Clinical usefulness of single photon emission tomography/computed tomography with stress analysis in early diagnoses of stem instability of noncemented hip arthroplasty.

OBJECTIVE: Hip pain arising from implant instability is generally caused by repetitive stress injury, which subsequently leads to induction or exacerbation of abnormal metabolism of bone around the implant. single photon emission tomography/computed tomography (SPECT-CT) has advantages in localizing areas of increased tracer uptake that reflects such abnormal bone metabolism. Therefore, we investigated whether the application of SPECT/CT with stress analysis can be an effective practice in evaluating the instability of stem in noncemented hip arthroplasty or not. METHOD: In total 16 patients were collected for unexplained painful hip arthroplasties. When physical examination and blood tests were unremarkable, radiographs were inconclusive and bone scan indicated increased scintigraphic uptake at the proximal part and at the tip of the stem; SPECT/CT was performed. Stem stability was assessed by measuring whether there was consistency between the increased scintigraphic uptake and the direction of the stress around the implant along with the location of the prosthesis. RESULT: Among the 16 symptomatic hips, 9 hips showed the stability of the stem, 3 hips showed the stem instability and 4 hips showed the acetabular loosening with the stem stability. With the application of SPECT/CT with stress analysis, 15 out of 16 (93.7%) cases were found to have the change in the diagnoses, and managements were implemented in 11 out of 16 (68.7%) cases. When comparing before and after SPECT/CT, there was no significant association in clinical diagnosis and management (Pearson chi- square test = 4.61 and 1.33, P = 0.33 and 0.25). CONCLUSION: SPECT/CT combined with stress analysis can be a useful tool in early diagnosis of stem instability and can assist surgeons in subsequent management and decision implementation when other radiographic imagings are inconclusive.

Clinical Evaluation of the Immune Colloidal Gold Method for Rapid Qualitative and Quantitative Measurement of Thyroid-Stimulating Hormone as an Assay for Hypothyroidism.

INTRODUCTION: The immune colloidal gold (ICG) method of measuring thyroid-stimulating hormone (TSH) is a rapid and easy-to-perform test, allowing off-site measurements. This study compared the clinical utility of the first ICG-based qualitative and quantitative TSH test methods in China with the third-generation serum TSH assay used worldwide. METHODS: Fingertip and venous blood was collected within 30 min from 283 patients initially suspected of hypothyroidism. TSH was measured in fingertip blood using ICG-based qualitative quantitative tests. Serum TSH in venous blood was tested using the third-generation serum TSH assay. Correlations between systems were tested by kappa or Spearman correlation coefficients. RESULTS: Compared with the third-generation serum TSH assay, the ICG-qualitative TSH test kit had a kappa coefficient of 0.86, a sensitivity of 85.00%, and a specificity of 99.38% in screening for hypothyroidism. The percentages of false negatives and false positives among all subjects were 6.38% and 0.35% respectively; the total consistency rate of the two methods was 93.26%. When compared with the third-generation serum TSH assay, the ICG-quantitative TSH analysis system had a Spearman correlation coefficient of 0.91, a sensitivity of 88.43%, and a specificity of 98.77%. The percentages of false negatives and false positives among all subjects were 4.95% and 0.71%, respectively; the total consistency rate of the two methods was 94.35%. CONCLUSION: Both ICG-based assays are easier and faster to perform than the third-generation, laboratory-based serum TSH assay method. The ICG-based methods showed acceptable performance in the simplified screening for hypothyroidism. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01921452. FUNDING: Merck Serono Co., Ltd.

Short-Term Side Effects after Radioiodine Treatment in Patients with Differentiated Thyroid Cancer.

