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Programmed cell death receptor 1 (PD-1)/PD-1 ligand (PD-L1) maintains immune tolerance of normal tissues and mediates immune escape of tumors. For autoimmune thyroiditis, thyroid follicular epithelial cells inhibit the damage of T cells by up-regulating PD-L1 expression. With the application of immune checkpoint inhibitors (ICIs) in the field of cancer therapy, the incidence of immune-related thyroid disorders caused by ICIs has increased. Thyroid function should be monitored during and after ICIs treatment to promptly diagnose primary and (or) secondary thyroid disorders. The PD-1/PD-L1 signaling directly stimulates thyroid cancer cells, and exerts inhibitory effects on tumor-infiltrating immune cells. Combination of ICIs targeting PD-1/PD-L1 with chemo-radiotherapy or targeted therapy is a promising therapeutic strategy in the treatment of refractory thyroid cancers.
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Objective:To explore the expression of indoleamine 2, 3-dioxygenase 1(IDO-1), lymphocyte-activation gene 3 (LAG-3) and T cell immunoglobulin domain and mucin domain-containing molecule 3 (TIM-3) in differentiated thyroid cancer (DTC), and the value of them on prognosis.Methods:From May 2014 to November 2015, 119 DTC patients (33 males, 86 females, media age: 42 years) who underwent surgical treatment in Shanghai Sixth People′s Hospital were retrospectively analyzed. The expressions of IDO-1, LAG-3 and TIM-3 in the specimens were analyzed by immunohistochemistry and the expression differences between cancer tissues and normal tissues were analyzed by χ2 test. The correlation of IDO-1, LAG-3 and TIM-3 with clinical characteristics were analyzed using logistic regression analysis. The patients were followed up for 5 years, and the relationships of the progression-free survival (PFS) rate with the expressions of the three immune checkpoints were analyzed by Kaplan-Meier method, log-rank test and Cox proportional hazard models. Results:The overall 5-year PFS rate for 119 DTC patients (median follow-up time: 55(2-66) months) was 76.47%(91/119). The positive expression rates of LAG-3 and TIM-3 in cancer tissues were 21.85%(26/119) and 78.15%(93/119) respectively, which were significantly higher than those in normal thyroid tissues (7.34%(8/109) and 62.39%(68/109); χ2 values: 9.43, 6.81, both P<0.05). While the positive expression rate of IDO-1 was 70.59%(84/119) in cancer tissues, which did not show a significant difference from that in normal thyroid tissues (64.22%(70/109); χ2=1.05, P>0.05). Factors associated with the positive expression of LAG-3 included tumors with a single lesion (odds ratio ( OR)=0.248, 95% CI: 0.086-0.716, P=0.010). Log-rank test ( χ2=4.96, P=0.026) and multivariate Cox regression analysis (hazard ratio ( HR)=2.239, 95% CI: 1.013-4.592, P=0.046) suggested that LAG-3 positive expression was an independent risk factor of PFS. The same analysis of TIM-3 found no clinicopathological factors related to TIM-3 positive expression ( OR: 0.309-3.084, all P>0.05) and no association between TIM-3 positive expression and PFS ( χ2=0.008, P=0.929). Conclusion:The expressions of LAG-3 and TIM-3 are significantly increased in DTC tissues, and the higher expression of LAG-3 is associated with the worse prognosis, suggesting that LAG-3 may be a potential target for immunotherapy in DTC patients.
