Increase in brown adipose tissue activity after weight loss in morbidly obese subjects.

CONTEXT: Stimulation of thermogenesis in brown adipose tissue (BAT) is a potential target to treat obesity. We earlier demonstrated that BAT activity is relatively low in obese subjects. It is unknown whether BAT can be recruited in adult humans. OBJECTIVE: To study the dynamics of BAT, we observed BAT activity in morbidly obese subjects before and after weight loss induced by bariatric surgery. DESIGN: This was an observational prospective cohort study. SETTING: The study was conducted at a referral center. PATIENTS: Ten morbidly obese subjects eligible for laparoscopic adjustable gastric banding surgery were studied before and 1 yr after bariatric surgery. MAIN OUTCOME MEASURE: The main outcome measure was BAT activity, as determined after acute cold stimulation using (18)F-fluorodeoxyglucose positron emission tomography and computed tomography. RESULTS: Before surgery, only two of 10 subjects showed active BAT. One year after surgery, the number of subjects with active BAT was increased to five. After weight loss, BAT-positive subjects had significantly higher nonshivering thermogenesis compared with BAT-negative subjects (P < 0.05). CONCLUSIONS: The results show that in humans BAT can be recruited in the regions in which it was also reported in lean subjects before. These results for the first time show recruitment of BAT in humans and may open the door for BAT-targeted treatments of obesity.

Blocking the saphenofemoral junction during ultrasound-guided foam sclerotherapy-- assessment of a presumed safety-measure procedure.

OBJECTIVES: Ultrasound-guided foam sclerotherapy (UGFS) is a technique in which a mixture of sclerosing drug and gas is used to treat varicose veins. Several authors have demonstrated transient systemic effects after UGFS. These effects are not well understood but probably originate from a systemic distribution of the sclerosing foam. Therefore, safety measures have been developed to prevent foam from flowing into the deep venous system. The aim of the study is to evaluate whether blockage of the saphenofemoral (SF) junction by either manual compression or surgical ligation prevents microbubbles from leaking into the deep venous circulation. METHODS: To detect the distribution of microbubbles, radioactive pertechnetate (99mTcO4-) was added to the foam solution. Initially, in vitro trials were performed in the laboratory to investigate the effect of 99mTc on foam stability. The time taken for foam to liquefy was measured for foam alone and for the mixture with 99mTc. In subsequent research, eight varicose great saphenous veins (GSVs) were treated by UGFS. In three patients, this treatment was preceded by surgical ligation of the SF junction. In three patients, the groin was manually compressed during UGFS. In two patients, UGFS was performed without compression of the groin. RESULTS: In vitro, 99mTc did not influence foam stability; after 2.6 min all foam had reduced to liquid, regardless of whether 99mTc had been added or not. In vivo trials showed that all patients showed a decrease in the cumulative amount of 99mTc detected in the GSV following polidocanol-99mTc mixture injection. However, the decrease of radioactivity was slightly reduced when compression or ligation of the SF junction was performed. CONCLUSIONS: Blocking the SF junction during UGFS using either manual compression or ligation does not prevent, but may reduce the flow of foam into the femoral vein.

99mTc Nanocoll: a radiopharmaceutical for sentinel node localisation in breast cancer--in vitro and in vivo results.

This study evaluated labelling efficiency and radiochemical purity of (99m)Tc colloid albumin to identify an optimal labelling protocol for sentinel node detection. Results indicate that a 72 h eluate is not recommended for high specific labelling of (99m)Tc colloid albumin. Ex vivo, significantly higher count rates were reached using a 2h eluate in vacuum or nitrogen. Labelling 26 MBq/microg (99m)Tc colloid albumin with a 2 h eluate under nitrogen is recommended because of the ease of labelling.

Identifying vulnerable carotid plaques by noninvasive imaging.

Stroke results in considerable morbidity and mortality. Prevention is therefore of particular importance. On the basis of large clinical trials, carotid endarterectomy (CEA) is performed in selected patient groups to prevent stroke. Patient symptomatology and degree of carotid stenosis are the main clinical grounds to perform CEA. However, many individual patients undergo surgery with its attendant risks without taking advantage of it, whereas in others CEA is probably incorrectly withheld. There is therefore an urgent need for new adjuncts to identify high-risk subgroups of patients who particularly benefit from potentially hazardous interventions. Multiple noninvasive imaging modalities have shown their potential to differentiate high-risk, vulnerable carotid plaques from stable plaques. The ultimate goal is to implement one or a combination of these imaging modalities in daily clinical practice. This review gives an up-to-date overview of the clinical potential of these imaging modalities in identifying patients with carotid atherosclerosis who are at high risk for developing stroke. Advantages and limitations of each imaging technique are outlined. Additionally, recommendations for future research are presented.

