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STUDY QUESTION What are the consequences of radioactive iodine (RAI) therapy for testicular function? SUMMARY ANSWER A single activity of 3.7 GBq RAI for differentiated thyroid carcinoma (DTC) treatment in young men transiently altered Sertoli cell function and induced sperm chromosomal abnormalities. WHAT IS KNOWN ALREADY Few studies, mainly retrospective, have reported the potential impacts of RAI on endocrine and exocrine testicular function. STUDY DESIGN, SIZE, DURATION A longitudinal prospective multi-center study on testicular function performed in DTC patients before a single 131I ablative activity of 3.7 GBq (V0) and at 3 months (V3) and 13 months (V13) after treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS Forty male patients, aged 18-55 years, with DTC participated. Hormonal analysis included FSH, LH, testosterone and inhibin B serum levels at V0, V3 and V13. Furthermore, sperm parameters, DNA fragmentation and sperm chromosomal abnormalities were evaluated at each time points. The differences in all parameters, between V0-V3, V0-V13 and V3-V13, were analyzed, using a Wilcoxon test. MAIN RESULTS AND THE ROLE OF CHANCE Prior to RAI administration, all patients had normal gonadal function. At V3, a statistically significant increase in FSH levels and a decrease in inhibin B levels were observed and sperm concentration, as well as the percentage of morphologically normal spermatozoa, were significantly decreased (P < 0.0001). These modifications were transient as both sperm concentration and normal morphology rate returned to baseline values at V13. However, at this later time point, FSH and inhibin B levels were still impacted by RAI administration but remained in the normal range. Although no DNA fragmentation was observed at V3 nor V13, our study revealed a statistically significant increase in the number of sperm chromosomal abnormalities both at V3 (P < 0.001) and V13 (P = 0.01). LIMITATIONS, REASONS FOR CAUTION Among the 40 patients included in the study, only 24 had all the parameters available at all visits. WIDER IMPLICATIONS OF THE FINDINGS Prospective studies with longer term follow up would be helpful to determine whether the chromosome abnormalities persist. These studies would be required before sperm banking should be suggested for all patients. However, sperm preservation for DTC patients who require cumulative radioiodine activities higher than 3.7 GBq should be proposed. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Programme Hospitalier de Recherche Clinique, AP-HP (No. P040419). The authors report no conflict of interest in this work. TRIAL REGISTRATION NUMBER NCT01150318.

Annales Francaises d'Oto-Rhino-Laryngologie et de pathologie cervico-faciale - Vol. 129 - N° 4 - p. 250-260

Background: Prospective evaluation of the role of 18FDG-PET/CT in patients with large primary operable breast cancer. Material and Methods: During 56 months, consecutive patients with large (>2cm) breast cancer and clinical stage IIA/IIB/IIIA (based on clinical examination, mammography, breast MRI and ultrasonography) underwent 18FDG-PET/CT. The nuclear physician was blind to the results of any other procedure (bone scan, chest X-ray, liver ultrasound, or thoraco-abdominal CT scan). Results: Out of the 131 examined patients, 36 had clinical stage IIA (34 T2 N0, 2 T1 N1), 48 stage IIB (20 T3 N0, 28 T2 N1), and 47 stage IIIA (29 T3 N1, 9 T2 N2, 9 T3 N2). 18FDG-PET/CT modified staging for 5.6% of stage IIA patients, for 14.6% of stage IIB patients, and for 27.6% of stage IIIA patients. However, within stage IIIA, the yield was specifically high among the 18 patients with N2 disease (56% stage modification). When considering stage IIB and primary operable IIIA (T3 N1) together, the yield of 18FDG-PET/CT was 13% (10/77); extra-axillary regional lymph nodes were detected in 5 and distant metastases in 7 patients. In this series, 18FDG-PET/CT outperformed bone scan with only 1 misclassification versus 8 for bone scan (p=0.036). Discussion: 18FDG-PET/CT provided useful information in 13% of patients with T3 N0 / T2 N1 / T3 N1 disease. The yield was more modest in patients with T2 N0 disease. The very high yield in the case of lymph nodes classified N2 demonstrates that stage IIIA comprises two quite distinct groups of patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-09-11.

Resume Apres une courte introduction rappelant l’interet du ciblage de l’hypoxie tumorale, les progres sur la comprehension des mecanismes mis en jeu a l’echelon cellulaire sont decrits, en insistant sur le role cle du facteur induit par l’hypoxie-HIF-1α, ainsi que ses liens avec l’angiogenese, les differentes methodes d’exploration de l’hypoxie sont rapidement passees en revue. Les traceurs confirmes en tomographie par emission de positons (18F-fluoromisonidazole et 18F-fluoroerythronitroimidazole) sont brievement rappeles. Les recentes publications sur deux nouveaux traceurs prometteurs, le Cu(II)-diacetyl-bis(N(4)-methylthiosemicarbazone) et le AZA marque au 18F sont presentees et l’interet de ces traceurs est discute.

Resume Nous rapportons le cas d’un homme suivi pour un seminome testiculaire et chez qui a ete decouvert une masse paravertebrale suspecte du fait de sa fixation franche du FDG a la TEP/TDM. Il s’agissait en fait d’un schwannome benin.

