[Laboratory variables and stratification of small-cell lung cancer patients: recommendations for therapeutic trials and for clinical practice guidelines]. / Variables biologiques et stratification des patients porteurs de cancer bronchopulmonaire à petites cellules: recommandations pour les essais cliniques et les guides de bonne pratique.

OBJECTIVE: To identify, through a systematic review of the literature, the laboratory variables that, in addition to performance status and to extent of the disease, would allow a more accurate stratification of small-cell lung cancer patients who participate in chemotherapy trials, with or without radiotherapy. Secondary aim: to compare the results of our systematic review with the recommendations made in current clinical practice guidelines. METHODS: Update of two recently published systematic reviews, without meta-analysis, following the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine, and taking into account the Consolidated Standards of Reporting Trials statement. RESULTS: Of 1143 publications retrieved, exclusion and inclusion criteria allow us to include 13 studies in our review. The three variables which were the most often found significant in multivariate statistical analysis, were: pre-therapeutic levels of laboratory variables (13/13), performance status (12/13), and degree of tumour invasion (10/10). Among the laboratory variables, serum lactate dehydrogenase (LDH) is the only one that was quite consistently found to be of independent prognostic significance, with p values or hazard ratios quite close to those obtained with performance status, or with extent of the disease. The recommendations made in the four clinical practice guidelines that we retrieved, are often vague regarding laboratory variables, and sometimes they even contradict each others. CONCLUSIONS: Available evidence would support the recommendation that pretreatment LDH should be systematically measured in order to stratify patients in therapeutic trials. If other laboratory variables were to be measured in addition to LDH for this purpose, it seems that alkaline phosphatase (ALP), and to a lesser extent, sodium and white blood cell counts, might be the best suited ones. Nevertheless, further studies are necessary to more clearly support this latter recommendation. Available evidence would not support the measurement of any other laboratory variable in this context, before, during, or after treatment. Our recommendations are more in agreement with the recommendations made in the clinical practice guidelines that use evidence-based methods than with the guidelines that do not.

[Primary small-cell bronchial cancer: value of serum tumor markers in the prognostic evaluation]. / Cancer bronchique primitif à petites cellules: intérêt du dosage des marqueurs tumoraux sériques pour l'évaluation pronostique.

TUMOR MARKERS: We reviewed the biomedical literature searching for the most well-documented serum markers with prognostic value independent of the usual radioclinical and histological parameters of small cell lung cancer. RELATIVE PROGNOSTIC VALUES: Neuron specific enolase (NSE) would have a pretherapeutic prognostic value better than LDH (lacto-dehydrogenase) and perhaps better than serum sodium, biocarbonates, and uric acid. The superiority of NSE over serum albumin remains to be proven. Although there are only a few reports, TK (thymine kinase), TPA (tissue polypeptide antigen), Cyfra 21-1 and/or IL-2 (interleukin-2) secretion might have better pretherapeutic prognostic value than NSE. We also found that iterative blood assays to follow therapeutic effects in patients with small-cell lung cancer have not been proven to provide independent prognostic information. CONCLUSION: As medical laboratory resources must be concentrated on priority exploitable assays, the currently available data would suggest that it is not necessary to routinely measure serum tumor markers, and in particular NSE, for the prognostic evaluation of small-cell lung cancer patients.

[Are the ATS (American Thoracic Society) and the ERS (European Respiratory Society) correct in not recommending routine tumor marker assays foeening, staging, or evaluation of non-small cell lung cancer?]. / Faut-il suivre les sociétés savantes de pneumologie dans leurs recommandations concernant l'utilisation des marqueurs tumoraux sériques pour l'évaluation pronostique des cancers bronchiques primitifs non à petites cellules?

The American Thoracic Society (ATS) and the European Respiratory Society (ERS) do not recommend routine tumor marker assay for screening, staging or evaluation of non-small-cell lung cancer (NSCLC). In contrast to this position, the statement of the French society of pneumology (Société de Pneumologie de Langue Française, SPLF) suggests such assays may be useful for prognostic evaluation of NSCLC (and certainly so before treatment) and that the usefulness of serum CEA (carcino-embryonic antigen) measurements before and after treatment is not clearly excluded. Our own review of the literature indicates that other routine tests less expensive than tumor markers such as LDH, prothrombin time, calcium, blood cell counts and even serum proteins might, alone or in combination, have a prognostic significance similar to, or even higher than, tumor markers. Since routine clinical laboratories have to set priorities for useful analyses, a clear reading of the biomedical literature suggests that it is not currently necessary to routinely measure serum tumor markers (including Cyfra 21-1) for the prognostic evaluation of NSCLC patients.

[Bibliographic analysis of the use of laboratory blood parameters for the prognosis of primary lung cancer]. / Analyse critique de la bibliographie sur l'utilisation de paramètres biologiques sanguins pour l'evaluation pronostique de cancer bronchopulmonaire primitif.

In the daily clinical practice, serum calcium, albumin, and cyfra 21-1, are the only laboratory parameters officially recommended for the prognostic evaluation of primary lung cancer patients by the American, European or French respiratory/thoracic societies (and only in non-small cell lung cancer). The present review of the biomedical literature suggests that serum calcium for non operable non-small cell lung cancer, serum orosomucoid (alpha1-acid-glycoprotein) and serum cyfra 21-1 for non-small cell lung cancer, and perhaps plasma prothrombin time, might be the best laboratory parameters for the pre-therapeutic prognostic evaluation of the lung cancer patients, independently from the usual radio-clinical and histological parameters. Further prognostic evaluation studies are necessary in order notably to compare the prognostic values of the aforementioned parameters, not only aimed at evaluating the value of their pre-therapeutic levels, but also aimed at evaluating the value of their post-therapeutic changes. A higher pluridisciplinarity for such future publications also seem necessary.

