated with aggressive antifungal therapy (81%), depending on the responsible fungi. This study underlines the need for early, repeated and systematic mycological wound samples to guide and adapt surgical and antifungal management in these filamentous fungal infections.

The aim of this study was to evaluate the adequacy and the conformity of prescriptions of new systemic antifungal drugs to guidelines and scientific data.Each prescription of liposomal amphotericin B (lip Amb), voriconazole, and caspofungin made between May 2003 and May 2004 in a teaching hospital were reviewed by an infectious diseases specialist. He used criteria based on marketing authorization, national recommendations, and scientific data.One hundred and fifteen files were studied during the 12-month period and 203 prescriptions analyzed. Most patients were immunodepressed. The indication of the treatment was appropriate for 127 prescriptions (62.6%). Dose and drug interactions were compliant with prescription rules for 158 prescriptions (77.8%). Among the causes of misuse, 16.3% concerned combinations of antifungals. Prescriptions of liposomal amphotericin B, voriconazole and caspofungin complied with guidelines respectively in 69.7, 60.6 and 36.8% of the cases. Among the 127 appropriate prescriptions, the use of cheaper molecules with an equivalent clinical effectiveness would have allowed saving 13.6% of the total cost of these prescriptions.This study will lead us to implement policies for new antifungal prescription.

Bronchial mucoepidermoid carcinoma represents less than 0.5% of malignant bronchopulmonary cancers. The factors of risk have not been clearly established. Consumption of cannabis could be incriminated, as is suggested by this case report.A 22 year-old man presented with a mucoepidermoid carcinoma of the middle bronchopulmonary lobe. This young man had consumed large quantities of tobacco and cannabis since the age of eleven.The relationship between this rare tumour and the addictions in this patient merit further discussion. The oncogenic role of cannabis smoke should be envisaged, and emphasis placed on the possible synergic effects of multiple addiction, in this case tobacco and cannabis.

To report a retrospective study concerning the impact of fused 18F-fluorodeoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography (CT) images on three-dimensional conformal radiation therapy (3D-CRT) planning for patients with non-small-cell lung cancer (NSCLC).One hundred and one patients consecutively treated for stages I-III NSCLC were studied. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same radiation treatment position. Images were coregistered using five fiducial markers. Target volume delineation was initially performed on the CT images and the corresponding FDG-PET data were subsequently used as an overlay to the CT data to define target volume.FDG-PET identified previously undetected distant metastatic disease in 8 patients making them ineligible for curative CRT (one patient presented some positive uptakes corresponding to concomitant pulmonary tuberculosis). Another patient was ineligible for curative treatment because fused CT/PET images demonstrated excessively extensive intrathoracic disease. The gross tumor volume (GTV) was decreased by CT/PET image fusion in 21 patients (23%) and was increased in 24 patients (26%). The GTV reduction wasor = 25% in 7 patients because CT/PET image fusion reduced pulmonary GTV in 6 patients (3 patients with atelectasis) and mediastinal nodal GTV in 1 patient. The GTV increase wasor = 25% in 14 patients due to an increase of the pulmonary GTV in 11 patients (4 patients with atelectasis) and detection of occult mediastinal lymph node involvement in 3 patients. Among 81 patients receiving a total doseor = 60 Gy at ICRU point, after CT/PET image fusion, the percentage of total lung volume receiving more than 20 Gy (VL20) increased in 15 cases and decreased in 22 cases. The percentage of total heart volume receiving more than 36 Gy increased in 8 patients and decreased in 14 patients. The spinal cord volume receiving at least 45 Gy (2 patients) decreased. After multivariate analysis, one single independent factor made significant effect of FDG/PET on the modification of the size of the GTV: tumor with atelectasis (P = 0.0001). Conclusion. - Our study confirms that integrated hybrid PET/CT in the treatment position and coregistered images have an impact on treatment planning and management of patients with NSCLC. FDG images using dedicated PET scanners with modern image fusion techniques and respiration-gated acquisition protocols could improve CT/PET image coregistration. However, prospective studies with histological correlation are necessary and the impact on treatment outcome remains to be demonstrated.

International audience; Pulmonary eosinophilia due to filariasis is a form of filarial infection which is frequent in endemic zones but very much rarer in Europe where it is always "imported". In this case report the authors specify the clinical characteristics and pathophysiology of this disease.