The abundance of published data on the neonatal effects of maternal Graves' disease (GD) contrasts with the paucity of information on fetal effects. In our yet unpublished study, we prospectively studied 72 pregnant women with a history of Graves' disease. Fetal ultrasonography was done at 22 and 32 weeks of gestational age. Fetal goiter was found at 32 weeks in 11 of the fetuses of the 41 mothers with positive TSH-receptor antibodies and/or antithyroid treatment and in none of the fetuses of the 31 other mothers. In the 11 fetuses with goiter, ultrasound findings (thyroid Doppler and bone maturation), fetal heart rate, and maternal antibody and antithyroid drug status effectively discriminated between hypothyroidism ( n =7) and hyperthyroidism ( n =4). One fetus with hyperthyroidism died in utero at 35 weeks from heart failure. Treatment was successful in the ten other fetuses. One fetus without goiter had moderate hypothyroidism at birth. This study showed that it is of the utmost importance to have the fetal thyroid scrutinized by an expert ultrasonographist and to have team work with obstetricians and paediatric endocrinologists in pregnant mothers with GD. This allowed us to accurately determine fetal thyroid status and to adapt the treatment in mothers successfully. Fetal hyperthyroidism does exist and needs an appropriate aggressive treatment.

Le traitement du carcinome differencie de la thyroide est chirurgical. Il est souvent complete par l’administration d’iode radioactif. A ce jour, les consequences de ce traitement sur la fonction testiculaire sont mal connues. Patients et methodes Notre etude prospective multicentrique PHRC N°P040419 a evalue (1) les dosages de FSH, LH, testosterone, inhibine B, (2) le spermogramme, (3) la fragmentation de l’ADN spermatique, (4) le taux d’aneuploidie analyse par FISH. Ces analyses ont ete realisees de base (V0), 3 mois (V3) et 13 mois (V13) apres une dose unique de 3,7 GBq d’I131. Resultats Quarante patients ont ete inclus. Leurs taux de LH et testosterone sont restes identiques. Au contraire, les taux de FSH ont augmente entre V0 et V3 (4 UI/L ± 3 (N : 3–7 UI/L) versus 9 UI/L ± 4,8 (p Discussion et conclusion Cette etude prospective montre une alteration de la FSH, de l’inhibine B et de la concentration spermatique, ainsi qu’un taux eleve d’anomalies chromosomiques. Ces resultats suggerent la necessite d’informer les hommes devant recevoir une dose de 3,7GBq 131I et d’evoquer avec eux une preservation de la fertilite.

Fetal thyroid goitres may reveal hormonal imbalance. This can jeopardize neurological development and fetal outcome even when early postnatal treatment is provided. We report a series of 11 goitres diagnosed antenatally in women with past or present thyroid disorders or discovered fortuitously on ultrasound scan. Fetuses presented with hyperthyroidism in three cases and hypothyroidism in eight. Hypothyroidism was iatrogenic in five cases, due to maternal anti-thyroid drugs. Hyperthyroidism was induced by transplacental transfer of thyroid stimulating antibodies (TSHrab). Accurate diagnosis of fetal thyroid status was obtained by fetal blood sampling but this invasive method was deemed necessary only in four cases as maternal clinical and biological data and ultrasound signs provided sufficient information to infer the type of thyroid disorder in the remaining patients. Fetal therapy relied on reduction of maternal antithyroid medication and, in selected cases, intra-amniotic injection of levothyroxin in hypothyroidism, and on administration of antithyroid drugs in hyperthyroidism. All newborns were healthy and none displayed consequences of severe thyroid imbalance. No caesarean section was performed for dystocia. Fetal thyroid goitres can be managed successfully with selected use of invasive diagnostic and therapeutic techniques.

PURPOSE Tissue polypeptide antigen (TPA) is a differentiation and proliferation tissue marker of epithelia. Increased serum levels were found in some patients with invasive bladder cancer. We present the results of a prospective study that evaluated the role of serum TPA (S-TPA) in bladder carcinoma. PATIENTS AND METHODS The series included 167 patients treated for invasive bladder cancer between 1989 and 1996. S-TPA concentrations were measured by radioimmunoassay before treatment, at the end of treatment, and during follow-up evaluation. The upper normal limit of the test was set at 80 UI/L. RESULTS With a specificity of 100%, the diagnostic sensitivity was 46%. Pretherapeutic S-TPA levels were significantly correlated with tumor stage (T2 v T3 and T4; P = .02), with nodal stage (N0 v N1 and N2; P = .00001), and with metastatic stage (M0 v M1; P = 10[-6]), but not with histologic grading (grade 1 and 2 v 3). In the subset of patients with normal pretherapeutic S-TPA levels, 95% had no residual disease at the end of treatment, compared with 53% of patients with initial elevated S-TPA (P = 10[-8]). Among patients who achieved a complete response, 27% experienced a relapse, with an increase of S-TPA in 72% of cases. The mean follow-up time was 20 +/- 17 months. For patients with normal pretherapeutic S-TPA levels, 3-year overall survival and disease-free survival rates were 76% and 67% respectively. These were 46% (P = .001) and 25% (P = 10[-7]), respectively, for patients with high pretherapeutic S-TPA. Multivariate analysis showed that S-TPA was an independent prognostic factor for survival (P = .03). CONCLUSION In invasive bladder cancer, S-TPA level is correlated with initial tumor stage. It is a valuable parameter for follow-up evaluation and appears to be a prognostic factor in multivariate analysis.

