| Secondary hyperparathyroidism is one of the main complications of end-stage chronic kidney disease.Due to the continuous improvement of dialysis treatment and technology,the lifetime of patients with end stage renal disease were prolonged,and the incidence of secondary hyperparathyroidism was getting higher and higher.In the early stage of secondary hyperparathyroidism,dialysis management and drug therapy can be used to control the development of it.However,with the course of the disease progresses,when drug treatment will be resistance or parathyroid hormone level continues to rise to a certain extent,surgery is often required for surgical intervention.The differences in secondary hyperparathyroidism disease management and concepts in various countries had led to the lack of uniform standards and detailed specifications in surgery.Moreover,the research of secondary hyperparathyroidism surgery was also very limited.Therefore,we focuses on the difficulties in clinical decisions that occurred during parathyroidectomy in secondary hyperparathyroidism.In the part I,a semi-quantitative analysis of 99 mTcMIBI which is routinely performed preoperatively in secondary hyperparathyroidism patients was carried out to explore the relationship between different degree of parathyroid 99mTc-MIBI accumulation and degree of pathological hyperplasia of parathyroid gland.Further analysis was to evaluate the value of 99mTc-MIBI imaging examination to assists surgeons in selecting the parathyroid with lowest degree of hyperplasia for autotransplantation during the operation.Part I found that 99mTc-MIBI imaging examination is effective in evaluating pathological hyperplasia of parathyroid glands preoperative,therefore,assists the surgeon in selecting the parathyroid with lowest degree of hyperplasia for autotransplantation during the operation.Part II was retrospective analysis of thyroid carcinoma concurrent with secondary hyperparathyroidism in incidence,tumor characteristics（such as diameter,extrathyroidal extension,lymph node metastasis）and prognostic characteristics,aimed to provide theoretical supports for surgeons to treat the thyroid carcinoma lesion in secondary hyperparathyroidism patients.We found that the prevalence of PTC is high in patients with SHPT.Compared with PTC in the general population,most of PTC with SHPT are occult thyroid carcinoma and present no significant difference in tumor pathological features and prognostic staging.Part I Utility of 99mTc-MIBI imaging examination in selecting autotransplantation parathyroid gland during parathyroidectomyPurpose At present,there is no quantitative evaluation method to judge the degree of pathological hyperplasia of parathyroid autograft during parathyroidectomy.Semiquantitative analysis of 99mTc-MIBI imaging examination results was carried out to explore the relationship between different degree of parathyroid 99mTc-MIBI accumulation and degree of pathological hyperplasia of parathyroid gland in secondary hyperparathyroidism（SHPT）patients.In our study,we aims to evaluate the value of 99mTc-MIBI imaging examination in evaluating degree of pathological hyperplasia of parathyroid gland,so as to assists the surgeon in selecting the parathyroid with lowest degree of hyperplasia during the operation.Methods SHPT patients who underwent total parathyroidectomy with autotransplantation（TPTX+AT）from May 2019 to January 2020 and had complete surgical specimen information were included.The clinical data of patients were collected through the medical record system,and the study cohort was finally constructed after completing the inclusion and exclusion criteria.Correlation analysis between different degree of parathyroid 99mTc-MIBI accumulation and the patient’s biochemical indicators on a patient basis.Subgroup analysis based on whether there is 99mTc-MIBI-negative parathyroid glands in a patient and whether there is hypocalcemia 6 months postoperatively.Then,the survival analysis of the grafts was carried out on the patients who were completely resected,and the relationship between degree of parathyroid 99 mTcMIBI accumulation and the various outcome indicators after the operation was explored.To explore the relationship between different degree of parathyroid 99mTc-MIBI accumulation and degree of pathological hyperplasia on a parathyroid basis,and the receiver operating characteristic curve（ROC）curve is used to evaluate the value of 99mTc-MIBI imaging examination in evaluating degree of pathological hyperplasia of parathyroid gland.Results From May 2019 to January 2020,a total of 101 SHPT patients with TPTX+AT and complete surgical specimen information were included.91 SHPT patients were finally included in the study through the inclusion and exclusion criteria.Among them,there were 48 male patients（52.75%）and 43 female patients（47.25%）.The average age was 49±10 years,and the average dialysis time was 7.69±3.19 years.In the subgroup analysis,the group of patients with 99mTc-MIBI negative parathyroid gland（s）had lower preoperative serum phosphate（1.89±0.44 VS 2.12±0.43,p=0.015）and higher serum calcium 6 months postoperative（2.25±0.22 VS 2.14±0.28,p=0.044）compared to the group of patients 99mTc-MIBI positive parathyroid gland（s）.After subgroup analysis of whether to use the parathyroid gland of lowest degree of parathyroid 99mTc-MIBI accumulation for autotransplantation,we found that postoperative both intact parathyroid hormone（i PTH）and i PTH 6 months postoperative were all lower in the group of autotransplantation with lowest uptake ratio of region interesting（URRI）parathyroid gland（11.33±17.77 VS 22.12±50.30,p=0.193;41.59±68.50 VS 79.07±133.87,p=0.106）,though there was no significant statistical difference due to the sample size.The patients were divided into two groups according to the