A Phase II Redifferentiation Trial with Dabrafenib-Trametinib and 131I in Metastatic Radioactive Iodine Refractory BRAF p.V600E-Mutated Differentiated Thyroid Cancer.

PURPOSE: To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation. PATIENTS AND METHODS: A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq-150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months. RESULTS: Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3-4 AEs in 7 patients. CONCLUSIONS: Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.

SFE-AFCE-SFMN 2022 Consensus on the management of thyroid nodules : What is the role of functional imaging and isotopic treatment?

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with the role of thyroid scintigraphy in the diagnosis of autonomous thyroid nodules, nuclear medicine in nodules with indeterminate cytology and iodine treatment for autonomous thyroid nodules.

Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer.

BACKGROUND: In patients with low-risk differentiated thyroid cancer undergoing thyroidectomy, the postoperative administration of radioiodine (iodine-131) is controversial in the absence of demonstrated benefits. METHODS: In this prospective, randomized, phase 3 trial, we assigned patients with low-risk differentiated thyroid cancer who were undergoing thyroidectomy to receive ablation with postoperative administration of radioiodine (1.1 GBq) after injections of recombinant human thyrotropin (radioiodine group) or to receive no postoperative radioiodine (no-radioiodine group). The primary objective was to assess whether no radioiodine therapy was noninferior to radioiodine therapy with respect to the absence of a composite end point that included functional, structural, and biologic abnormalities at 3 years. Noninferiority was defined as a between-group difference of less than 5 percentage points in the percentage of patients who did not have events that included the presence of abnormal foci of radioiodine uptake on whole-body scanning that required subsequent treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or elevated levels of thyroglobulin or thyroglobulin antibodies. Secondary end points included prognostic factors for events and molecular characterization. RESULTS: Among 730 patients who could be evaluated 3 years after randomization, the percentage of patients without an event was 95.6% (95% confidence interval [CI], 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI, 93.3 to 97.7) in the radioiodine group, a difference of -0.3 percentage points (two-sided 90% CI, -2.7 to 2.2), a result that met the noninferiority criteria. Events consisted of structural or functional abnormalities in 8 patients and biologic abnormalities in 23 patients with 25 events. Events were more frequent in patients with a postoperative serum thyroglobulin level of more than 1 ng per milliliter during thyroid hormone treatment. Molecular alterations were similar in patients with or without an event. No treatment-related adverse events were reported. CONCLUSIONS: In patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years. (Funded by the French National Cancer Institute; ESTIMABL2 ClinicalTrials.gov number, NCT01837745.).

Intermittent versus continuous administration of pazopanib in progressive radioiodine refractory thyroid carcinoma: Final results of the randomised, multicenter, open-label phase II trial PAZOTHYR.

INTRODUCTION: Multikinase inhibitor (MKI) treatments have shown efficacy in progressive radioiodine refractory thyroid cancers (RAIR-TC), but most patients experienced substantial adverse effects. This randomised multicentric study investigated intermittent versus continuous pazopanib administration. PATIENTS AND METHODS: The PAZOTHYR study included RAIR-TC patients with progressive disease in the last 12 months, who may have received one prior MKI. RAIR-TC patients received pazopanib for 6 months, and patients with stable disease or tumour response were randomly assigned (1:1) to receive continuous (CP) or intermittent (IP) pazopanib until progression. The primary end-point was time to treatment failure (TTF) defined as the time from randomisation to permanent discontinuation of pazopanib, due to any cause. One hundred randomised patients were needed to demonstrate an increase from 50% (CP) to 70% (IP) (hazard ratio (HR) 0.515, 80% power) in the rate of patients still under treatment 6 months (6m-SuT) post-randomisation. Secondary end-points included the overall response rate (ORR), progression-free survival (PFS) under pazopanib and safety. RESULTS: RAIR-TC patients (168) enrolled from June 18, 2013 to January 16, 2018, received 6-month pazopanib treatment and showed 35.6% (95% CI 28.2-43.6) best response rate and 89.4% (83.5-93.7) disease control rate. One hundred patients were randomised (IP:50; CP:50). With a median follow-up of 31.3 months, median TTF was not statistically different between arms (IP:14.7, 95% confidence interval (CI) 9.3-17.4; CP:11.9, 95% CI 7.5-15.6) months (HR 0.79, 0.49-1.27). 6m-SuT rates were similar (IP:80% 66.0-88.7%; CP:78% 63.8-87.2%). Median PFS under pazopanib were not statistically different (IP:5.7 4.8-7.8; CP: 9.2 7.3-11.1) months (HR 1.36, 0.88-2.12). Pazopanib-related adverse events grade 3-4 occurred in 36 (IP: 19, 38%; CP: 17, 34%) randomised patients. Seven pazopanib-related deaths occurred. CONCLUSIONS: Intermittent administration of pazopanib did not demonstrate significant superiority in efficacy or tolerance compared with continuous treatment. An intermittent administration scheme cannot be recommended outside clinical trials. This study was registered with ClinicalTrial.gov, number NCT01813136.