European Annals of Otorhinolaryngology, Head and Neck Diseases - Vol. 129 - N° 4 - p. 197-206

Background. Tissue polypeptide antigen (TPA) is a differentiation and a proliferation tissue marker of non-squamous epithelia. Increased urinary and serum TPA (S-TPA) levels were found in some patients with invasive bladder cancer. The authors report the results of a prospective study evaluating the role of serum TPA (S-TPA) in bladder carcinoma. Methods. S-TPA concentrations were measured by radioimmunoassay in 53 patients with invasive bladder tumor before treatment, at the end of treatment, and during follow-up. The upper normal limit of the test was set at 80 UI/ml. Results. With a specificity of 100%, the diagnostic sensitivity of the test was 54.7%. S-TPA was increased in 88% of patients with N1 + N2 disease compared with 38.8% of the patients with N0 disease (P = 0.01) and in 100% of patients with metastatic disease and 48% of patients with nonmetastatic disease (P = 0.01). S-TPA was increased in 23% of patients with total macroscopic debulking and in 68% of patients with persistent macroscopic disease (P = 0.004). For patients staged N0 M0, no statistical correlation between S-TPA level and debulking by transurethral resection (TUR) was found (P = 0.15). In the subset of patients with normal pretherapeutic S-TPA levels, 75% achieved a complete response, compared with 44.8% of the patients with initial elevated S-TPA levels (P = 0.04). However, there was no statistically significant relationship between pretherapeutic S-TPA levels and immediate response to treatment according to the stratification for tumor volume after initial debulking by TUR. For a mean follow-up of 15 months ± 7 months, median survival time and 1-year survival rates were studied in the subset of patients with limited disease (N0 M0) according to the pretherapeutic S-TPA levels. The median survival time was not reached, and the 1-year survival rate was 80% when the initial S-TPA level was normal; these were 10 months and 44%, respectively, when the S-TPA level was high (P < 0.01). Among the 31 patients who achieved a complete response, 9 experienced a relapse, with an increase of the S-TPA level in 8 patients. Conclusions. The S-TPA level is correlated with initial tumor volume. It appears to be a prognostic factor and a valuable parameter for follow-up.

As compared to conventional axillary dissection, the sentinel node technique is accompanied by reduced morbidity and shorter hospital stay. Based on available data, the use of this technique does not seem to yield higher rates of axillary recurrence. A combination of both radioisotope detection and blue dye increases the identification rate, while also reducing false-negative rate. Surgical results are optimized when preoperative lymphoscintigraphy mapping is obtained in addition to peroperative probe detection. Considering the site of injection, the subareolar injection can be easy to apply even in case of non-palpable tumours, and gives higher count rates. However, the intraparenchymal, peritumoral, injection is necessary to evidence cases of extra-axillary drainage (internal mammary, infra- or supraclavicular) that is present in about 20% of patients. With the advent of hybrid cameras (SPECT-CT), the topography of these extra-axillary nodes can be given with high precision. Use of the sentinel node technique has been accompanied by an increase in the percent of patients with node involvement, due to an increased detection of micrometastases inferior or equal to 2 mm. Following an overview of basic principles, and of the main results with the sentinel node technique we focus the discussion on several points that are still open to debate, such as: 1) which group of patients can benefit from the sentinel node technique? 2) What is the optimal methodology? 3) What is the prognostic significance of micrometastases and of isolated tumour cells? 4) What attention should be given to extra-axillary drainage?

The present paper addresses the advantages and limits of PET-CT in the work-up of cervical cancer. PET-CT is not to be overlooked in initial staging. It is useful to assess involvement of pelvic and lumbar lymph nodes. It can improve staging accuracy and help guide initial treatment such as optimisation of radiation therapy fields. Given its limited spatial resolution however, PET does not seem so adequate to document tumours less than 5 mm in diameter. It is not warranted for staging carcinoma in situ (FIGO stage 0) or preclinical carcinoma (FIGO stage 1A1 and 1A2). Furthermore MRI performances are best as far as local extension and tumour volume measurement are concerned. PET brings prognostic information. High initial uptake in tumour tissue or persistent increased uptake at completion of treatment indicates rather poor prognosis. PET is useful to evaluate therapy, but its exact role in this issue remains to be further refined. Finally, PET-CT can document early recurrence of disease.

