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.

Comparison of open liver resection and RFA for the treatment of solitary 3-5-cmhepatocellular carcinoma: a retrospective study.

BACKGROUND: The goal of this study was to compare the postoperative results of liver resection and radiofrequency ablation (RFA) for the treatment of small hepatocellular carcinoma (HCC) (3-5 cm). PATIENTS AND METHODS: We retrospectively collected 122 cases of small solitary HCC treated at our center from Jan 2011 to Dec 2015, with diameters in the range of 3-5 cm. According to the treatment program received at our center, the patients were divided into liver resection (72 patients) and RFA (50 patients) groups. RESULT: In comparison with the RFA group, the resection group had a longer operative time, greater intraoperative blood loss (P < 0.01), more hepatic inflow occlusion, and a longer postoperative hospital stay (P < 0.01). The 1-, 3-, and 5-year expected overall survival rates and tumor-free survival rates were comparable between the two groups. Cox regression analysis showed that neither resection nor RFA was a significant risk factor for overall or tumor-free survival in HCC. CONCLUSIONS: For solitary HCC of 3-5 cm in diameter, RFA can achieve better in-hospital clinical results and similar long-term outcomes than resection and can be considered for wide application, especially for central-location cases.

The use of The Bethesda System for Reporting Thyroid Cytopathology in a Chinese population: An analysis of 13 351 specimens.

AIMS: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has been widely adopted since its introduction. In this study, we aimed to report our experience using this reporting system at a College of American Pathologists (CAP)-accredited hospital laboratory in a large series of Chinese patients. METHODS: All patients who underwent preoperative ultrasound-guided thyroid fine-needle aspiration (FNA) from January 2011 to August 2016 were retrospectively analyzed. Thyroid FNAs were classified according to the Bethesda System. For patients who underwent subsequent surgery at our institution, the diagnostic performance of the preoperative FNA was further analyzed according to four different calculation criteria. All of the follicular variants of papillary thyroid carcinoma specimens were reviewed to exclude NIFTP (noninvasive follicular thyroid neoplasm with papillary-like nuclear features). RESULTS: A total of 13 351 thyroid FNAs were included in this analysis. Of the 12 530 sampled patients, 3594 (28.7%) underwent thyroidectomy, and the malignancy rates for each cytological category were as follows: 66.7% unsatisfactory, 14.2% benign, 53.5% undetermined significance, 30.2% follicular neoplasm, 82.0% suspicious, and 99.1% malignant. Only 12 (0.36% of all PTC) patients were reclassified as having NIFTP. The sensitivities of the preoperative FNAs were all above 95.0% and were as high as 99.0%. The specificities ranged from 50.3% to 63.9%, depending on which criteria were used. The positive predictive value was 95.4% for criteria 1 and 2 and was 94.2% for criteria 3 and 4. The negative predictive values ranged from 64.5% to 85.8%. The diagnostic accuracies all exceeded 90.0%, with the highest being 94.8%. CONCLUSION: This study revealed the great efficacy and accuracy of TBSRTC in a large Chinese population for the first time.

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.

Preoperative adjuvant transarterial chemoembolization cannot improve the long term outcome of radical therapies for hepatocellular carcinoma.

Combinations of transarterial chemoembolization (TACE) and radical therapies (pretransplantation, resection and radiofrequency ablation) for hepatocellular carcinoma (HCC) have been reported as controversial issues in recent years. A consecutive sample of 1560 patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B HCC who underwent solitary Radiofrequency ablation (RFA), resection or liver transplantation (LT) or adjuvant pre-operative TACE were included. The 1-, 3- and 5-year overall survival rates and tumor-free survival rates were comparable between the solitary radical therapy group and TACE combined group in the whole group and in each of the subgroups (RFA, resection and LT) (P > 0.05). In the subgroup analysis, according to BCLC stage A or B, the advantages of adjuvant TACE were also not observed (P > 0.05). A Neutrophil-lymphocyte ratio (NLR) more than 4, multiple tumor targets, BCLC stage B, and poor histological grade were significant contributors to the overall and tumor-free survival rates. In conclusions, our results indicated that preoperative adjuvant TACE did not prolong long-term overall or tumor-free survival, but LT should nevertheless be considered the first choice for BCLC stage A or B HCC patients. Radical therapies should be performed very carefully in BCLC stage B HCC patients.