[Cross-cultural adaptation of the French version of the thyroid cancer-specific quality of life questionnaire: THYCA-QoL]. / Adaptation transculturelle en Français du questionnaire évaluant la qualité de vie des patients opérés d'un cancer de la thyroïde : THYCA-QoL.

INTRODUCTION: The aim of this study was to translate into French the 24 items of the THYCA-QoL questionnaire used in thyroid cancers and then to study its psychometric properties. MATERIALS AND METHODS: The THYCA-QoL is a specific questionnaire for evaluating the quality of life of patients undergoing thyroid cancer surgery. It consists of 24 items and is divided into seven dimensions and six isolated questions. The translation has been carried out according to the recommendations of the EORTC. Validation of the translated version was obtained by finding a consensus of experts for each of the items. RESULTS: All the original questions of the questionnaire have been adapted into French. The translated questionnaire, named THYCA-CoL-fr, was tested on 60 patients (65 % female), mean age 54.5 years. All questions were well accepted and understood and no missing data were reported. Eight patients (13 %) proposed an item correction to the questionnaire. No attenuation effects (floor or ceiling) were detected. The internal structure was comparable to the original questionnaire: Cronbach α coefficients varied from 0.53 for the oropharyngeal dimension to 0.88 for the voice dimension. The scree-plot highlighted the seven dimensions of the English version. CONCLUSION: THYCA-QoL-fr is the first specific French language questionnaire to evaluate the quality of life in thyroid cancer patients undergoing surgery. These first exploratory psychometric results confirmed the conceptual similarity of the French translation and the English version.

Effect of Buparlisib, a Pan-Class I PI3K Inhibitor, in Refractory Follicular and Poorly Differentiated Thyroid Cancer.

BACKGROUND: Dysregulation of the phosphatidylinositol 3-kinase (PI3K) pathway is frequent in advanced follicular (FTC) and poorly differentiated thyroid (PDTC) carcinomas and has been implicated in oncogenesis and tumor progression. This study investigated the efficacy and safety of buparlisib, a pan-PI3K inhibitor in radioiodine refractory FTC and PDTC. METHODS: The primary endpoint of this open-label, multicenter, phase 2 pilot study was progression-free survival (PFS) at 6 months. The sample size was determined considering that a PFS ≤50% at 6 months would denote an absence of benefits (null hypothesis). Secondary endpoints were objective response rate, PFS at 12 months, overall survival at 6 and 12 months, and safety based on the frequency and severity of adverse events (AEs). RESULTS: Forty-three patients (19M/24 F; median age: 67 years) with metastatic, radioiodine refractory, progressive disease received buparlisib, 100 mg, daily. Histology was PDTC in 25 (58%), FTC in 17 (40%), and Hürthle cell carcinoma in 1 (2%). RAS mutation was found in 44% (12/27) and activation of the PI3K pathway in 35% (8/23) of tested tumors. The probability of PFS was 41.7% [95% confidence interval (CI) 7.7-55.5] at 6 months and 20.9% [CI 0-35.7] at 12 months, lower than the 50% expected PFS. At 6 months, 25.6% patients had stable disease, 48.8% were progressive and 25.6% had stopped treatment due to AE. The response to therapy was not influenced by age, sex, histology, or genetic alterations. The overall survivals at 6 and 12 months were 85.9% [CI 76-97] and 78.7 % [CI 67-92], respectively. The mean tumor growth rate decreased from 3.78 mm/month [CI 2.61-4.95] before treatment to 0.8 mm/month [CI -0.2-1.88] during treatment (p < 0.02). Severe grade 3-4 AEs occurred in 27 patients (63%), including hepatitis (25%), hyperglycemia (21%), mood disorders (12%), and skin toxicity (12%), with favorable outcome after temporary or permanent treatment discontinuation or dose reduction. CONCLUSIONS: Buparlisib did not result in significant efficacy in advanced FTC and PDTC. However, the decrease in tumor growth rate may suggest incomplete inhibition of oncogenic pathways and/or escape mechanisms. This should lead to evaluate combined therapy associating inhibitors of both the PI3K and mitogen-activated protein kinase pathways.

