Hongliang Fu

Low- or high-dose radioiodine remnant ablation for differentiated thyroid carcinoma: a meta-analysis.

CONTEXT There is uncertainty over the dose of (131)I required for thyroid remnant ablation. Most previous studies have been inadequately powered to establish the best fixed dose of (131)I for effective ablation. OBJECTIVE The aim of the study was to assess the effects of low- vs high-dose regimens of radioiodine in thyroid remnant ablation for patients with differentiated thyroid carcinoma. DATA SOURCES Sources included the Cochrane Library, MEDLINE, EMBASE, and SCOPUS (all until September 2012). STUDY SELECTION Randomized controlled trials that assess the efficacy of low- or high-dose of radioiodine ablation of thyroid remnants were collected. DATA EXTRACTION Two authors performed the data extraction independently. DATA SYNTHESIS Nine randomized controlled trials involving 2569 patients were included. The 1100-MBq vs the 3700-MBq radioiodine showed no statistically significant difference in successful thyroid remnant ablation (risk ratio [RR], 0.91 [0.79 to 1.04]; P = .15), both the 1100 vs the 1850 MBq (RR, 0.95 [0.83 to 1.10]; P = .52) and the 1850 vs the 3700 MBq (RR, 1.00 [0.85 to 1.17]; P = .98) also showed no significant differences (95% confidence intervals were calculated for each estimate). Also, no significant differences existed in quality-of-life scores on the SF-36 between different (131)I-dose groups both on the day of ablation (RR, 0.15 [-0.65 to 0.96], P = .71; I(2) = 29%, P = .24) and 3 months after ablation (RR, -1.1 [-2.37 to 0.17], P = .09; I(2) = 22%, P = .26). A low dose of 1100 MBq radioiodine showed significant benefits in reducing adverse effects (total RR, 0.65 [0.55 to 0.77], P < .1; I(2) = 31%, P =.14) and shorter hospital isolation (RR, 0.4 [0.32 to 0.50]; P < .05). CONCLUSIONS The low dose of 1100 MBq radioiodine activity is sufficient for thyroid remnant ablation as compared to 3700 MBq radioiodine activity with similar quality of life, less common adverse effects, and a shorter hospital stay.

The role of single-photon emission computed tomography/computed tomography for precise localization of metastases in patients with differentiated thyroid cancer

PURPOSE It is very important in the management of patients with differentiated thyroid cancer (DTC) to precisely localize the foci of I-131 uptake, but it is difficult because of a lack of anatomic landmarks. The purpose of this study was to investigate the added value of I-131 single-photon emission computed tomography (SPECT)/computed tomography (CT) fusion imaging using a hybrid system in patients with DTC. METHODS Ninety-four patients with DTC underwent I-131 SPECT/CT using a hybrid tomography consisting of a dual-head variable-angle gamma camera and a low-dose X-ray tube. Results were compared with I-131 whole-body scan (WBS). SPECT/CT was performed 5-7 days after administration of a therapeutic dose of I-131. Fusion images were constructed by combining the digital CT and SPECT images on a computer workstation. RESULTS Compared with I-131 WBS, SPECT/CT imaging had improved the precise localization in 21% (20/94) of patients. In addition, SPECT/CT provided additional clinical data in 12 of the patients examined (12/94) and also caused physicians to reconsider the (131)I therapeutic approach in 22 patients. CONCLUSION The results of the current study indicate that the addition of I-131 SPECT/CT to WBS can improve the localization of metastases in patients with DTC. It may also detect metastases missed by WBS and adjust the therapy plan.

Dedifferentiation of differentiated thyroid carcinoma cell line FTC-133 is enhanced by 131I pretreatment

