Applying Ultrasound-Biomarker Combined System For Preoperative Diagnosis,Postoperative Surveillance And Prognosis Indication Of Parathyroid Carcinoma

Part I B-mode Ultrasound Combined with Biochemical Parameters for Establishing a Predictive Model to Diagnose Parathyroid Carcinoma Preoperatively in Patients with Primary HyperparathyroidismObjectives Parathyroid cancer(PC)is rare,but fatal condition.Preoperative prediction of PC remains challenging but meaningful.The aim of this study was to determine an effective model to predict PC in patients with parathyroid lesions>1.5 cm.Methods Firstly,we retrospectively enrolled 30 patients with PC matched to 60 patients with parathyroid adenoma or hyperplasia by admission year.All patients were diagnosed with primary hyperparathyroidism(pHPT)and had parathyroid lesions>1.5 cm.Ultrasonic features of the two patient groups,as well as demographic,clinical and biochemical characteristics were compared.Best subset selection and multivariate logistic regression analysis were conducted to identify the independent risk factors of PC.ROC curve,calibration curve and decision curve analysis were developed to evaluate the applicability of the new model.Subsequently,21 patients with PC and 42 patients with parathyroid adenoma were enrolled as a validation group.The model was evaluated by the data of validation group using ROC curve and calibration curve.Finally,a decision tree was put forward for clinical practicability.Results The best subset selection method and multiple logistic regression analysis showed that ultrasonic features of DR(two diameters’ ratio of the lesion)and tumor infiltration in conjunction with intact parathyroid hormone(iPTH)level(model 1)were independent predictors of malignancy.Meanwhile,DR,shape and tumor infiltration(model 2)were found to be risk factors when only ultrasonic features were included in the multivariate analysis.The decision curve analysis showed that model 1 outperforms model 2 with a better net benefit and a wider range of threshold probabilities.The AUC value of the model in the training set and the validation set were 0.9556 and 0.9762,respectively.The calibration curves both showed fairly predictive power(p=0.715,p=1.000,respectively).The decision tree demonstrated a simplified diagnostic flow of PC,taking infiltration on ultrasonography,DR<1.7 and iPTH>490 pg/mL as key nodes.Conclusions Ultrasonic features in combination with iPTH level may be an applicable model for predicting PC and has a better potential to facilitate decision-making preoperatively.Part II Shear Wave Elastography for Differentiating Parathyroid Neoplasms with Malignant Diagnosis or Uncertain Malignant Potential from Parathyroid Adenomas:Initial ExperienceObjective Parathyroid carcinoma(PC)and atypical parathyroid tumor(APT)are rare parathyroid disorders carrying the risk of recurrence of varying degrees.This study aims to explore the value of 2D-shear wave elastography(SWE)in the discrimination of PC/APT among suspicious parathyroid lesions.Methods and materials In this prospective study,patients with primary hyperparathyroidism and suspicious parathyroid lesions on ultrasonography(US)were recruited.All the lesions were assessed by SWE before surgery.The velocity(m/s),Young’s modulus(kPa),and elastogram of SWE were compared between pathologically proven parathyroid carcinoma or atypical parathyroid tumor(Group 1)and parathyroid adenoma(Group 2).All the SWE parameters were displayed at the setting of 50 or 70 kPa.Correlations between SWE and the lesion size as well as biochemical parameters were analyzed.Results of 42 target lesions enrolled for analysis,the mean shear wave velocity(SWV)between the two groups was 2.40 m/s vs.1.85 m/s,respectively,while the mean Young’s modulus(YM)was 18.20 kPa vs.10.90 kPa,respectively.The cut-off values were 2.25m/s and 17.05 kPa correspondingly.The sensitivity and specificity of the mean SWV and YM were 0.61 vs.0.88,0.61 vs.1.00,respectively.The area under the curve(AUC)were 0.830 vs.0.859[95%confidence interval(CI)0.706-0.954 vs.0.744-0.973],respectively.In contrast,the max SWV and Young’s modulus showed a better sensitivity of 0.72 and 0.78,respectively.The "colored lesion" and "stiff rim" patterns on the elastogram were more indicated in parathyroid carcinoma and atypical parathyroid tumor,whereas the negative elastogram prevailed in parathyroid adenoma.The SWV and YM values of the parathyroid lesions were independent of the tumor size,but the max SWV and YM slightly correlated with serum iPTH level(r=0.313,p=0.044;r=0.341,p=0.027;respectively).Conclusions 2D-shear wave elastography plays a useful role in the preoperative assessment of parathyroid lesions with suspicious malignancy.The mean SWV and Young’s modulus are advised as the favored diagnostic parameter with the best AUC and excellent specificities,while the max SWV and Young’s modulus are more sensitive to distinguish the PC and APT compared with other parameters.Part Ⅲ The Prognostic Value of Ultrasound Features and Parafibromin Expression in Primary Parathyroid Carcinoma and Clinical-Ultrasound Scheme for Identifying Locoregional Recurrence of Parathyroid Carcinoma.Objectives To investigate prognostic factors related with parathyroid carcinoma based upon ultrasound parameters and parafibromin expression.Meanwhile,to summarize the clinical and sonographic features of locoregional recurrence of parathyroid carcinoma.Methods Between 2000/01-2022/07,thirty-four PC patients with detailed preoperative ultrasonography were enrolled in the research.The pathology specimens of them were stained with parafibromin and categorized into two groups according to the staining statusthe parafibromin positive group and the parafibromin negative group.Cox regression were used to compare and identify the independent prognostic factors regarding disease-free survival and overall survival.The 29 locoregional recurrences of 21 parathyroid carcinoma patients were documented and described in the form of one-to-one table.The ultrasound features of the 29 recurrences at the neck were summarized and presented in the form of number(N)and precent.The correlations between the tumor burden(cumulative tumor sizes)and the intact parathyroid hormone were analyzed.Results Patients with negative immunohistochemical staining of parafibromin were at higher risk for recurrence(HR:5.9,p=0.009).Whereas,calcification identified on preoperative ultrasonography was shown to be a risk factor of death regarding the OS(HR:9.439,p=0.046).As for the parathyroid carcinoma relapsed at neck,the median size of the largest recurrent lesion at each relapse was 1.8 cm(range 0.8-3.8 cm).Ultrasound images showed hypoechoic solid nodules in 28 relapses(96.6%),inhomogeneous echo-texture in 28 relapses(96.6%),intralesional echogenic septa-like structures in 21 relapses(72.4%),intralesional cystic change in two relapses(6.9%),infiltrative or blurred boundary in 20 relapses(69.0%),irregular shape in 22 relapses(75.9%),marked vascularization on color Doppler imaging in 19 relapses(65.5%),multiple lesions in 26 relapses(89.7%),contralateral recurrence in 3 relapses(10.3%),and subcutaneous recurrence in 10 relapses(34.5%).None of the recurrent lesions exhibited calcification.The total size of all the recurrent lesions at each relapse fairly correlated with the serum intact parathyroid hormone levels(r=0.450;p=0.014).Patients eventually diagnosed with PC relapse could have the benign pathologic diagnosis at the first surgery and negative MIBI findings when recurrences happened.Conclusions The negative immunohistochemical staining of parafibromin and calcification identified on preoperative ultrasonography are risk factors as for the DFS and OS of PC patients,respectively.There are clinical-sonographic characteristics and evaluation traps worthy of attention when the postoperative ultrasound monitoring of locoregional recurrence of PC is performed.