OBJECTIVES: I-131 therapy for differentiated thyroid cancer (DTC) could induce adverse effects. The purpose of this study was to report and analyze symptoms after I-131 treatment within the hospitalization and present relevant medical intervention. METHODS: I-131 doses ranging from 3.7 to 9.25 GBq (100-250 mCi) were administrated for thyroid remnant ablation or treating DTC metastases. 117 patients with DTC for I-131 therapy were monitored through the video and intercommunicating with standardized questionnaire at different time points after I-131 oral administration. Adverse effects were recorded and relevant clinical factors were analyzed. RESULTS: Among all the 117 patients, 55 cases complained of neck's pain or swelling and 79 cases presented with gastrointestinal symptoms. Pain or swelling of salivary gland occurred in 15 patients, headache and vertigo in 10, insomnia in 9, vocal cord paralysis in 6, fatigue or general malaise in 6, and foreign body sensation in 5. Body numbness and urinary symptoms were observed in only 1 case, respectively. Those side effects were related with sex, pre-I-131 treatment TSH levels, frequency of I-131 therapy, and lymph node metastases. CONCLUSIONS: Short-term side effects after I-131 therapy for DTC patients varied individually; severe symptoms were not uncommon but generally did not need emergent medical intervention.

FAM172A protein promotes the proliferation of human papillary thyroid carcinoma cells via the p38 mitogen-activated protein kinase pathway.

Family with sequence similarity 172, member A (FAM172A), was cloned from human aortic tissues and confirmed in our previous study in 2009, however, its functions remain to be fully elucidated. In our previous studies, the protein expression of FAM172A in human aortic smooth muscle cells was found to be upregulated by high glucose in a concentration­ and time­dependent manner. Several reports have shown that insulin resistance is associated with papillary thyroid carcinoma (PTC). Thus, in the present study, the protein expression levels of FAM172A in human papillary thyroid carcinoma were investigated, and the effect of the FAM172A protein on the proliferation of IHH­4 human papillary thyroid carcinoma cells, and its potential molecular underlying mechanisms were examined. Immunohistochemistry and western blotting demonstrated that the protein expression of FAM172A in papillary thyroid carcinoma tissues was not only significantly higher than that in noncancerous tissues adjacent to the carcinoma tissues, but it was also markedly higher than that in normal thyroid and thyroid adenoma tissues. Overexpression of the FAM172A protein activated the p38 MAPK pathway, but not the PI3K and AMPK pathways, in the IHH­4 cells. In addition, overexpression of the FAM172A protein accelerated IHH­4 cell proliferation, compared with the control group, and the pro­proliferative effect of FAM172A protein on IHH4 cells was markedly attenuated by SB202190, an inhibitor of p38 MAPK. Taken together, these results suggest that the FAM172A protein is expressed at high levels in human PTC, which may promote cell proliferation via activation of the p38 MAPK signaling pathway, and be involved in the pathogenesis of PTC.

Localized subacute thyroiditis presenting as a painful hot nodule.

BACKGROUND: A diagnosis of subacute thyroiditis is readily considered when patients present with a particular set of typical clinical characteristics. Subacute thyroiditis sometimes presents as a solitary cold nodule; however, the presence of a hot nodule in patients with subacute thyroiditis is exceedingly rare. CASE PRESENTATION: Here, the case of a 57-year-old woman complaining of pain in the left neck and fatigue for two weeks is presented. Physical examination revealed a painful and tender nodule with a diameter of approximately 1.5 cm in the left neck, although all laboratory tests, including white blood cell count, neutrophil percentage, erythrocyte sedimentation rate (ESR), thyroid function, and thyroglobin levels, were normal. A neck ultrasound revealed a hypoechoic mass (1.5 × 0.8 cm) in the left thyroid, and thyroid scintigraphy of the left thyroid with Technetium-99 m (99 m-Tc) demonstrated a focal accumulation of radiotracer. Furthermore, fine-needle aspiration biopsy from the nodule revealed the presence of multinuclear giant cells. The patient was well; there was no cervical mass detected upon palpation following two months of prednisone treatment, and follow-up ultrasound screening and scintigraphy demonstrated the disappearance of the nodule. CONCLUSION: This case, presenting with a localized painful hot nodule, normal thyroid function, normal ESR, and normal serum thyroglobulin levels, is a rare case of subacute thyroiditis, which should be considered during differential diagnosis.

FDG-anorectic parathyroid carcinoma with FDG-avid bone metastasis on PET/CT images.