The purpose of this work was to assess results obtained with the MIP (mitomycin 6 mg/m(2) day 1, ifosfamide 1500 mg/m(2) days 1,2, 3, cisplatin 30 mg/m(2) days 1,2, 3) chemotherapy protocol combined with cisplatin-sensitized chest radiotherapy as developed in the French multicentric trial on perioperative chemotherapy.Thirty-five patients with grade III non-small-cell lung cancer (NSCLC) were given two or three starter MIP cycles every 4 weeks then underwent radiation therapy for six weeks for a total dose of 60 Gy with injection of 8 mg/m(2) cisplatin every day for the first two weeks and the last two weeks of treatment. In case of objective response (OR) to MIP before radiotherapy, the MIP protocol was repeated for one to four supplementary cycles according to tolerance.The rate of OR after MIP was 51% and after chemoradiotherapy it was 69%. Toxic effects were limited to one death due to aplasia and 18 cases of grade 3-4 toxicity, mainly due to hematology disorders. Moderate esophagitis was observed in ten cases. Median survival was 13.5 months. Survival rates were 57% and 29% at one and two years.This novel scheme, which can be improved, has demonstrated its efficacy. Tolerance is satisfactory and the cost is low compared with associations using "new" drugs.

The purpose of this study was to report 30 cases of missed lung cancers and describe characteristics of each case. Reasons for misdiagnosis were analyzed from the report. Each radiograph was subsequently reviewed by a panel of two experts who quantified several parameters regarding image analysis and film quality. Lesions were not described in 67 % of the cases and were misinterpreted as benign processes in 33 % of cases. Comparison to previous chest radiographs and clinical information were seldom available on the report. Size of the lesions varied between 1 and 7 cm, location was primarily apical and paramediastinal, normal anatomy was highly or moderately complex in 87 %, and distracting lesions were present in 63 % of the cases. Image quality was considered perfect in 3 cases only. Among all the factors responsible for missed lung cancer, certain factors can be improved as film quality, comparison with previous radiographs, and better awareness of clinical information.

Scopulariopsis brevicaulis is a causal agent of onchomycosis. We report the unusual clinical manifestations caused by this opportunist fungus.A 61-year-old man consulted in February 1997 for a budding lesion located on the right medial malleolus. This patient had had a liver transplantation for primary biliary cirrhosis in 1990 and had been taking prednisone and cyclosporine since this time. Cyclosporine had been recently replaced by tacrolimus. The histology examination of a lesion specimen taken from the ankle evidenced a dermal mycosis due to opportunist filamentous fungus. Total excision was performed. The patient then developed nodular lesions of the left elbow during the summer of 1997. Mycology culture of a skin biopsy grew numerous colonies of Scopulariopsis brevicaulis. Excision of the elbow lesion was delayed due to hospitalization for suspected graft rejection and development of insulin-dependent diabetes. The elbow lesion was then resected followed by a skin graft. The mycology examination identified the same causal agent.This liver transplant recipient developed two unusual extra-ungual localizations (ankle and elbow) of a Scopulariopsis brevicaulis infection. Chronic immunosuppression favored development of the infection with a pseudo-epithéliomatous presentation. The histology and mycology examinations were necessary for positive diagnosis.

High voltage electrical trauma may cause severe visceral injuries. We report a case of direct electrical injury to the lung parenchyma, without evidence of any thoracic wall contact injury, in an electrician who sustained a 20 kV-electrical shock while working in a substation cubicle. The diagnosis of a true electrical burn of the left lower lobe was suggested early on by imaging and then confirmed by surgical exploration, histological findings and the significant improvement of the patient's condition following resection of the infarcted lobe. All possible causes of bronchial and pulmonary pathologies in such a context were ruled out. The fatal outcome of two previous similar cases and the generally high mortality of any electrical visceral injury support early surgical management as the only rational life-saving treatment. Current pathophysiological knowledge substantiates the theory of an isolated visceral injury located far away from the contact wounds. However, the pathogenesis of such severe injuries is not entirely understood.

Dyspnea is the principal clinical feature of pulmonary leukostasis, a syndrome called "poumon hyperleucocytaire" in French. It is a common complication of chronic myeloid leukemia. In the course of pulmonary carcinoma, leukocytosis is frequently noted. One of the etiologies is a paraneoplastic syndrome with production of colony stimulating factor. We report a case of pulmonary hyperleukostasis following antineoplastic chemotherapy for pulmonary carcinoma.