Outcome after ablation in patients with low-risk thyroid cancer (ESTIMABL1): 5-year follow-up results of a randomised, phase 3, equivalence trial.

BACKGROUND: In ESTIMABL1, a randomised phase 3 trial of radioactive iodine (131I) administration after complete surgical resection in patients with low-risk thyroid cancer, 92% of patients had complete thyroid ablation at 6-10 months, defined as a recombinant human thyroid-stimulating hormone (rhTSH)-stimulated serum thyroglobulin concentration of 1 ng/mL or less and normal findings on neck ultrasonography. Equivalence was shown between low-activity (1·1 GBq) and high-activity (3·7 GBq) radioactive iodine and also between the use of rhTSH injections and thyroid hormone withdrawal. Here, we report outcomes after 5 years of follow-up. METHODS: This multicentre, randomised, open-label, equivalence trial was done at 24 centres in France. Between March 28, 2007, and Feb 25, 2010, we randomly assigned (1:1:1:1) adults with low-risk differentiated thyroid carcinoma who had undergone total thyroidectomy to one of four strategies, each combining one of two methods of thyrotropin stimulation (rhTSH or thyroid hormone withdrawal) and one of two radioactive iodine activities (1·1 GBq or 3·7 GBq). Randomisation was by computer-generated sequence, with variable block size. Follow-up consisted of a yearly serum thyroglobulin measurement on levothyroxine treatment. Measurement of rhTSH-stimulated thyroglobulin and neck ultrasonography were done at the discretion of the treating physician. No evidence of disease was defined as serum thyroglobulin of 1 ng/mL or less on levothyroxine treatment and normal results on neck ultrasonography, when performed. This study was registered with ClinicalTrials.gov, number NCT00435851. FINDINGS: 726 patients (97% of the 752 patients originally randomised) were followed up. At a median follow-up since randomisation of 5·4 years (range 0·5-9·2), 715 (98%) had no evidence of disease. The other 11 had either structural disease (n=4), raised serum thyroglobulin concentration (n=5), or indeterminate findings on neck ultrasonography (n=2). At ablation, six of these patients had received 1·1 GBq radioactive iodine (five after rhTSH and one after withdrawal) and five had received 3·7 GBq (two after rhTSH and three after withdrawal). TSH-stimulated (either after rhTSH injections or thyroid hormone withdrawal according to the treatment group) thyroglobulin concentration measured at the time of ablation was prognostic for structural disease status at ablation, ablation status at 6-10 months, and the final outcome. INTERPRETATION: Our findings suggest that disease recurrence was not related to the strategy used for ablation. These data validate the use of 1·1 GBq radioactive iodine after rhTSH for postoperative ablation in patients with low-risk thyroid cancer. FUNDING: French National Cancer Institute (INCa), French Ministry of Health, and Sanofi Genzyme.

Iodinated Contrast Agents Perturb Iodide Uptake by the Thyroid Independently of Free Iodide.

