[IFCT-0302 trial: randomised study comparing two follow-up schedules in completely resected non-small cell lung cancer]. / Protocole IFCT-0302: essai randomisé de deux schémas de surveillance dans les cancers bronchiques non à petites cellules complètement réséqués.

BACKGROUND: The authorities advocate a minimalist attitude towards the follow-up of resected bronchial carcinoma (clinical examination and chest x-ray). A survey showed that 70% of French respiratory physicians have chosen to use the CT scanner and often endoscopy. The published data are equivocal and are often based on retrospective studies. Lung cancer is a good model for a study of post-operative surveillance. Recurrences often occur in easily observed areas, they may be detected while still asymptomatic and are sometimes potentially curable. Second primary tumours may develop at the same site. METHODS: The Intergroupe Francophone de Cancerologie Thoracique (IFCT) has initiated a trial comparing simple follow-up (clinical examination, chest x-ray) with a more intensive follow-up (CT scan, fibreoptic bronchoscopy). The surveillance will take place every 6 months for 2 years and then annually until 5 years. EXPECTED RESULTS: The main aim is to determine whether intensive follow-up improves patient survival. The opposite question is equally important. If an expensive and demanding follow-up does not affect the chances of cure these results will influence our practice.

[Lung cancer in the elderly: performance status and/or geriatric indices?]. / Cancer bronchique du sujet âgé: performance status et/ou indices gériatriques?

INTRODUCTION: Demographic aging poses a problem of management in patients over 65 years old with lung cancer (LC). Performance status (PS) is an index of global activity that, in part, determines treatment. Geriatric indices allow a multifactorial assessment of the elderly subject. The aim of our study is to evaluate whether PS correlates with the geriatric indices in elderly patients with lung cancer. METHODS: In a single centre prospective study the geriatric indices (ADL, IADL, PINI, MMS) and the Charlson score (CS) were measured before treatment. RESULTS: Forty one patients aged 75.7 +/- 6.6 years were included in the study. PS 3-4 was found in 15% of patients and 44% had stage IV disease. Half of them were ADL dependent and 95% were IADL dependent. A MMS<24 was found in 29% and 17% had a PINI > 20. The CS was 2.7 +/- 2.1. There was a correlation between PS and the geriatric indices but no correlation between PS and CS. CONCLUSION: PS is significantly correlated with the geriatric indices but is independent of CS. PS appears to be a good parameter for the assessment of global activity in the elderly subject with LC.

Minocycline pneumonitis and eosinophilia. A report on eight patients.

We identified eight patients (six women and two men) who had pulmonary infiltrates during treatment with minocycline hydrochloride between 1989 and 1992 in French referral centers for drug-induced pulmonary diseases. Clinical files, chest roentgenograms, computed tomographic scans, pulmonary function, and bronchoalveolar lavage data were reviewed. Minocycline treatment was given for acne (n = 4), genital infection (n = 3), and Lyme disease (n = 1). The duration of treatment averaged 13 +/- 5 days (mean +/- SE); the total dose, 2060 +/- 540 mg. Patients presented with dyspnea (n = 8), fever (n = 7), dry cough (n = 5), hemoptysis (n = 1), chest pain (n = 2), fatigue (n = 3), and rash (n = 3). Chest roentgenograms showed bilateral infiltrates in all cases. Pulmonary function was measured in five patients; four had airflow obstruction and two had mild restriction. Blood gas tests demonstrated hypoxemia in seven patients (58 +/- 3 mmHg). Seven patients had blood eosinophilia (1.76 +/- 0.2 x 10(9)/L). Bronchoalveolar lavage (performed in seven patients) showed an increased proportion of eosinophils (0.30 +/- 0.07). The Cd4+/CD8+ ratio was determined in four cases and was low in three. Transbronchial lung biopsy, performed in two patients, showed interstitial pneumonitis in both patients, with marked infiltration by eosinophils in one patient. The outcome was favorable in all patients. Because of severe symptoms, steroid therapy was required in three patients. Rechallenge was not attempted. We conclude that minocycline can induce the syndrome of pulmonary infiltrates and eosinophilia, that presenting symptoms may be severe and may culminate in transient respiratory failure, and that the disease has a favorable prognosis.

Lung perfusion scans and hemodynamics in acute and chronic pulmonary embolism.