A 53-year-old man complained of aggravated left hip pain of more than 2 months. Whole-body (18)F-FDG PET/CT revealed only 1 hypermetabolic lesion in the left ilium. Histopathologic examination of the lesion suggested metastatic disease. Blood tests documented mildly elevated blood calcium and parathyroid hormone. Subsequent neck ultrasonography, contrast-enhanced CT, and dual-phase scintigraphy with (99m)Tc-MIBI showed a right parathyroid tumor, which was confirmed to be a parathyroid carcinoma postoperatively. We report a case of parathyroid carcinoma rarely encountered with a FDG-negative primary but a FDG-positive metastasis on PET/CT images.

FDG PET/CT showing erythema nodosum associated with tuberculous lymphadenitis.

Erythema nodosum (EN) is histopathologically an acute septal panniculitis of subcutaneous adipose lobule. It can be either idiopathic or secondary to various underlying conditions. A female patient with EN underwent FDG PET/CT to search underlying cause. The images showed enlarged lymph nodes in the mediastinum with moderately elevated FDG uptake and multifocal increased FDG uptake over her lower extremities. The patient's condition was subsequently diagnosed with EN associated with mediastinal tuberculous lymphadenitis based on skin biopsy, tuberculin skin test, and treatment response.

High prevalence of vitamin D insufficiency in China: relationship with the levels of parathyroid hormone and markers of bone turnover.

There is a lack of large-scale studies on vitamin D status and its relationship to parathyroid hormone (PTH) and bone turnover markers in adults living in Shanghai. The objectives were to determine the prevalence of vitamin D insufficiency in Shanghai and to investigate the relationship of 25(OH)D with parathyroid function and bone turnover markers. This cross-sectional study involved 649 men and 1939 women aged 20-89 years who were randomly sampled in Shanghai. Serum concentrations of 25(OH)D, PTH, albumin, and bone turnover markers were measured. During the winter season, the prevalence of vitamin D insufficiency (<30 ng/mL) was 84% in males and 89% in females. The prevalence of vitamin D deficiency (<20 ng/mL) was 30% in males and 46% in females. With increasing serum 25(OH)D concentrations categorized as <10, 10-20, 20-30, and ≥30 ng/mL, the mean PTH and bone turnover markers levels gradually decreasd in both sexes (p<0.001). There was an inverse relationship between the serum 25(OH)D and PTH concentrations in both genders, but no threshold of 25(OH)D at which PTH levels plateaued was observed. There were modest but significantly inverse relationships between the levels of 25(OH)D and bone turnover markers, but no plateau was observed for serum 25(OH)D levels up to 40 ng/mL.

Imaging proliferation in human leukemia-tumor bearing mice with (18)F-FLT: Comparison with (18)F-FDG PET.

Leukemia threatens human life due to its uncontrolled proliferative malignancy. 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) has been suggested as a new positron emission tomography (PET) tracer for imaging tumor proliferation. The aim of the study was to investigate the usefulness of (18)F-FLT PET for imaging human leukemia-tumor bearing mice, compared with fluorine-18-fluorodesoxyglucose ((18)F-FDG PET). In vitro the experiments of (18)F-FLT and (18)F-FDG uptake were performed in K562 cell lines at various time points and radioactive tracer uptake was measured in a gamma counter. (18)F-FLT and (18)F-FDG PET imaging were performed both in the same mouse when eight tumor-bearing mice models of human chronic myeloid leukemia were established successfully by injecting K562 cells. Regions of interest were drawn over the tumor, the crossed normal tissue was regarded as background and the ratio of tumor to non-tumor counts (T/NT) in tissues was calculated. A higher uptake of (18)F-FLT (15min, 5.73±0.05%; 30min, 5.90±0.06%; 60min, 6.16±0.19%; 120min, 6.32±0.08%) than that of (18)F-FDG (15min, 1.05±0.10%; 30min, 1.11±0.14%; 60min, 1.14±0.37%; 120 min, 1.36±0.25%) was observed in K562 cells in the tracer uptake experiment. Ratios of T/NT of (18)F-FLT PET (0.5h, 5.39±0.42; 1h, 4.88±0.43; 2h, 3.81±0.38) were higher than those of (18)F-FDG PET/CT (0.5h, 0.34±0.12; 1h, 0.21±0.06; 2h, 0.13±0.05) after injection. Both uptake and T/NT differences of (18)F-FLT versus (18)F-FDG were significant (P>0.05). In conclusion, (18)F-FLT and (18)F-FDG quantitative and semi-quantitative uptake measurements resulting from cell lines and PET imaging respectively suggested a promising potential of (18)F-FLT for metabolic imaging of human chronic myeloid leukemia.