Perturbation of thyroid iodide uptake is a well-documented side effect of the use of iodinated contrast media (ICM) administered intravenously. This side effect is thought to be mediated by free iodide in ICM formulations, but this hypothesis has never been formally proven. The aim of the present study was to assess the validity of this hypothesis. Methods: We used mass spectrometry analysis to quantify free-iodide contamination in ICM. Established cell lines expressing the Na/I symporter (NIS) were used to quantify the effect of ICM on iodide uptake. SPECT/CT was used to measure the in vivo uptake of 99mTc-pertechnetate and 123I in 2 NIS-expressing mouse tissues, thyroid and salivary glands. Scintiscans of ICM-naïve and ICM-administered patients were compared. Immunohistologic and Western blot analyses were performed to evaluate NIS protein expression in these organs. Results: Although free iodide was present in ICM formulations, in vitro uptake of iodide by NIS-expressing cells was not significantly affected by ICM. In mice, intravenous or sublingual administration of ICM led to a reduction in radiotracer uptake by the thyroid, accompanied by a dramatic reduction in NIS protein expression in this tissue. In the salivary glands, neither radiotracer uptake nor NIS protein expression was affected by ICM. The thyroid-selective effect of ICM was also observed in humans. Administration of potassium iodide as a source of free iodide led to a diminution of 99mTc-pertechnetate uptake in both mouse thyroid and mouse salivary glands. Altogether, these data rule out a direct intervention of free iodide in the perturbation of thyroid uptake and suggest a direct and selective effect of ICM on the thyroid. Conclusion: We demonstrated that ICM reduce thyroid uptake of iodide independently of free iodide. This effect is due to a specific and dramatic decrease in NIS expression in thyrocytes. These data cast serious doubt on the relevance of measuring urinary iodide concentration to evaluate the delay between ICM administration and radioiodine therapy in patients with differentiated thyroid carcinoma. Finally, the ability of ICM to perturb iodide uptake in the thyroid may be used in radioprotection.

[Is FDG TEP CT practice changing in the management of sarcomas in adults?]. / Évaluation de l'utilisation de la TEP au FDG pour le bilan des sarcomes de l'adulte en pratique quotidienne.

BACKGROUND: FDG PET (PET)±computed tomography (CT) has increasingly been used in some areas of oncology imaging. It is sometimes performed outside recommendations, at diagnosis or monitoring of sarcomas. We assessed the value of PET-CT in routine practice in sarcomas. MATERIAL AND METHODS: All consecutive sarcoma adult patient charts presented at the multidisciplinary sarcoma meeting in a tertiary care center over a period of 10months were examined in order to analyze the performances of PET-CT when available. RESULTS: Of 232 patients, 50 (21 %) underwent a PET-CT. Sensitivity and specificity of PET-CT were 94.7 %, 57.1 %, respectively. SUV values were highly variable, including for a given histology or grade. PET-CT resulted in practice changing in 14 % of cases. When extrapulmonary metastases are suspected and for some subtypes of sarcomas, PET-CT could provide additional information because in view of its good sensitivity. CONCLUSION: Given the most frequent pulmonary tropism, first hand chest CT may be sufficient at first diagnostic work-up for the detection of pulmonary metastases. However, the relatively poor specificity suggests that further analyses should be performed to identify clinical situations where PET-CT may be of added value compared to current standards.

Single-Photon Emission Computed Tomography for Preclinical Assessment of Thyroid Radioiodide Uptake Following Various Combinations of Preparative Measures.

BACKGROUND: MicroSPECT/CT imaging was used to quantitatively evaluate how iodide uptake in the mouse thyroid is influenced by (i) route of iodine administration; (ii) injection of recombinant human thyrotropin (rhTSH); and (iii) low iodide diet (LID) in euthyroid and triiodothyronine (T3)-treated mice. METHODS: Pertechnetate (99mTcO4-) and 123I thyroid uptake in euthyroid and T3-treated animals fed either a normal-iodine diet (NID) or an LID, treated or not with rhTSH, and radiotracer administered intravenously, subcutaneously, intraperitoneally or by gavage, were assessed using microSPECT/CT imaging. Western blotting was performed to measure sodium/iodide symporter expression levels in the thyroid. RESULTS: Systemic administration of radioiodide resulted in a higher (2.35-fold in NID mice) accumulation of iodide in the thyroid than oral administration. Mice fed LID with systemic radioiodide administration showed a further two-fold increase in thyroid iodide uptake to yield a ∼5-fold increase in uptake compared to the standard NID/oral route. Although rhTSH injections stimulated thyroid activity in both euthyroid and T3-treated mice fed the NID, uptake levels for T3-treated mice remained low compared with those for the euthyroid mice. Combining LID and rhTSH in T3-treated mice resulted in a 2.8-fold higher uptake compared with NID/T3/rhTSH mice and helped restore thyroid activity to levels equivalent to those of euthyroid animals. CONCLUSIONS: Systemic radioiodide administration results in higher thyroidal iodide levels than oral administration, particularly in LID-fed mice. These data highlight the importance of LID, both in euthyroid and T3-treated, rhTSH-injected mice. Extrapolated to human patients, and in the context of clinical guidelines for the preparation of differentiated thyroid cancer patients, our data indicate that LID can potentiate the efficacy of rhTSH treatment in T3-treated patients.

