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.

[18F]-FDG positron imaging in clinical management of lymphoma patients.

[18F]-FDG is a glucose analogue labelled with a short-lived positron emitter. During the past decade, it has been proposed to detect in vivo lymphoma lesions with PET, a new non-invasive imaging modality. We aimed at reviewing the current experience with FDG in several clinical settings of lymphoma. Due to the lack of specificity of FDG for lymphoma, histology remains compulsory to establish the diagnosis. Nevertheless, in the case of AIDS, FDG imaging has been proposed to differentiate lymphoma and opportunistic infections in brain lesions. To explore lymphoma extension, FDG-PET highlights more lesions than CT or the clinical examination and results in upstaging 13% of cases. It could also be used for selecting a site for biopsy when the location considered first clinically is difficult to access. Staging lymphoma with FDG-PET also provides baseline images for subsequent evaluation of therapy, which is one of the most promising indications: a negative scan predicts response to therapy and subsequent remission with a predictive value of 89%, and a positive scan either reflects resistance or predicts relapse with a predictive value of 83%. The current achievement of FDG imaging is the early detection of recurrence or of viable tissue in residual masses that remain several months after treatment. Both its sensitivity (84%) and its specificity (95%) overwhelm the values of conventional imaging, mainly CT and gallium-67 scintigraphy. When PET, as a new clinical imaging modality, is not yet widely demanded by clinicians and/or the number of FDG examinations is less than 500 per year, a 'hybrid' gamma-camera or CDET can be an alternative to dedicated PET. For 3 years, we have been using FDG-CDET in the 2D mode without attenuation correction, and obtained the following accuracy in a total of 40 examinations that could be evaluated: 85% for assessment of chemotherapy and 92% to detect recurrences and evaluate residual masses. Our preliminary results also stress the interest in FDG examination in childhood lymphoma, with the same indications as in adults.

CFTR, MDR1, and MRP1 immunolocalization in normal human nasal respiratory mucosa.

CFTR (cystic fibrosis transmembrane conductance regulator), MDR1 (multidrug resistance), and MRP1 (multidrug resistance-associated protein), members of the ABC transporter superfamily, possess multiple functions, particularly Cl(-), anion, and glutathione conjugate transport and cell detoxification. They are also hypothesized to have a number of complementary functions. It is generally accepted that data obtained from nasal mucosa can be extrapolated to lower airway cell physiology. The aim of the present study was to investigate by immunohistochemistry the differential localization of CFTR, MDR1, and MRP1 in the normal mucosa of 10 human nasal turbinates. In ciliated epithelial cells, CFTR was inconstantly expressed at the apical cell surface, intense membranous labeling was observed for MDR1, and intense cytoplasmic labeling was observed for MRP1. In the glands, a higher level of expression was observed on serous cells, at the apical surface (for CFTR), on lateral membranes (for MDR1), and with an intracytoplasmic distribution (for MRP1). In conclusion, CFTR, MDR1 and MRP1 are expressed in the epithelium and glands of the nasal respiratory mucosa, but with different patterns of expression. These results suggest major roles for CFTR, MDR1, and MRP1 in serous glandular cells and a protective function for MDR1 and MRP1 in respiratory ciliated cells. (J Histochem Cytochem 48:1215-1222, 2000)

Tissue and cell distribution of the multidrug resistance-associated protein (MRP) in mouse intestine and kidney.

The multidrug resistance-associated protein (MRP) that is involved in drug resistance and the export of glutathione-conjugated substrates may not have the same epithelial cell membrane distribution as the P-glycoprotein encoded by the MDR gene. Because intestinal and kidney epithelial cells are polarized cells endowed distinct secreting and absorptive ion and protein transport capacities, we investigated the tissue and cell distribution of MRP in adult mouse small intestine, colon, and kidney by immunohistochemistry. Western blot analyses revealed the 190-kD MRP protein in these tissues. MRP was found in the basolateral membranes of intestinal crypt cells, mainly Paneth cells, but not in differentiated enterocytes. All the cells lining the crypt-villous axis of the colon wall contained MRP. MRP was found in the glomeruli, ascending limb cells, and basolateral membranes of the distal and collecting tubule cells of the kidney but not in proximal tubule cells. Cultured mouse intestinal m-ICcl2 cells and renal distal mpkDCT cells that have retained the features typical of intestinal crypt and renal distal epithelial cells, respectively, also possess MRP in their basolateral membranes. The patterns of subcellular and cellular distribution indicate that MRP may have a specific role in the basolateral transport of endogenous compounds in Paneth, renal distal, and collecting tubule cells.