Ex vivo liver resection followed by autotransplantation to a patient with advanced alveolar echinococcosis with a replacement of the retrohepatic inferior vena cava using autogenous vein grafting: a case report and literature review.

Alveolar echinococcosis (AE) of the liver is a rare disease. In advanced cases of this parasitic disease, the inferior vena cava (IVC) can be invaded; in these cases, the optimal treatment is liver transplantation and replacement of the IVC. Considering the donor shortage and the drawbacks of immunosuppressive therapy, ex vivo liver resection followed by autotransplantation may be the first choice for these patients. We report the first case of advanced AE successfully treated by an ex vivo liver resection, followed by autotransplantation with a replacement of the retrohepatic IVC using autogenous vein grafting. This graft included the following regions: the bilateral great saphenous vein, part of the retrohepatic inferior vena and the middle hepatic vein with no invasion, the inferior mesenteric vein, and part of the side wall of the infrahepatic vena cava. This patient had an uneventful postoperative recovery; currently, she has been enjoying a normal life and is 12 months postoperative with no immunosuppressive therapy or AE recurrence.In conclusion, ex vivo liver resection followed by autotransplantation with a replacement of the retrohepatic IVC using autogenous vein grafting might be a useful surgical practice for advanced AE.

Barcelona clinic liver cancer stage B hepatocellular carcinoma: transarterial chemoembolization or hepatic resection?

According to the Barcelona Clinic Liver Cancer (BCLC) guidelines, transarterial chemoembolization (TACE) is recommended for BCLC stage B hepatocellular carcinoma (HCC). However, an investigation of the use of resection for BCLC stage B is needed. Therefore, we compared the efficacy and safety of hepatic resection (HR) with that of TACE in treating intermediate HCC.We retrospectively enrolled 923 patients with BCLC stage B HCC who underwent TACE (490 cases) or HR (433 cases). The baseline characteristics, postoperative recoveries, and long-term overall survival rates of the patients in these 2 groups were compared. Subgroup analyses and comparisons were also performed between the 2 groups.The baseline demographic and tumor characteristics, in-hospital mortality rate, and 30-day mortality rate were comparable between the 2 groups. However, the patients in the resection group suffered from more serious complications compared with those in the TACE group (11.1% vs 4.7%, respectively, P < 0.01) as well as longer hospital stays (P < 0.05). The resection patients had significantly better overall survival rates than the TACE patients (P < 0.01). In the TACE group, patients with Lipiodol retention showed much higher 1-, 3-, and 5-year overall survival rates than those in the noncompact Lipiodol retention group (P < 0.01). Subgroup analyses revealed that patients with 1 to 3 tumor targets showed much better 1-, 3-, and 5-year overall survival rates in the resection group (P < 0.01), but no difference was observed for the patients with >3 targets.Our clinical analysis suggests that patients with BCLC stage B HCC should be recommended for resection when 1 to 3 targets are present, whereas TACE should be recommended when >3 targets are present.

Preoperative transcatheter arterial chemoembolization for resectable hepatocellular carcinoma: a single center analysis.

BACKGROUND AND AIM: The effect of preoperative transcatheter arterial chemoembolization (TACE) on the short- and long-term outcome of resectable hepatocellular carcinoma (HCC) is controversial. We conducted a retrospective evaluation of this aspect using data from our center. MATERIAL AND METHODS: A total of 656 consecutive patients who underwent curative resection of HCC were divided into two groups based on the preoperative TACE: the liver resection (LR) group (405 cases) and the TACE-LR group (183 cases). Overall and disease-free survival curves were constructed using the Kaplan-Meier method and compared with the log-rank test. The significance of differences in survival was tested using a log-rank test. Univariate and multivariate analyses were used to identify the factors that best predicted overall survival or tumor free survival. RESULTS: Although the cost of LR showed no difference between groups, the overall cost was significantly higher in the combined group than in the LR group (P < 0.001). The complication rate after resection was also comparable between the two groups. In regard to long-term outcome, the 1-, 3-, and 5-year overall survival rates were 83.7, 68.9 and 57.5%, respectively, after direct liver resection and 80.9, 65.0 and 54.1%, respectively, after combined TACE and resection (P = 0.739). The 1-, 3-, and 5-year recurrence- free survival rates were also comparable between two groups (P = 0.205). Both univariate analysis and multivariate analysis showed that macro-vascular invasion was the factor that best predicted overall survival or tumor-free survival rate. CONCLUSION: Preoperative TACE has comparable intraoperative and short-term outcomes but more overall cost due to repeated TACE, and the procedure did not significantly improve the overall or tumor-free survival rate. Preoperative TACE should not, therefore, be recommended as a routine procedure before resection for resectable HCCs particularly in cases due to underlying hepatitis B virus (HBV).

