Maurice Radermecker

Whole-body 18FDG positron emission tomography in the staging of non-small cell lung cancer

Despite advances in morphological imaging, some patients with lung cancer are found to have nonresectable disease at surgery or die of recurrence within yr of surgery. We performed a prospective study in 109 patients to compare the accuracy of whole-body positron emission tomography (PET) using fluorine-18 deoxyglucose (18FDG) and conventional imaging (CI) methods for the staging of non-small cell lung cancer (NSCLC). When CI or PET study suggested metastatic disease, confirmation was obtained by biopsy or follow-up information. As compared to CI, 18FDG-PET correctly changed the N stage in 22 patients (33%) and the M stage in 15 patients (14%). For the detection of distant metastases, PET study showed five false-positive sites and no false-negative cases. Currently, the accuracy of PET in the detection of M stage is 96%. Our study shows that visual interpretation of whole-body fluorine-18 deoxyglucose-positron emission tomography images can improve the diagnostic accuracy in the staging of non-small cell lung cancer. Further experience is needed to establish if metabolic imaging would be a cost-effective tool in the future management of lung cancer.

Staging of the mediastinum: value of positron emission tomography imaging in non-small cell lung cancer

Recent studies have shown limitations of morphological imaging in staging mediastinal lymph node involvement in lung cancer. In contrast to computed tomography (CT), which depends primarily on anatomical imaging features, positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) depends mainly on the metabolic characteristics of a tissue for the diagnosis of disease. We have performed a prospective study comparing FDG-PET and CT of the thorax in the presurgical assessment of the mediastinum in 50 patients with newly diagnosed non-small cell lung cancer (NSCLC). CT and PET scans were interpreted separately, and results were compared to pathological staging obtained during thoracotomy. Hilar or mediastinal lymph node involvement was present in 58%. In staging for lymph node involvement, CT had a sensitivity of 72% and specificity of 81%, whereas PET had a sensitivity and specificity of 90% and 86%, respectively. When the PET study was compared to histological results, there were four cases showing more advanced mediastinal involvement with PET and four cases showing less involvement with PET. From our preliminary results, we conclude that positron emission tomography with 18-fluorodeoxyglucose is significantly more accurate than computed tomography in the mediastinal staging of non-small cell lung cancer.

Histamine-induced inhibition of neutrophil chemotaxis and T-lymphocyte proliferation in man

Histamine inhibits in vitro human neutrophil chemotaxis and T‐lymphocyte proliferation via H2 receptors. The aim of this study was to verify these inhibitory effects of histamine in man in vivo. Healthy volunteers were challenged with histamine by intravenous (1 mg), subcutaneous (1 mg) and inhalatory (2.4 mg) routes. Venous blood was taken before and at different times after challenge. Neutrophil chemotaxis was studied by the Boyden assay and T‐lymphocyte proliferation by counting H3‐thymidine incorporation in cultured mononuclear cells. Plasma histamine was measured by radioimmunoassay. Histamine infusion caused transient systemic symptoms as well as a significant decrease of neutrophil chemotaxis (x̄−26%± 6) and of PHA‐pulsed T‐lymphocyte proliferation (x̄−16%± 6) 4 h after histamine challenge. Subcutaneous injection of histamine caused only a significant decrease of neutrophil chemotaxis (x̄−24%± 15) 4 h after injection. Histamine inhalation was well tolerated and caused a significant depression of neutrophil chemotaxis (x̄−40%± 15) and of T‐lymphocyte proliferation (x̄−27%± 6) 2 and 4 h after the challenge. Histamine challenges were always accompanied by a rapid and transient rise in plasma histamine. Inhalation of an H3 agonist (impromidine) but not of an H2 agonist (betahistine) caused a decrease of neutrophil chemotaxis and of T‐lymphocyte proliferation. Oral pretreatment with an H1 antagonist (cimetidine) before histamine inhalation prevented histamine‐induced decrease of neutrophil chemotaxis and T‐lymphocyte proliferation, whereas astemizole, an H3 antagonist, had no effect. In conclusion, during the few hours following administration, exogenous histamine in man causes a depression of neutrophil chemotaxis and T‐lymphocyte proliferation via H2 receptors. These observations are consistent with the concept that endogenous histamine may exert some modulatory effects on inflammatory and immune cells in man.

Staging of non-small-cell lung cancer by whole-body fluorine-18 deoxyglucose positron emission tomography

Positron emission tomography (PET) using fluorine-18 deoxyglucose (FDG), showing increased FDG uptake and retention in malignant cells, has been proven useful to differentiate malignant from benign tissue. We undertook a prospective study in 61 patients to compare the accuracy of whole-body FDG PET and conventional imaging (CI) methods for the staging of nonsmall-cell lung cancer (NSCLC). CI included chest and abdomen computed tomographic scanning and bone scintigraphy. When CI or PET study suggested metastatic disease, confirmation was obtained by biopsy or clinical or radiological follow-up. As compared to CI, PET correctly changed the N stage in 13 patients (21%) and the M stage in six patients (10%). There were three false-positive and no false-negative distant PET findings. Our preliminary results show that whole-body FDG PET can improve the diagnostic accuracy in the staging of NSCLC.

Increased frequency of bronchial hyperresponsiveness in patients with inflammatory bowel disease.