Quality of life, clinical outcomes and safety of early prophylactic levothyroxine administration in patients with Graves' hyperthyroidism undergoing radioiodine therapy: a randomized controlled study.

OBJECTIVE: While radioiodine therapy is commonly used for treating Graves' disease, a prolonged and clinical hypothyroidism may result in disabling symptoms leading to deterioration of quality of life (QoL) of patients. Introducing levothyroxine (LT4) treatment in the early post-therapeutic period may be an interesting approach to limit this phenomenon. METHODS: A multicenter, prospective, open-label randomized controlled trial enrolled 94 patients with Graves' hyperthyroidism randomly assigned to the experimental group (n=46) (group A: early prophylactic LT4 treatment) or the control group (n=48) (group B: standard follow-up). The primary endpoint was the 6-month QoL. The secondary endpoints were other QoL scores such as Graves' ophthalmopathy (GO) outcomes, thyroid function tests and safety. RESULTS: The primary endpoint at 6 months was achieved: the mental composite score (MCS) of Short Form 36 (SF-36) was significantly higher in group A compared to group B (P=0.009). Four other dimension scores of the SF-36 and four dimension scores of the thyroid-specific patient-reported outcome (ThyPRO) significantly differed between the two groups, indicating better QoL in group A. After adjustment for variables, the early LT4 administration strategy was found as an independent factor for only two scores of SF-36: the MCS and the general health (GH) score. There were no differences in GO, final thyroid status and changes in the anti-TSH receptor antibodies (TRAbs) levels between the two groups. No adverse cardiovascular event was reported. CONCLUSION: Early LT4 administration post-radioactive iodine (RAI) could represent a safe potential benefit for patients with regard to QoL. The optimal strategy taking into account administered RAI activities and LT4 treatment dosage and timing remains to be determined.

Strategies of radioiodine ablation in patients with low-risk thyroid cancer.

BACKGROUND: It is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after a complete surgical resection. The administration of the smallest possible amount of radioiodine would improve care. METHODS: In our randomized, phase 3 trial, we compared two thyrotropin-stimulation methods (thyroid hormone withdrawal and use of recombinant human thyrotropin) and two radioiodine ((131)I) doses (i.e., administered activities) (1.1 GBq and 3.7 GBq) in a 2-by-2 design. Inclusion criteria were an age of 18 years or older; total thyroidectomy for differentiated thyroid carcinoma; tumor-node-metastasis (TNM) stage, ascertained on pathological examination (p) of a surgical specimen, of pT1 (with tumor diameter ≤1 cm) and N1 or Nx, pT1 (with tumor diameter >1 to 2 cm) and any N stage, or pT2N0; absence of distant metastasis; and no iodine contamination. Thyroid ablation was assessed 8 months after radioiodine administration by neck ultrasonography and measurement of recombinant human thyrotropin-stimulated thyroglobulin. Comparisons were based on an equivalence framework. RESULTS: There were 752 patients enrolled between 2007 and 2010; 92% had papillary cancer. There were no unexpected serious adverse events. In the 684 patients with data that could be evaluated, ultrasonography of the neck was normal in 652 (95%), and the stimulated thyroglobulin level was 1.0 ng per milliliter or less in 621 of the 652 patients (95%) without detectable thyroglobulin antibodies. Thyroid ablation was complete in 631 of the 684 patients (92%). The ablation rate was equivalent between the (131)I doses and between the thyrotropin-stimulation methods. CONCLUSIONS: The use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer. (Funded by the French National Cancer Institute [INCa] and the French Ministry of Health; ClinicalTrials.gov number, NCT00435851; INCa number, RECF0447.).