INTRODUCTION Differentiated thyroid carcinoma (DTC) usually has a high iodine uptake. However, dedifferentiation of DTC with decreased or no radioiodine ((131)I) uptake is observed in clinical practice, with poor prognosis. The aim of this study was to investigate the effects of (131)I radiation on radioiodine uptake (RAIU) and the expression of thyroid-specific molecules. METHODS FTC-133 cells were treated with (131)I, the dosage dictated by methylthiazol tetrazolium test results and preliminary experiments. The experimental cell group was incubated with (131)I for 48 h and then cultured for 3 months in (131)I-free medium. The control group was set without (131)I. Primary cells were defined as the blank group. Following treatment, RAIU was measured with a gamma counter as the counts/cell number. Na(+)/I(-) symporter (NIS), thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO) and thyroglobulin (Tg) levels were detected by Western blotting and radioimmunoassay, and their mRNAs were detected by real-time polymerase chain reaction. RESULTS RAIU of FTC-133 cells decreased gradually after coincubation with (131)I and did not recover even if (131)I was removed. The relative RAIU of the control and experimental groups was 0.567 and 0.182, respectively, a statistically significant difference (P<.01). Expression of NIS, TSHR, TPO and Tg decreased in the experimental group to a statistically significant degree compared to that of controls (P<.05). CONCLUSION Changes in the mRNA levels were in accordance with the expression of thyroid-specific proteins. Thus, FTC-133 cells undergo dedifferentiation during long-term culture in vitro, and (131)I may promote this progress.

Use of 18F-FDG-PET-CT for Assessment of Response to Neoadjuvant Chemotherapy in Children With Wilms Tumor.

Purpose: The aim of this study was to evaluate the predictive value of fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG-PET-CT) in the assessment of histologic response to neoadjuvant chemotherapy in children with Wilms tumors (WTs). Materials and Methods: We prospectively registered 12 patients with WTs who were treated with 2 cycles of neoadjuvant chemotherapy and surgery. All patients underwent sequential 18F-FDG-PET-CT before (PET-CT1) and after (PET-CT2) neoadjuvant chemotherapy. Maximum standardized uptake value (SUVmax) was measured on PET-CT1 (SUV1) and PET-CT2 (SUV2). The percentage change in SUVmax (SUVmax reduction) was calculated. After surgery the effects of neoadjuvant chemotherapy were graded histopathologically: ≥90% necrosis indicated a good response and <90% necrosis was considered a poor response. The correlation between SUVmax reduction and histologic response was estimated using the Spearman correlation coefficient. Results: Among the 12 patients who underwent PET-CT before and after chemotherapy, SUVmax reduction was significantly different between the good response group and the poor response group (P=0.035). A significant, in terms of P value, correlation was found between pathologic response and SUVmax reduction (r=0.700; 95% confidence interval, 0.060-0.935; P=0.011). A threshold of 66% reduction in SUVmax was identified, with which partition, there were 8 good histologic responders (≥66% decrease in SUVmax) and 4 poor responders. The histologic complete response rate of the good responders was 87.5%, whereas that of poor responders was 0%. SUV1≥7 and SUV2≥2.4 were both considered to be with high risk of recurrence. In patients with SUV1≥7, 4/5 cases relapsed and 4/6 patients with SUV2≥2.4 relapsed. Conclusions: As there seems to be a good correlation of changes in SUVmax and histologic response, PET-CT has the potential of predicting the response to neoadjuvant chemotherapy in children with WT. SUV1 and SUV2 by themselves might be a good prognosticator of the clinical outcome of WT pediatric patients treated with International Society of Pediatric Oncology protocols, although the reduction rate of SUVmax is much less powerful for prognosis.

Comparison of 18F-AIF-NOTA-PRGD2 and 18F-FDG uptake in lymph node metastasis of differentiated thyroid cancer.