Although bronchopulmonary manifestations are rare in inflammatory bowel diseases (IBD), subclinical abnormalities have been described in up to 50% of cases. The pathophysiology of these abnormalities remains unknown. However, a latent inflammation of the bronchial mucosa secondary to the inflammation of the intestinal mucosa has been suggested. This subclinical inflammation may lead to increased bronchial responsiveness. We studied the bronchial responsiveness in 38 inflammatory bowel disease (IBD) patients, using the methacholine test. Bronchial hyperresponsiveness was defined by a PC20M <16 mg/ml. Twenty‐four healthy controls were also studied. There was no significant difference in baseline FEV1 between IBD patients and controls. However, there was a significantly greater fall in FEV1 in the IBD patients at the concentrations of methacholine tested. The frequency of bronchial hyperresponsiveness was significantly higher in the IBD population (45%) than in controls (17%; P<0.03). Atopy, defined by skin test, was more common in IBD patients (42%) than in controls (21%). Even when only nonatopic subjects were considered, the frequency of bronchial hyperresponsiveness was significantly higher in IBD patients (41%) than in controls (5%; P<0.02). Thus, subclinical bronchial hyperresponsiveness is common in IBD, and may be considered a further extraintestinal manifestation.

Bronchial Eosinophilic Infiltration in Crohn's Disease in the Absence of Pulmonary Disease

Immunological and functional bronchopulmonary abnormalities may be present in up to two‐thirds of patients with Crohns disease. Having recently described a mild increase in methacholine airways responsiveness in these patients, we investigated whether this physiological abnormality is associated with bronchial inflammation since it has previously been described in asthma.

SUBSTANCE P-INDUCED HISTAMINE RELEASE FROM HUMAN BASOPHILS, SKIN AND LUNG FRAGMENTS : EFFECT OF NEDOCROMIL SODIUM AND THEOPHYLLINE

We compared histamine release induced by substance P with those obtained with classical secretagogues on human basophils, lung and skin fragments. We also tested the capacity of nedocromil sodium and theophylline to inhibit histamine release in these 3 experimental models. Substance P (10(-4) M) caused a noncytotoxic histamine release (about 10% of total) from basophils, lung and skin fragments. Substance P-induced histamine release was always smaller than that obtained with optimal doses of anti-IgE, formyl-methionine phenylalanine or compound 48/80. Nedocromil sodium did not prevent secretagogue-induced histamine release from basophils or sliced skin. In contrast, it significantly inhibited anti-IgE- or substance P-induced histamine release from human lung. Theophylline caused a dose-related inhibition on these 3 models. We conclude that substance P is a modest secretagogue for human basophils and mast cells, and that skin and lung mast cells are heterogeneous with respect to their response to nedocromil sodium.

Serum IgE Levels in Protozoal and Helminthic Infections

Serum IgE concentration is measured, according to the Rowe modification of the Mancini technique, in non-atopic patients suffering from various helminthic or protozoal infections. Our results indicate

Depression of Neutrophil Chemotaxis in Atopic Individuals

Neutrophil chemotaxis was compared in normal and atopic individuals using a modified Boyden chamber with as chemotactant, autologous serum either unactivated or activated by zymosan or an endotoxin-containing house dust preparation. A high incidence of defective leukotaxis was found in atopics when cells were opposed to activated serum. The cause of this abnormality is not intrinsic to the leukocytes since random migration and chemotaxis towards unactivated serum were comparable in normal and atopic subjects. The defect persisted when atopic leukocytes were opposed to activated normal serum and the chemotactic response of normal neutrophils was not imparied when tested against activated atopic serum. Leukotaxis was significantly depressed by incubating atopic leukocytes with allergen to which they were sensitized, suggesting an inhibitory effect of mediators of anaphylaxis. Histamine inhibited in vitro neutrophil chemotaxis in normal and atopic subjects. This inhibition was dose-related and significantly more pronounced in atopics. Incubation of atopic leukocytes with an H2 antagonist, cimetidine, was capable of enhancing their chemotactic responsiveness towards activated autologous serum to levels observed in normal controls. In the same conditions, an H1 blocker, promethazine, was without effect. These data indicate that the leukotactic dysfunction of atopic individuals results from an abnormal sensitivity of these leukocytes to histamine which, in the chemotactic chamber, may be released from basophils by products of complement activation and, in some experimental conditions, by antigen to which cells are sensitized.

Neurophysins as markers of vasopressin and oxytocin release. A study in carcinoma of the lung.

Vasopressin-neurophysin (hNpI), oxytocin-neurophysin (hNpII) and blood osmolality were assayed before any treatment in basal conditions in 35 patients suffering from lung carcinoma (20 oat cell, 6 undifferentiated and 9 well-differentiated epidermoid cell carcinomas). Plasma vasopressin (antidiuretic hormone, ADH) was also assayed in 7 of the 20 patients suffering from oat cell carcinoma. We found a close correlation (r = 0.98) between plasma ADH and hNpI levels in the 7 patients. Further, hNpI was elevated in 13 out of the 20 oat cell carcinoma patients and in none of the epidermoid-cell carcinoma group; however, searching for an abnormality of ADH secretion as reflected by a detectable plasma hNpI level together with subnormal plasma osmolality revealed 2 additional positive results in the oat cell carcinoma group, and 2 out of the 6 in the undifferentiated-cell carcinoma group. hNpII was increased together with an increase in hNpI in 6 oat cell carcinoma patients; it was specifically increased without hNpI increment in 2 additional oat cell carcinoma patients and in 2 patients of the undifferentiated-cell carcinoma group (different from the 2 positive for the hNpI-osmolality ratio). hNpI and hNpII were normal in the majority of undifferentiated and all of the differentiated epidermoid-cell carcinoma group. Hence, our results show that simultaneous measurements of hNpI, hNpII, and blood osmolality could detect abnormalities in 17 out of 20 oat cell carcinoma patients, in 4 of the 9 undifferentiated-cell carcinoma patients, but in none of the differentiated epidermoid-cell carcinoma patients, suggesting that the neurophysin assay can be used for the early detection of oat cell- and possibly other neuroendocrine-derived carcinomas.