occurrence of hypocalcemia 6 months after the operation,total URRI total（9.51±4.54 VS 12.73±5.05,p=0.002）and URRI max（3.93±2.19 VS 5.38±2.70,p=0.006）of the non-hypocalcemia group were lower than hypocalcemia group.Further multivariable logistic regression analyze showed that the preoperative 99mTc-MIBI accumulation of the patient’s parathyroid glands is an independent risk factor for hypocalcemia 6 months postoperatively,and a higher level of parathyroid 99mTc-MIBI accumulation can suggest the patient’s hypocalcemia 6 months postoperatively.In the analysis of parathyroid specimens,216 hyperplastic parathyroid glands included 17 cases（7.87%）of diffuse hyperplasia（DH）and 32 cases（14.81%）of early nodularity hyperplasia（ENH）,146 cases（67.59%）of nodular hyperplasia（NH）and 21 cases（9.72%）of single nodule（SN）.There was a significant correlation between degree of parathyroid hyperplasia and glandular weight（p<0.001）,glandular volume（p<0.001）,and the expression of（proliferating cell nuclear antigen）PCNA（p=0.005）.Further analysis showed degree of parathyroid 99mTc-MIBI accumulation were significantly positive correlated with glandular weight（R2=0.343,weight=299.1*URRI+93.85,p<0.001）,glandular volume（R2=0.240,volume=176.9*URRI+96.70,p<0.001,）,PCNA（R2=0.035,PCNA=18.55*URRI+264.4,p=0.006）and degrees of pathological hyperplasia（p<0.001）.The above results indicate that the degree of parathyroid 99mTc-MIBI accumulation is closely related to the degree of parathyroid hyperplasia.Finally,the degree of parathyroid 99mTc-MIBI accumulation is used to predict the degree of parathyroid hyperplasia.For evaluating diffuse type and nodular type in 216 parathyroid glands,location of the parathyroid glands（AUC=0.599,p=0.035）、 volume（AUC=0.890,p<0.001）、 weight（AUC=0.895,p<0.001）can distinguish the degree of parathyroid hyperplasia,and URRI also shows good predictive ability（AUC=0.771,p<0.001）;Evaluation of nodular subtype among 167 parathyroid glands: distinguishing between nodular hyperplasia and single nodule,location of the parathyroid glands cannot be distinguished well（AUC=0.597,p=0.152）,while volume（AUC=0.692,p=0.005）and weight（AUC=0.735,p<0.001）can distinguish the degree of parathyroid hyperplasia,and URRI has best predictive ability among these factors which AUC reached 0.819,higher than the predictive ability of volume or weight,p<0.001.Conclusion It is effective in evaluating pathological hyperplasia of parathyroid glands preoperative,therefore,assists the surgeon in selecting the parathyroid with lowest degree of hyperplasia for autotransplantation during the operation.In addition,the different degree of parathyroid glands accumulation in 99mTc-MIBI imaging examination is related to the serum calcium 6 months after TPTX+AT,suggesting the occurrence of hypocalcemia（6 months after TPTX+AT）.Part II Clinicopathological and prognostic study of secondary hyperparathyroidism concurrence with papillary thyroid carcinomaPurpose Coexistence of primary hyperparathyroidism（PHPT）and papillary thyroid carcinoma is common and may be associative with more aggressive papillary thyroid carcinoma（PTC）for higher rates of extrathyroidal extension and multicentricity.However,it remains unclear whether secondary hyperparathyroidism（SHPT）accounts for more invasive papillary thyroid carcinoma in terms of morbidity,tumor pathological characteristics and prognosis.This study aimed to provide theoretical supports for surgeons to treat the thyroid carcinoma lesion in secondary hyperparathyroidism patients through a retrospective analysis of thyroid carcinoma concurrent with secondary hyperparathyroidism in incidence,tumor characteristics and prognostic.Methods A total of 531 patients diagnosed of SHPT and underwent surgery were evaluated retrospectively from January 2013 to December 2018 in the first affiliated hospital of the Zhejiang University.Patients’ demographics,operation records and follow-up information were recorded and analyzed.Among them,34 patients had PTC concurrent with SHPT（PTC+SHPT）were enrolled.Control subjects were derived through 1:4 matching for age,sex and gender pathological subtype.136 patients of papillary thyroid carcinoma were selected as control group after matching 1:4 for age,gender and pathological subtype.Results There were 34 patients coexisting with PTC+SHPT among the 531 surgery patients diagnosed as SHPT（6.4%）.Mean tumor diameter of PTC+SHPT group was smaller than that in PTC group（5.59 mm vs 8.69 mm,p<0.001）.The proportion of tumor diameter less than 10 mm in PTC+SHPT group were significantly higher than that in PTC group [29（85.29%）vs 86（63.24%）,p=0.014].There were no statistically significant difference among the tumor multicentricity [15（44.12%）vs 39（28.68%）,p=0.066],tumor bilaterality [9（26.47%）vs 29（21.32%）,p=0.499],tumor extrathyroidal extension [2（5.88%）vs19（13.97%）,p=0.255] and lymph node metastasizes rate [12（35.29%）vs 49（36.03%）,p=1.000].We found differences between PTC+SHPT group and PTC group patients with respect to contralateral thyroidectomy [10（29.41%）vs 70（51.47%）,p=0.023] and central lymph node dissection [22（64.71%）vs 125（91.91%）,p <0.001].There was no significant difference between PTC+SHPT group and PTC group in prognostic staging [33（97.06%）vs 122（89.71%）,p=0.309] and recurrence（mean followup time 36 months vs 39 months,p=0.33）.Conclusion The prevalence of PTC is high in patients with SHPT.Compared with PTC in the general population,most of PTC with SHPT are occult thyroid carcinoma and present no significant difference in tumor pathological features and prognostic staging.It is necessary for surgeons to make more adequate preoperative prediction and do more careful examination during the surgery in case of missing the coexistence of PTC in SHPT patients. |
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