Assessment of age as different variable types for determining survival in differentiated thyroid cancer.

PURPOSE: The current tumor, node, metastasis (TNM) system uses an age of 55 years as a threshold for differentiated thyroid cancer (DTC). The aim of our study was to explore the concept of using age as a continuous variable. METHODS: A total of 36,559 patients with DTC in the Surveillance, Epidemiology, and End Results (SEER) database and 7491 patients in our centers were enrolled. Overall survival (OS) and cancer-specific survival (CSS) were compared. Furthermore, the different statistical model performance of the 6th edition TNM system and age cutoffs for papillary (PTC) and follicular thyroid cancer (FTC) were assessed. Then, a nomogram was built and validated to evaluate the efficacy of age as a continuous variable for predicting survival. RESULTS: The OS and CSS of patients with DTC were significantly increased in patients <55 years compared with those aged ≥55 years. However, no significant differences in prognosis were observed in certain groups as patients between 50 and 60 years were stratified by 1-year increments. Furthermore, the highest concordance index (C-index) was observed in the TNM staging without an age cutoff in SEER database (0.895), our two centers (0.877) and receiver operating characteristic (ROC) curves showed different age cutoffs for PTC and FTC. More importantly, the nomogram incorporating age as a continuous variable showed a favorable area under the ROC curve and calibration for training and validation groups. CONCLUSIONS: The utilization of age as a continuous variable is a rational approach for predicting outcome in DTC patients.

Prognostic implications of extranodal extension in papillary thyroid carcinomas: A propensity score matching analysis and proposal for incorporation into current tumor, lymph node, metastasis staging.

BACKGROUND: The current American Joint Committee on Cancer tumor, lymph node, metastasis cancer staging system for papillary thyroid carcinoma places low weight on extranodal extension. This study examined the prognostic implications of extranodal extension in papillary thyroid carcinoma patients and attempted to design a new staging system incorporating extranodal extension. METHODS: We reviewed data from 6,165 consecutive papillary thyroid carcinoma patients from 2012 to 2018. Patients with extrathyroidal extension or extranodal extension were included and then divided into 3 groups: extrathyroidal extension (papillary thyroid carcinoma with extrathyroidal extension but without extranodal extension, N = 457); extranodal extension (papillary thyroid carcinoma with extranodal extension but without extrathyroidal extension, N = 116); and extrathyroidal extension and extranodal extension (papillary thyroid carcinoma with both extrathyroidal extension and extranodal extension, N = 116). Recurrence-free survival and cancer-specific survival were compared before and after adjusting for differences using propensity score matching owing to observed heterogeneity in baseline characteristics in the original cohort. Recurrence-free survival and cancer-specific survival were also compared between patients with and without extranodal extension after matching at a 1:1 ratio. Cox proportional hazards regression analyses were used to identify the relationships of factors associated with structural recurrent disease in the node-positive subset. Then a new staging system incorporating extranodal extension was established, and the discrimination of the new staging system for recurrence-free survival and cancer-specific survival was investigated. RESULTS: Of the 6,165 patients with papillary thyroid carcinoma, extrathyroidal extension was found in 573 (9.3%) patients, and extranodal extension was observed in 232 (3.8%) patients. The recurrence-free survival and cancer-specific survival rates of patients with extranodal extension were similar to those of patients with extrathyroidal extension (all P > .05). Patients with extrathyroidal extension and extranodal extension experienced worse recurrence-free survival than patients with extrathyroidal extension or extranodal extension and even worse cancer-specific survival than patients with extrathyroidal extension (all P < .05). The recurrence-free survival and cancer-specific survival rates of patients with extranodal extension were worse than those of patients without extranodal extension (P = .003; P = .048). Cox proportional hazards regression analysis demonstrated that after propensity score matching, extranodal extension (hazard ratio 1.911; 95% confidence interval 1.568-3.609; P < .001) remained an independent predictor of structural recurrent disease in patients with node-positive papillary thyroid carcinoma. After incorporating extranodal extension into the current tumor, lymph node, metastasis classification, the new staging system presented a better discrimination for recurrence-free survival and cancer-specific survival for those with lymph node metastasis. CONCLUSION: Papillary thyroid carcinoma patients with extranodal extension present worse prognosis, and incorporating extranodal extension in tumor, lymph node, metastasis classification identifies poor-risk patients more accurately.

Intraoperative application of inactivated Pseudomonas aeruginosa in patients undergoing lateral neck dissection for metastatic thyroid cancer: A randomized, parallel group, placebo-controlled trial.