Design and activity verification of human parathyroid hormone (1-34) mutant protein / 药学学报

Through protein-protein BLAST of homologous sequences in different species in NCBI database and preliminary simulating molecular docking and molecular dynamics by computer software discovery studio 3.1, three amino acids R25K26K27 of natural human parathyroid hormone (1-34) with Q25E26L27 were mutated and the biological activity of the mutant peptide was evaluated. Result showed that: root mean superposition deviation RMSD value between PTH (1-34)-(RKK-QEL) and PTH (1-34) peptide main chain was 2.509 3, indicating that the differences between the two main chain structural conformation was relatively small; the interaction energy between PTH (1-34)-(RKK-QEL) and its receptor protein PTH1R had been enhanced by 7.5% compared to nature PTH (1-34), from -554.083 kcal x mol(-1) to -599.253 kcal x mol(-1); the number of hydrogen bonds was increased from 32 to 38; PTH (1-34)-(RKK-QEL) can significantly stimulate the RANKL gene expression (P < 0.01) while inhibiting the OPG gene expression (P < 0.01) in UAMS-32P cells; in the co-culture system of UAMS-32P cells and mouse primary femur bone marrow cells, PTH (1-34)-(RKK-QEL) stimulated the formation of osteoclasts (P < 0.01) and had a higher biological activity than PTH (1-34) standard reagents.

A new sandwich ELISA method for quantitative analysis of fusion protein IL-2-HSA / 中国药科大学学报

A double antibody sandwich ELISA for quantitative analysis of recombinant fusion protein IL-2-HSA was constructed using a polyclonal antibody to human IL-2 for capture and a monoclonal antibody to HSA with HRP-labeled conjugate for detection.The optimal concentration of the first coating antibody and detection antibody were 2 μg/mL and 0.5 μg/mL,respectively.Regression equation of the linear calibration curve was:y = 0.442 9 x-1.143 3 with a correlation coefficient of 0.996 6,and the linear detection ranged from 39.06 ng/mL to 1 250 ng/mL.Recovery from the supernatant of fermentation broth was 98.13% to 102.94%.The specificity assay indicated that it had little cross-reactions with IL-2 and HSA.The soundness analysis suggested that fermentation broth,mouse serum and dilution had no influence on the method.The present method can be used in the studies on fermentation,purification and clinical diagnosis.

Expression and purification of IFNbeta-HSA fusion protein in Pichia pastoris / 生物工程学报

In order to obtain enough fusion protein for developing preclinical studies of IFNbeta-HAS, we screened Pichia pastoris transformants expressing high-level protein by immunology method. The yield of IFNbeta-HSA was about 500 mg/L by fed-batch fermentation. The purity of IFNbeta-HSA reached 96% through the steps of ultrafiltration, Blue Sepharose FF, Ni2+-IMAC and DEAE Sepharose FF. Analysis of Western blotting showed that IFNbeta-HSA had the antigenicity of IFNbeta and HSA. The specific activity was about 1.96 x 10(7) IU/mg by standard survival activity test on WISH cells challenged with VSV virus. This study provided a method to produce IFNbeta-HSA.

Establishment and application of screening method for DPPIV inhibitors in vitro / 中国药理学通报

Aim To develop a model for screening DPPIV inhibitor from Chinese Herbal medicine.Methods With Gly-Pro-PNA as a substrate,DPPIV activity was assayed by the chromogenic substrate.The concentration of DPPIV and Gly-Pro-PNA,temperature,pH and reaction time were optimized.Results The optimal enzymatic reaction system was as follows:DPPIV 0.5 U?L-1,Gly-Pro-PNA 0.262 ?mol?L-1,37℃,pH 8.2,reaction for 60 min.Further more,many kinds of herbal abstracts were screened and some had the DPPIV inhibitory function,such as Leech,Poria cum Radix Pini and Buddleja officinalis Maxim.Conclusion The model can be used to screen for DPPIV inhibitors in vitro.