Diagnosis of partial and total physeal arrest by bone single-photon emission computed tomography.

Bone single-photon emission computed tomography (SPECT), capable of creating maps of the distribution of osteoblastic activity in every spatial plane of a physis, should provide images of diagnostic value in the case of patients suffering from growth arrests (epiphysiodeses). Seventy-five bone SPECT scans were obtained in 64 children suspected to have developed physeal arrests. The transaxial slices of the physis, in the case of partial epiphysiodeses: (a) indicated the percentage of the remaining normal physis, (b) located the bony bridge within the physis and (c) showed the slowdown of the growth of the remaining normal physis induced by the bony bridge in some children. Misdiagnosis occurred in six patients. For total epiphysiodeses, the radionuclide diagnosis was confirmed in 20 of 21 patients. Radionuclide, x-ray and MRI examinations in the study of growth disturbances were found to be complementary.

Intraoperative localization of neuroblastoma in children with 123I- or 125I-radiolabeled metaiodobenzylguanidine.

BACKGROUND: This study describes a novel method of intraoperative localization of neuroblastoma with a gamma-detecting probe, to detect in situ tumor binding of radiolabeled 123I- or 125I-metaiodobenzylguanidine (MIBG) and improve the quality of tumor resection. METHODS: Fifty-eight children underwent 66 surgical procedures with intraoperative detection of radiolabeled MIBG. All patients with positive MIBG scintiscans at diagnosis were included in the study. A tumor/background ratio exceeding 2:1 at the time of operation was considered positive, indicating a significant uptake of MIBG, compatible with the presence of malignant cells. The surgeons were requested to evaluate the contribution of the method to the surgical procedure. Sensitivity and specificity of the method with either 123I-labeled MIBG or 125I-labeled MIBG, on the basis of correlations between probe findings and pathologic analysis of 288 resected specimens, were determined. RESULTS: Intraoperative detection was helpful in 65% of surgical procedures, allowing a better definition of tumor limits and extension to locoregional nodes or detection of small and nonpalpable tumors in sites with difficult surgical access, especially during operation for relapse. The detection was not contributory in 35% of the procedures (well-localized tumors, thoracic neuroblastoma for technical reasons, highly differentiated tumors as ganglioneuroma, and tumors with mainly necrosis or fibrosis). The sensitivity of 123I and 125I was the same (91% and 92%), but the specificity of 125I (85%) was significantly higher than that of 123I (55%) (p < 0.005). CONCLUSIONS: First, this study demonstrates the feasibility of intraoperative detection, with radiolabeled MIBG, of neuroblastoma in children. We advocate the use of 125I rather than 123I. Second, the method is useful to improve the quality of macroscopic resection in widespread neuroblastoma with nodal involvement, in sites with difficult access, and in operations for relapse.

Changes in biophysical parameters and in phospholipid composition associated with resistance to doxorubicin.

Friend leukemia cells (FLC) resistant to different concentrations of doxorubicin were used to investigate the biochemical and biophysical changes associated with resistance. We have found that fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene analyzed on single cell level increased in resistant as compared to sensitive FLC. Furthermore, phospholipid analysis of sensitive and doxorubicin-resistant cells revealed changes in ratios of phosphatidyl-choline to phosphatidyl-ethanolamine and phosphatidyl-choline to sphingomyelin. These results correlate with decreased electrophoretic mobility in resistant cells. Our results indicate that changes in cell structure occur with the level of resistance to doxorubicin. These changes are probably the consequence rather than the cause of resistance.

[Electrophoresis applied to the analysis and separation of cells]. / L'électrophorèse appliquée à l'analyse et à la séparation des cellules.