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Objective:To investigate the diagnostic efficacy and clinical application value of 99Tc m-diethylene triamine pentaacetic acid (DTPA) SPECT/CT imaging in cerebrospinal fluid leakage (CSFL). Methods:A total of 23 patients (11 males, 12 females; age (44.2±15.1) years) who underwent endoscopic repair surgery for suspected CSFL in Shanghai Jiao Tong University Affiliated Sixth People′s Hospital between April 2018 and January 2020 were retrospectively reviewed. All patients performed 99Tc m-DTPA SPECT/CT imaging, paranasal sinus high resolution CT (HRCT) and MRI before surgery. The diagnostic efficacies of 3 imaging techniques were calculated according to the result of surgery regarded as the golden standard. χ2 test was used to compare the qualitative and localized diagnostic efficacies of 3 imaging techniques for CSFL. Results:Of 23 patients, 21 were finally confirmed with CSFL and 24 leak locations were identified according to the results of surgery; the other 2 patients had no obvious CSFL and no leak location was found during the operation. The sensitivity and accuracy of 99Tc m-DTPA SPECT/CT, MRI and HRCT for the diagnosis of CSFL were 100%(21/21) and 95.7%(22/23), 85.7%(18/21) and 82.6%(19/23), 76.2%(16/21) and 69.6%(16/23), respectively. The accuracy of 99Tc m-DTPA SPECT/CT, MRI and HRCT for the diagnosis of leak location was 79.2%(19/24), 50.0%(12/24) and 45.8%(11/24), respectively. There was no statistically significant difference of diagnostic efficacies for CSFL among 3 imaging techniques ( χ2 values: 0.451-3.453, all P>0.05). For leak location, the diagnostic efficacy of 99Tc m-DTPA SPECT/CT was significantly better than that of MRI and HRCT ( χ2 values: 4.463, 5.689, both P<0.05). Conclusion:99Tc m-DTPA SPECT/CT imaging shows an excellent diagnosis efficacy not only for CSFL but also for leak location, which is helpful for guiding surgery.
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Objective:To explore the efficacy of percutaneous osteoplasty (POP) combined with 131I therapy in patients with bone metastases from differentiated thyroid carcinoma (DTC) and assess the survival. Methods:From Januray 2008 to January 2020, 29 DTC patients with bone metastases (16 males, 13 females, age range: 24-64 years) who received POP combined with 131I therapy in Shanghai Sixth People′s Hospital were retrospectively analyzed. Clinical data and characteristics of patients were analyzed. The efficacy and prognosis were evaluated based on the changes of serum thyroglobulin (Tg) and relieving condition of bone pain after the combined treatment. χ2 test was used to determine the association between clinical characteristics and efficacy, and Kaplan-Meier analysis was used to estimate the overall survival (OS) rate. Results:The biochemical response rate of serum Tg was 68.97% (20/29) after the combined treatment. For the influence on changes of serum Tg, whether or not combined with non-osseous distant metastasis, and cumulative dose of 131I treatment(≥22.2 vs <22.2 GBq) were statistically significant ( χ2 values: 5.448 and 4.371, both P<0.05). The rate of bone pain relief was 65.52%(19/29). Age (≥55 vs <55 years) and the cumulative dose of 131I treatment had statistically influences on bone relief ( χ2 values: 7.486 and 5.154, both P<0.05). The 5-years OS rate of patients was 87.68%, while the 10-years OS rate was 65.76%. Conclusion:POP combined with 131I therapy is effective on relieving the pain, reducing the serum Tg to some extent, and improving the long-term survival of DTC patients with bone metastasis.
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Objective To investigate the effects of microRNA (miR)106a on the proliferation, apoptosis, migration and invasion of thyroid cancer cells in vitro.Methods 8505C and CGTH-W3 cell lines were used in the study.Overexpression and inhibition of miR106a were achieved by transfection of lentiviral vectors.The changes of gene expression were detected by quantitative real-time PCR (qRT-PCR) and Western blot analysis.Cell viability and apoptosis were evaluated by MTT assay and flow cytometry analysis, respectively.The caspase-9 activities in parental CGTH-W3 and 8505C cells and transfected sublines were measured.Wound healing and Transwell invasion assays were performed to determine cell migration and invasion.Two-sample t test and one-way analysis of variance were used to analyze the data.Results The level of miR106a in 8505C was up-regulated when compared to that in CGTH-W3 cells (t=10.28, P<0.01).Scrambled control and miR106a(-) were also successfully transfected into cells.Inhibition of miR106a suppressed cell viability, migration and invasion while promoted apoptosis and caspase-9 activity of 8505C cells, with significant differences among 8505C, 8505C-control, 8505C-miR106a(-) cells (F=147.0, 19.2, 100.3, 537.8, 804.3;all P<0.01).Overexpression of miR106a promoted cell viability, migration and invasion while inhibited apoptosis and caspase-9 activity of CGTH-W3 cells, with significant differences among CGTH-W3, CGTH-W3-control, CGTH-W3-miR106a(+) cells(F=9.2, 13.3, 622.8, 12.3, 19.6, all P<0.01).In addition, miR106a may up-regulate the expression of MEKK2 and p-ERK1/2.Conclusion Acting as an onco-miR, miR106a might promote the proliferation, migration and invasion of thyroid cancer cells and inhibit their apoptosis in vitro.
