[Lung autofluorescence. Preliminary study of two systems without laser illumination or photosensitization]. / Autofluorescence bronchique. Etude préliminaire portant sur deux systèmes sans illumination laser ni photosensibilisation.

When illuminated with a certain wavelength, lung tissue emits a weak fluorescence. The fluorescence from normal tissue is different from that from diseased tissue. This technique can thus be used for early diagnosis of precancerous lesions. Technical manipulations are required to amplify the fluorescence signal. Numerous studies have used the LIFE (Lung Imaging Fluorescent Endoscope) to study lung diseases. This system of detection uses a laser helium-cadmium excitation source; the principal photosensitizing agents are hematoporphyrin derivatives. The cost, bulkiness and secondary effects have limited diffusion of this type of photodynamic diagnostic system. We have used 2 systems (SAFE 1000 Pentax and D-LIGHT Storz) successively in a prospective study to analyze autofluorescence of lung tissue without laser illumination or photosensitization. Fifty-four patients were selected for their risk factors. We were able to detect one case of severe dysplasia but did not identify any case of carcinoma in situ. Among 18 cases, 16 were evident with white light. Two were detected with autofluorescence used to orient biopsies while white light had only revealed a common inflammatory aspect. Thirty-nine low-grade lesions (metaplasia, dysplasia) were found. The systems are easy to use. Lower cost would allow more widespread use of these systems currently reserved for risk populations. These techniques broaden the scope of interventional endoscopy.

[Treatment of bronchial tumors with high-frequency thermocoagulation. Preliminary studies]. / Traitement des tumeurs bronchiques par thermocoagulation haute fréquence. Etude préliminaire.

Several techniques are available for endobroncheal tissue destruction. The cost and nature of the effect of the different techniques are determining factors in deciding on which equipment to use. Electrocoagulation is an old method which has practically been abandoned in favour of high frequency coagulation. This technique has an immediate effect, somewhat like the laser. We treated 32 patients with inoperable malignant (17) or benign (5) tumours obstructing the trachea or the bronchi. Response to treatment was evaluated on clinical manifestations and endoscopic findings. Haemostasis was obtained in 11/12 cases and tumour destruction of more than 50% in 27/32 cases. Complications included haemoptysia in 2 patients followed by death due to respiratory failure in 1. The ERBOTOM ACC 450 equipment was piloted with a microcomputer to control the power output automatically. White coagulation was induced by slow heating up to 70-100 degrees C causing tissue vaporization. The cost of this multiple applications of this equipment is competitive.

The operation and efficacy of cryosurgical, nitrous oxide-driven cryoprobe. I. Cryoprobe physical characteristics: their effects on cell cryodestruction.

For specification of the requirements for efficient cell cryodestruction in tumors, we tested a N2O-driven cryoprobe on experimental models. The cryoprobe was a 3-mm-diameter type for operation via fiber optic bronchoscopes in respiratory medicine. The freezing process, namely the "ice-ball" formation around the cryoprobe tip, was monitored with an impedancemeter. Physical characteristics and formation kinetics of the ice-ball formation (volume, diameter, freezing rate) were studied under defined experimental conditions in various biological liquids, including saline, serum, whole blood, and tumor cell suspensions (rat ascitic hepatoma), either plain or supplemented with gelling agents to approximate solid tumor consistency. Cell destruction (i.e., cryotoxicity to cells) within the ice ball produced in rat ascitic hepatoma was assessed in two ways: the cells, collected after ice-ball thawing, were (1) seeded and cultured according to methods currently in use, or (2) injected into a rat to check for possible development of ascites. Both tests showed that cryotoxicity correlated with freezing rate within the ice ball, cell mortality was total next to the cryoprobe tip (i.e., site of highest freezing rate), while it was absent within the ice-ball periphery. In the area in between, mortality varied gradually. Together our experimental results show that cryotoxicity to cells may be improved by increasing the freezing rate (e.g., by brief precooling of the cryoprobe). Furthermore, for tumor cryosurgery, since cell mortality is maximal next to the cryoprobe, we point out that higher efficacy might be achieved by several overlapping short freezing spots in tumoral tissue, instead of one single prolonged freeze.

Tumor fixation of bleomycin labeled with 57 cobalt before and after cryotherapy of bronchial carcinoma.

The combined effect of cryotherapy and chemotherapy was studied in 12 patients with bronchial carcinoma. Radiolabeled (57 Co) Bleomycin (BLM) was injected intravenously and initial detection was carried out with a gamma-camera. Plasma half-life and clearance of 57 Co-BLM, as well as tumor/normal tissues ratios were calculated. The same protocol was performed 15 days later immediately after cryotherapy. A mean increase of 30% of radiolabeled BLM was found in the tumor area after cryotherapy, and pharmacokinetic data were significantly different after cryotherapy. The vascular component of cryodestruction offers an explanation for these results, with trapping of the anticancer drug in the tumor and immediately surrounding area due to vascular stasis. It seems that chemotherapy may be more effective after cryotherapy, and a multicenter study is in progress to evaluate the association of cryo-chemotherapy in France.

Pleural and lung cryobiopsies during thoracoscopy.

Cryotherapy through rigid bronchoscopy has been used in the past three years in the treatment of endobronchial tumors. We performed pleural and lung cryobiopsies during thoracoscopy. The hemostatic properties and the quality of the histopathologic specimens obtained using this technique offer an innovative approach to the diagnosis of pleural effusion with associated lung disease.