A widespread application of integrin αvβ3 imaging has been emerging in both pre-clinical and clinical studies. But few studies reported its value as compared with 18F-FDG PET, especially for differentiated thyroid cancer (DTC). In this study, we compared the tracer uptake of 18F-AIF-NOTA-PRGD2 and 18F-FDG in lymph node metastasis of DTC to evaluate 18F-AIF-NOTA-PRGD2 as compared with 18F-FDG. Methods 20 DTC patients with presumptive lymph node metastasis were examined with 18F-AIF-NOTA-PRGD2 and 18F-FDG PET/CT. 16 patients undergoing fine needle aspiration biopsy (FNAB) were evaluated by cytology results. For lesions without FNAB, the findings of clinical staging procedures served as the standard of reference (including neck ultrasound and serum thyroglobulin). Results A total of 39 presumptive lymph node metastases were visualized on PET/CT images. 35 lesions were confirmed as malignant by FNAB and other clinical findings. The mean 18F-AIF-NOTA-PRGD2 in radioactive iodine-refractory (RAIR) lesions and benign lesions were 2.5±0.9 and 2.8±0.9 respectively. The mean SUV for 18F-FDG in all malignant lesions was 4.5±1.6 while in benign lesions it was 3.3±1.2. For all malignant lesions, the mean SUV for 18F-FDG was significantly higher than that for 18F-AIF-NOTA-PRGD2 (P<0.05). No significant correlation was found between the SUVs of 18F-AIF-NOTA-PRGD2 and 18F-FDG for 35 lesions (r = 0.114, P = 0.515). Moreover, 15 lesions of which the diameter larger than 1.5cm had higher 18F-AIF-NOTA-PRGD2 uptake as compared with the lesions smaller than 1.5cm. Conclusion Although most lymph node metastases of DTC showed abnormal uptake of 18F-AIF-NOTA-PRGD2, its diagnostic value was inferior to 18F-FDG. No correlation was found between the uptake of 18F-AIF-NOTA-PRGD2 and 18F-FDG, which may suggest the two tracers provide complementary information in DTC lesions.

Re-induction of cell differentiation and 131I uptake in dedifferentiated FTC-133 cell line by TSHR gene transfection

INTRODUCTION Radioiodine therapy is commonly used to treat differentiated thyroid cancer (DTC), but a major challenge is dedifferentiation of DTC with the loss of radioiodine uptake. TSHR is a key molecule regulating thyrocyte proliferation and function. This study aimed to test the therapeutic potential of TSHR in dedifferentiated DTC by gene transfection in order to restore cell differentiation and radioiodine uptake. METHODS Dedifferentiated FTC-133 (dFTC-133) cells were obtained by monoclonal culture of FTC-133 cell line after (131)I radiation. Recombinant plasmid pcDNA3.1-hTSHR was transfected into dFTC-133 cells by using Lipofectamine 2000 reagent. Immunofluorescence analysis was carried out to confirm TSHR expression and its location. Radioiodine uptake assay was thereafter investigated. mRNAs and proteins of TSHR and other thyroid differentiated markers were detected by real-time PCR and western blot respectively. RESULTS Among the thyroid specific genes in dFTC-133 cells with stable low radioiodine uptake, TSHR was down-regulated most significantly compared with FTC-133. Then, after TSHR gene transfection, augmented expression of TSHR was observed in dFTC-133 cell surface and cytoplasm by immunofluorescence analysis. It was found that (125)I uptake was 2.9 times higher (t=28.63, P<.01) in cells with TSHR transfection than control. The mRNAs of TSHR, NIS, TPO and Tg were also significantly increased by 1.7 times (t=13.8, P<.05), 4 times (t=28.52, P<.05), 1.5 times (t=14.43, P<.05) and 2.2 times (t=19.83, P<.05) respectively compared with control group. CONCLUSION Decreased TSHR expression correlated with FTC-133 ongoing dedifferentiation. TSHR transfection contributed to the re-differentiation of dedifferentiated thyroid follicular carcinoma cells.

The study of influence factors on 131I treatment of differentiated thyroid carcinoma with lymph node metastases

OBJECTIVE Thyroid carcinoma is the most common malignant endocrine tumor, which comprises 1% in all human tumors. As for differentiated thyroid carcinoma (DTC), lymph nodes are the most common metastatic site for which the major treatment is (131)I therapy. This retrospective study aimed to investigate the therapeutic effect and analyze the influence factors on (131)I treatment of DTC with lymph node metastases. METHODS Collecting clinical data of 66 DTC patients with lymph node metastases at the Department of Nuclear Medicine, Xin Hua Hospital from January 1996 to January 2006. Investigating the therapeutic effect firstly and then dividing 66 patients into an eliminated group and an uneliminated group according to the evaluation criteria of the therapeutic effect. Finally, observing the differences between the two groups. The significant differences in the following 10 influence factors were determined: gender, age, pathological type, the periods from the thyroidectomy to the first (131)I therapy, when the metastases were found, the history of resection of the lymph node metastases, the uptake of (18)F-FDG in the lymph node metastases, remnant thyroid, multiple metastases, and the cumulative dose of (131)I. This retrospective study was analyzed by Student t test, chi(2) test, and Fishers exact test. RESULTS Of all 66 patients with lymph node metastatic DTC treated by (131)I therapy, 31 patients (46.97%) had complete elimination. Twenty-seven patients were improved or controlled, and the overall effective rate reached 87.88%. The elimination rate of lymph node metastases in patients with resection was significantly higher than in those without resection (chi(2)=5.561, P=.018<0.05). The elimination rate of lymph node metastases in patients with (18)F-FDG uptake was significantly higher than in those without (18)F-FDG uptake (chi(2)=4.014, P=.045<.05). There was no significant difference in the elimination rate among the patients with various values in the other eight factors. CONCLUSIONS (131)I Therapy is an effective treatment of lymph node metastatic DTC. The history of resection of the lymph node metastases and the uptake of (18)F-FDG in the lymph node metastases were the influence factors on the therapeutic effect, whereas the other eight factors were probably not.