To assess whether the addition of cisplatin (100 mg/m(2) administered intravenously on Day 1) to CDE (cyclophosphamide [1000 mg/m(2) on Day 1], doxorubicin [45 mg/m(2) on Day 1], and etoposide [150 mg/m(2) on Days 1 and 2] combination is useful in the treatment of patients with small cell lung carcinoma (SCLC).In a multicenter clinical trial, 457 patients were randomized from May 1988 to March 1993 to receive either CDE (n = 228) or cisplatin-CDE (PCDE, n = 229) chemotherapy every 4 weeks for 6 cycles. As patients with limited SCLC were included in a concomitant trial assessing thoracic radiotherapy, the current study mainly included patients with extensive stage (79%) or limited stage disease and a contraindication for thoracic radiotherapy.The objective response rate was higher in the cisplatin-CDE group (72%) than in the CDE group (53%) (P = 0.0001). The median overall survival was similar for the groups that received CDE (266 days) and PCDE (271 days) (P = 0.93, log rank test). A higher fatal neutropenia rate was observed in the PCDE group (n = 23) than in the CDE group (n = 4) (P0.001, log rank test), mainly for patients with extensive disease (n = 26; P = 0.015, log rank test).The addition of cisplatin to a CDE regimen is toxic to patients with extensive SCLC and does not improve overall survival. The PCDE combination must be avoided for patients with extensive SCLC; CDE or cisplatin-etoposide combinations remain standard chemotherapy for these patients. The PCDE combination associated with granulocyte-colony stimulating factors could only be assessed in patients with good prognoses.

Although thoracic radiotherapy is considered to be useful for the treatment of patients with small cell lung carcinoma (SCLC), its optimal administration schedule is still controversial.In a multicenter clinical trial, 164 patients with limited SCLC (of whom 156 were eligible for the study) were randomized to receive either concurrent thoracic irradiation, initiated immediately after the second cycle of chemotherapy (Days 30-64) at a dose of 50 grays in 20 fractions, or alternating thoracic irradiation, scheduled in 3 courses between the second, third, fourth, and fifth cycles of chemotherapy with a 7-day rest period after and before chemotherapy at a dose of 20 grays in 8 fractions (Days 36-47 and Days 64-75) and then 15 grays in 6 fractions (Days 92-101). The same chemotherapy regimen (cyclophosphamide-doxorubicin or vindesine-etoposide) was administered every 4 weeks in both groups.Concurrent radiotherapy-induced lung toxicity led to early termination of this trial when a significant difference was observed (6 cases vs. 1, P = 0.05, 2-sided log rank test). Objective response rates were 89% in the 82 patients of the concurrent radiotherapy group and 95% in the 74 patients of the alternating radiotherapy group. Median survival periods were 13.5 and 14.0 months, respectively, with no significant difference between the two survival distributions (P = 0.15, 2-sided log rank test). Toxic deaths due to bone marrow hypoplasia were similar in both groups (3 vs. 2), but mortality due to lung toxicity (pulmonary fibrosis) was more frequent with concurrent radiotherapy (6 patients) than with alternating radiotherapy (1 patient) in long term analysis (P = 0.05, 2-sided log rank test).Although no statistically significant overall survival difference was observed between the two radiation therapy schedules, the better tolerance of the alternating schedule justifies the choice of this schedule with this chemotherapy regimen, although it may not be applicable to other chemotherapy regimens.

to compare standard and alternating administration of chemotherapy combinations in small cell lung cancer (SCLC) patients.in a multicenter clinical trial, 394 previously untreated SCLC patients were randomised to receive, every 4 weeks, eight courses of either a standard regimen with CCNU, cyclophosphamide, adriamycin (CCA) and VP16 or an alternating regimen (CCA regimen alternating with cisplatin-vindesine-VP16).overall response rate was higher in the standard group (78%) than in the alternating group (64%) (P = 0.0001). Complete response rate was also higher in the standard group (32%) than in the alternating group (18%) (P = 0.004). The median survival in the overall SCLC population was 306 days in the standard group and 272 days in the alternating group (P = 0.08). In limited SCLC patients, median survival was higher in the standard group (421 days) than in the alternating group (328 days) (P = 0.01). Grade III/IV haematological toxicity was lower in patients in the alternating group (25 versus 47%) (P0.001).the standard regimen was better than the alternating regimen for patients with limited forms of SCLC. The alternating regimen, associated with better haematological safety and ensuring a fairly similar survival, may be considered in patients with extensive SCLC. Pleiomorphic resistance mechanisms to chemotherapy make it difficult to define a non-cross-resistant chemotherapy regimen.