The present paper describes the theory and practice of cell/particle electrophoresis: the migration of cells/particles free to move in suspension under the influence of an applied electrical field, without any undue damage of cell membranes. The technique is quite different from high voltage electrophoresis on gels and paper. The quantitative biophysical parameter, never likely to be zero, is the electrophoretic mobility, experimentally determined by the cell electrophoresis apparatus, and mathematically related to the electrokinetic or the zeta potential. A detailed description of the analytical and preparative electrophoresis is given. Data are presented on the electrophoretic properties of bone tissue cells and cells of the immune system.

Intraoperative bone scintigraphy in orthopaedic surgery.

A sterilisable radiation probe of small dimensions was designed to locate the lesions at orthopaedic surgical sites according to the procedure of intraoperative bone scintigraphy. The probe has a collimated opening 2 mm in diameter. It is connected to a portable radioactivity counter which converts the disintegration rates detected at surgical sites into an acoustic signal that increases steeply with increasing disintegration rate. The acoustic signal enables the surgeons and isotope specialists to readily monitor radioactivity in the region of interest without attention being distracted from the surgical site. Dimethylaminodiphosphonate (designated SF44) was the osteotropic radiopharmaceutical chosen for carrying out intraoperative bone scintigraphy, since the available data show that this chemical increases the pathological: normal bone uptake ratio of the lesion by 25% compared to the usual diphosphonates. Forty-seven orthopaedic interventions were carried out according to the intraoperative bone scintigraphy procedure. They showed that this procedure facilitated the rapid location of the lesion, the objective termination of the operation, less frequently the reduction in dimension of the excised areas, and rarely the simplification of the surgical technique. Practice of intraoperative bone scintigraphy requires proper training and caution.

Relationships between H-2 Region and surface characteristics of mouse spleen cells.

The purpose of this investigation was to study whether allelic variations at the H-2 region which induce differences in the peptide composition of some glycoproteins of cell surface, also induce variations in electrical charges at the cell membrane. The surface charge was assessed by the electrophoretic mobility of the cell. Tests with different congenic strains were undertaken on spleen cells which were assumed to contain two major lymphocyte populations with different surface charge. The data show that the mean electrophoretic mobility of the low mobility lymphocytes was independent of the strain. By contrast, some H-2 haplotypes give 8% difference in surface charge of high mobility lymphocytes. These results suggest that the H-2 region plays a role in the regulation of ionized groups of cell surface in some but not all populations of spleen lymphocytes. The high and low mobility lymphocyte populations are assumed to represent T and B lymphocytes, respectively. The proportions of T lymphocytes obtained with electrophoretic marker were higher than those observed in other strains with currently available markers. It is suggested that the high mobility population contains T and "null" lymphocytes. Moreover, the data show that the H-2 region controls the relative proportions of T (or T and "null") and B lymphocytes, the H-2s specificity inducing a B/T ratio different from that induced by other specificities.

Desepiphysiodesis--elimination of partial premature epiphyseal closure. Experience of 17 cases.

Between 1975 and 1990, 17 growth plates have been operated on by epiphyseal bridge resection. The children were from 4 years and 10 months to 13 years and 10 months old. The etiology of partial closure was traumatic (10 times), caused by therapeutic mistakes (3 times), septic osteomyelitis (1 case), purpura fulminans (1 case), unknown (2 cases). There was always length discrepancy or deformity of bone. The regions that have been subjected to treatment were distal femur, proximal tibia, distal tibia, distal radius. Evaluation of the bone bridge was made by tomoscintigraphies and recently by MR imaging and computed tomoscintigraphy. The bone bridge size was from 2.5% to 60% of the growth plate surface; surgical technique consists of resection of bone bridge connecting epiphysis and metaphysis which is replaced by methyl metacrylate. In 16 cases simultaneous corrective osteotomy was performed. Results are poor, there were only two good results and 8 failures; seven results were medium. The failures can all be explained by mistakes in technique or indication, except one. Indications are post-traumatic narrow bridges in young children. It would be useful to know the vitality of the residual growth plate.

[Value of bone scintigraphy]. / Intérêts de la scintigraphie osseuse.