Efficacy of lentiviral-mediated transfection of hTSHR in poorly differentiated thyroid carcinoma cell line.

INTRODUCTION Dedifferentiated thyroid cancer is often incurable because it does not respond to radioiodine. This study aimed to investigate iodide uptake and the expressions of thyroid-specific molecules after the transfection of human thyrotropin receptor (hTSHR) gene in poorly differentiated follicular thyroid cancer cell line (FTC-133). METHODS pGC-FU-hTSHR-GFP-lentivirus and pGC-FU-GFP-lentivirus were added into FTC-133 cells respectively. The parental cells were defined as the blank group. Cells transduced with pGC-FU-GFP and pGC-FU-hTSHR-GFP were defined as the control group and experimental group respectively. The efficiency of transfection was observed under a fluorescence microscope. (125)I uptake by FTC-133 was analyzed by measuring the radioactivity. Real time-PCR, western blotting and radioimmunoassay were applied to detect the expressions of mRNAs and proteins of Na(+)/I(-) symporter (NIS), thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO) and thyroglobulin (Tg) in FTC-133. RESULTS The green fluorescence was present in 80% of the transduced cells under fluorescence microscope. The iodine uptake of cells transduced with pGC-FU-TSHR-GFP was 3.3 times higher than that in the other two groups (P<0.01). NIS, TSHR, TPO and Tg had been significantly up-regulated in the experimental group as compared to the control group (P<0.01) and the blank group (P<0.01). CONCLUSION The hTSHR transfection in FTC-133 improved the expression of thyroid-specific molecules including TSHR, NIS, TPO and Tg and radioiodide uptake.

Expression of Notch 1 receptor associated with tumor aggressiveness in papillary thyroid carcinoma

Aim The aim of this study was to assess if the expression of Notch 1 receptor is associated with tumor aggressiveness in papillary thyroid carcinomas (PTCs). Patients and methods By searching the electronic medical record system of Xin Hua Hospital, all cases of PTC patients who underwent thyroidectomy in the hospital between 2013 and 2014 were retrieved. Then, the cases of patients who had a history of any other malignancy or whose thyroid tumor specimen was not available for assay were rejected. Finally, 68 cases of PTC patients were obtained. Formalin-fixed paraffin-embedded tissue blocks of these patients were studied by immunohistochemistry to learn the expression of Notch 1 receptor. Meanwhile, the clinical data of these patients including sex, age, size of the tumor, presence of node metastasis or distant metastasis, and presence of capsule invasion and tumor multicentricity were collected. Pearson’s chi-square test or Fisher’s exact test was used for measuring statistical differences in categorical variables. All the statistical tests were two-sided. A P-value <0.05 was considered to be statistically significant. Results A total of 19 male and 49 female PTC patients with a mean age of 44.8±13.6 years (range 18–78 years) were studied. Notch 1 receptor expression was found in 15/68 (22%) samples of PTC. The expression of Notch 1 receptor was significantly associated with tumor size (P=0.021), distant metastasis (P=0.008), capsule invasion (P=0.001), tumor multicentricity (P=0.018), and age (P=0.033). However, the expression of Notch 1 receptor was not significantly correlated with node metastasis (P=0.096) and sex (P=0.901). Conclusion The expression of Notch 1 receptor is associated with tumor aggressiveness in PTC, and may be used as a molecular marker of tumor invasiveness in PTC. PTC patients who show positive expression of Notch 1 receptor may benefit from radioiodine remnant ablation.