Postoperative radiotherapy is commonly used to treat patients with completely resected nonsmall cell lung carcinoma, but its effect on overall survival has not been established.After undergoing complete surgical resection, 728 patients with non-small cell lung carcinoma (221 Stage I, 180 Stage II, and 327 Stage III) were randomized to receive either postoperative radiotherapy at a total dose of 60 gray or observation only . The main end point was overall survival.At the reference date, 218 of 355 patients in the control group had died and 262 of 373 in the radiotherapy group had died. Five-year overall survival was 43% for the control group and 30% for the radiotherapy group (P = 0.002, log rank test; relative risk [RR]: 1.33; 95% confidence interval [CI]: 1.11-1.59). This result was not modified by adjustment for potential prognostic factors. The excess mortality rate for the radiotherapy group was due to an excess of intercurrent deaths (P = 0.0001; RR: 3.47; the 5-year intercurrent death rate was 8% for the control group and 31% for the radiotherapy group). Radiotherapy had no significant effect on local recurrence (RR: 0.85; 95% CI: 0.64-1.14) and no effect on metastasis (RR: 1.06; 95% CI: 0.85-1.31). The rate of non-cancer-related death increased with the dose per fraction delivered.

Twenty-two candidemia happened in our hospital from January 1997 to may 1998. We studied the clinical evolution of the patients and the sensitivity of the yeasts to antifungal therapy (Fungitest and E-Test method). We found 11 Candida albicans (CA), 10 Candida non albicans (CNA) (3 C. glabrata, 2 C. parapsilosis, 4 C. tropicalis, 1 C. krusei) and 1 Saccharomyces cerevisiae. The mean age of the patients was 56.4 years. There were 13 men and 9 women. We found one group of 8 (36.4%) oncohematological patients, one group of 8 (36.4%) patients with abdominal surgery, one group of 3 (13.6%) children and one group of 3 adults (13.6%) who spent more than 10 days in an intensive care unit. Ten times, these candidemia were associated with bacteriemia, 4 times with several bacteria. Three patients died because of the candidemia, 2 times with CNA and one time with CA. There wasn't any resistance to amphotericin B or ketoconazole. All the CA and 3 CNA (30%) remained sensitive to the four antifungal drugs we used (amphotericin B, ketoconazole, fluconazole, itraconazole). The 3 C. glabrata and the C. krusei were resistant or limit to fluconazole. Since the generalization of the use of fluconazole, the epidemiology is marked by the emergence of new strains of CA with high level of resistance to azols, and of CNA. In our hospital, the CA remain preponderant and only the CNA are resistant to fluconazole making difficult the choice of empiric treatment for serious fungemia.

RISK AWARENESS: Use of psychostimulants is spreading in France, particularly at "techno" dances. The generic term "ecstasy" covers a wide variety of molecules with variable formulations. The situation is a true public health problem, generally concerning very young subjects who must be informed of the risks involved. Knowledge of the chemical makeup of the products currently used is needed to provide valid information and reduce risks.Two types of chemical analysis are used for rapid controls. A coloration test is used by the Rave mission implemented by "Médecins du Monde". More elaborate analysis methods are used to identify the active substances and quantify the compounds in the different "tablets".Rapid controls give a means of quickly identifying samples containing methylenedioxyamphetamines and distinguishing them from other samples which may contain any number of substances with unknown toxicity. A precise analysis of 73 samples has shown highly variable compositions with 22% actually containing methylenedioxyamphetamines.Precise analytical knowledge of the drugs circulating in "techno" dances has revealed the extreme danger of a large number of the substances used. A continuous control of ongoing consumption is required to correctly warn the users and reduce risk.

To determine the prognostic significance of supraclavicular lymph node (SCLN) involvement in small cell lung cancer.Patients (1,370) with small cell lung cancer were included in four consecutive clinical trials and classified as having either limited or extensive forms of disease using the Veterans Administration staging system.SCLN was present in 17% of patients (n = 234). Median survival was 258 days for patients with SCLN (n = 234) and 297 days for patients without SCLN (n = 1136) (p = 0.002). SCLN involvement was correlated with the presence of distant metastases at baseline (169 vs 65, p =0.001). Median survival was 375 days for patients with limited forms without SCLN (n = 529), 332 days for those with limited forms with SCLN (n = 65) (p = 0.12), 244 days for those with extensive forms without SCLN (n = 604), and 228 days for those with extensive forms with SCLN (n = 169) (p = 0.94). The 2-year survival rates were 17%, 12%, 2%, and 4%, respectively. Cox models confirmed that SCLN did not provide any significant additional prognostic information.SCLN is highly correlated with extensive forms explaining its overall prognostic value. In limited disease, SCLN is only a minor poor prognostic factor, not justifying any amendment to the staging system currently used.