Clinical impact of cervical lymph node involvement and central neck dissection in patients with papillary thyroid carcinoma: a retrospective analysis of 368 cases.

The impact of cervical lymph node metastases and the optimal surgical management of the neck in patients with papillary thyroid carcinoma (PTC) remain controversial. The objectives of this retrospective study were to determine, in patients with PTC, the predictive factors and the impact on tumor recurrence rate of cervical lymph node involvement, and to evaluate the oncologic results and the morbidity of central neck dissection (CND). We reviewed the records of patients who had undergone surgical treatment for PTC at our institution between 1990 and 2000. A total of 368 patients (86 men and 282 women) were included in this study. Young age (p = 0.02), tumor size (p = 0.001) and extrathyroidal tumor extension (p = 0.003) were significant predictive factors of cervical lymph node metastatic involvement (multivariate analysis). Initial metastatic cervical lymph node involvement was identified as an independent risk factor of tumor recurrence (multivariate analysis, p = 0.01). Metastatic lymph node(s) were found in prophylactic CND specimens in 31% of the patients. CND increased the risk of postoperative hypocalcemia (p = 0.008) and of permanent hypoparathyroidism (p = 0.002). In conclusion, cervical lymph node metastatic involvement at the time of initial surgery is an independent risk factor of tumor recurrence. CND provided an up-staging of more than 30% of patients with a clinically N0 neck, but was associated with significant morbidity regarding parathyroid function.

Lethal, malignant, metastatic struma ovarii.

BACKGROUND: Struma ovarii (SO) is extremely rare, with less than 200 reported cases in the medical literature. SO is defined by the presence of an ovarian tumor containing thyroid tissue as the predominant cell type. Malignant transformation is rare and lethal cases of SO are even rarer. We report on a patient presenting with left ovarian cystic SO and lethal outcome. SUMMARY: A 45-year-old woman was diagnosed with a follicular variant of papillary carcinoma on laparotomy and left salpingo-oophorectomy. She had persistently elevated serum thyroglobulin following total thyroidectomy + radioiodine and second-look surgery. Imaging scan analysis showed pelvic tumor recurrence and hypervascular liver metastases during follow-up as well as peritoneal carcinomatosis in the pelvis, right abdominal wall, and malignant ascites. The patient died from cachexia at 37 months after diagnosis. CONCLUSIONS: Such an aggressive malignant disease and lethal course of SO is rare. Total thyroidectomy is mandatory to exclude a primary thyroid neoplasm and for radioiodine therapy and follow-up. SO may spread to contralateral ovary, pelvic nodes, peritoneum, liver, lungs, and bones through hematogeneous spread, which is different from the dissemination pattern of papillary thyroid carcinomas. Imaging highlights the mixed behavior of this ovarian tumor.

Venous obstruction of thyroid malignancy origin: the Antoine Lacassagne Institute experience.

BACKGROUND AND AIMS: To show the benefits of Ultrasonography in the diagnosis of great vein involvement in the neck and mediastinum in thyroid malignancies (primary or secondary) in our experience and to report patient outcomes. METHODS: Clinical data were collected from the thyroid unit database of the Antoine Lacassagne Institute. RESULTS: Of 1171 patients with thyroid cancer treated at our institution over the last 18 years, we retrospectively identified nine patients (0.8%), three women and six men, aged 34-81 years (median age: 70 years) presenting with malignant thyroid tumor of median diameter 45 mm (range: 23-87) having venous obstruction of thyroid malignancy origin. Two patients underwent multimodal therapy. All other patients underwent external beam radiation therapy alone +/- chemotherapy or palliative care. Ultrasound (US) provided particularly useful information on venous involvement characteristics. Median survival was 7 months and median progression-free survival was 6 months. Survival in our series was worse than that of previously reported series despite diagnosis of vein involvement at an early stage in 2/3 cases using US. CONCLUSION: Despite small numbers of patients, it seems that aggressive treatment modalities including surgery are required to improve survival. In our experience, US was a useful non-invasive method to describe tumor extensions to great veins of the neck (invasion versus compression, tumor thrombus versus blood clot) and should be recommended to depict early venous invasion in cases of suspected thyroid malignancy.