Artificial radioactivity enables visualisation of the principal organs in the form is scintiscans, introduces a new order of sensitivity in quantitative hormonal analysis, thanks to radio-immunology, and remains unrivalled in compartmental analyses of the various metabolism of the diagnosis of local skeletal conditions is reviewed, and the indications for this quantitative examination are described for the diagnosis of numerous bony metabolic diseases. Finally, mono- and bi- photonic absorptiometries, the latest developments in isotopic techniques, are introduced. They are likely to provide numerical data on the state of mineralisation of bony tissue. The use of these nuclear techniques for the diagnosis and surveillance of osteoporosis is detailed.

[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.

[Primary Gougerot-Sjogren syndrome. Spontaneous one-year course of clinical, biological and histological signs]. / Syndrome de Gougerot-Sjögren primaire. Evolution spontanée sur un an des signes cliniques, biologiques et histologiques.

OBJECTIVES: The natural clinical course of primary Sjögren's syndrome was followed in 8 patients to identify the concomitant functional, clinical, biological, scintigraphic and histological manifestations of the disease. METHODS: The diagnosis of primary Sjögren's syndrome was made on the basis of functional signs (ocular or salivary sicca syndrome) and 2 positive tests among the 3 objective ocular tests (Schirmer's test, break-up time, Rose Bengale). Work-up included recording of functional and clinical signs, ophthalmologic examination and laboratory tests at diagnosis and every 3 months for 12 months. Scintigraphy of the salivary glands was performed together with a biopsy at diagnosis and at 12 months. RESULTS: No one parameter varied significantly over a 1 year period demonstrating the lack of need for renewed examinations for diagnosis or regular follow-up. CONCLUSION: This is the first report providing a homogeneous series studied by one team over a determined period of time. It demonstrates that clinical, biological and anatomic criteria for primary Sjögren's syndrome do not show any correlation between functional signs and objective ocular tests.

[Bilateral diaphyseal hyperostosis of the leg bones in adults. Apropos of a case]. / Hyperostose diaphysaire bilatérale des os de la jambe de l'adulte. A propos d'un cas.

A new case of bilateral, diaphyseal hyperostosis of the leg bones is reported. Strictly unilateral symptoms appeared when the patient was 35 years old consisting of unbearable pain in the middle section of the antero-medial side of the left leg. Diagnosis was based on X-rays and a pre-operative bone scintiscan, showing localised hyperfixation opposite the pain site. Preoperative locating using a radioactive marker enabled circumscribed but complete excision of the hyperfixation site. This diagnosis was confirmed by the pathologist examination. The patient, who experienced immediate relief after surgery, has remained pain-free for one year to date. The relationship between this case and Camurati-Engelmann disease (diaphyseal dysplasia) is discussed.

[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.

-Bone tomoscintigraphy in osteoarticular pathology-. / La tomoscintigraphie osseuse en pathologie ostéo-articulaire.

Bone single photon emission computed tomography is an effective method for demonstrating partial or total physeal arrest by the proportionality of osteoblastic activity in the physeal regions of interest. The technique complements computed tomography which is not precise in identifying progressive thinning of the physeal bar, and magnetic resonance imaging which does not demonstrate the progressive disappearance of the cartilaginous signal. The radionuclide examination may be a unique imaging method to differentiate between generaled delays in growth and complete fusion at the growth plate.

Didactic review of 175 radionuclide-guided excisions of osteoid osteomas.

The complete removal of a lesion which resembles, or is covered by adjacent tissue may be difficult. Therefore, the capacity of certain lesions to specifically concentrate a radiopharmaceutical has been used to orient progress during surgery. Usually, the measurements of radioactivity in the operative field are carried out by means of small, handy radiation-detecting probes which can be sterilized. "Intra-operative nuclear medicine" or "radionuclide-guided surgery" has steadily gained in importance. However, this technique is not being taught. Our study, based on radionuclide-guided surgery of 175 orthopaedic patients suspected of having osteoid osteoma, is well suited to teach the particularities of intra-operative radiation detection, as well as the collaboration between the nuclear physician and the surgeon in the operating theatre.