Do blood cell counts have an independent prognostic value in primary lung cancer?

A review of the biomedical literature suggests that lymphocyte and neutrophil counts are probably the only blood cell count parameters whose independent pre-therapeutic prognostic values are significantly documented in lung cancer (and only in non small cell lung cancer). The independent pre-therapeutic prognostic value of these two parameters remains quite controversial however, and further studies should be conducted, and in particular, comparisons between neutrophils, lymphocytes, and serum cyfra 21-1. For the therapeutic follow-up, further prognostic evaluation studies are also necessary for blood cell count parameters as well as for serum cyfra 21-1. Clinical biologists still have to convince clinicians and/or journal editors that it is not scientifically acceptable for publications to omit detailing the analytical and pre-analytical methodologies used for blood cell count measurements.

Epidemiologically related and unrelated strains of Pseudomonas aeruginosa serotype O12 cannot be distinguished by phenotypic and genotypic typing.

A clonal origin for European isolates of antibiotic multi-resistant Pseudomonas aeruginosa serotype O12 has been suggested. This study was designed to assess the value and limitations of several typing methods for the investigation of outbreaks due to this serotype. In Hôpital de Rodez, France, this organism is endemic, and a prospective clinical epidemiological study was undertaken over a 15 month period, encompassing all patients at the hospital from whom P. aeruginosa O12 was isolated. All isolates were examined by auxanogram, antibiogram, phage-typing, electrophoresis of esterases and pulsed-field gel electrophoresis of DNA. The results suggest that (1) the methods used did not clearly differentiate between clinically-related and epidemiologically-unrelated European isolates, (2) in Hôpital de Rodez, while some isolates were likely to have been transmitted from patient-to-patient, most infections or colonizations with this organism were sporadic and their origin is unknown. The limits of typing methods for the investigation of outbreaks of nosocomial infection with multi-resistant P. aeruginosa O12 are emphasized.

[Bactericidal activity of quinolones (including sparfloxacin) against Enterococcus; in vitro antagonisms with gentamicin]. / Bactéricidie des quinolones (dont la sparfloxacine) vis-à-vis d'Enterococcus; antagonismes in vitro en présence de gentamicine.

We selected 20 clinical Enterococcus isolates in order to represent the different types of amoxicillin and/or gentamicin-resistance present in our hospital. Bacteriostatic and bactericidal activities of amoxicillin, pefloxacin, ofloxacin, ciprofloxacin, sparfloxacin, vancomycin, alone or associated with gentamicin, were evaluated on those 20 isolates. Sparfloxacin or ciprofloxacin were more frequently bacteriostatic and/or bactericidal than pefloxacin or ofloxacin. The effect of quinolones and gentamicin in combination use was not only synergistic but antagonistic, which is not in agreement with others' results.

Progesterone treatment in chylothorax associated with pulmonary tuberous sclerosis.

We report the case of a young woman with tuberous sclerosis who developed a chylous pleural effusion after several invasive procedures for treatment of recurring pneumothoraces. Oophorectomy was rejected by the patient and progesterone therapy initiated. Medroxyprogesterone acetate administration led to a complete disappearance of the chylothorax in 8 months. The patient was kept on therapy, and no recurrence of pleural effusion has been observed up to the present (22 months follow-up). However, a progressive deterioration in pulmonary function was observed, with a significant decrease in pulmonary transfer factor and increase in airway obstruction. In conclusion, this report demonstrates an objective benefit of progesterone therapy on chylous effusion associated with pulmonary tuberous sclerosis.

Usefulness of a computerized expert system associated with systematic O-serotyping for the early detection of outbreaks of hospital acquired infections and for the presumptive antibiotic therapy of Pseudomonas aeruginosa infections.

Over a four-year period, the systematic O-serotyping of all Pseudomonas aeruginosa isolated in Hôpital de Rodez associated with the use of a computerized expert system, facilitated the early detection of two outbreaks of nosocomial infections with multiresistant serotype O:11 and multiresistant serotype O:12 P. aeruginosa respectively involving ten patients over 16 months and six patients over six months. Over this four-year period, serotype O:12 represented 14% of 404 clinical isolates of P. aeruginosa, and most isolates of this serotype were resistant to multiple antibiotics. Combination experiments showed that fosfomycin/amikacin together were active against 86% of O:12 isolates. Fosfomycin/amikacin might be considered as a therapeutic alternative to ceftazime/amikacin for the presumptive antipseudomonal therapy of serotype O:12 infections.

[Orosomucoid prealbumin ratio in bronchopulmonary cancers]. / Rapport orosomucoïde sur préalbumine dans les cancers broncho-pulmonaires.

Lung cancer is a common pathology with high mortality due to late diagnosis. The 1987 TNM classification clearly defines the different steps and their prognosis. Although the prognostic value of some biological parameters (mainly serum LDH, sodium and/or albumin) has been established, these are not much used. We have prospectively studied the serum levels of seven proteins (RBP, prealbumin, albumin, transferrin, haptoglobin, orosomucoid, CRP) and we demonstrate the predominant value of prealbumin for the establishment of the prognosis of lung cancer; determination of orosomucoid increases the prognostic value of prealbumin. We confirm, for lung cancer, the prognostic value of the orosomucoid-prealbumin ratio, already known for other cancers.