The role of (124)I-PET in diagnosis and treatment of thyroid carcinoma.

Iodine-124 is a positron-emitting iodine isotope, enabling measurement of iodine uptake using positron emission tomography (PET). There is a number of situations where the use of (124)I-PET/computed tomography (CT) can improve the current clinical practice in the diagnosis and treatment of thyroid cancer. Firstly, (124)I-PET/CT can aid in the staging of patients, because of better detection of metastatic disease and measurement of metabolic tumour volume, and thus separate low-risk from high risk patients. Secondly, the much higher sensitivity and spatial resolution of PET compared to gamma scintigraphy can also improve detection of recurrent disease. Furthermore, (124)I-PET can be used for patient-specific radioiodine therapy radiation dosimetry. Simultaneous administration of the therapeutic dose of (131)I and a tracer dose of (124)I allows for accurate measurement of iodine uptake during therapy. The decay scheme of (124)I, with few positrons and many gamma rays emitted per decay, often simultaneously, poses a challenge to quantitative PET imaging. Improved correction methods and the use of last-generation PET/CT scanners with faster electronics and better energy resolution can overcome this.

(99M)Technetium-sestamibi scintimammography in non-palpable breast lesions found on screening X-ray mammography.

OBJECTIVE: The sensitivity and specificity of (99m)Tc-sestamibi scintimammography in patients with non-palpable breast lesions diagnosed by screening mammography and the value of (99m)Tc-sestamibi to detect axillary lymph node metastases was determined. METHODS: Between September 2000 and December 2003, 103 females with non-palpable breast lesions were included for further evaluation. X-ray mammography was repeated and 99mTc-sestamibi scintimammography performed within one-week. Anterior, and left and right lateral images were obtained. The scintimammography was analysed by 2 experienced observers who were blinded to the clinical, pathological, and radiological results. The sensitivity and specificity of scintimammography to diagnose non-palpable lesion(s), including the axillary regions, was compared with histopathology, clinical, and radiological follow up. RESULTS: Two patients (one non-small lung cancer and one non-Hodgkin's disease) were excluded. Both showed (99m)Tc-sestamibi avid lesions in the breast and axillary region. In the remaining 101 patients, 37 true positive (TP), 4 false positive (FP), 52 true negative (TN), and 8 false negative (FN) breast carcinomas were found. The specificity was 92.8%, sensitivity 82.2%, positive predictive value (PPV) 90.2%, and negative predictive value (NPV) 86.6%. (99m)Tc-sestamibi scintimammography showed axillary lesions in 5/15 (33%) patients with axillary lymph node metastasis. CONCLUSION: In patients with non-palpable lesions diagnosed by screening- X-ray-mammography, (99m)Tc-sestamibi scintimammography provided high specificity and PPV. Furthermore, (99m)Tc-sestamibi scintimammography detected 33% of patients with axillary lymph node metastases. Therefore, (99m)Tc-sestamibi scintimammography could be of incremental value in the surgical work-up of these patients.

Proteus syndrome: a rare cause of hemihypertrophy and macrodactyly on bone scanning.

Proteus syndrome is a rare, sporadic genetic disorder characterized by overgrowth of multiple different tissues in a mosaic pattern. It is associated with connective tissue nevi, epidermal nevi, disproportionate overgrowth of multiple tissues, vascular malformations, characteristic tumors, and specific facial anomalies. Joseph Merrick, popularly known as the Elephant Man, is now believed to have suffered from Proteus syndrome. A case of Proteus syndrome and associated findings on bone scintigraphy are presented.

Evaluation of pulmonary nodules: comparison of a prototype dual crystal (LSO/NAI) dual head coincidence camera and full ring positron emission tomography (PET).