Differentiated thyroid cancer, when adequately treated, has an overall good prognosis. However, 10-15% of patients develop distant metastases. The presence of metastases is an important prognostic factor that negatively affects survival. For (131)I-avid distant metastases, (131)I therapy is a very effective treatment modality that induces complete remission in about a third of patients. These figures may be even higher in case of early diagnosis, when tumor burden is still limited. Additional measures may include surgery and/or external beam radiation therapy. Cytotoxic chemotherapy is largely ineffective in patients with progressive, poorly differentiated cancer. These patients should be candidates for trials with new molecularly targeted therapeutic agents. In this paper, a review of diagnostic modalities, prognostic factors and therapeutic options for patients with distant metastases is proposed. In particular, the prognostic value of the early discovery of metastatic disease will be underlined.

Stimulation by recombinant human thyroid-stimulating hormone (rhTSH) has gained wide acceptance as an alternative to thyroid hormone withdrawal in the management of patients with differentiated thyroid cancer. RhTSH has the advantage to avoid both the clinical consequences of hypothyroidism, with a positive impact on quality of life and work productivity, and the risk of cancer growth due to the long-lasting endogenous thyrotropin stimulation. RhTSH is a heterodimeric glycoprotein produced by recombinant DNA technology that has the ability to stimulate thyroglobulin production and radioiodine uptake by thyroid cells. RhTSH is now widely used in the follow-up of thyroid cancer patients in order to improve sensitivity of thyroglobulin (Tg) measurement as well as in preparation of (131)I diagnostic whole-body scan. Although initially approved only for diagnostic purposes, rhTSH has been now approved both in Europe and in the United States for remnant ablation in low-risk patients. As far as residual or metastatic cancer treatment, rhTSH has been initially used on a compassionate need basis for elderly and frailer patients and for patients in whom the withdrawal of thyroid hormone was medically contraindicated. Nowadays, there is a trend for widening the use of rhTSH in therapy, in order to avoid hypothyroidism and the concern about the effect of prolonged endogenous thyroid-stimulating hormone stimulation on cancerous cells. Unfortunately, the studies which address the efficacy of rhTSH in cancer treatment are still scarce and the opportunity of its clinical application remains controversial. In addition, rhTSH has been shown to improve the accuracy of [(18)F]-2-fluoro-deoxy-D-glucose positron emission tomography to detect non-functioning thyroid cancer. Although all studies agree on that rhTSH is much better tolerated from the clinical point of view than thyroid hormone withdrawal, there is some controversy about its comparative ability to raise Tg levels and concentrate radioiodine in cancerous thyroid cells. The aim of this paper is to review the performances of rhTSH as compared to hypothyroidism, considering Tg stimulation and diagnostic whole-body scan sensitivity during follow-up, and its effectiveness for normal remnant ablation and for therapy of metastatic disease.

Background: Serum thyroglobulin (Tg) is the marker of differentiated thyroid cancer after initial treatment and TSH stimulation increases its sensitivity for the diagnosis of recurrent disease. Aim: The goal of the study is to compare the diagnostic values of seven methods for serum Tg measurement for detecting recurrent disease both during L-T4 treatment and after TSH stimulation. Methods: Thyroid cancer patients who had no evidence of persistent disease after initial treatment (total thyroidectomy and radioiodine ablation) were studied at 3 months on L-T4 treatment (Tg1) and then at 9–12 months after withdrawal or recombinant human TSH stimulation (Tg2). Sera with anti-Tg antibodies or with an abnormal recovery test result were excluded from Tg analysis with the corresponding assay. The results of serum Tg determination were compared to the clinical status of the patient at the end of follow-up. Results: Thirty recurrences were detected among 944 patients. A control 131I total body scan had a low sensitivity, a low specificity, and a low clinical impact. Assuming a common cutoff for all Tg assays at 0.9 ng/ml, sensitivity ranged from 19–40% and 68–76% and specificity ranged from 92–97% and 81–91% for Tg 1 and Tg2, respectively. Using assays with a functional sensitivity at 0.2–0.3 ng/ml, sensitivity was 54–63% and specificity was 89% for Tg1. Using the two methods with a lowest functional sensitivity at 0.02 and 0.11 ng/ml resulted in a higher sensitivity for Tg1 (81% and 78%), but at the expense of a loss of specificity (42% and 63%); finally, for these two methods, using an optimized functional sensitivity according to receiver operating characteristic curves at 0.22 and 0.27 ng/ml resulted in a sensitivity at 65% and specificity at 85–87% for Tg1. Conclusion: Using an assay with a lower functional sensitivity may give an earlier indication of the presence of Tg in the serum on L-T4 treatment and may be used to study the trend in serum Tg without performing any TSH stimulation. Serum Tg determination obtained after TSH stimulation still permits a more reliable assessment of cure and patient’s reassurance.

