[Impact of positron emission tomography on clinical management of potentially resectable non-small-cell lung cancer: a French prospective multicenter study]. / Impact de la tomographie par émission de positons au 18-FDG dans la prise en charge des patients porteurs d'un cancer bronchique non à petites cellules a priori opérable. Etude prospective multicentrique française.

BACKGROUND: Whole-body (18)F-deoxyglucose positron emission tomography (FDG-PET) has the potential to improve the management of non-small-cell lung cancer (NSCLC). We prospectively evaluated the impact of combining FDG-PET with conventional staging methods, including computed tomography (CT), on the staging and management of patients with potentially resectable NSCLC. METHODS: Ninety-four consecutive patients with newly diagnosed/suspected NSCLC were enrolled. Each patient was first staged by using conventional methods, and then by FDG-PET. FDG-PET results were forwarded in a sealed envelope and divulged at the weekly staff meeting on staging and treatment, only after "Decision 1", based on conventional staging, had been reached by consensus; reevaluation taking FDG-PET into account yielded "Decision 2". The validity of these latter decisions was analyzed retrospectively. RESULTS: Eighty-nine patients were eligible. Relative to standard imaging, FDG-PET led to clinical staging changes in 26 (29.2%) patients. The stage was lowered in eight cases (9%) and raised in 18 cases (20.2%). "Decision 2" differed from "Decision 1" in 19 patients, modifying the surgical procedure in four cases, indicating other investigations to confirm FDG-PET evidence of metastases in 12 cases, or modifying the medical treatment in three cases. These modifications were retrospectively justified in 9/19 cases, and consisted of 2/4 modifications of the surgical procedure (one hilar and one adrenal metastasis not confirmed histologically), 4/12 further investigations (axillary and liver biopsies, mediastinoscopy, occult colon cancer) and three indications for palliative treatment, in patients who all died within 3 months after FDG-PET. CONCLUSIONS: Based on FDG-PET, management was modified in 19/89 (21.3%) patients, but these changes were justified in only 9/89 patients (10.1%). FDG-PET can detect asymptomatic local and distant metastases and improves the preoperative assessment of NSCLC, thereby avoiding unnecessary surgery. However, histological verification is required because of the risk of false-positive results.

[Coagulase-negative staphylococcal osteomyelitis in preterm infants: a proposal for a diagnostic procedure]. / Ostéomyélites à staphylocoque coagulase négative chez le prématuré : proposition de démarche diagnostique.

Acute osteomyelitis, although a rare complication in neonates, is a diagnostic and therapeutic challenge. Successful treatment to avoid functional sequelae depends on early recognition of infection and rapid initiation of therapy. Although Staphylococcus aureus is the most common causative agent, coagulase-negative Staphylococcus (CONS), well known for bloodstream infection, can be involved in neonatal osteomyelitis. Risk factors of osteomyelitis include prematurity and invasive procedures, such as long-term central venous catheterization. We report on 3 cases of acute CONS osteomyelitis in preterm infants presenting with prolonged CONS bacteremia. Bacteremia persisted despite antibiotic treatment in accordance with antibiograms and despite removal of the intravascular device. All catheter cultures were negative and osteomyelitis was not located on the limb where the central catheter had been inserted in all cases. Osteomyelitis diagnosis may be difficult in neonates because of the paucity of clinical signs. In our observations, (99m)Tc scintigraphy was the key investigation for diagnosis and detection of multiple sites of bone infection. The place of this investigation is discussed in relation to other imaging techniques. These observations suggest that in the context of persisting CONS bacteremia, a secondary bone infection should be considered. Scintigraphy is a discriminating diagnostic tool.

Radiolabeled bivalent haptens for tumor immunodetection and radioimmunotherapy.

The pretargeting technique referred to as the Affinity Enhancement System (AES) uses bispecific antibodies and radiolabeled bivalent haptens that bind cooperatively to target cells in vivo. Experimental and clinical data demonstrate that DTPA bivalent haptens can deliver large radiation doses to tumor cells with high tumor to normal tissue contrast ratios and long activity residence time in tumors. Preliminary clinical results of radioimmunotherapy of medullary thyroid carcinomas and lung cancers look promising. Very encouraging results in biodistribution and radioimmunotherapy experiments in animals have been obtained with new haptens bearing two histamine-hemisuccinate suitable for 131I, 99mTc and 188Re labeling. Targeting isotopes to double antigen positive tumor cells provides a binding enhancement that increases specificity for tumor cells as compared to single antigen targeting on normal cells. This approach may be beneficial for targeting isotopes to B type acute lymphoblastic leukemia and Burkitt lymphoma, as well as others tumors co-expressing two markers of low specificity, and might increase tumor irradiation with minimal irradiation of normal cells.

Distribution of I-BZA (N-2-diethylaminoethyl-4-iodobenzamide) in grafted melanoma and normal skin: a study by secondary ion mass spectroscopy.