PURPOSE: To determine the concordance of a prototype dual head coincidence camera (LSO-PS) and full ring PET (BGO-PET) using (18)F-fluorodeoxyglucose (FDG) in the evaluation of pulmonary nodules (PNs). MATERIALS AND METHODS: Patients referred for evaluation of < or =3 PNs (< or =3 cm diameter) were prospectively studied on the same day with both BGO-PET and LSO-PS. Imaging was performed at 60 and 120 min after injection of 370MBq FDG, respectively. Images were independently interpreted by four observers with each observer blinded to the other modality for the same patient. Lesions were scored in terms of relative intensity versus background. Non-attenuation corrected (nonAC) BGO-PET was used as the reference test. RESULTS: Forty-seven patients with 54 PNs (mean diameter 1.7 cm, S.D. 0.7) were included. Twelve nodules were in the < or =1.0 cm - 27 in the 1.1-2.0 cm - and 15 in the 2.1-3.0 cm range. Interobserver agreement was similar for both FDG imaging modalities. Using a sensitive assessment strategy with LSO-PS (> or = faint intensity deemed positive), there was a 97% (38/39, 95%CI 87-100%) concordance with BGO-PET and one false positive case with LSO-PS. Conservative reading (moderate or intense intensity deemed positive) resulted in a 92% (36/39, 95%CI 80-97%) concordance with BGO-PET, without false positives. The only lesion missed by LSO-PS using both assessment strategies involved a nodule 1.5 cm diameter that demonstrated moderate increased FDG uptake on BGO-PET. CONCLUSION: Depending on the test positivity criteria, LSO-PS demonstrates a high concordance (92-97%) with nonAC BGO-PET for the characterization of pulmonary nodules.

Accuracy of diagnostic imaging techniques in the diagnosis of aseptic loosening of the femoral component of a hip prosthesis: a meta-analysis.

In this meta-analysis we included 32 English-language articles published between January 1975 and June 2004 on the diagnostic performance of plain radiography, subtraction arthrography, nuclear arthrography and bone scintigraphy in detecting aseptic loosening of the femoral component, using criteria based on the Cochrane systematic review of screening and diagnostic tests. The mean sensitivity and specificity were, respectively, 82% (95% confidence interval (CI) 76 to 87) and 81% (95% CI 73 to 87) for plain radiography and 85% (95% CI 75 to 91) and 83% (95% CI 75 to 89) for nuclear arthrography. Pooled sensitivity and specificity were, respectively, 86% (95% CI 74 to 93) and 85% (95% CI 77 to 91) for subtraction arthrography and 85% (95% CI 79 to 89) and 72% (95% CI 64 to 79) for bone scintigraphy. Although the diagnostic performance of the imaging techniques was not significantly different, plain radiography and bone scintigraphy are preferred for the assessment of a femoral component because of their efficacy and lower risk of patient morbidity.

[18F]fluorodeoxyglucose uptake in recurrent thyroid cancer is related to hexokinase i expression in the primary tumor.

Patients suspected of recurrent differentiated thyroid cancer (DTC) may require "blind" (131)I therapy, with the disadvantage of unpredictable efficacy and toxicity. Alternatively, positron emission tomography (PET) with [(18)F]fluorodeoxyglucose ((18)FDG) can document the recurrence, thereby rationalizing therapeutic options. This study compared (18)FDG uptake in vivo with biomarkers expected to be involved in the underlying biological mechanisms. Additionally, we investigated whether such features were present in the primary tumors. Preoperatively, 19 patients with recurrent DTC underwent PET. (18)FDG uptake was compared with histological and immunohistochemical features in surgical specimens of recurrent and primary tumor. Thirteen of 19 recurrences were positive at PET, and (18)FDG uptake was associated with the expression of hexokinase type I (HK I; P = 0.011). All lesions with HK I overexpression were positive on (18)FDG PET. HK I expression in the original primary tumor and the metastases was similar in 82% (rho = 0.648; P = 0.005). In suspected recurrent thyroid cancer, stratification for (18)FDG PET may benefit from pretest immunohistochemical analysis of HK I of the primary tumor, as HK I negativity indicates a low likelihood of PET positivity.

In search of an unknown primary tumour presenting with extracervical metastases: the diagnostic performance of FDG-PET.