Development of the sentinel lymph node (SLN) biopsy the last 10 years has changed surgical approach of solid tumor treatment and particularly of melanoma. The aim of our study was to analyze in our hospital, the feasibility of the SLN biopsy technique in order to define a better prognostic classification of melanomas.Between July 1999 and October 2003, 97 patients were included in this study in our center. Criteria for inclusion were cutaneo-mucosal melanoma of Breslowor=1,5 mm, and/or Clarckor=IV, and/or ulceration, and/or signs of regression, before any surgical margins.Lymphoscintigraphy (LS) identified at least 1 SLN in 94 cases/97 (97%), thus permitting intraoperative SLN mapping and sentinel node biopsy of at least 1 lymph node in 88 cases/94 (94%). Failure of the SLN procedure was noted in 9 cases: in 3 cases, no lymph node was individualized by LS, in 1 patient, intraoperative SLN mapping failed to find the previously identified SLN and in 5 cases, a SLN was identified by LS and intraoperative mapping but could not be removed because of its deep location and difficulty of dissection. In 17 patients, removal of one or two "non sentinel lymph node(s)" was (were) made by the surgeon because of its (their) suspected aspect (black or large). Among the 88 patients who had dissection of at least 1 SLN, a micrometastasis was detected by standard histological evaluation and/or immunohistochemical stains in 14 cases (16%) and into a "non SLN" in 2 cases (2,3%). The median follow up of patients was 16 months (1- 48 months). Among the 14 patients with positive SLN, 6 (43%) relapsed. The other eight were in complete remission of their melanoma with a mean follow up of 11,44 months . Among the 74 patients with negative SLN, 7 (9,5%) developed a recurrence. Among the 9 patients in whom any sentinel lymph node have been removed, 3 had a relapse (one in transit than on lymph nodes, and two on lymph nodes).Our results are in accordance with the literature, and confirm the feasibility of SLN mapping and of SLN histological analysis in our center. We described in this study technical problems we encountered. Our study also show the prognostic value of this technique. However, advantage in global survey of sentinel node dissection and regional lymph node dissection in cases of micrometastases has still to be demonstrated.

The measurement of iodine is a widely accepted method to explore iodine disorders. The most precise estimation is the determination of the urinary iodine in 24-hour collections. Urine collection is notoriously difficult to obtain, specially in children. In these conditions, serum measurement could be a method to overcome these limitations. We describe a colorimetric method adapted on a microtiter plate, with optimized serum mineralization conditions. The method is linear to 2400 nmol/L with a detection limit of 75 nmol/L. Precision is below 10%. The method was validated against one automatic technique. We conclude that this relatively simple method could be an additional tool to explore dysthyroidism.

In vitro thyroid function tests are among the most frequently prescribed laboratory procedures. Serum triiodothyronine (T3) tests are seldom necessary as a first-level measurement. Our objectives were to measure the proportion of T3 measurements relative to all in vitro thyroid function tests in a large hospital network and to investigate the contributions of various interventions to change prescribers'behavior. We performed two cross-sectional surveys in 1995 and 1998 in the 50 Paris University hospitals. Questionnaires were mailed to the heads of the 30 laboratories performing thyroid function tests. One-month orders of free and total thyroxine, free and total T3 and thyrotropin were recorded; changes in T3 measurement orders between the two periods were estimated and association with interventions were expressed as odds ratios and 95% confidence intervals. Twenty-five heads of laboratory responded to both surveys. In 1995, T3 measurements constituted 21% of in vitro thyroid function test ordering, which seems to us exceedingly high. The decrease in T3 measurement ordering observed in 1998 (15% of thyroid function test ordering) was independently associated with multiple behavioral changes: educational interventions, structured test form use and year of prescription.

High-risk differentiated thyroid carcinoma is the most frequent thyroid tumor of "poor prognosis": this mainly includes patients with extra-thyroidal invasion, or distant metastases, younger patients (16 years old), and older patients (45 years old). Among them, metastatic patients with multiple organ involvement at the time of initial diagnosis have the higher risk of cancer death. Additionally, certain histological subtypes are classically more aggressive, and bilateral cervical lymph-nodes metastases or mediastinal involvement may also impart a poorer overall prognosis. More aggressive therapy to produce undetectable thyrotropin levels is usually recommended, although the benefit of such therapy and how long to maintain thyrotropin suppression has not been definitively established. As about two-thirds of the recurrences occur within the first decade after initial treatment, this first decade seems particularly critical, even if follow-up is necessary throughout the patient's life as recurrences may also occur over several decades. Coupled thyroglobulin (Tg) and Tg antibody (TgAb) assay is the first-line tool in their follow-up. Tg measurement obtained either after LThyroxine withdrawal or rhTSH stimulation may permit the selection of patients for scanning with a high dose of 131-I. When either basal Tg level is high or TgAb increases, it appears preferable to schedule patients directly for 131-I therapy followed by a post-therapy WBS. Therefore, the discovery of foci of 131-I uptake is possible in 60 to 80% of such patients. 131-I therapy is proposed as long as metastases trap 131-I without any limit to the cumulative dose of 131-I, although the risk of leukemia rises slightly above a 500 mCi (18,500 MBq) cumulative dose. But when 131-I post therapeutic WBS is negative, any further administration of 131-I is not justified. Alternative imaging procedure is thus required to detect metastases that have lost their capacity to concentrate 131-I. Conventional imaging with ultrasonography of the neck, a CT scan or an MRI of the neck and the chest and bone imaging, and even non-conventional imaging with other isotope procedures, such as 18-FDG whole-body scanning, are nowadays indicated. The goal is to localize those metastases in order to propose the more adequate therapeutic options.