Brain metastasis from follicular thyroid carcinoma: treatment with sorafenib.

BACKGROUND: Sorafenib has shown promise in the treatment of patients with advanced or metastatic thyroid carcinoma. However, its therapeutic effect has not been assessed in patients with brain metastases from follicular thyroid carcinoma (FTC). Here, we report a patient in whom this treatment was employed with a relatively favorable response. PATIENT AND METHODS: A 56-year-old woman had a thyroidectomy 8 years previously for FTC. She subsequently developed lung metastases, for which she received seven courses of radioiodine ((131)I) therapy. She developed right hemiplegia and other symptoms and was found to have a ≈ 5-cm lesion in the left parietal lobe. Radiosurgery with a total dose of 28 Gy (7 Gy/day, for 4 days) to treat her brain metastatic lesion was ineffective, and she was referred to us. We treated her with sorafenib, 200 mg orally, on a twice-daily basis. The effect of this intervention was assessed clinically and radiographically using Response Evaluation Criteria in Solid Tumors (RECIST). SUMMARY: Symptoms and signs improved dramatically and continuously after initiation of sorafenib treatment. Partial response (PR) in the brain metastasis and stable disease (SD) in lung metastatic lesions were verified by consecutive imaging findings for more than one year. Despite alopecia, other treatment-related adverse events did not occur. CONCLUSIONS: Targeted therapy such as with sorafenib could be an effective alternative therapeutic strategy in the treatment of progressive brain metastasis from differentiated thyroid carcinoma (DTC) when surgery, external beam radiation, and (131)I are not suitable or give poor outcomes. A paradigm of sustained low dose of sorafenib (200 mg,twice a day) may be well-tolerated without compromising maintenance of the therapeutic effect.

111In-labeled cystine-knot peptides based on the Agouti-related protein for targeting tumor angiogenesis.

Agouti-related protein (AgRP) is a 4-kDa cystine-knot peptide of human origin with four disulfide bonds and four solvent-exposed loops. The cell adhesion receptor integrin α(v)ß(3) is an important tumor angiogenesis factor that determines the invasiveness and metastatic ability of many malignant tumors. AgRP mutants have been engineered to bind to integrin α(v)ß(3) with high affinity and specificity using directed evolution. Here, AgRP mutants 7C and 6E were radiolabeled with (111)In and evaluated for in vivo targeting of tumor integrin α(v)ß(3) receptors. AgRP peptides were conjugated to the metal chelator 1, 4, 7, 10-tetra-azacyclododecane- N, N', N″, N'''-tetraacetic acid (DOTA) and radiolabeled with (111)In. The stability of the radiopeptides (111)In-DOTA-AgRP-7C and (111)In-DOTA-AgRP-6E was tested in phosphate-buffered saline (PBS) and mouse serum, respectively. Cell uptake assays of the radiolabeled peptides were performed in U87MG cell lines. Biodistribution studies were performed to evaluate the in vivo performance of the two resulting probes using mice bearing integrin-expressing U87MG xenograft tumors. Both AgRP peptides were easily labeled with (111)In in high yield and radiochemical purity (>99%). The two probes exhibited high stability in phosphate-buffered saline and mouse serum. Compared with (111)In-DOTA-AgRP-6E, (111)In-DOTA-AgRP-7C showed increased U87MG tumor uptake and longer tumor retention (5.74 ± 1.60 and 1.29 ± 0.02%ID/g at 0.5 and 24 h, resp.), which was consistent with measurements of cell uptake. Moreover, the tumor uptake of (111)In-DOTA-AgRP-7C was specifically inhibited by coinjection with an excess of the integrin-binding peptidomimetic c(RGDyK). Thus, (111)In-DOTA-AgRP-7C is a promising probe for targeting integrin α(v)ß(3) positive tumors in living subjects.