A retrospective study was carried out to determine the performance of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with unknown primary tumours presenting with metastases external to the neck. All patients referred to an academic PET centre (July, 1997 to December, 2000) presenting with an extracervical metastasis and no prior systemic therapy were eligible. The minimum follow-up period was 11 months. From 63 eligible cases, known metastases were FDG avid in all but one neuroendocrine process. PET scans were retrospectively classified as positive for a primary tumour (n=29), i.e. revealing at least one anatomical site suspected to be the primary tumour. This was confirmed in 16, either by histology (n=10) or radiological and clinical follow-up (n=6). There were four false positive cases. In nine patients, the primary tumour was never confirmed. Of the remaining 33 negative PET scans the primary tumour was clinically not found in 18. Follow-up and additional pathology investigations demonstrated the primary tumour in 15. A survey on clinical usefulness of PET (response rate 83%) suggested that PET positively contributed to diagnostic understanding in 29 of 52 evaluable cases. Applied late in the diagnostic trajectory, approximately four patients need to be scanned by PET in order to find one primary tumour. However, in addition to direct demonstration of unknown primaries, there appears to be a positive effect on the diagnostic work-up of these patients of a similar magnitude.

Effect of increased (99m)Tc/(99)Tc ratios on count rates in sentinel node procedures: a randomised study.

The aim of this study was to evaluate the count rates of sentinel lymph nodes (SLNs) in patients with breast cancer in the operating theatre, using (99m)Tc-Nanocoll with different ratios of technetium-99m to technetium-99. After written informed consent had been obtained, we tested different ratios of (99m)Tc/(99)Tc-Nanocoll in a double-blinded randomised study performed in 161 patients. Twenty-five MBq/ microg (99m)Tc-colloid albumin was prepared in vacuum. In 87 patients (group A) a 2-h elution was used and in 74 patients (group B) a 24-h elution was used. Patients were subcategorised into subgroups 1 and 3, in which an SLN procedure for breast carcinoma was performed simultaneously with lumpectomy, and subgroups 2 and 4, in which an SLN procedure was performed 2-3 weeks after prior excision biopsy. All patients were injected along the lateral border of the areola (two injections: 50 MBq/0.3 ml intradermally and 50 MBq/2 ml intraparenchymally). Ex vivo measurement of count rates was performed with a gamma probe. Comparing groups A and B in respect of registered counts per second (cps) of excised SLNs, a significant difference was found ( P<0.004). When comparisons were made between subgroups 1 and 2 (2-h elution) and between subgroups 3 and 4 (24-h elution) in respect of registered cps of excised SLNs, no significant difference was found (subgroup 1 vs 2, P=0.825; subgroup 3 vs 4, P=0.915). Use of a 2-h elution in vacuum yielded a significantly higher count rate of maximum specific activity of (99m)Tc-colloid albumin in SLNs than was achieved using a 24-h elution in vacuum. SLN procedures performed 2-3 weeks after prior excision biopsy proved reliable as compared to SLN procedures performed simultaneously with lumpectomy.

How morphometric analysis of metastatic load predicts the (un)usefulness of PET scanning: the case of lymph node staging in melanoma.

BACKGROUND: In primary cutaneous melanoma, the sentinel node (SN) biopsy is an accurate method for the staging of the lymph nodes. Positron emission tomography (PET) has been suggested as a useful alternative. However, the sensitivity of PET may be too low to detect SN metastases, which are often small. AIM: To predict the value of PET for initial lymph node staging in melanoma based on morphometric analysis of SN metastatic load, without exposing patients to PET. MATERIALS AND METHODS: In 59 SN positive patients with melanoma, the sizes of tumour deposits in the SNs and subsequent dissection specimens were measured by morphometry and correlated with the detection limits of current and future PET scanners. RESULTS: The median tumour volume within the basin was 0.15 mm(3) (range, 0.0001-118.86). Seventy per cent of these deposits were smaller than 1 mm(3). State of the art PET scanners that have a resolution of about 5 mm would detect only 15-49% of positive basins. Logistic regression analysis revealed no pretest indicators identifying patients expected to have a positive PET. However, the SN tumour load was a significant and single predictor of the presence of PET detectable residual tumour. CONCLUSION: Morphometric analysis of metastatic load predicts that PET scanning is unable to detect most metastatic deposits in sentinel lymph nodes of patients with melanoma because the metastases are often small. Therefore, the SN biopsy remains the preferred method for initial regional staging.