18F-FDG PET has been shown to effectively detect differentiated thyroid carcinoma (DTC) metastases with impaired iodine-trapping ability. This article evaluates the potential contribution of FDG PET in the follow-up of patients with differentiated thyroid carcinoma, elevated thyroglobulin (Tg) levels, and negative whole-body scan results obtained after high doses of (131)I.We prospectively assessed the ability of FDG to detect metastases in 37 DTC patients who had undergone total thyroidectomy and radioactive ablation and presented with persistent disease, as assessed from elevated Tg levels and negative results of whole-body scans performed after therapeutic doses of (131)I. Additional conventional imaging procedures were performed to detect residual disease, and the patients were divided into 2 groups: group 1, with positive conventional imaging findings (n = 10), and group 2, with negative conventional imaging findings (n = 27).FDG PET showed positive findings in 28 patients and accurately localized tumor sites in 89% of them. In group 1, FDG PET confirmed 17 of 18 previously known tumor sites and detected 11 additional sites. In group 2, FDG PET findings were positive in 19 of 27 patients with no previously detected metastases. PET was effective for both low- and high-stage tumors. The FDG data led to a change in the clinical management of 29 of 37 patients with further surgical resection in 23 patients, 14 of whom achieved disease-free status, and external radiation therapy in 4 patients.FDG PET is able to detect metastases undetected by (131)I posttherapy whole-body scanning in patients with elevated Tg levels. It should be proposed as a first-line investigation in patients with persistent disease but negative findings on (131)I whole-body scans after treatment.

An increasing number of multiparametric immuno-analysers for PSA assays are available. As different immuno-assays may vary in their analytical quality and their accuracy for the follow-up of patients, expertise is necessary for each new assay.The PSA assay on the Vitros-ECi analyser has been evaluated and compared with the PSA assay from the Kryptor analyser.Variation coefficients were 0.91 to 1.98% for within-run assays, and 4.2% to 5.4% for interassay (PSA levels = 0.8 microgram/L to 33.6 micrograms/L). Dilution tests showed 93 to 136% recovery until 70 micrograms/L PSA. Functional sensitivity was estimated at 0.03 microgram/L. Equimolarity of the test was confirmed. Correlation of PSA levels measured with Vitros-ECi and Kryptor analysers displayed a correlation coefficient r2 of 0.9716. The half-lives and doubling times of PSA were similar using both methods.Vitros-ECi PSA assay meets the major criteria for the management of prostate cancer patients.

The authors describe a patient with follicular thyroid carcinoma who was receiving continuous ambulatory peritoneal dialysis to manage end-stage renal disease. To deliver radioiodine therapy to ablate thyroid remnants safely and under optimal conditions, the behavior of 37 MBq (1 mCi) I-131 was followed daily for 3 days. Blood activity and total body count decreased with a half-life of 100 hours (4.17 days). The daily iodide removal rate, estimated as a percentage of the total administrated activity, was low: 5.3% to 8.6% in peritoneal dialysate and 1.3% to 2.2% in urine. The thyroid uptake, measured using a probe, was 2.4% to 2.1% from day 1 to day 3 and 1.9% later at day 8. The volume of thyroid remnants was determined by ultrasonography to be 0.6 g. The patient received a reduced ablative I-131 dose of 814 MBq (22 mCi). Radiation emitted from the patient after I-131 therapy, monitored using a radiation monitor probe located at a distance of 1 meter, decreased with an effective half-life of 70 hours (2.9 days). The integration of the curve from t = 0 showed a level always less than 25 microSv/hour as early as 24 hours after treatment. Because the iodine removal rate is continuous but low in a case of peritoneal dialysis, smaller therapeutic doses must be administered to deliver maximal radiation to residual thyroid tissue while minimizing excessive radiation exposure to patients, their families, and medical staff.

Fetal thyroid goitres may reveal hormonal imbalance. This can jeopardize neurological development and fetal outcome even when early postnatal treatment is provided. We report a series of 11 goitres diagnosed antenatally in women with past or present thyroid disorders or discovered fortuitously on ultrasound scan. Fetuses presented with hyperthyroidism in three cases and hypothyroidism in eight. Hypothyroidism was iatrogenic in five cases, due to maternal anti-thyroid drugs. Hyperthyroidism was induced by transplacental transfer of thyroid stimulating antibodies (TSHrab). Accurate diagnosis of fetal thyroid status was obtained by fetal blood sampling but this invasive method was deemed necessary only in four cases as maternal clinical and biological data and ultrasound signs provided sufficient information to infer the type of thyroid disorder in the remaining patients. Fetal therapy relied on reduction of maternal antithyroid medication and, in selected cases, intra-amniotic injection of levothyroxin in hypothyroidism, and on administration of antithyroid drugs in hyperthyroidism. All newborns were healthy and none displayed consequences of severe thyroid imbalance. No caesarean section was performed for dystocia. Fetal thyroid goitres can be managed successfully with selected use of invasive diagnostic and therapeutic techniques.

