[(18)F]FDG in childhood lymphoma: clinical utility and impact on management.

Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) is a very useful technique for the imaging of lymphomas in the adult population. It provides unique information about the behaviour of malignant cells and contributes to more accurate staging of the illness and better assessment of response to therapy. The purpose of this study was to evaluate the usefulness of FDG PET in childhood lymphoma compared with conventional imaging methods (CIMs) and clinical data. Between July 1998 and August 2001, 42 FDG PET examinations were performed using a dedicated PET system (27 examinations) or a hybrid coincidence PET system (15 examinations) for initial tumour staging ( n=7), restaging ( n=5) or assessment of response to therapy or residual masses ( n=30) in 27 children with Hodgkin's disease (HD) ( n=20) or non-Hodgkin's lymphoma (NHL) ( n=7). FDG PET results were compared with CIM findings and clinical data. Since 2000, a standardised questionnaire for evaluation of the clinical impact of FDG PET on both staging and therapy has been sent to the 16 referring physicians and 13 have replied. In all children, FDG PET was performed without any side-effects. FDG PET was found to be very sensitive (Se=12/12) for staging and restaging of the illness, showing more lesions than CIMs, with a 50% patient upstaging rate (6/12). It was very accurate for monitoring response to therapy and for characterisation of residual masses. False-positive results were observed in two NHL patients with thymic uptake and one false-negative result was obtained in a patient whose NHL relapsed 1 month after a negative FDG PET. The questionnaire emphasised the impact of FDG PET on clinical management, which was modified on the basis of the FDG PET results in 23% of patients. As previously demonstrated in the adult population, FDG PET appeared to be a very sensitive imaging technique for staging and restaging of lymphoma in children and was very useful for monitoring the response to therapy.

[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)

Metaiodobenzylguanidine assessment of metastatic neuroblastoma: observer dependency and chemosensitivity evaluation. The SFOP Group.

BACKGROUND: In children over 1 year of age with metastatic neuroblastoma, clearance of metaiodobenzylguanidine (MIBG) skeletal uptake after four courses of induction chemotherapy is one of the most powerful prognostic factors. How subjective is quantification of MIBG uptake, and can earlier MIBG scintigraphy separate good and bad responders? PROCEDURE: The data from 47 patients who received uniform induction therapy were reviewed. A novel scoring system of MIBG update intensity was proposed. Initial, intermediate (after two courses), and final (after four courses) intensities were scored (0 to 21 points) independently by six different observers. The initial global score and the relative score (calculated by dividing the global score after two courses by the initial score) were compared to the final score. Good responders were those who scored 0 at final MIBG. RESULTS: Between two observers, the correlation coefficient for the global score was superior to 0.80, in nine of ten comparisons established between observers 1-5. The initial score did not predict the final score insofar as only nine of fourteen patients with low initial scores were good responders. The relative score also failed to predict outcome; only six of ten patients with favorable relative score (i.e., <20%), were good responders. CONCLUSIONS: This scoring system is reliable and may be used in multicentric trials. However, both initial and relative scores failed to predict final outcome. Thus, intermediate MIBG may be omitted during induction therapy assessment.

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.

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.

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.

-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.

Osteoid osteoma: CT-guided percutaneous excision confirmed with immediate follow-up scintigraphy in 16 outpatients.

PURPOSE: To evaluate treatment of osteoid osteoma with computed tomography (CT)-guided percutaneous excision and immediate follow-up scintigraphy. MATERIALS AND METHODS: Sixteen consecutive adolescent and adult patients underwent CT-guided percutaneous excision of a nidus with 14-gauge biopsy cutting needles, with local anesthesia. After the presence of nidus was confirmed at immediate follow-up scintigraphy, curettage of the bored cavity was performed to remove any residual fragments of the nidus. Scintigraphic and histologic findings were correlated. RESULTS: The nidus was removed successfully in 14 of the 16 patients, with no complications (mean follow-up, 15 months; range, 3-25 months). In five of the 14 patients, immediate follow-up scintigraphy showed incomplete resection of the nidus and immediate second resection was successful. Surgical resection was necessary in two of the 16 patients. CONCLUSION: CT-guided percutaneous excision with immediate follow-up scintigraphy was safe and effective for localization and removal of osteoid osteoma in outpatients.

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.

[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.

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.

Gadolinium-DOTA enhanced MRI of painful osseous crises in children with sickle cell anemia.

In order to evaluate the role of gadolinium-DOTA enhanced MRI in the management of painful osseous crises in children with sickle cell anemia (SCA), nine children with SCA underwent MRI, bone scans and ultrasonographic studies during 11 osseous crises. Imaging findings were compared with the final diagnosis: three acute osteomyelitis (AO) and 16 acute infarcts (AI). MRI could not differentiate AO from AI. The appearance of severe AI was very misleading and was similar to the usual appearance of AO, including soft tissue changes, periosteal reaction and patterns of enhancement. Gadolinium-DOTA enhanced MRI was useful for determining the anatomic site and extent of AO or AI and for distinguishing between necrotic material, fluid collection and vascularized inflammatory tissue. It can also help to guide the aspiration of intraosseous, subperiosteal and soft tissue fluid collections.

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 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.

[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.

Isolation procedures for blood lymphocytes produce artifacts. Detection by changes of electrophoretic mobilities of lymphocytes.

The changes induced in the distribution of the electrophoretic mobility (EPM) of human peripheral blood lymphocytes (HPBL), by various methods used to prepare the lymphocyte suspensions and eliminate platelets from them, were investigated on blood samples collected from healthy individuals and thrombopenic patients. Data showed that the distribution of the lymphocyte EPMs, i.e., the "lymphocyte electrophoregram," was dependent on the method chosen to enrich the suspension in the cell type of interest. The relative percentages of the low and high mobility cells, the two main subpopulations defined by lymphocyte electrophoresis, were different. The most striking artifactual differences in the lymphocyte electrophoregram were induced by the method of elimination of platelets; the distribution was unimodal and asymmetric when thrombin was used and bimodal when the blood sample, or the lymphocyte suspension, was placed on ice for 30 min (as is the practice in some laboratories). The "split" of the lymphocyte electrophoregram was found to be reversible within 90 min. Similar changes were observed on lymphocyte suspensions and blood samples of thrombopenic patients when the step for the elimination of platelets was not involved.

[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.