Perfusion SPECT findings in a suspected case of Rasmussen encephalitis.

We report the case of a 35-year-old who was referred for brain perfusion single photon emission computed tomography (SPECT) for pharmacoresistant epilepsy. Her medical history included brain surgery for an inflammatory lesion of unknown origin at age 23 before partial epilepsy occurred. The seizures became refractory to standard antiepileptic drugs and she developed epileptic negative myoclonus of the right upper limb, nocturnal motor seizures, and progressive intellectual impairment. Neurological symptoms slowly worsened with mild aphasia and right visual neglect. Inter-ictal brain SPECT showed decreased cerebral blood flow on the left hemisphere corresponding on magnetic resonance imaging (MRI) with moderate left hemiatrophy, a left frontal defect in accordance with the history of surgery, and a crossed cerebellar diaschisis. Clinical and imaging data were in favor of a late-onset form of Rasmussen encephalitis. Rasmussen syndrome is a rare unilateral devastating disease with childhood onset that can also occur in adulthood, characterized by intractable epileptic seizures associated with progressive neurological deterioration and unilateral progressive atrophy. Brain perfusion SPECT can speed up the diagnosis when exhibiting a strictly unilateral hemispheric hypoperfusion in such a clinical context. It can also guide brain biopsy in cases of inconclusive MRI.

[Unexpected focal bowel 18-FDG uptake sites: should they be systematically investigated?]. / Hyperfixations intestinales focales de découverte fortuite sur la TEP au 18-FDG : faut-il proposer une exploration de façon systématique ?

The purpose of the present study was to retrospectively evaluate the nature and significance of unexpected focal 18-FDG uptake localized by PET/CT within the intestinal tract. Methods. The data of 4,033 PET/CT were retrospectively reviewed. One hundred and eighty PET/CT showed unexpected focal uptakes (patients with known intestinal neoplasia were excluded). Among them, 42 patients corresponding to 47 focal uptake sites were investigated by endoscopy or surgery. Results. Height endoscopy results were negative (17%). We found 25 adenomatous polyps (53.2%), 10 neoplasms (21.3%) and 4 inflammatory lesions (8.5%). 18-FDG uptake values were not statistically different between the 4 groups. Conclusion. Eighty-three percent of unexpected intestinal foci of hypermetabolism are either inflammatory, malignant or premalignant lesions. These results justify systematic investigation of these lesions.

Low-molecular-weight fucoidan enhances the proangiogenic phenotype of endothelial progenitor cells.

Endothelial progenitor cell (EPC) transplantation is a potential means of inducing neovascularization in vivo. However, the number of circulating EPC is relatively small, it may thus be necessary to enhance their proangiogenic properties ex vivo prior to injection in vivo. Fucoidan has previously been shown to potentiate in vitro tube formation by mature endothelial cells in the presence of basic fibroblast growth factor (FGF-2). We therefore examined whether fucoidan, alone or combined with FGF-2, could increase EPC proangiogenic potency in vitro. EPC exposure to 10 microg/ml fucoidan induced a proangiogenic phenotype, including cell proliferation (p < 0.01) and migration (p < 0.01); moreover, differentiation into vascular cords occurred in the presence of FGF-2 (p < 0.01). This latter effect correlated with upregulation of the cell-surface #alpha6 integrin subunit of the laminin receptor (p < 0.05). Compared to untreated HUVEC, untreated EPC #alpha6 expression and adhesion to laminin were enhanced two-fold. Fucoidan treatment further enhanced HUVEC but not EPC adhesion to laminin. These results show that fucoidan enhances the proangiogenic properties of EPC and suggest that ex vivo fucoidan preconditioning of EPC might lead to increased neovascularization when injected into ischemic tissues.