UNLABELLED: To assess the relationship between pulmonary vascular obstruction and hemodynamic status in acute pulmonary embolism (APE) and in chronic thromboembolic pulmonary hypertension (CTEPH), perfusion lung scan and hemodynamic measurements were obtained in 31 consecutive patients with APE and in 45 with CTEPH. METHODS: Lung scans were scored independently by two experience observers who determined the percentage of vascular obstruction (PVOs). Mean pulmonary artery pressure (PAP) and total pulmonary resistance (TPR) were obtained during right heart catheterization. In patients with APE, measurements were recorded within a 1-hr interval before and 12 hours after thrombolysis. This yielded 62 paired PVOs values with concomitant PAP and TPR measurements. In patients with CTEPH, data were recorded within a 3-day interval. RESULTS: Mean PVOs (%) values were similar in APE and CTEPH patients (59 +/- 13 vs. 58 +/- 15), whereas PAP and TPR were significantly higher in CTEPH patients (51 +/- 17 mmHg and 23 +/- 11 U/m2, respectively) than in APE patients (23 +/- 8 mmHg and 9 +/- 5 U/m2, respectively, p < 0.001). In APE patients, significant hyperbolic correlations were found linking PVOs with PAP and TPR (r = 0.75, p < 0.01 for PAP; r = 0.71, p < 0.01 for TPR). In CTEPH, there were no significant correlations between PVOs and PAP or TPR. For the same level of PVOs, patients with CTEPH had higher PAP and TPR value than patients with APE. CONCLUSION: In APE without prior cardiopulmonary disease, increases in PAP and TPR are correlated in a nonlinear fashion with the degree of pulmonary vascular obstruction as assessed by lung scanning. In CTEPH patients, the higher PAP and TPR values as compared to APE patients with comparable degrees of PVOs are consistent with previous reports that pulmonary hypertension in CTEPH is due not only to the obstruction of proximal pulmonary arteries but also to remodeling of small distal arteries in nonoccluded areas.

Surgical management of unresolved pulmonary embolism. A personal series of 72 patients.

Chronic thromboembolic pulmonary hypertension (CT-E PH) is a rare and aberrant outcome of acute pulmonary embolism. Because it has become a potentially curable form of pulmonary hypertension, the frequency of recognized cases has increased. We report a case series of 72 patients with CT-E PH evaluated in our institution between 1984 and 1993, and discuss diagnostic clues and therapeutic approaches. All patients complained of dyspnea on exertion, a history of acute thromboembolic event, and lung murmurs were found in 60% and 17% of patients, respectively. The presence of a disorder of coagulation was found in 30% of the patients tested, the most common abnormality being lupus anticoagulant. The key noninvasive study for diagnosis was the lung perfusion scan which showed at least one segmental or larger perfusion defect in all patients. Pulmonary angiography confirmed the diagnosis in all cases, and sometimes associated to intravascular ultrasound imaging, established the feasibility of thromboendarterectomy. Medical therapy included the use of long-term oral anticoagulant, and in the case of lower limb venous thrombosis, inferior vena cava filtration. Finally two surgical procedures were discussed in selected patients: thromboendarterectomy and lung transplantation. Since 1988, eight patients have benefited from lung transplantation (six patients are still alive), and 11 patients underwent thromboendarterectomy which was successful in 9 patients with a dramatic functional and hemodynamic improvement.

Hemodynamic effects of bolus vs 2-h infusion of alteplase in acute massive pulmonary embolism. A randomized controlled multicenter trial.

Four centers participated in a double-blind study in which 53 patients with angiographically documented acute massive pulmonary embolism (baseline Miller index > or = 17/34 and mean pulmonary artery pressure > or = 20 mm Hg) were randomly assigned to treatment with either 0.6 mg/kg bolus injection of alteplase over 15 min with a maximum dose of 50 mg (bolus group; n = 36), or 100 mg of alteplase over 2 h (2-h group; n = 17). The primary objective was to compare the rapidity of resolution of pulmonary embolism as judged by the change in total pulmonary resistance (TPR) over the initial first hour. Further objectives were to evaluate the changes in TPR over the next 11 h and the degree of lung scan resolution at 20 to 28 h. At 1 h, TPR decreased by 29 +/- 17 percent in the bolus group and by 36 +/- 16 percent in the 2-h group (mean +/- SD; p = 0.19). Continuous monitoring of TPR revealed that this variable improved in both groups without significant intergroup differences over the 12-h study period, although TPR decreased initially faster in the 2-h group. At 20 to 28 h, the absolute improvements in the lung scan perfusion defect were 14 +/- 12 percent in the bolus group compared with 13 +/- 9 percent in the 2-h group, with no significant intergroup differences. Major bleeding occurred in one patient of the 2-h group (6 percent) and in three patients of the bolus group (8 percent) (p > 0.5). Four patients (three from the bolus group and one from the 2-h group) may have experienced recurrent pulmonary embolism during the hospital stay. Neither death nor intracranial bleeding occurred.