Iodobenzamides labelled with radioactive iodine are undergoing clinical evaluation as imaging and potential therapeutic agents in malignant melanomas. However, the uptake mechanism in melanic tissues remains controversial. Using secondary ion mass spectrometry (SIMS), we studied the microscopic distribution of N-(2 diethylaminoethyl)-4 iodobenzamide (I-BZA) in B16 murine melanoma inoculated to C57BL/6J1 Co mice as well as in normal pigmented skin. SIMS provides specific detection of iodine-127 atoms entering 127I-BZA composition. In B16 melanoma, 127I-BZA distribution was found to be heterogeneous, with focal areas of high concentration corresponding to cells rich in melanin pigments. In skin, SIMS analysis showed 127I-BZA distribution appearing as multiple small selective concentration areas within the epidermis. The number of these foci decreased from the stratum basale towards the stratum corneum. In both tissues, the intracellular location appeared specifically intracytoplasmic, with no apparent nuclear uptake. Distribution of this molecule mirrored that of melanin pigments. There was no enhancement of uptake at the membrane site. These results suggest that, in melanic tumors as well as in normal pigmented tissue, specific uptake of 127I-BZA occurs in pigment cells, with a possible link to melanin pigments.

Successful surgical removal of occult metastases of medullary thyroid carcinoma recurrences with the help of immunoscintigraphy and radioimmunoguided surgery.

Patients with recurrent or metastatic medullary thyroid carcinoma (MTC) were referred for pretargeted immunoscintigraphy (Affinity Enhancement System; AES) and radioimmunoguided surgery (RIGS). Data collected from 13 patients establish that whole-body AES immunoscintigraphy revealed metastases < 360 mg and RIGS detected micrometastases (5-15 mg). All tissue samples removed by the surgeon were diagnosed by histology and immunohistochemistry of calcitonin to check the accuracy of IS and RIGS results. AES immunoscintigraphy is very sensitive. Of 34 metastases or recurrences detected, 22 had escaped physical examination or conventional imaging. The accuracy of RIGS was 86%, its sensitivity 75%, and its specificity was 90% (n = 208). IS and RIGS detected occult tumors that would have escaped surgery, clearly demonstrating clinical benefit. Serum calcitonin (normal, 10 pg/ml) and carcinoembryonic antigen (normal, 5 ng/ml) of two patients were restored to normal. In patients whose tumors were discovered, progression of their disease was slowed, as evidenced by the large decrease in serum calcitonin and carcinoembryonic antigen, an important prognostic factor. Surgery was canceled in one case where IS detected distant metastases out of surgical reach. Thus, AES immunoscintigraphy and RIGS might be of valuable help for the surgical management of medullary thyroid carcinoma.

Biological consequences of the heterogeneous irradiation of lymphocytes during technetium-99m hexamethylpropylene amine oxime white blood cell labelling.

Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) labelling of white blood cells, routinely used for the detection of infection, results in the incorporation of radioactivity by polymorphonuclear leucocytes and also lymphocytes and can induce cell lesions in the latter case. The aim of this study was therefore to acquire data on the morphological and functional status of labelled lymphocytes present in the 99mTc-HMPAO leucocyte mixture and to determine the cellular consequences of labelling. The mean radioactivity associated with lymphocytes was 325 +/- 10.8 kBq/10(6) lymphocytes under standard labelling conditions. Microautoradiographic studies showed that labelling was heterogeneous (4% intensely labelled cells), which prevented calculation of the mean absorbed dose. The frequency of chromosomal aberrations (dicentrics and rings) in the labelled lymphocytes for 380 kBq/10(6) cells was 1.08 +/- 0.09 but no abnormality was observed in the unlabelled control lymphocytes. The plating efficiency of labelled lymphocytes was reduced, as compared with that for control cells, but some lymphocytes were still able to form clones and were still "alive" by radiobiological definition. It is therefore suggested that lymphocytes should be removed from 99mTc-HMPAO cell preparations before administration to patients.

The influence of tracer localization on the electron dose rate delivered to the cell nucleus.

UNLABELLED: The radiation dose rate delivered by electron emissions of 99mTc, 123I, 111In, 67Ga and 201Tl was evaluated at the subcellular level. METHODS: Spherical models of sources were used to simulate various cellular localizations of radionuclides. These models were applied to large lymphocytes, assuming uniform distributions of radioactivity throughout the nucleus, the cytoplasm or the cell membrane surface. RESULTS: The graphs of the absorbed dose rate plotted according to the distance from the center of the cell show that the dose rate strongly depends on the subcellular distribution of the radioisotope. The absorbed dose rate D(0) at the center of the cell delivered by a constant cellular radioactivity of 99mTc, 123I, 111In, 67Ga and 201Tl is respectively 94, 21, 18, 74 and 76 times higher if the radioactivity is localized within the cell nucleus than if it is situated only on the cell membrane. D(0) for subcellular localizations was compared to D(0) obtained by assuming uniform distribution of radioactivity throughout the cell. This latter assumption may underestimate the dose rate from 2.8- to 3.2-fold if the tracer is exclusively localized within the nucleus or overestimate from 4.3- to 30-fold if the tracer is localized within the cytoplasm or on the cell membrane, depending on the radionuclide. CONCLUSION: Such findings show that the localization of radiopharmaceuticals at the subcellular level plays a crucial role in determining the actual dose delivered to the cell nucleus in diagnostic nuclear medicine procedures.

