The monoclonal antibody Po66 is an IgG1 immunoglobulin isolated from a human bronchial squamous carcinoma and directed against a carbohydrate binding protein, Po66-CBP, belonging to the galectin ...family involved in neoplastic processes. This Po66 antibody has been shown to be useful for immunoscintigraphic detection of squamous cell carcinoma metastasis. We examined the expression of Po66-CBP in a wider range of primary or secondary malignant tumors of the lung of various histological types. We studied 52 specimens of broncho-pulmonary tumors including 41 primary squamous, glandular or neuro-endocrine tumors and 11 secondary tumors of glandular, connective tissue, melanocytic or germinal origin as well as 9 extra-pulmonary primary tumors with histological types similar to lung metastases. An immunohistochemical study was performed using an amplification system on paraffin-embedded sections. All histological types were positive for Po66 antibody, the cell origin giving no influence on the expression of Po66-CBP. There was however a relation between Po66-CBP expression and the degree of differentiation notably for squamous cell cancer and neuro-endocrine tumors. The metastatic character of the tumor tissue did not affect Po66-CBP expression.
Respiratory failure (RF) is a frequent cause of death among patients with bilateral bronchiectasis. An ICU admission is commonly required, and neither short-term or long-term outcomes have been ...studied.
We performed a retrospective study over a 10-year period (January 1990 to March 2000). All patients with bilateral bronchiectasis admitted for the first time in the medical ICU for RF were reviewed. Patients with cystic fibrosis were excluded.
Forty-eight patients (mean age ± SD, 63 ± 11 years; mean simplified acute physiology score SAPS II, 32 ± 12) of whom 25% received long-term oxygen therapy (LTOT) were identified. All the patients were treated with intensive medical care, associated with noninvasive ventilation in 13 patients (27%), and 26 patients (54%) required intubation. Nine patients (19%) died in the ICU. The 1-year mortality rate was 40%. Among the variables recorded at ICU admission, age > 65 years (p = 0.002), SAPS II score > 32 (p = 0.012), use of LTOT (p = 0.047), and intubation (p = 0.027) were associated with reduced survival in univariate analysis by Cox regression. Multivariate analysis by Cox proportional hazard model showed that age > 65 years (relative risk RR, 2.70; 95% confidence interval CI, 1.15 to 6.29) and use of LTOT (RR, 2.52; 95% CI, 1.15 to 5.54) were independently associated with reduced survival.
We performed the first study providing information related to the impact of the first ICU stay for RF on long-term outcomes for patients with bilateral bronchiectasis. Age > 65 years and prior use of LTOT were associated with reduced survival.
Le syndrome des antisynthétases correspond à une myopathie inflammatoire fréquemment associée à une atteinte pulmonaire, surtout parenchymateuse (pneumopathie infiltrante diffuse) et plus rarement ...vasculaire (hypertension pulmonaire). Devant un tableau clinique et radiologique évocateur, la présence d’anticorps anti-ARNt synthétases signe le diagnostic. Les plus fréquents de ces auto-anticorps sont les anti-Jo1, les anti-PL7 et les anti-PL12. De nombreuses manifestations cliniques extrathoraciques associées à l’atteinte pulmonaire peuvent orienter le diagnostic : myalgies ou déficit musculaire, phénomène de Raynaud, polyarthrite, fièvre et « mains de mécaniciens ». Une augmentation des créatine-phospho-kinases est quasi constante. Le recours à l’électromyogramme, à l’imagerie musculaire par résonance magnétique ou à l’histologie n’est pas systématique. Néanmoins, il existe une grande variabilité des symptômes et de leur sévérité d’un patient à l’autre ou au long de l’évolution de la maladie. L’atteinte pulmonaire est un facteur pronostic majeur et incite à traiter de manière intensive les patients, principalement par corticothérapie systémique, voire d’emblée par association corticoïdes et immunosuppresseurs. Mieux connaître cette pathologie qui est souvent de révélation pneumologique permettrait d’améliorer le diagnostic et la prise en charge thérapeutique, voire même le pronostic.
Antisynthetase syndrome is an inflammatory myopathy frequently associated with pulmonary manifestations, especially interstitial lung diseases, and uncommonly pulmonary hypertension. In the context of a suggestive clinical and radiological picture, positive anti-RNA synthetase antibodies confirm the diagnosis. Anti-Jo1, anti-PL7, and anti-PL12 antibodies are the more commonly encountered. The presence of a number of extra-thoracic manifestations in association with pulmonary disease may suggest the diagnosis. These include: myalgia or muscular deficit, Raynaud's phenomenon, polyarthritis, fever, mechanics hands. Serum creatine kinase levels are usually increased. Electromyogram, muscular magnetic resonance imaging or muscle pathology are not mandatory to make the diagnosis. There is a high variability in symptoms and severity, between patients but also during the course of the disease in the same patient. The presence of an interstitial lung disease is a major prognostic factor and an indication for more intensive treatment, principally with systemic corticosteroids with or without immunosuppressive drugs. Improving respiratory physicians’ knowledge of this disease, which is often revealed by its pulmonary manifestations, should help diagnosis, therapeutic management, and possibly prognosis.
Purpose: to compare standard and alternating administration of chemotherapy combinations in small cell lung cancer (SCLC) patients. Material and methods: 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). Results: 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%) (
P<0.001). Conclusion: 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.