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DTC is the most common endocrine carcinoma and its routine treatment consists of total thyroidectomy and 131I thyroid remnant ablation.Currently,standard follow-up for DTC comprises Tg measurement and neck ultrasound as well as an additional radioiodine scan when indicated.As thyroid cells are assumed to be the only source of Tg in serum,circulating Tg serves as an excellent marker of persistent or recurrent disease in DTC follow-up.With the development of highly sensitive Tg assays,now it is possible to detect very low Tg concentrations which reflect minimal amounts of thyroid tissue without the need for TSH stimulation.This review is to introduce clinical implications of highly sensitive Tg assays.
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Thyroid cancer is the most frequent endocrine cancer and its incidence is progressively growing.Bone metastasis is are not uncommon in clinic.The efficacy is limited for patients with single treatment.However,multi-disciplinary combination therapy,combined with thyroid surgery,bone tumor surgery,nuclear medicine could get better outcomes and improve the life quality of the patients.
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Background and purpose:The evaluation of treatment response is one of the most important building blocks in determining the best strategy for the management of malignant tumors. In lymphoma and several solid cancer types, PET/CT-based response evaluation has been shown to be valuable, especially in visualizing the effect of the targeted treatment, which induces tumor activity changes not necessarily followed by tumor shrinkage. This study aimed to evaluate the role of18F-FDG PET/CT in the monitoring of response to sorafenib treatment in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients; and to compare the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) with the European Organization for Research and Treatment of Cancer (EORTC) criteria.Methods:This was a single-center retrospective analysis of 14 patients with RR-DTC treated with sorafenib in the period from Dec. 2011 to Dec. 2014. A Wilcoxon signed-rank sum test was used to assess the differences in percentage changes between the sum of diameter and ∑SUVmax. These values of responses were statistically compared using the chi-square test (Fisher’s exact test). The differences in PFS between response categories according to either RECIST 1.1 or the EORTC criteria were evaluated using the Wilcoxon signed-rank sum test. The Spearman rank correlation coefficient was estimated between PFS and either morphologic (RECIST 1.1) or metabolic response (EORTC criteria) categories.Results:There was an agreement between the RECIST 1.1 and EORTC criteria in 10 of the 14 patients (χ2=2.345,P=0.424). The remaining 4 patients with SD in-cluded 2 patients with PMR and 2 patients with PMD. Differences in PFS among different response categories according to either RECIST 1.1 (χ2=8.571,P=0.003) or EORTC criteria (χ2=8.781,P=0.003) were statistically significant. Correlations were found between PFS and either morphologic (r=0.741,P=0.002) or metabolic (r=0.816,P=0.0004) response criteria. Conclusion:18F-FDG PET/CT imaging is of value in the monitoring of response to sorafenib in patients with RR-DTC. Although RECIST 1.1 and EORTC criteria agree in 71.4% patients, PET-based metabolic response criteria seems to be more accurate in predicting therapeutic outcome and may be more suitable than morphologic response criteria for the eval-uation of response to targeted therapy.