The aim of this study was to analyze SCLC patients beyond 30 months, particularly their outcome, their way of life, and factors which could influence relapses, second-primary cancers and death.Between January 1986 and May 1995, 263 SCLC patients who survived longer than 30 months were included from 52 French institutions. The analysis was performed on the 155 cases confirmed by a pathologic review.Physical, mental and psychological states were considered as normal at 30 months in respectively 70.3%, 87.7% and 67.7% of patients, not influenced by prophylactic cranial irradiation, number of chemotherapy cycles, CCNU or cisplatin. Therapeutic sequelae were neurological impairment (13%), pulmonary fibrosis (18%) and cardiac disorders (11%) at 30 months. Return to work was possible for 40% of patients in the first two years following diagnosis. Among 43 relapsing patients, 33 benefited from a second-line treatment. Their median survival was 12 months since retreatment, and seven patients have survived again longer than 30 months. Age60 at the time of diagnosis was found as an independent factor increasing the risk of relapse beyond 30 months (OR = 2.46, IC 95% (1.16-5.26), P = 0.01). The risk of relapse became less than 10% beyond five years. Twenty patients (13%) developed a second primary cancer in a mean time of 58.6 months. The risk of second primary cancer was increased by a number of chemotherapy cycles6 (OR = 3.25, IC 95% (1.08-9.8) P = 0.02) and by an age60 (OR = 2.92, IC 95% (1.07-7.97), P = 0.03). Five- and 10-year survival rates were respectively 68% and 44%. In these patients having reached a 30-month survival, three independent factors were predictive of a survival longer than five years: ageor = 60 at the time of diagnosis (OR = 2.85, IC 95% (1.23-6.6), P = 0.01), chest radiotherapy (OR = 3.1, IC 95% (1.28-7.69), P = 0.006) and absence of relapse (OR = 4.5, IC 95% (1.75-12.5), P = 0.002). This study suggests that: 1) therapeutic sequelae are rather mild, allowing return to work in 40% of patients; 2) relapsing 30-month survivors can benefit from second-line treatment; 3) SCLC cure can be achieved with a 10-year follow-up.

The records of 1,371 patients with small cell carcinoma of the lung (SCLC) treated between 1983 and 1994, were reviewed for the occurrence of second primary malignancies (SPM). One was excluded for analysis because of insufficient data. Eight synchronous SPM (SSPM) and 8 metachronous SPM (MSPM) were identified, SSPM included non-small cell lung cancer in 6 patients, 1 head and neck cancer and 1 oesophageal cancer. Median survival after the diagnosis of SSPM was 6 months. The MSPM were detected between 1 and 6 years after the diagnosis of SCLC. MSPM included lung cancer (3 patients), gastrointestinal malignancies (2 patients), 1 hematologic malignancy, 1 prostatic cancer and 1 head and neck cancer. The median survival time after the diagnosis of MSPM was 4 months. Occurrence of SPM is a singular pattern of patients with SCLC. Tobacco consumption, genetic factors and carcinogenic effects of multimodality treatment are supposed mechanisms to explain SPM.

We report the case of a 57-year-old patient with primary malignant melanoma of the mediastinum who survived nine months despite immunotherapy, radiotherapy and chemotherapy. The primary nature of the intrathoracic melanoma was difficult to prove. Definitive diagnosis was based on the uniform morphology of the melanoma which showed junctional anomalies at the histology examination with tracheo-bronchial and esophageal localizations as well as on the absence of other patent or formerly resected melanocyte-rich localizations (skin, mucosa, ocular) at clinical examination and autopsy.

The effect of adjuvant chemotherapy after resection of nonsmall cell lung cancer (NSCLC) remains an unresolved question.From October, 1982, to November, 1986, 267 patients with resected NSCLC were included in a randomized trial. The adjuvant allocated treatments were either postoperative radiotherapy, 60 Gy in 6 weeks (radiotherapy group = 129 patients), or three courses of postoperative COPAC (cyclophosphamide, doxorubicin, cisplatin, vincristine, lomustine) chemotherapy followed by a similar radiotherapy schedule (chemotherapy/radiotherapy group = 138 patients).The sex ratio (M:F) was 19/1; mean age was 57 +/- 9 years. According to postoperative staging, 8 patients were Stage I, 70 were Stage II, and 189 were Stage III. The histologic type was squamous cell carcinoma in 175 patients, adenocarcinoma in 57, and large cell carcinoma in 35. The minimum follow-up was 6 years. Four patients were lost to follow-up. Death was recorded in 233 patients. No significant difference was observed in terms of disease free interval (P = 0.47, log-rank test), or overall survival (P = 0.68, log-rank test). With respect to the first site of relapse, distant metastasis occurred more frequently in the radiotherapy group (P = 0.09, log-rank test) whereas local relapse occurred similarly in both groups (P = 0.27). An interaction was observed between lymph node involvement and treatment in terms of overall survival.The COPAC chemotherapy as postoperative treatment failed to improve overall survival in patients with resected NSCLC receiving postoperative radiotherapy but decreased the pattern of metastatic progression, mainly in the N2 patients.