[Radio-isotope assays of vitamin B 12: value of the Kappa test in a multicenter evaluation]. / Dosages radio-isotopiques de la vitamine B12: intérêt du test Kappa dans une évaluation multicentrique.

Owing to the lack of a reference technique and of an international cobalamin (vitamin B12) standard, and the large discrepancy between laboratory norms, the authors performed a multicentric study to compare five RIA kits usually used. First, classical tests were used to evaluate the analytical performances of each kit. Results did not demonstrate any superiority of one kit over another. Secondly, B12 values were classified among three categories (low, normal and high) characterized by laboratory and then manufacturer norms. The concordance between these two "judgments" was evaluated with the Kappa coefficient. In addition, the Kappa index proved that the norms supplied by the manufacturer were better than those of laboratories. But mean Kappa coefficient established for each norm gave us an unsatisfactory result. Third, clinical informations allowed to improve the classification of the patients. New limits were defined for each technique and should be tested further, routinely in each laboratory.

[Value of peroperative scintigraphy in detecting accessory spleens]. / Intérêt de la scintigraphie peropératoire pour repérer les rates accessoires.

We report a case of accessory spleen, 1 cm in diameter, responsible for recurrence of an idiopathic thrombocytopenic purpura after splenectomy. This case is original in that the accessory spleen could only be detected by transoperative scintigraphy. Transoperative scintigraphy is a simple method to be used when one or several unrecognized accessory spleens are responsible for recurrence of a blood disease after excision of the principal spleen.

[The peroperative isotopic location of osteoid osteomas and other lesions exhibiting increased uptake on scintigraphy]. / Le repérage isotopique per-opératoire des ostéomes ostéoïdes et autres lésions hyperfixantes à la scintigraphie.

The technique, advantages and pitfalls of the isotopic localization and control during operation in orthopaedic surgery were evaluated throughout 28 interventions on lesions, which exhibited an increased uptake of a radioactive bone-seeker: the dimethyl-aminodiphosphonate, provisionally designated SF44 (Laboratoires Solabco, Coutras, France). For bone scanning, following the injection of this radiopharmaceutical that increased by 25% the lesion to normal bone ratio compared to the data for the diphosphonates in current use, the localization of lesions at surgical sites was carried out with the use of a sterilisable small radiation probe of a circular cross section 2 mm in diameter (Quartz et Silice, Paris, France). The probe was connected to a portable electronic device that converted the rates of radioactive disintegration into an acoustic signal, which increased with increasing radioactivity (Novelec, Meylan, France). The method was atraumatic and has proved to be useful at various times of the operation. More often, it was used to locate the lesion on the exposed bone. It enabled monitoring the progress of excisions and allowed to shorten their dimensions. The method was of great value at the end of the intervention for ensuring a complete excision as indicated by the lack of any residual focus of increased uptake detectable on the periphery of the operative site. Isotopic control during an operation is fully efficient to locate osteoid osteomas and other circumscribed lesions of the skeleton that give rise to an increased uptake of radioactivity.

Hemodynamic tolerance and plasma volume variations during plasma exchange. Replacement fluid: albumin alone or albumin plus gelatin?

Little is known about mechanisms of systemic hypotension frequently reported during plasma exchange (PE). Type of substitution fluids may interfere with hemodynamic tolerance. In a prospective study, right heart catheterization was performed during 18 PE by filtration with isovolumic substitution. Blood volume was measured with 51Cr tagged erythrocytes and plasma volume (PV) calculated from hematocrit. Substitution fluids were either albumin (A; n = 9) or A + gelatin (A + G; n = 9). In both groups, PE induces significant (p less than 0.01) decreases of mean arterial pressure: group A: - 21 +/- 14%; group A + G: - 23 +/- 15%; of pulmonary wedge pressure: group A: - 41 +/- 33%; group A + G: - 36 +/- 22%; of cardiac index: group A: - 38 +/- 18%; group A + G: - 25 +/- 15%. Plasma volume also decreases after PE: group A: - 13.5 +/- 4%; group A + G: - 18.5 +/- 4%. None of the variations are significantly different between the two groups. So we think that substitution with albumin alone has no advantage for hemodynamic tolerance.

The kinetics of intestinal calcium absorption in the rat: an analytical and model building study.

The experimental data obtained from in vivo single pass perfusion of duodenal, jejunal, and ileal intestinal segments of 33- and 50-day-old rats have been used to test a series of models for calcium absorption. Each model was checked for the statistical validity and goodness-of-fit with the experimental data. The model adopted for the duodenum and jejunum had two major components, one saturable and the other nonsaturable, and a minor secretory component. This model was not applicable to ileal calcium absorption. Here the secretory component appeared to be much more important, and the absorption parameters varied in such a manner as to suggest that this intestinal segment was capable of short term autoregulation of dietary calcium absorption.