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Objective To compare signal characteristics and image qualities of MR diffusion-weighted imaging (DWI)at 1.5T and 3.0T in patients with the complex adnexal masses.Methods Magnetic resonance imaging including routine MRI and DWI(b=0 s/mm2 ,400 s/mm2 , 600 s/mm2 ,800 s/mm2 ,1 000 s/mm2 )of 1.5T (50 patients with 31 benign and 1 9 malignant lesions )and 3.0T (53 patients with 29 benign and 24 malignant lesions )were performed in 103 patients with histopathologically proved adnexal masses.The optimal b value was analyzed,and the apparent diffusion coefficient (ADC)value and signal intensity (SI)value and contrast to noise ratio (CNR)of solid and cystic components in adnexal masses from both 1.5T and 3.0T MR were respectively compared statistically.Results The 800 s/mm2 was the optimal b value in demonstrating adnexal masses at 1.5T and 3.0T.The CNR of solid and cystic components in adnexal masses were significantly higher at 3.0T than at 1.5T on all b values(all P =0.000).The difference in ADC value of solid lesions between 1.5T and 3.0T on all b values DWI had no statistically significant (all P >0.05),nor did the difference in SI value of solid lesions as well as ADC value of cystic lesions on b800 DWI(P >0.05).Conclusion MR diffusion-weighted imaging at 3.0T compared with 1.5T has quantitative and qualitative advantages of evaluating for adnexal masses,while the 800 s/mm2 is the optimal b value for both of them.
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Objective To investigate the patterns of change in thyroid functional parameters ( serum TSH,FT3, and FT4 ) in patients with papillary thyroid cancer (PTC) before and after the initial 131I treatment for thyroidal remnant ablation. Methods Seventy-four PTC patients, treated with 3.7 GBq 131 I therapy, were divided into two groups, group A with serum TSH＜30 mIU/L and group B with serum TSH ≥30 mIU/L the day before 131I treatment. Five days after the treatment, the patients were re-examined for serum FT3, FT4, and TSH levels.Results In group A (22 cases), 5 days after the 131I ablation treatment, FT4significantly increased by 88% and FT3 by 87%, while TSH decreased by 87% (all P＜0. 05 ), and 45% (10/22)cases manifested the signs of transient thyrotoxicosis. In group B (52 cases)after treatment, individual variance of FT3 and FT4 was obvious,with FT4 decreased by 13% and FT3 decreased by 14% ( both P＜0. 05 ), while TSH slightly increased by an average of 6% ( P＞0.05 ). Conclusion After the initial 131 I ablation therapy for thyroidal remnant, the thyroid hormone levels in some PTC patients significantly increase while in others may slightly decrease in the early stage. The supplementary and suppressive therapy after 131I ablation for PTC patients might be individualized depending on the thyroid hormone determination.
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Objective To investigate the application value of free plasma metanephrines metanephrine(MN) and normetanephrine (NM) measured with enzyme immunoassay (EIA), NM in diagnosis of pheochromocytoma. Methods Histologically confirmed pheochromocytomas (n=30) and control patients with hypertension (n=51) were enrolled in the study. Blood tests for free plasma metanephrines(MN and NM) were performed with a commercially available EIA kit and the results were compared with [3] I-metaiedobenzyl guanidine (MIBG) whole body scan findings. Results The whole body scan was positive in all pheochromocytoma patients and negative in 15 control patients with 100% accuracy. The median values in the 2 groups were 59.3 ng/L and 33.7 ng/L (Z=-2. 440, P<0.05) for MN, 652.0 ng/L and 36. 3 ng/L (Z=-6.699, P<0.001) for NM, with 96. 7% (29/30) sensitivity, 86. 3% (44/51)specificity and 90.1% (73/81) accuracy for their combination ( either or both positive). There was no significantly statistical difference when compared with 13I-MIBG whole body scan findings (100. 0% ,P >0. 05). Conclusion The results show that the EIA method may be eligible as an alternative to HPLC for plasma metanephrines determination in the identification of pheochromocytoma.