To learn the value of bronchoscopy and biopsy in the early diagnosis of inhalation injury ARDS.Burn Center, CHU Saint-Antoine, Paris, France.130 consecutively admitted burn patients were bronchoscoped on admission.The appearance of the bronchial tree was recorded, and biopsies were taken from spurs of the proximal and distal branches of the right bronchi.Either bronchoscopy or biopsy was positive in 46 cases. Twenty three of 44 patients with chemical inhalation injury developed ARDS (52%). Of 83 negative cases only 6 developed ARDS (7%).Bronchoscopy with biopsy is useful in predicting the development of ARDS in burn patients.

Pretherapeutic prognostic factors for patients given chemotherapy for small cell lung carcinoma have been widely studied. We evaluated response to chemotherapy in patients included in 4 multicentric trials with less restrictive entry criteria in order to determine the contribution of clinical outcome as a predictive factor.Pretherapeutic and therapeutic prognostic factors were assessed in 1280 patients included in 4 successive multicentric therapeutic trials on chemotherapy for small cell lung carcinoma conducted from January 1, 1983 to April 1, 1992. Logrank test for univariate analysis and Cox's stepwise method for multivariate analysis were used to evaluate the results.Univariate analysis identified pretherapeutic factors as significant for prognosis: Karnofsky index (p0.0001), alkaline phosphatase level (p0.0002), white cell count (p0.0005), age (p = 0.0007), presence of brain metastasis (p = 0.0004), presence of liver metastasis (p = 0.03), initial extension (p = 0.04). Multivariate analysis taking into account pretherapeutic and therapeutic factors demonstrated that complete response after the second and after the sixth treatment session were predictive of longer survival (p = 0.0001). This factor was more powerful than all the pretherapeutic factors including the Karnofsky index, initial extension and brain metastasis.For patients with small cell lung carcinoma, the prognostic value of early response to chemotherapy suggests that high-doses should be used starting at the first session.

A positive influence of anticoagulant treatment in small cell lung cancer (SCLC) has been suggested by experimental and clinical data.In a multicenter clinical trial, 277 patients with SCLC were randomized either to receive or not to receive subcutaneous heparin injections for 5 weeks at effective doses, which were monitored by blood coagulation tests. All patients received one of the two chemotherapy regimens studied in this trial, for eight courses in the case of patients with complete or partial response, and subsequently were randomized to receive delayed thoracic radiotherapy after these eight courses.In comparison to the 139 patients who did not receive heparin, the 138 patients who received anticoagulant treatment obtained better complete response rates (37% vs. 23%, P = 0.004), better median survival (317 days vs. 261 days, P = 0.01), and better survival rates at 1, 2, and 3 years (40% vs. 30%, 11% vs. 9% and 9% vs. 6%, respectively). At subgroups analysis, the results on survival were obtained for limited forms (P = 0.03) but not for extensive diseases (P = 0.31). No important bleeding or thrombocytopenia was related to heparin treatment.These results confirm the value of anticoagulant treatment in SCLC, already suspected for warfarin and now proven for heparin, but the modes of administration and the biologic explanations for this activity still warrant further investigation.

The purpose of this trial is to assess the possible benefit of neoadjuvant chemotherapy before surgery in patients with operable non-small cell lung cancer. Patients with operable stages I (except T 1N0), II, or IIIA disease are eligible for this ongoing trial. Patients are randomized into two arms. Surgery is performed first in group I; patients found to have T3 tumors or N2 lymph nodes are given postoperative radiotherapy. Group 2 patients start with two cycles of chemotherapy; following surgery, two more cycles are administered in responder patients and, as in group I, patients with T3 tumors or N2 lymph nodes are given radiotherapy. Chemotherapy is the MIP protocol: mitomycin 6 mg/m2 day I, ifosfamide 1.5 g/m2 days 1 to 3, cisplatin 30 mg/m2 days I to 3, and mesna 1,200 mg/m2 days 1 to 3. One hundred fifty patients were enrolled between June 1991 and September 1993. By the time this report was prepared, 117 patients had completed all assigned treatment, 63 in group I and 54 in group 2. There were two ineligible patients, one in each group. Forty-nine patients underwent thoracotomy in the chemotherapy-surgery group and 62 in the surgery-only group. There was only one progression after two cycles of chemotherapy. Rates of exploratory and incomplete surgery were 17% in group I and 12% in group 2. The trial is ongoing.