Feasibility of a randomized trial on adjuvant radio-iodine therapy in differentiated thyroid cancer.

BACKGROUND: Justification for adjuvant radio-iodine (I-131) therapy in differentiated thyroid cancer (DTC) is purely based on retrospective data. This is true for ablative therapy and even more so for high-dosage adjuvant schedules. Randomized trials on the latter application are considered impossible due to anticipated formidable sample sizes required in a disease with an overall excellent prognosis like DTC. OBJECTIVE: To develop and validate a model that could stratify for risk of recurrence, rather than survival, as is usually done in prognostic indices, and secondly, to use this model to estimate the sample size required for a randomized trial. DESIGN, PATIENTS AND RESULTS: From databases of three large Dutch centres, we identified 342 consecutive patients without known residual DTC after (near-) total thyroidectomy. Using Cox proportional hazards analysis, a model was validated that clearly distinguished risk categories of recurrence using commonly available baseline variables. The model included age, N stage at presentation and T stage in papillary carcinoma. According to this stratification, a subset of patients at substantial risk for relapse (30-40%) was identified. They could be eligible for a trial assessing the impact of high-dose adjuvant I-131 on recurrence rates. Assuming a clinically relevant effect of 30% reduction of relapses, 290 patients would have to be entered in either arm (alpha 0.05, power 80%). CONCLUSION: We conclude that even though a randomized trial on this issue will be difficult to design and conduct, sample size is not the main problem.

Prospective use of serial questionnaires to evaluate the therapeutic efficacy of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in suspected lung cancer.

BACKGROUND: A study was undertaken to study the effect of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the diagnosis and management of clinically problematic patients with suspected non-small cell lung cancer (NSCLC). METHODS: A prospective before-after study was performed in a cohort of all 164 patients (university/community settings) referred for PET between August 1997 and July 1999. PET was restricted to cases where non-invasive tests had failed to solve clinical problems. The impact on diagnostic understanding and management was assessed using questionnaires (intended treatment without PET, actual treatment choice after PET, post hoc clinical assessment). RESULTS: Diagnostic problems especially pertained to unclear radiological findings (n=112; 63%), mediastinal staging (n=36; 20%), and distant staging issues (n=16; 9%). PET findings were validated by reviewing medical records. PET had a positive influence on diagnostic understanding in 84%. Improved diagnostic understanding solely based on PET was reported in 26%. According to referring physicians, PET resulted in beneficial change of treatment in 50%. Cancelled surgery was the most frequent change in treatment after PET (35%). CONCLUSION: FDG PET applied as "add on" technology in patients with these clinical problems appears to be a clinically useful tool, directly improving treatment choice in 25% of patients. The value of increased confidence induced by PET scanning requires further evaluation.

Rapid evaluation of FDG imaging alternatives using head-to-head comparisons of full ring and gamma camera based PET scanners--a systematic review.

AIM: While FDG full ring PET (FRPET) has been gradually accepted in oncology, the role of the cheaper gamma camera based alternatives (GCPET) is less clear. Since technology is evolving rapidly, "tracker trials" would be most helpful to provide a first approximation of the relative merits of these alternatives. As difference in scanner sensitivity is the key variable, head-to-head comparison with FRPET is an attractive study design. This systematic review summarises such studies. METHODS: Nine studies were identified until July 1, 2000. Two observers assessed the methodological quality (Cochrane criteria), and extracted data. RESULTS: The studies comprised a variety of tumours and indications. The reported GC- and FRPET agreement for detection of malignant lesions ranged from 55 to 100%, but with methodological limitations (blinding, standardisation, limited patient spectrum). Mean lesion diameter was 2.9 cm (SD 1.8), with only about 20% < 1.5 cm. The 3 studies with the highest quality reported concordances of 74-79%, for the studied lesion spectrum. Contrast at GCPET was lower than that of FRPET, contrast and detection agreement were positively related. Logistic regression analysis suggested that pre-test indicators might be used to predict FRPET-GCPET concordance. CONCLUSION: In spite of methodological limitations, "first generation" GCPET devices detected sufficient FRPET positive lesions to allow prospective evaluation in clinical situations where the impact of FRPET is not confined to detection of small lesions (< 1.5 cm). The efficiency of head-to-head comparative studies would benefit from application in a clinically relevant patient spectrum, with proper blinding and standardisation of acquisition procedures.