BACKGROUND: We hypothesize that the intraoperative, prophylactic application of Pseudomonas aeruginosa can decrease postoperative chylous fistula and enhance recovery after surgery in patients with thyroid cancer undergoing lateral neck lymph node dissection. METHOD: In this single-center trial, we assigned randomly 200 patients with thyroid cancer who had proven lateral lymph node metastasis to groups receiving either 2 mL Pseudomonas aeruginosa spray (Pseudomonas aeruginosa group) or 2 mL saline spray (control group) in the lateral cervical surgical field. The primary end points were the rate of chylous fistula, mean difference in the duration and volume of drainage fluid, days of postoperative hospital stay, and overall cost. The secondary end points included the red blood cell count and triglyceride level in the drainage, the white blood cell count in the blood, fever, local pain, development of a pleural effusion, and tumor recurrence. RESULTS: Patients treated with Pseudomonas aeruginosa had a decrease in macroscopic chylous fistula compared with controls (0 vs 6%, P = .025). There were fewer days to drain-tube removal, a less volume of drainage fluid, fewer postoperative days of hospital stay, and a lesser red blood cell count in the drainage fluid in the Pseudomonas aeruginosa group than in the control group (all P < .05). No severe side effects of the Pseudomonas aeruginosa spray with respect to fever, pain, or pleural effusion were observed. Pseudomonas aeruginosa spraying did not affect postoperative recurrence of the thyroid cancer. CONCLUSION: Intraoperative spraying of inactivated Pseudomonas aeruginosa in the lateral neck compartment can decrease the development of chylous fistula and enhance postoperative recovery.

Using a nomogram based on preoperative serum fibrinogen levels to predict recurrence of papillary thyroid carcinoma.

BACKGROUND: Hyperfibrinogenemia is increasingly being recognized as an important risk factor related to cancer stage, development and outcomes. We evaluated whether preoperative serum fibrinogen levels predict recurrence of papillary thyroid carcinoma (PTC). METHODS: We retrospectively collected data for 1023 PTC patients who underwent surgery at our institution from Aug 2014 to Aug 2016. In total, 414 patients (from Aug 2014 to Dec 2015) were used as the training set to build the model, and 609 patients (from Jan 2016 to Aug 2016) were used as the testing set to validate the model. RESULTS: In the training set, PTC cases with high serum fibrinogen levels were more likely to have multiple PTCs (P = 0.001) and to exhibit surrounding tissue or organ invasion (both P < 0.01). Moreover, PTC patients with higher serum fibrinogen levels were also more likely to have an advanced tumor stage (T, P = 0.001) and distance metastasis (P < 0.001), and these patients had a significantly higher rate of postoperative PTC recurrence (P = 0.002). All of these findings were validated in the testing set. The results of univariate and multivariate analyses indicated that hyperfibrinogenemia was a risk factor for PTC recurrence. The identified risk factors were incorporated into a nomogram and validated using the testing set (C-index = 0.811, 95% CI: 0.762-0.871). CONCLUSION: PTC cases with hyperfibrinogenemia are more likely to have an advanced TNM stage and have a higher rate of PTC recurrence. Our nomogram could be used to objectively and accurately predict PTC recurrence in a clinical setting.

A Nomogram Based on the Characteristics of Metastatic Lymph Nodes to Predict Papillary Thyroid Carcinoma Recurrence.

BACKGROUND: The extent of metastatic lymph node (LN) invasion was not considered in the postoperative stratification of the recurrence risk of papillary thyroid carcinoma (PTC) in the 2015 American Thyroid Association (ATA) guidelines, and the recommended risk stratification cannot be applied to individuals. A nomogram based on these risk factors was developed based on the risk factors to predict individual recurrence risk. METHODS: Data from 1788 PTC patients at the West China Hospital and 306 cases from the Shang Jin Nan Fu Hospital between August 2013 and July 2015 were included in this study. The 1788 cases were randomized into two groups-the training set (896 cases) and the testing set (896 cases)-and 306 cases were used as the external evaluation set. RESULTS: Univariate and multivariate analyses identified the following independent prognostic factors associated with recurrence in the three independent sets and the combined set (p < 0.01): LN invasion in the capsule or organ, more than five metastatic LNs, and a largest metastatic LN diameter >3 cm. Importantly, PTC patients showed significantly different recurrence rates depending on the extent of LN invasion in the three sets and in the combined set (p < 0.001). The nomogram was developed based on the risk factors in the training set and was validated in the independent testing and validation sets. CONCLUSION: The largest LN metastasis diameter, number of metastatic LNs, and the extent of extranodal invasion had significant prognostic value for predicting the risk of recurrence. Based on the characteristics of the thyroidal PTC lesion and metastatic LNs, the nomogram showed good prediction of recurrence in individual PTC patients.

Independent predictors and lymph node metastasis characteristics of multifocal papillary thyroid cancer.