A first described chest wall metastasis from colon cancer demonstrated with (18)F-FDG PET/CT.

It is well known that, haematogenous colon cancer metastases are most commonly found in the liver, less likely in the lungs through the paravertebral venous system and rarely in other organs. Sporadic clinical cases of colon cancer metastases to the abdominal wall, the thyroid or the adrenal glands have been reported. Here, we present an uncommon case of chest wall metastasis from colon cancer demonstrated with 2-fluoro [fluorine-18]-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT). A 52 years old female patient was examined after she felt a swelling mass above her left breast. Tumor makers, such as serum cancer embryonic antigen (CEA) 146.22kU/L (normal range:0.00~37.0kU/L) and CA19-9 (258.16µg/L (normal range:0.00~10.0µg/L) and neuron-specific enolase (NSE) 78.2 (normal range: 0.00~17.00) were abnormally high. Chest CT revealed the soft tissue density mass on the left anterior chest wall with invasion of left 4th rib, and CT-guided biopsy showed a poorly differentiated adenocarcinoma of unkown origin. The patient was then referred for the (18)F-FDG-PET scan which was performed one hour after the intravenous injection of 370MBq of (18)F-FDG (Discovery Camera, VCT, GE, USA) and showed in addition to the chest mass, abnormal (18)F-FDG accumulation in both lungs, left supraclavicular and peritoneal lymph nodes. Furthermore, high (18)F-FDG uptake was detected in the sigmoid. Pathology findings from colonoscopy confirmed that this was a sigmoid colon adenocarcinoma. So far, chest wall metastasis from colon cancer as an initial finding has not been reported. Usually, an initial chest wall mass is hardly suspected to be a colon cancer metastasis. Abnormal serum tumor markers such as CEA and CA19-9 supported the diagnosis of a gastrointestinal adenocarcinoma. In our case, we found high serum NSE and normal findings of bowel wall on the CT scan, thus without the positive (18)F-FDG findings, one would probably consider as first diagnosis: chest wall metastasis from lung cancer, or a neuroendocrine tumor. The unusual finding in this case was that on the CT images there was no obvious local density of the intestine, no bowel wall thickening, or suspicious nodular lesions. Segmental (18)F-FDG accumulation seen in the sigmoid colon had early maximum standardized uptake value (SUV(max)) 7.3 and in 1h delayed estimation, 8.1. Colonoscopy showed that the (18)F-FDG-avid area at the colon was circular and thickened. "Hot" lesions found in both lungs, the supraclavicular and retroperitoneal lymph nodes by (18)F-FDG PET/CT scan were considered to be most probably metastases from colon adenocarcinoma. In conclusion, PET as a rather simple procedure and less dependent on bowel preparation diagnosed the primary colon cancer, its metastases and specifically a first described chest wall metastasis, while CT alone did not show the primary tumor.

Response to sorafenib at a low dose in patients with radioiodine-refractory pulmonary metastases from papillary thyroid carcinoma.