[Chronic pulmonary heart disease: therapeutic indications]. / Coeur pulmonaire chronique postembolique. Indications thérapeutiques.

Chronic thromboembolic cor pulmonale is a serious condition and its frequency seems to be on the increase. The authors report their personal experience of 100 cases and review the literature to describe the natural history, diagnostic strategy and therapeutic indications of this condition. The mechanisms of this aberrant evolution of acute pulmonary embolism are unknown. They key symptom is effort dyspnea without a ventilatory deficit. The most useful diagnostic investigations are Doppler echocardiography and perfusion pulmonary scintigraphy. The diagnosis is confirmed by pulmonary angiography which, with the aid of a thoracic CT scan or endovascular techniques (ultrasonography or angioscopy), allow assessment of the feasibility of thromboendarteriectomy. Medical treatment is based on long-term anticoagulation, in some cases of lower limb thrombosis associated with interruption of the inferior vena cava. Two possible curative surgical techniques are available in selected patients; thromboendarteriectomy and pulmonary transplantation, the relative indications of which are listed. Of all the causes of pulmonary hypertension, chronic thromboembolic cor pulmonary should be systematically looked for because curative surgical treatment is possible in some cases.

[Pulmonary arterial hypertension of chronic thromboembolic origin; therapeutic indications]. / Hypertension artérielle pulmonaire d'origine thrombo-embolique chronique; indications thérapeutiques.

Chronic thromboembolic pulmonary hypertension is a rare complication of acute pulmonary embolism. The therapeutic approach to the disease is addressed, based on a series of 81 patients referred to our department between 1984 and 1993. Medical treatment associates long-term anticoagulant therapy and, in some cases, inferior vena cava interruption. Two surgical procedures are available in selected patients: lung transplantation and pulmonary thrombo-endareterectomy. Lung transplantation has been performed in 8 patients since 1988 with 6 survivors with a maximal follow-up of 5 years. Twelve patients underwent pulmonary thromboendareterectomy with in 9 patients a dramatic functional and haemodynamic improvement. Chronic thromboembolism should be systematically investigated as the cause of pulmonary hypertension considering that in selected cases, curative surgery is possible.

[Gastric volvulus associated with Zenker's diverticulum: a rare cause of recurrent pneumopathy]. / Volvulus gastrique associé à un diverticule de Zenker: une cause rare de pneumopathie récidivante.

We report on a case of a patient with recurrent pneumonia related to a pharygo-esophageal (Zenker's) diverticulum associated with a chronic thoracic gastric volvulus. Mechanism, diagnosis and treatment of this rare disease are discussed.

[Pulmonary embolism. Risk factors of venous thromboembolic disease]. / Embolie pulmonaire. Facteurs de risque de la maladie thrombo-embolique veineuse.

RISK FACTORS: Management of deep venous thromboembolism both in terms of diagnosis and therapeutic and prophylactic strategies has been greatly improved by advances in knowledge of the main acquired and intrinsic risk factors. RESISTANCE TO ACTIVATED PROTEIN C: This is by far the most frequent coagulation disorder predisposing to venous thromboembolism. Other intrinsic factors favoring thrombus formation (anti-thrombin II, protein C or protein S deficiencies) are much more uncommon. Laboratory tests in search for these anomalies are indicated essentially for patients who develop repeated episodes of venous thrombus formation. PROPHYLAXIS: Excepting specific cases, anticoagulant prophylaxis is not indicated in any of these anomalies beyond the usual treatment of a first episode. Among the risk factors for acquired deep vein thromboembolism, only surgery and certain obstetrical indications have been investigated sufficiently to define validated prophylaxis strategies. For medical risks, the benefit of anticoagulant prophylaxis has been demonstrated in certain disease states such as cancer, antiphospholipid syndrome and the acute phase of myocardial infarction although no widely accepted strategy has yet been established.

[Mycoplasma pneumoniae pneumopathy. 10 cases]. / Pneumopathie à Mycoplasma pneumoniae. 10 observations.