The multifocal papillary thyroid cancer (PTC), with more aggressive and poorer prognosis, is not rare in papillary histotype. Few studies evaluated risk factors and lymph node metastasis in multifocal PTC. The aim of this present study focusing on risk factors and lymph node metastasis characteristics in multifocal PTC was excepted to assist clinical decisions regarding surgery.It was a retrospective study. The 1249 consecutive patients with PTC were reviewed. Of these, 570 patients who met the criteria were selected: 285 with solitary papillary thyroid cancer and 285 with multifocal PTC. The risk factors and lymph node metastasis in multifocal PTC were investigated by univariate and multivariate analysis.Multifocal PTC showed a higher positive rate of capsular invasion, extrathyroidal extension, tumor size >10 mm, pathological T classification, N+ stage, local recurrence, and radioactive iodine ablation (RAI). Capsular invasion (hazard ratio [HR], 1.589; 95% confidence interval [CI],1.352-1.984), advanced pathological T classification (HR, 3.582; 95% CI, 2.184-5.870), and pathological N+ stage (HR, 1.872; 95% CI, 1.278-2.742) were related to increased risk of multifocality and there was a significant increased HR for central neck compartment involvement in male sex (HR, 2.694; 95% CI, 1.740-4.169), advanced pathological T classification (HR, 2.403; 95% CI, 1.479-3.907) and multifocality (HR, 1.988; 95% CI, 1.361-2.906).There is a significant association between capsular invasion, advanced pathological T classification, N+ stage, and multifocal PTC. Total thyroidectomy plus prophylactic bilateral central lymph node dissection should be recommended during surgery due to a stronger predilection for level VI lymph node metastasis in multifocal PTC.

Radioiodide treatment mediated by adenovirus transfer of human sodium iodide symporter gene into androgen-independent prostate cancer / 生物医学工程学杂志

This study sought to probe the feasibility of instituting a radioiodide treatment for androgen-independent prostate cancer by adenovirus transfer of the hNIS gene. A recombinant adenovirus, Ad-CMV-NIS, that expressed the NIS gene under the control of cytomegalovirus (CMV) promoter was constructed. In vitro, after infection with Ad-CMV-NIS,PC-3 prostate cancer cells exhibited an uptake of perchlorate-sensitive iodide, approximately 120 times higher than that exhibited by negative control Ad-CMV-GFP-infected cells. The half-time of efflux was 26.6 min. Clonogenic assays demonstrated that Ad-CMV-NIS-infected cancer cells were selectively killed by exposure to 131I. In vivo, Ad-CMV-NIS infected tumors showed significant radioiodine accumulation (16.30 +/- 8.72)% ID/g at 2h postinjection) with an effective half-life of 5.4h. The tumor could be clearly visualized by 131I scintigraphy. These data indicate that infection with Ad-CMV-NIS is an efficient way to induce radioiodide uptake in vitro and in vivo, thus suggesting that NIS-based gene therapy has the potential for use in androgen-independent prostate cancer.

Screening for endocrine exophthalmos-associated genes/cDNA fragments / 生物医学工程学杂志

This study was conducted to screen the endocrine exophthalmos-associated genes or cDNA fragments and provide a basis for exploring the pathogenesis. The cDNA from the thyroid tissues of patients with hyperthyroidism and endocrine exophthalmos (HT&EE) was used as tester cDNA, and that from the thyroid tissues of patients with HT but free from EE was used as driver cDNA. The subtractive PCR products between tester and driver cDNA were obtained through two cycles of subtraction hybridization and two cycles of PCR by using suppression subtractive hybridization, and then were inserted into pT-Adv, a cloning vector. The ligated DNAs were transformed into E. coli DH5alpha competent cells and incubated for proper blue/white color development. Forty-eight white colonies were randomly picked and their inserts were colony PCR amplified. The PCR product from one of the colonies contained two inserts; the others contained single insert, having a size of 0.2 kb to 2 kb. The inserts of transformants were arrayed on nylon membrane. After cDNA/Rsa I digestion the thyroid tissues of patients with HT, and of patients with HT&EE, were labeled with digoxigenin; the nylon membranes were then hybridized respectively with the two cDNA probes for a high throughput screening for positive clones. The clones which were hybridized with the cDNA probe of HE&EE patients but not hybridized with the probe of the HT patients or showed only faint signal of hybridization, were chosen as positive clones and their inserts were candidates for the endocrine exophthalmos genes or cDNA fragments. About 50% of the clones were confirmed as positive clones. The cDNA fragments in the positive clones were the endocrine exophthalmos-associated genes or cDNA fragments. Endocrine exophthalmos

Therapy for Graves' ophthalmopathy / 生物医学工程学杂志

Graves' ophthalmopathy (GO) is also called thyroid-related eye disease, infiltrative ophthalmopathy, which is related with the autoimmunity of thyroid, especially hyperthyroidism. Its morbidity ragnes from five percent to ten percent of hyperthyroidism, and the morbidity of male patients is higher than that of the female patients. The treatment of severe GO is a difficult task for doctors. The therapeutic effect is not always satisfactory. In order to solve this knotty problem, researchers have been devoting themselves to the development of new therapeutic methods. Here, the development of the therapies for GO is introduced, and the trends of treatments are prospected.

The feasibility of unilateral neck exploration for parathyroid adenoma / 中国普通外科杂志

Objective To investigate the feasibility of unilateral neck exploration for parathyroid adenoma. Methods The clinical data of preoperative image localization and intraoperative unilateral neck exploration of 15 cases of parathyroid adenoma from 1996 to 2002 in our hospital were analyzed retrospectively. Results Unilateral neck explorations of the 15 cases were performed successfully with the guidance of preoperative ultrasonography , CT, MRI and 99m Tc MIBI scans, and the treatment effect was satisfactory. Conclusion Unilateral neck exploration of parathyroid adenoma could be feasible if accurate preoperative image localizations are available.