Reproducibility and clinical value of 18F-fluorodeoxyglucose positron emission tomography in recurrent melanoma.

The purpose of this study was to assess the reproducibility and clinical impact of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in patients with (suspected) recurrent melanoma. The clinical value of PET was prospectively measured in 58 consecutive patients referred for PET because of unresolved clinical questions after conventional work-up. Diagnostic understanding and therapy choice by referring physicians were evaluated before, directly after, and 6 months after PET. Observer agreement of PET readings was measured with respect to various parameters (interpretation, number and localization of lesions, 'clinically decisive' metastases), using intra-class correlation coefficients. FDG PET improved diagnostic understanding in 33 cases (57%). In six patients (10%), diagnostic understanding was solely based on PET information. According to the attending clinicians, PET contributed to a positive change of planned treatment in 23 patients (40%) and increased confidence in the chosen treatment in 23 (40%). Observer agreement of PET readings was very high (intra-class correlation coefficients were between 0.87 and 0.94). The diagnostic value related especially to the whole-body scan technique and the superior specificity, compared to conventional work-up. It is concluded that, in problematical cases with (suspected) recurrent melanoma, 18F-FDG PET had considerable impact on diagnostic understanding and management. Together with the excellent observer reliability, these results justify further studies to determine the optimal place of PET in routine diagnostic algorithms in recurrent melanoma.

Practice, efficacy and cost of staging suspected non-small cell lung cancer: a retrospective study in two Dutch hospitals.

BACKGROUND: A study was undertaken to investigate the clinical practice, yield, and costs of preoperative staging in patients with suspected NSCLC and to obtain baseline data for prospective studies on the cost effectiveness of (18)F-fluorodeoxyglucose positron emission tomography in the management of these patients. METHODS: A retrospective study of the medical records of all patients with suspected NSCLC was performed during a 2 year interval (1993-4) in an academic and a large community hospital. RESULTS: Three hundred and ninety five patients with suspected NSCLC were identified; 58 were deemed to be medically inoperable and 337 patients proceeded to the staging process. Staging required a mean (SD) of 5.1 (1.5) diagnostic tests per patient (excluding thoracotomy) carried out over a median period of 20 days (IQR 10-31). Many of the tests (including both invasive and non-invasive) were done because previous imaging tests had suggested metastases, and in most cases the results of initial tests proved to be false positives. After clinical staging, 168 patients were considered to be resectable (stage I/II) and 144 patients underwent surgery with curative intent. At surgery 33 patients (23% of those who underwent surgery) were found to have irresectable lesions and 19 (13%) had a benign lesion. Surgery was also considered to be futile in 22 patients (15%) who developed metastases or local recurrence within 12 months following radical surgery. Hospital admission was responsible for most of the costs. CONCLUSION: In many patients staging involved considerable effort in terms of the number of diagnostic tests, the duration of the staging period and the cost, with limited success in preventing futile surgery. Failures relate to the quality of diagnostic preparation at every level of the TNM staging system.

Clonally related but phenotypically divergent human cancer cell lines derived from a single follicular thyroid cancer recurrence (TT2609).

Starting from different regional samples taken from a heterogeneous follicular thyroid cancer recurrence in a male patient, a series of cell cultures was initiated. Three stable cancer cell lines were successfully established (TT2609-A02, TT2609-B02, and TT2609-C02) and kept in continuous culture for more than 3 years. The lines are each characterized by a unique set of biological parameters such as morphology, ploidy state, cell proliferation rate, ultrastructure, thyroid marker expression, p53 expression, karyogram, agar clonogenic capacity and tumorigenicity as xenografts in nude mice. These characterization studies point to a marked heterogeneity at the level of the clinical tumor recurrence. Karyotype analysis of the cell lines showed a pattern of aberrations indicating that the lines are clonally related and that the A02 and C02 lines are subsequently derived from the more "original" tumor cell type B02 after a tetraploidization event. It is concluded that the obtained cell lines represent an in vitro/in vivo model for human follicular thyroid cancer. The availability of a series of cell lines for human follicular thyroid cancer, mimicking the biological heterogeneity observed in patient tumors, enables both detailed fundamental investigation of thyroid cancer cell biology and the experimental exploration of new treatment approaches.