To determine the distribution of orders for hormonal tests assessing thyroid function in a hospital setting. To collect the opinion of physicians specialized in endocrinology concerning free triodothyronine (FT3) assessment.Using a cross-sectional survey numbers of free thyroxine (FT4), total T4 (TT4), FT3, total T3 (TT3), and TSH tests were collected from the heads of laboratory assessing thyroid function in June 95 at the Assistance Publique-Hôpitaux de Paris (AP-HP). Cost for these tests was estimated. The physicians of the AP-HP specialized in endocrinology were asked through a questionnaire for circumstances justifying FT3 test ordering.Twenty-eight laboratories (93%) responded: 28455 measurements (TSH: 43%, FT4: 33%, TT4: 2%, FT3: 20%, TT3: 2%) were performed and were valued at 3.4 million French Francs. Proportions of T4 (36%) and T3 (20%) tests were lower in hospitals with an inpatient department of endocrinology than in hospitals with an outpatient clinic with specialists in endocrinology (T4: 36%; T3: 27%) or with no endocrinology unit (T4: 33%, T3: 27%); proportion of TSH tests was higher in hospitals with an inpatient endocrinology unit (respectively 44%, 40%, 32%). Forty-two endocrinologists (76%) from 21 departments answered. Follow-up of treatment with amiodarone and euthyroid sick syndrome were considered the only conditions justifying FT3 test ordering.Though the opinion of physicians specialized in endocrinology was not uniform regarding recommendations for TT3 or FT3 tests as a first-line measurement, the cost of these tests has been estimated at 650 thousand Francs for a month at the AP-HP.

We compared the BTA (bladder tumor antigen) stat test with the BTA TRAK assay in patients highly suspicious of bladder cancer.The BTA stat and the BTA TRAK tests are two immunoassays that detect human complement factor H related protein in urine, employing the same antibody pair. The BTA stat is a qualitative test which can be performed in a consultation setting. The BTA TRAK is a quantitative test that is performed in the laboratory. Consecutive patients highly suspicious of bladder cancer were included in this prospective blinded trial to assess the clinical performances of the two methods.A total of 81 patients were tested using BTA stat and BTA TRAK before cystoscopy. A tumor was identified in 49 patients. BTA TRAK (38/49 true-positive cases) was more sensitive than BTA stat (32/49) in detecting bladder cancer (p0.05). When considering the subgroups of bladder cancer by stage and grade, the difference remained significant for low-grade and low-stage tumors. There was no significant difference between BTA TRAK and BTA stat as regards specificity (20/32 and 23/32 true-negative cases, respectively; p = 0.2).BTA TRAK with a cutoff of 14 U/ml had a significantly higher sensitivity than BTA stat in the detection of low-grade and low-stage bladder cancer.

The aim of this study was to evaluate the ability of MRI to detect recurrent differentiated thyroid carcinomas developed in the neck or the upper mediastinum.MRI was performed in 25 patients, and was compared in 5 cases with surgery. In 20 cases it was compared with I-131 scintigraphy (100 mCi in 14 cases and 5 mCi in 6 cases). The sensibility, specificity and overall accuracy of MRI was respectively: 100%, 66.6%, 82.6%.MRI is a good technique to detect recurrent thyroid carcinomas. It is specially interesting to investigate patients with a biological suspicion of recurrence and a negative scintigraphy. Mediastinal localisations that cannot be detected by US can be detected by MRI.

We demonstrate several advantages of SPECT in parathyroid scintigraphy.Forty-four parathyroid 99mTc-MIBI scintigrams were obtained before surgery in 43 patients suffering from hyperparathyroidism. For each patient, we obtained dynamic views and planar and SPECT images of the neck and thorax. For 15 patients, we also acquired a delayed static view of the neck 2 hr after tracer injection. Abnormal thyroid-area glands were detected with factor analysis of dynamic structure (FADS) of the initial dynamic acquisition. In the 15 patients with delayed views of the neck, we compared FADS and the double-phase study results to detect glands in the thyroid uptake area. Glands outside the thyroid area were demonstrated on planar views. The location of enlarged glands was more precisely defined on the tomographic slices. The anatomic and histologic findings and the evolution of hypercalcemia after surgery were taken as reference.Sixty-four abnormal glands were found during surgery, including 39 observed in patients who underwent reoperation for persistent or recurrent hyperparathyroidism. Twenty-two of these glands were in an abnormal location, including 10 in the mediastinum. SPECT allowed the detection of three glands not demonstrated on planar views or FADS. Fifty-eight glands were correctly localized scintigraphically, including 34 in patients who underwent reoperation. Therefore, SPECT raised the sensitivity from 86% to 90.5% and from 79.5% to 87% in the reoperated patients. Tracer uptake in the low mediastinal area was better analyzed on tomographic slices than on planar views. Only seven false-positive results were depicted by planar views or FADS; none were depicted on SPECT.A combination of FADS and SPECT permits detection of small glands, even in a posterior location, inside or outside the thyroid area. This scintigraphic method enables the surgeon to define more precisely details about the location of the enlarged gland and contributes to improved parathyroid surgery.