OBJECTIVES: Describe the different features of a common disease: Mycoplasma pneumoniae pneumonia. PATIENTS AND METHODS: The hospital files of 10 consecutive patients with microbiologically proven Mycoplasma pneumoniae pneumonia were reviewed retrospectively. These 10 patients were hospitalized over a 15-month period among 150 patients admitted to the Versailles general hospital for community-acquired pneumonia. We compared our series with data in the literature. RESULTS: Most of the patients with Mycoplasma pneumoniae pneumonia were young apparently healthy adults. A bronchial risk factor (smoking, allergy) was however found in 60% of the patients. The principle symptom was persistent cough (100%), with fever and joint pain, or sometimes headache and signs of ENT involvement. Dyspnea was frequent, related more to associated bronchospasticity than to the severity of the pneumonia. Radiographic findings were quite variable. In one case hemolytic anemia and cold agglutinins suggested the diagnosis. Certain diagnosis was based on positive serology after hospitalization due to the long delay between symptom onset and hospitalization. The prehospital period was characterized by a succession of ineffective empirical antibiotic regimens. In routine practice, macrolides or fluoroquinolones administered for 2 to 3 weeks are the empirical antibiotics of choice. Outcome is generally favorable with rapid clinical and radiological improvement. Antibiotic therapy is not however sufficient alone to achieve improvement in the respiratory impairment: bronchodilators and corticosteroids are necessary to treat the bronchospasticity. CONCLUSION: Despite the benign nature of community-acquired pneumonia due to Mycoplasma pneumoniae, clinical manifestations, particularly bronchial inflammation may have important consequences.

[Pulmonary arterial hypertension of chronic thrombo-embolic origin. 70 patients]. / Hypertension artérielle pulmonaire d'origine thrombo-embolique chronique. 70 malades.

OBJECTIVES: Chronic thrombo-embolic pulmonary hypertension is a rare and aberrant outcome of acute pulmonary embolism. Because it has become a potentially curable form of pulmonary hypertension, the frequency of recognized cases has increased. We report a case series of 70 patients with chronic thromboembolic pulmonary hypertension evaluated in our institution between 1984 and 1993, and discuss diagnostic clues and therapeutic approaches. RESULTS: All patients complained of dyspnoea on exertion. A history of acute thrombo-embolic events and lung murmurs were found in 60% and 17% of patients respectively. Coagulation disorders were found in 30% of the patients tested; the most common abnormality was lupus anticoagulant. The key non-invasive study for diagnosis was the lung perfusion scan which showed at least one segmental or wider perfusion defects in all patients. Pulmonary angiography confirmed the diagnosis in all cases and, sometimes associated with intravascular ultrasound imaging, established the feasibility of thromboendarterectomy. Medical therapy included the use of long-term oral anticoagulant, and in case of lower limb venous thrombosis, inferior vena cava filtration. Finally two surgical procedures were discussed in selected patients: thromboendarterectomy and lung transplantation. Since 1988, eight patients have benefited from lung transplantation (six patients are still alive) and 11 patients underwent thromboendarterectomy which was successful in 9 patients leading to dramatic functional and haemodynamic improvement. CONCLUSION: Chronic thrombo-embolic pulmonary hypertension is a severe, sometimes fatal, disease which can be successfully treated by pulmonary thromboendartectomy and lung transplantation.

[Severe varicella pneumopathy in health adults. Apropos of a case]. / Pneumopathies varicelleuses graves de l'adulte sain. A propos d'une observation.

The authors report a new case of respiratory distress syndrome which occurred as complication of varicella in an otherwise healthy adult patient. The case is well documented by images and immunological studies which are discussed in the light of recently published data.

[Primary non-small-cell lung cancer: analysis of 419 T1 (

T1 tumors have the best prognosis among primary non-small-cell lung cancers, basically because surgery is generally possible. Among 5.667 patients with primary lung cancer included in the KBP-2000-CPHG study, we examined the characteristics of 419 T1 tumors, i.e. 9.2% of the non-small-cell cancers. Compared with the group of patients with non-T1 tumors, patients with T1 tumors were younger (p=0.0007). They had an equivalent percentage of squamous-cell tumors but more adenocarcinomas (40.3% versus 35.5%, p=0.05). TNM staging showed that 27.6% of the T1 tumors were metastatic at diagnosis (stage IV) with 12.4% T1N0M1 nad 15.2% T1N1-3M1. For the M0 tumors, 52.2% were T1N0 (stage IA) and 20.1% were T1N1-3. Squamous-cell tumors were significantly more frequent among the T1M1 tumors (p=0.07). More than one quarter (27.6%) of the T1 tumors were in stage IV, pointing out the importance of the initial work-up. This findings suggests we should revisit strategies in order to take into account new diagnostic possibilities. Likewise for the therapeutic strategy. Combinations using chemotherapy, surgery and radiotherapy should be better defined for this group of tumors.