BACKGROUND: Sorafenib has shown promise in the treatment of patients with advanced or metastatic thyroid carcinoma. However, the optimal dose has not been established and data on Chinese population are not available. We conducted a study to assess the responses to sorafenib at a low dose of 200 mg twice daily in patients with progressive radioiodine-refractory pulmonary metastases from papillary thyroid carcinoma (PTC). PATIENTS AND METHODS: Eligible patients received sorafenib 200 mg orally twice daily. Responses were assessed using Response Evaluation Criteria in Solid Tumors and adverse events were assessed periodically. The end points included response rate and progression-free survival. RESULTS: Nine patients with radioiodine-refractory PTC were enrolled in the study and treated for a minimum of 13 weeks. The objective partial response rate was 33%. The stable disease rate was 44%. The mean progression-free survival was 42 weeks (95% confidence interval, 29.5 to 53.9). Two patients showed disease progression, and one of them died at 4 months after beginning of treatment. There was a marked and rapid change in the serum thyroglobulin level after start of treatment, with a mean decrease of 60% within 12 weeks, consistent with radiographic findings. Although the types of toxicities were consistent with other sorafenib trials, their severity was relatively mild. None of the patients discontinued sorafenib or reduced their dose because of treatment-related adverse events. CONCLUSION: Sorafenib at a dose of 200 mg twice daily has a potential therapeutic effect and is well tolerated in Chinese patients with PTC and radioiodine-refractory pulmonary metastases. Further study is warranted with a larger cohort of patients.

Bone turnover markers in patients with differentiated thyroid carcinoma after levothyroxine withdrawal.

BACKGROUND: Patients receiving postoperative radioiodine therapy for advanced differentiated thyroid carcinoma (DTC) are repeatedly in short-term thyroid hormone deficiency, whose bone turnover state is not fully understood. METHODS: Serum bone turnover markers (BTMs), bone specific alkaline phosphatase (BALP), type 1 procollagen N-terminal propeptide (P1NP), osteocalcin (OC), and the beta-isomerized C-terminal telopeptide of type 1 collagen (beta-CTx) were measured in 50 adult male DTC patients after 4-week suspension of levothyroxine replacement therapy and 40 matched euthyroid controls. Relationships between parameters of thyroid function (free triiodothyronine, FT3; free thyroxine, FT4; thyroid stimulating hormone, TSH) and the BTMs were studied. RESULTS: The patients had significantly decreased OC (-37.6%, P<0.001) and beta-CTx (-35.5%, P<0.001) compared with the controls, showing FT3 as the independent risk factor for OC (R2=0.425, P<0.001) and beta-CTx (R2=0.124, P<0.001). Partial correlation analysis showed that only FT3 was significantly correlated with OC after controlling FT4 and TSH (r=0.362, P=0.001). CONCLUSIONS: DTC patients have moderately decreased bone turnover after short-term suspension of thyroxine suppressive therapy, with serum FT3 concentration as the predominant and independent risk factor.

Predictive value of osteocalcin in bone metastatic differentiated thyroid carcinoma.

OBJECTIVES: To evaluate the diagnostic value of serum osteocalcin in the detection of bone metastases from differentiated thyroid carcinoma (DTC). DESIGN AND METHODS: Serum samples from DTC patients with (DTC BM+, n=19) or without bone metastases (DTC BM-, n=19), and matched healthy volunteers (n=30) were tested for serum osteocalcin with electrochemiluminescent immunoassay. RESULTS: Osteocalcin was higher in DTC BM+ than in DTC BM- patients (+35.8%, p=0.002), acting as an independent risk factor for bone metastases (R(2)=0.142, p=0.039). The sensitivity was 78.9% and the specificity was 63.2% at a cut-off value of 11.2 microg/L. CONCLUSIONS: Serial measurements of osteocalcin could be useful in the detection of bone metastases from DTC.

Outcome after high-dose radioiodine therapy for advanced differentiated thyroid carcinoma in childhood.

OBJECTIVE: To evaluate the clinical outcome in childhood patients receiving postoperative high-dose radioiodine therapy for advanced differentiated thyroid carcinoma. METHOD: Patients under 18 years old with neck diseases (n = 4) or distant metastases (n = 10) received postoperative radioiodine ablation and repeated treatments for a median of 2 (0.8 10) years with an averaged activity of 25.0 (7.0 72.2) GBq. RESULTS: Partial remission was achieved in 6, stable disease in 6 and progressive disease in 2 patients, without severe side effects except for two Grade 1 and one Grade 2 WHO haematological toxicity. The median survival time from diagnosis to the last treatment sessions was 5.3 (range, 0.7 14.5) years. CONCLUSION: High-dose radioiodine treatment was well tolerated with satisfactory outcome in childhood patients with advanced differentiated thyroid carcinoma.