The long-term survivors of SCLC are described in 3 different types of study: analysis of prognostic factors of phase II and III chemotherapy trials (3,4,5,6,7,17,18), epidemiological studies (8) and medical registries of LTS (9,10). A small number of patients with small cell lung cancer achieve long-term survival. Most of these patients have a disease limited to the chest at the time of diagnosis. The major concerns of these LTSs are: the relapse of the SCLC, the occurrence of a second primary tumour and the occurrence of a disease related to tobacco consumption. About 20% of the LTSs die of non-cancer related causes and this exceeds the age adjusted mortality. There is a high risk of relapse in the first 4 years after the diagnosis; this risk decreases later, but relapses may be seen until 7 years. Nearly 8% of LTSs developed a SPTs are alive at 8 years; this indicates that cure is possible in SCLC, however, these patients account for less than 3% of the overall population.

In small-cell lung cancer, the optimal combination of chemotherapy and radiotherapy is not clearly established. To assess the value of delayed thoracic radiotherapy, we performed a randomized clinical trial in 53 complete responder patients after eight courses of chemotherapy. Twenty-seven patients received a mean of 46.5 Gy-equivalent of radiotherapy and 26 patients received no treatment until relapse. No patient dropped out of the study. Median survival time from radiotherapy randomization was 316 days in the radiotherapy group and 496 days in the no radiotherapy group. No difference was observed in survival between the two groups (p = 0.66, log-rank test) perhaps because of the small sample size. In fact, this delayed thoracic radiotherapy seemed to worsen the outcome of complete responders with small-cell lung cancer and should be avoided.

Experimental, and more recently, clinical data have suggested the influence of hemostasis in the spread of malignant disease.To complete research in this type of coagulation and cancer, a multicentric randomized clinical trial was performed, including 303 patients with small cell lung cancer (SCLC), treated by the addition of aspirin at 1 g/day (a dosage at which aspirin is considered to be a platelet aggregation inhibitor) to combined chemotherapy.Survival was not increased in the aspirin-treated group (P = 0.90). The analysis according to the extent of disease (limited or extensive disease) did not modify that conclusion.This result does not confirm the hypothesis that, in SCLC, aspirin (a platelet aggregation inhibitor) reduces metastasis formation and local tumor thrombogenesis.

In sterile hospital units filamentous fungal infections are an unacceptable risk in patients with prolonged agranulocytosis. The occurrence of 3 successive cases in the Sterile unit of University Hospital of Grenoble prompted us to investigate in all elements of sterile unit, and notably food-processing. Two cooked rice dishes given to these patients were found to contain a substantial amount of Aspergillus fumigatus and were probably responsible for these infections. A more detailed study was carried out to evaluate the degree of food contamination by fungi in sterile unit. The study included 97 cooked dishes which had been sterilized in a 250 degrees oven for 40 minutes and 176 industrially packed foods delivered in single packs (e.g. milk and its derivatives, sweets and drinks). Each foodstuff was mycologically examined 3 to 5 times in different packs according to a procedure used in food analysis laboratories and raised to the standards of mycological examination. In this way, a 3-monthly food testing protocol in sterile unit could be set up. This protocol has a dual purpose: regular checking of the cooked dishes chain and maximum diversification of the dishes.

The purpose of this study was to assess: 1) the percentage of human immunodeficiency virus (HIV)-infected patients with suspected Pneumocystis carinii pneumonia (PCP) but unable to undergo the induced sputum procedure, together with the reasons involved; 2) the sensitivity and specificity of induced sputum procedure, using conventional stains and an immunofluorescence test; and 3) the cost of introducing induced sputum procedure for the diagnosis of PCP. One hundred and thirty eight HIV-infected patients with suspected PCP underwent induced sputum procedure and bronchoalveolar lavage (BAL). P. carinii was identified in induced sputum and BAL samples using conventional and immunofluorescence staining. The economic analysis took into account the direct costs of the two procedures. The induced sputum procedure was either not feasible or unsuccessful in 29% of the patients. The sensitivity of induced sputum, using conventional and immunofluorescence staining, was 0.27 and 0.56 respectively. The economic analysis showed that the two strategies (systematic BAL versus BAL only after negative induced sputum) are equivalent in cost terms when the induced sputum to BAL cost ratio is equal to the product of the prevalence of PCP by the sensitivity of induced sputum procedure. We conclude that the immunofluorescence test should be the reference technique for induced sputum samples, whilst conventional stains are more clinically relevant for BAL samples. The cost of introducing induced sputum should take into account the sensitivity of induced sputum and the prevalence of PCP in the suspected population.