[Effect of tinzaparin on survival in non-small-cell lung cancer after surgery. TILT: tinzaparin in lung tumours]. / Effet de la tinzaparine sur la mortalité du cancer bronchique non à petites cellules opéré.

BACKGROUND: Experimental and clinical findings suggest that low molecular-weight heparins may improve overall survival in patients with cancer. The evidence is still limited and additional studies are needed to confirm these preliminary findings. METHODS: Patients with completely resected stage I, II or IIIA (T3N1) histologically confirmed non-small-cell lung cancer will be included in a prospective, controlled, randomized, multicenter open trial. Patients in the control group will receive usual postoperative care including chemotherapy when indicated. Patients in the experimental group will receive tinzaparin given subcutaneously as a daily 100 IU/kg dose for 90 days along with usual postoperative care. Patients will be followed-up for three to eight years. Main end-point is the overall survival. Five hundred and fifty patients are needed to demonstrate a 10% absolute increase in survival in the experimental group. EXPECTED RESULTS: A 10% absolute increase in the survival rate is expected in the patients receiving tinzaparin.

[Long-term survivors of advanced non-small-cell lung cancer: characterisation and prognostic factors in a retrospective study]. / Longs survivants de cancers bronchiques non à petites cellules stades IIIB-IV.

INTRODUCTION: The prognosis of non-small cell lung cancer (NSCLC) is poor, especially for advanced stages IIIB-IV. Clinical experience shows that the evolution of the disease is heterogeneous. A small number of patients survive more than 2 years after diagnosis; they are called long term survivors (LS). The aim of our study was to characterise this subgroup of patients. METHODS: A retrospective study in the respiratory department of a general hospital including all patients with a proven diagnosis of NSCLC stage IIIB and IV. RESULTS: 169 patients were included (43 females). There were 13.6% LS. Two thirds of the patients were PS 0-1, 84.6% were stage IIIBw-IV. Adenocarcinoma was the predominant histological type. Univariate analysis revealed that long term survival was associated with a Charlson's score < or = 2, PS 0-1, a normal white blood cell count at diagnosis, adenocarcinoma histology, response (RP) to first line treatment and treatment with a tyrosine-kinase inhibitor (TKI). In multivariate analysis only PS 0-1, RP and treatment with a TKI were independent factors for longer survival. CONCLUSION: LS exist and represent 13.6% of our patients. TKI appear to offer new opportunities for these patients.

Assessment of the respiratory compliance in awake subjects using pressure support.

Pressure support (PS), a new mode of ventilatory assistance, is known to induce respiratory muscle relaxation. It was used to obtain reliable measurements of the compliance of the respiratory system (Crs) in awake subjects. PS was applied, through a mouthpiece, at four successive levels (0, 0.75, 1 and 1.25 kPa) to 30 healthy subjects. At the highest PS level, the subject's relaxation was obtained as assessed by a decrease in the occlusion pressure from 0.10 +/- 0.06 to 0.05 +/- 0.04 kPa, whereas the minute ventilation increased (from 7.5 +/- 1.5 to 13.8 +/- 3.3 l.min-1), and the end-tidal carbon dioxide tension (PCO2) decreased (from 5.0 +/- 0.4 to 3.2 +/- 0.5 kPa) below its apnoea threshold. In three subjects, respiratory muscle relaxation was confirmed by a fall in diaphragmatic electromyographic activity. Crs was calculated as the ratio of the tidal volume to the corresponding end-inspiratory airway pressure (i.e. PS level) since, at end inspiration, a zero-flow period was obtained. Crs was highly correlated (r = 0.77) to the height (Ht) of the subjects: Crs (l.kPa-1) = 3.56 x Ht (m) -4.86 (+/- 0.23), allowing normal values to be determined. In order to evaluate the applicability of the method to patients, Crs was measured in four patients with scoliosis, and was found to range from 45-82% of the predicted values. It is suggested that this simple method of Crs determination may be used to characterize various chest wall or pulmonary diseases.