[Cryotherapy in the treatment of tracheobronchial obstructions of tumor origin]. / La cryothérapie dans le traitement des obstructions trachéo-bronchiques d'origine tumorale.

The effects of cold on tissues result in necrosis through crystallisation and thrombosis. These properties, utilized for many years in certain fields of medicine, can now be applied to bronchial tumours, using semi-rigid or flexible cryodes introduced into bronchoscopes. In our experience the results, evaluated by clinical, radiological, endoscopic or even histological improvement, were good in 7 out of 8 cases of benign tumours and in 16 out of 30 cases of malignant tumours. Complications were minimal. This relatively cheap and very simple method constitutes a good alternative to laser in the same pathologies.

Bronchoscopic cryotherapy for airway strictures caused by tumors.

This study reports an application of cryosurgery for the treatment of tracheobronchial tumors. Bronchoscopic cryotherapy can be applied in patients who are not candidates for other traditional therapy. The technique utilizes a nitrous oxide cryoprobe, introduced through a rigid bronchoscope. The principal feature of this probe is to be nonrigid. The cryodestruction is controlled by an impedance metric method. The study group consisted of 27 patients ranging in age from 39 to 88 years. The most frequent diagnosis was squamous cell carcinoma (14). For malignant tumors, the objective was obtained in 13 cases out of 21. Cryotherapy successfully destroyed five benign granulomas. Four or six days after cryotherapy, bronchial biopsy specimens usually showed a necrotic substance, and tumoral tissues were entirely destroyed. The time of survival is probably extended and the quality of life bettered. Most visible tumors are now reached with a flexible cryoprobe, inserted in a flexible bronchoscope.

Fluorescence as a guide to bronchial biopsy.

The presence of fluorescence was assessed in 34 unselected patients undergoing bronchoscopy, 11 of whom suffered from bronchial carcinoma. Bronchoscopic inspection was carried out with white light and then repeated with blue light after the injection of 2 ml of 10% sodium fluoresceinate. Fluorescence was graded visually. Seventy six pairs of biopsy specimens were obtained. Of 38 specimens from non fluorescent areas, histological appearances were normal in 34. Slight inflammation was observed in three biopsy specimens, and in one there was evidence of tumour even though the specimen was obtained some distance from the primary tumour. Of 38 biopsy specimens from fluorescent areas, histological examination showed appearances of moderate inflammation in 10, severe inflammation in 10, tuberculosis in one, and carcinoma in 11. In six instances histological appearances were normal. Five normal subjects who were smokers were also examined by the same technique. Appearances of metaplasia were found more often in areas showing fluorescence than in areas not showing fluorescence. Bronchial fluorescence is considered to be related to alteration in vascularity and is not specific for carcinoma. The most fluorescent areas are generally the most pathological and visible tumour is very fluorescent, but moderate degrees of fluorescence are difficult to interpret. Biopsy of every fluorescent area seems excessive.

[Clinical problems posed by the consumption of antithrombin III induced by heparin]. / Problèmes cliniques posés par la consommation de l'antithrombine III par l'héparine.

Two cases of resistance to the heparin treatment, induced by large consumption of antithrombin III, are reported. Normally small, this consumption does not automatically call for the systematic dosage of Antithrombin III for each treatment using heparin. On the other hand, any clinical or biological resistance to higher doses of heparin, any personal or family history of thrombosis necessitate the administration of Antithrombin III. Where there is an acquired or congenital deficit, an injection of Antithrombin III corrects the disorder and reduces the risk of thrombosis. In the case of a heparin-antivitamin K relay, it is essential to achieve complete biological effectiveness of the antivitamins K to interrupt the administration of the heparin.

Correlation between precancerous bronchial metaplasia and cigarette consumption, and preliminary results of retinoid treatment.

Vitamin A and its derivatives, so-called retinoids, can prevent squamous metaplasia induced not only by vitamin A deficiency but also by carcinogenic hydrocarbons. An aromatic retinoid, such as ET1, has been shown to prevent chemically induced papillomas in mice and to amplify certain immunologic reactions. Heavy smokers, 106 volunteers, were submitted to fibrobronchoscopy with bronchial biopsies. An index of metaplasia (IM) was calculated on the basis of microscopical examination of a total of 9,633 sections of 1,010 biopsies. Despite the subjectivity of the estimates of cigarette consumption, this was significantly (P less than 0.02) and positively correlated to the IM. Eighty-five percent of the women had a low IM as compared to only 42% of the men (P less than 0.01), although there was no significant difference in the reported cigarette consumption. Fifty-two subjects had an IM greater than 15% and were given 25 mg ET1 orally daily for 6 months. The bronchoscopy was repeated in 30 patients following completion of the 6-month treatment. The IM was significantly (P less than 0.01) reduced after treatment.

[Primary interstitial pneumopathies].

Primitive interstitial pneumopathies are only a temporary classification. They seem to be due to an evolution for the worse of a "diffuse alveolar damage" of unknown origin. Evolution towards pulmonary fibrosis and respiratory insufficiency is their common risk. Etiopathogenic hypotheses would favour the immunological etiology. A diagnosis of primitive interstitial pneumopathy is reached by elmination when no known cause can be found. Liebow's classification remains valuable for pathology but is debatable where anatomo-clinical correlations, etiological hypotheses and the eventual effect of treatment are concerned. Today these primitive forms still represent 40% of the interstitial lung diseases, the causes of which are progressively discovered.