A rapid (25 min) single tracer scintigraphic method to localize parathyroid gland abnormalities was evaluated in 24 patients with hyperparathyroidism.Scintigraphy was performed with 99mTc-sestamibi prior to surgery. A 25-min dynamic series centered on the neck was acquired immediately after injection of 99mTc-MIBI. Two planar static views were obtained after 1 and 2 hr. To identify abnormal parathyroid tissue in the thyroid uptake area, a factor analysis of dynamic structure (FADS) was applied to the dynamic acquisition. The results were compared to the analysis of the two planar static views.FADS demonstrated abnormal uptake of the tracer in the thyroid area for 26 of the 31 parathyroid glands found to be abnormal at surgery (5/6 adenomas, 21/25 hyperplastic glands). In three cases, FADS demonstrated parathyroid uptake despite the absence of parathyroid tissue at surgery. FADS revealed as specific and more sensitive than the visual analysis of the two static views, since only 13/30 glands were still visible after 1 hr, and 5/26 after 2 hr. Furthermore, a study with two static views was found to be less sensitive for the detection of hyperplastic glands.FADS99mTc-MIBI is performed in less time than existing scintigraphic protocols. It is a promising method to detect abnormal parathyroid glands in the cervical area with a single tracer.

Differentiation of normal myeloid cells is accompanied by the increase of high-affinity GM-CSF receptors necessary for progenitor proliferation/differentiation and mature neutrophil function. All-trans retinoic acid (ATRA) induces terminal differentiation of acute promyelocytic leukemia cells (AML3 subtype). We report in this study that AML3 cells, like other AML subtypes, harbor high-affinity GM-CSF R (n = 138.3 +/- 69.3 sites/cell, Kd = 76.9 +/- 68.8 pM). In all cases, incubation with ATRA induces either an increase in the number of affinity of GM-CSF R (n = 212.7 +/- 116.2 sites/cell, Kd = 43.2 +/- 22.5 pM). The data presented show that modulation of GM-CSF receptors cells is correlated to the degree of ATRA-induced granulocytic differentiation but not to increased cell growth.

The recent production of erythropoietin (EPO) by cloning and expression of the human gene in mammalian cells has enabled, not only the treatment of severe anemias due to a defect in EPO production by the kidney, but also the development of sensitive immunoassays (Erslev et al. 1987) which allow large-scale study of EPO levels in human disorders.

Systematic screening for prostate cancer was carried out in 600 men over 50 years of age by the industrial medicine departments of four big companies in the Paris region. The exploratory methods included prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) assays, rectal palpation and two-dimensional transrectal ultrasonography. Biopsy of the prostate was performed either when the PSA level was above 5 ng/ml or when rectal palpation gave suspicious results, or when ultrasonography showed abnormal images. A total of 93 biopsies were performed, and 18 cases of cancer were detected. Eleven of these 18 patients underwent radical prostatectomy. The PSA assay, with an accepted limit of 5 ng/ml, detected 17 out of 18 cancers but was not very specific. The PAP assay had low sensitivity (only 5 positive results). Combined PAP assay and rectal palpation provided high sensitivity and good specificity. Transrectal ultrasonography was helpful only to determine the site of biopsy and the distribution of the lesions.

Radioimmunoassay of erythropoietin (EPO) has been used for evaluating its clinical usefulness in distinguishing polycythaemia vera (PV) from pure erythrocytosis (PE). A normal log distribution (13.40 mU/ml +/- 2.45) was observed in the 66 reference samples. Similar results were observed in 29 pure thrombocytaemias (13.23 +/- 5.19). In PV patients, whether in clinical remission or in active phase, the EPO titer was lower than normal values (respectively 7.32 +/- 3.63 and 6.59 +/- 2.75), without any correlation with the haematocrit (44 to 51% and 52 to 71%). In the anaemic cases (excessive therapy, spent phase, myelofibrosis), a slight excess of EPO titer was observed, but less than expected when taking the hematocrit into account. In contrast, pure erythrocytosis is a very heterogeneous group, with the highest EPO values in the well-defined secondary cases, and normal or slightly excessive values in most of the cases, but with some low values similar to those observed in PV cases. In term of PV diagnosis, a 90% predictive value is observed when a "cut-off" value of 11 mU/ml is chosen. When the "cut-off" is 16 mU/ml, no PV case was observed beyond this value. We conclude that EPO assay is useful in myeloproliferative diseases from a practical point of view.

The first hint to the nature of the thyroid microsomal antigen was provided by the observation that TPO was antigenical1y related to the microsomal antigen1. Then TPO was purified by monoclonal antibody (mAb) assisted affinity chromatography and shown to react with autoimmune antibodies (aAb) in serum of patients with autoimmune thyroid diseases 2. Titers of anti-TPO and anti-microsomal aAb in serum were found significantly correlated3 which suggested that TPO effectively was the microsomal antigen. Other groups of investigators confirmed that anti-thyroid aAb reacted with TPO, but proposed that TPO was only a part of a putative microsomal antigen complex 5 - 8. To answer the question whether TPO effectively was the microsomal antigen or only a part of i t we undertook different experiments based on the use of highly purified human TPO and mAb to it 9-11