Deoxyribonucleic acid (DNA) content of bronchopulmonary neuroendocrine tumours was measured by flow cytometry in order to investigate correlations between ploidy, S-phase fraction (SPF) and two histological classifications (World Health Organization (WHO), Warren and Gould), and clinical staging. A paraffin-embedded technique was used on 20 surgical specimens. Cases comprised (according to the classification of Warren and Gould) 7 carcinoids, 3 well-differentiated neuroendocrine carcinomas (WDNC), 6 intermediate neuroendocrine carcinomas (INC), and 4 small cell neuroendocrine carcinomas (SCNC). DNA aneuploidy was demonstrated in 3 out of 7 of the carcinoids, 3 out of 9 of the WDNCs and INCs, and 2 out of 4 of the SCNCs. A variable SPF was found in each group, except for the SCNCs which showed a constantly high SPF. In our small series, no correlation was noted between high SPF or aneuploidy and metastases. In conclusion, we observed no diagnostic value of malignancy for DNA aneuploidy. The SCNC group appeared to be an homogeneous group according to the SPF compared to the small cell carcinoma (SCC) group of the WHO classification. This and the prognostic incidence of high SPF need to be further studied.

A case of squamous cell bronchial carcinoma developed 8 years after treatment of a small cell carcinoma is reported. Three hypotheses may be put forward to explain this sequence of events: either a squamous cell line was selected from within an initially mixed tumour, or the small cell carcinoma differentiated into a squamous cell carcinoma, or a second primary tumour developed independently. All this is purely speculative, but the long doubling time implied by the first two hypotheses would be in favour of a second primary tumour.

Of 320 patients with small cell lung cancer (SCLC) entered into a clinical trial of chemotherapy between January 1983 and September 1985, 106 patients achieved a complete response. The induction chemotherapy used was lomustine 60 mg.m-2 p.o., cyclophosphamide 1 g.m-2 i.v., doxorubicin 45 mg.m-2 i.v. and etoposide 150 mg.m-2 i.v., every four weeks. Lomustine was only given for the first three cycles. Seventy nine of the 106 patients still in complete response after six chemotherapy cycles were subsequently randomized to receive either six more cycles or no more treatment until relapse. In this group of 79 patients, a difference was shown from the time of inclusion between the 51 patients with limited disease and the 28 patients with disseminated disease, with overall median survivals of 395 and 165 days, respectively, (p = 0.0002). No difference was shown between the two treatment groups: the median survival was 332 days from the time of second randomization with a two year survival rate of 28% for the patients randomized to receive six more cycles and 246 days and 22% for those randomized to receive no more treatment (add 147 days to obtain overall median survival). Continuing chemotherapy for more than six cycles to patients in complete response did not improve survival.

This retrospective study of 149 patients with small cell lung cancer highlights the value of bronchial endoscopies combined with biopsies for the follow-up of these cases. A control endoscopy performed during the third month showed that macroscopic lesions had completely disappeared in 42 percent of the patients. Each subsequent endoscopy offered a probability rising from 20 to 50 percent of diagnosing a recurrence in the patients explored. Our study particularly demonstrates the usefulness of bronchial biopsy at the initial site of the lesion, even when the bronchial mucosa seems to have returned to normal, since this biopsy is positive in 4.5 percent of the cases.

Five cases of Wegener's granulomatosis treated with cyclophosphamide (CPM) and prednisolone are reported. Four of these patients received intermittent intravenous boluses of cyclophosphamide with the aim of improving the prognosis and renal function and at the same time to attenuate any haematological or vesical toxicity of CPM. The initial response to treatment by boluses of CPM was favourable in all cases but three patients presented with relapses, which were sometimes repeated and boluses of CPM did not enable a remission to be maintained at the time. Recourse to continuous oral therapy in place of bolus therapy proved viable for the maintenance of remission in two cases. The bladder and haematological tolerance to the bolus was satisfactory but an episode of severe neutropenia led to an adaptation of the dose of CPM. The intermittent administration above all the low cumulative dose of CPM obtained with the boluses will explain the better vesical and haematological tolerance observed depending on the capacity to maintain a prolonged remission. The indications for boluses of CPM in the treatment of Wegener's granulomatosis remain uncertain and do not seem to be totally without inconvenience.

Between March 1978 and May 1981, 219 patients suffering from non-small cell primary bronchial carcinoma underwent surgical excision which was intended to be curative. Three weeks later the patients were randomised into two groups: 1. A control group, with no other treatment following excision (110 patients). 2. A non-specific immunotherapy group (109 patients). The immunostimulant used was an aqueous suspension of heat killed mycobacterium smegmatis administered subcutaneously once a month. The trial was analysed on December 1, 1982. There were 117 recurrences and 112 deceased. There was no significant difference as regard survival without relapse or overall survival; all causes of death were included.