Since idiopathic chronic eosinophilic pneumonia (ICEP) and asthma are frequently associated, their possible reciprocal influence on clinical presentation and evolution were investigated. The clinical ...and follow-up features of 53 cases of ICEP, of which 41 (77%) had asthma, were reviewed retrospectively. Asthma preceded the diagnosis of ICEP in 26 patients, was contemporaneous in eight patients, and developed 17 +/- 12 months after ICEP in seven patients. Presentation of ICEP was similar in asthmatics and nonasthmatics with the exception of a higher level of total immunoglobulin E in the former group. Patients with asthma at the time of diagnosis of ICEP were more likely to remain free of relapse of ICEP (56 versus 23%) and had a lower number of relapses per year of follow-up (median 0 versus 0.24). Moreover, they were treated more frequently with long-term inhaled corticosteroids (88 versus 31%) at last follow-up. Asthma got worse after the diagnosis of ICEP and frequently required long-term oral corticosteroids. To conclude, among patients with idiopathic chronic eosinophilic pneumonia, asthmatics have a lower frequency of relapse than nonasthmatics, possibly because of a higher use of inhaled corticosteroids. The occurrence of idiopathic chronic eosinophilic pneumonia in asthmatics is often associated with the development of severe asthma.
Les résultats de l’étude randomisée contrôlée WEGENT ont démontré, à 28 mois, que le méthotrexate (MTX) est aussi efficace que l’azathioprine (AZA) pour maintenir la rémission au cours de la ...granulomatose avec polyangéite (Wegener) (GPA) et de la polyangéite microscopique (PAM) sévère 1. Cette nouvelle étude propose d’analyser le suivi à long terme des patients inclus dans l’étude WEGENT.
Le suivi à long terme des 126 patients inclus dans l’essai WEGENT entre 1999 et 2004 a été analysé. Les données de survie, d’utilisation d’immunosuppresseurs, de rechutes, cancers, infections et la morbidité cardiovasculaire ont été recueillies. Les patients ont été analysés selon leur groupe de randomisation. Les paramètres démographiques, cliniques, et biologiques à l’inclusion ont été évalués afin de déterminer s’ils étaient des facteurs pronostiques de décès ou de rechute en analyse multivariée.
Le suivi médian est de 11,8ans. La survie globale à 10ans est de 74,8 % IC 95 %, 64,5–86,9 pour le bras AZA et 79,9 % IC 95 %, 70,3–90,7 pour le bras MTX, sans différence significative (HR MTX vs AZA=0,79 IC 95 %, 0,37–1,70 ; p=0,55). Il n’y a pas de différence à long terme entre les deux bras pour la fréquence des effets indésirables, des effets indésirables sévères, des infections, des cancers, le taux de rechute et le taux de rechute sévère. La survie sans rechute à 10ans est de 26,3 % IC 95 %, 17,3–40,1 sous AZA et 35,1 % IC 95 %, 24,9-49,4 sous MTX, sans différence significative entre les deux (HR MTX vs AZA=0,78 IC 95 %, 0,51–1,20 ; p=0,26). De même, la survie à 10ans sans effet indésirable sévère est comparable entre les deux groupes (HR MTX vs AZA=1,02 IC 95 %, 0,64–1,63 ; p=0,93), comme la survie sans rechute ni effet indésirable sévère (HR MTX vs AZA=1,04 IC 95 %, 0,66–1,63 ; p=0,87). En restreignant l’analyse aux 97 patients atteints de GPA, aucune différence n’est constatée pour les paramètres de survie entre les deux bras. La survie sans rechute est moindre dans le groupe des patients atteints de GPA par rapport à ceux atteints de PAM (HR 2,16 IC 95 %, 1,22–3,83 ; p=0,009). Les analyses multivariées ont retenu la dose de prednisone à la fin du traitement d’entretien de 1 an (HR 1,18 IC 95 %, 1,09–1,29 ; p<0,001), la durée du traitement par prednisone (HR 1,01 IC 95 %, 1,00–1,02 ; p<0,04), et la positivité des ANCA-PR3 (HR 3,68 IC 95 %, 2,07–6,55 ; p<0,001) comme facteurs significativement associés aux rechutes à long terme. Chaque mois supplémentaire ou milligramme additionnel de prednisone à la fin du traitement d’entretien augmentait la probabilité de rechute ou de décès de 1 % ou 15 %, respectivement.
Cette analyse à long terme confirme que l’AZA et le MTX représentent deux alternatives thérapeutiques comparables pour maintenir la rémission au cours de la GPA et de la PAM. Si la survie globale est acceptable, les rechutes et les effets indésirables restent fréquents. Des alternatives thérapeutiques sont nécessaires pour réduire le taux de rechute à long terme des vascularites associées aux ANCA.
The efficacy of radioimmunotherapy of tumours with radiolabelled monoclonal antibodies (MAbs) depends on the amount of antibody taken up by the tumour and on its intratumoral distribution. In the ...case of MAbs directed against intracellular antigens, increasing the permeability of the cytoplasmic membrane may augment the bioavailability of the antigen for the antibody. This raises the question whether the induction of tumour necrosis by chemotherapy can enhance the tumour uptake of radiolabelled monoclonal antibodies. In this work, the effect of doxorubicin on the biodistribution of Po66, an MAb directed against an intracellular antigen, was studied in nude mice grafted with the human non-small-cell lung carcinoma cell line SK-MES-1. After injection on day 0 of 125I-labelled Po66, tumour radioactivity increased up to days 3-5, and then remained unchanged to day 14. The combined administration of 125I-labelled Po66 with 8 mg kg-1 doxorubicin, in two doses separated by 7 days, doubled the radioactivity retained by the tumour. Histological and historadiographic analysis showed, however, that the drug induced cellular damage. In the absence of doxorubicin, the accumulation of Po66 was restricted to some necrotic areas, whereas with doxorubicin the necrosis was more extensive and the antibody more evenly distributed. These results suggest that chemotherapy and immunoradiotherapy combined would enhance tumour uptake of radioisotope and promote more homogenous distribution of the radiolabelled MAb. This would promote eradication of the remaining drug-resistant cells in tumours.
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