Met-PET/CT raises the rate of correctly localized single parathyroid adenomas in patients with negative cUS and MIBI-SPECT/CT and increases the number of focussed surgical approaches.

on behalf of the NEKAR study groupObjective: In this retrospective cohort study, we describe the clinical presentation and workup of parathyroid carcinoma (PC) and determine its clinical prognostic parameters. Primary outcome was recurrence free survival. Summary Background Data: PC is an orphan malignancy for which diagnostic workup and treatment is not established. Methods: Eighty-three patients were diagnosed with PC between 1986 and 2018. Disease-specific and recurrence-free survivals were estimated with the Kaplan-Meier method. Risk factors for recurrence were identified by binary logistic regression with adjustment for age and sex. Thirty-nine tumors underwent central histopathological review. Results: Renal (39.8%), gastrointestinal (24.1%), bone (22.9%), and psychiatric (19.3%) symptoms were the most common symptoms. Surgical treatment was heterogeneous [parathyroidectomy [PTx)] alone: 22.9%; PTx and hemithyroidectomy: 24.1%; en bloc resection 15.7%; others 37.3%] and complications of surgery were frequent (recurrent laryngeal nerve palsy 25.3%; hypoparathyroidism 6%). Recurrence of PC was observed in 32 of 83 cases. In univariate analysis, rate of recurrence was reduced when extended initial surgery had been performed (P ¼ 0.04). In multivariate analysis low T status [odds ratio (OR) ¼ 2.65, 95% confidence interval (CI) 1.02-6.88, P ¼ 0.045], N0 stage at initial diagnosis (OR ¼ 6.32, 95% CI 1.33-30.01, P ¼ 0.02), Ki-67 <10% (OR ¼ 14.07, 95% CI 2.09-94.9, P ¼ 0.007), and postoperative biochemical remission (OR ¼ 0.023, 95% CI 0.001-0.52, P ¼ 0.018) were beneficial prognostic parameters for recurrence-free survival. Conclusion: Despite a favorable overall prognosis, PC shows high rates of recurrence leading to repeated surgery and postoperative recurrent laryngeal nerve palsy and hypoparathyroidism. In view of the reduced recurrence rate in cases of extended surgery, ipsilateral completion surgery may be considered when PC is confirmed.

Purpose A successful focused surgical approach in primary hyperparathyroidism (pHPT) relies on accurate preoperative localization of the parathyroid adenoma (PA). Most often, ultrasound is followed by [99mTc]-sestamibi scintigraphy, but the value of this approach is disputed. Here, we evaluated the diagnostic approach in patients with surgically treated pHPT in our center with the aim to further refine preoperative diagnostic procedures. Methods A single-center retrospective analysis of patients with pHPT from 01/2005 to 08/2021 was carried out followed by evaluation of the preoperative imaging modalities to localize PA. The localization of the PA had to be confirmed intraoperatively by the fresh frozen section and significant dropping of the intraoperative parathyroid hormone (PTH) levels. Results From 658 patients diagnosed with pHPT, 30 patients were excluded from the analysis because of surgery for recurrent or persistent disease. Median age of patients was 58.0 (13–93) years and 71% were female. Neck ultrasound was carried out in 91.7% and localized a PA in 76.6%. In 23.4% (135/576) of the patients, preoperative neck ultrasound did not detect a PA. In this group, [99mTc]-sestamibi correctly identified PA in only 25.4% of patients. In contrast, in the same cohort, the use of [11C]-methionine or [11C]-choline PET resulted in the correct identification of PA in 79.4% of patients (OR 13.23; 95% CI 5.24–33.56). Conclusion [11C]-Methionine or [11C]-choline PET/CT are superior second-line imaging methods to select patients for a focused surgical approach when previous ultrasound failed to identify PA.

Parathyroid carcinoma (PC) is an orphan malignancy accounting for only ~1% of all cases with primary hyperparathyroidism. The localization of recurrent PC is of critical importance and can be exceedingly difficult to diagnose and sometimes futile when common sites of recurrence in the neck and chest cannot be confirmed. Here, we present the diagnostic workup, molecular analysis and multimodal therapy of a 46-year old woman with the extraordinary manifestation of abdominal lymph node metastases 12 years after primary diagnosis of PC. The patient was referred to our endocrine tumor center in 2016 with the aim to localize the tumor causative of symptomatic biochemical recurrence. In view of the extensive previous workup we decided to perform [18F]FDG-PET-CT. A pathological lymph node in the liver hilus showed slightly increased FDG-uptake and hence was suspected as site of recurrence. Selective venous sampling confirmed increased parathyroid hormone concentration in liver veins. Abdominal lymph node metastasis was resected and histopathological examination confirmed PC. Within four months, the patient experienced biochemical recurrence and based on high tumor mutational burden detected in the surgical specimen by whole exome sequencing the patient received immunotherapy with pembrolizumab that led to a biochemical response. Subsequent to disease progression repeated abdominal lymph node resection was performed in 10/2018, 01/2019 and in 01/2020. Up to now (12/2020) the patient is biochemically free of disease. In conclusion, a multimodal diagnostic approach and therapy in an interdisciplinary setting is needed for patients with rare endocrine tumors. Molecular analyses may inform additional treatment options including checkpoint inhibitors such as pembrolizumab.

Purpose Repeat surgery in patients with primary hyperparathyroidism (pHPT) is associated with an increased risk of complications and failure. This stresses the need for optimized strategies to accurately localize a parathyroid adenoma before repeat surgery is performed. However, evidence on the extent of required diagnostics for a structured approach is sparse. Methods A retrospective single-center evaluation of 28 patients with an indication for surgery due to pHPT and previous thyroid or parathyroid surgery was performed. Diagnostic workup, surgical approach, and outcome in terms of complications and successful removement of parathyroid adenoma with biochemical cure were evaluated. Results Neck ultrasound, sestamibi scintigraphy, C11-methionine PET-CT, and selective parathyroid hormone venous sampling, but not MRI imaging, effectively detected the presence of a parathyroid adenoma with high positive predictive values. Biochemical cure was revealed by normalization of calcium and parathormone levels 24–48h after surgery and was achieved in 26/28 patients (92.9%) with an overall low rate of complications. Concordant localization by at least two diagnostic modalities enabled focused surgery with success rates of 100%, whereas inconclusive localization significantly increased the rate of bilateral explorations and significantly reduced the rate of biochemical cure to 80%. Conclusion These findings suggest that two concordant diagnostic modalities are sufficient to accurately localize parathyroid adenoma before repeat surgery for pHPT. In cases of poor localization, extended diagnostic procedures are warranted to enhance surgical success rates. We suggest an algorithm for better orientation when repeat surgery is intended in patients with pHPT.

Summary Background After partial resection of the thyroid gland, a second operation referred to as “completion thyroidectomy” may be required if histopathological analysis indicates the presence of differentiated thyroid cancer (DTC). Although there is little evidence, it is assumed that the time point of completion thyroidectomy is not critical for oncological prognosis of patients with DTC. We assessed whether patients with total thyroidectomy (TTx) in a two‐step procedure have an equal long‐term prognosis with regard to disease‐specific survival (DSS) compared to patients immediately undergoing total thyroidectomy in a one‐step procedure. Methods A database study using the Würzburg thyroid cancer database with 2258 patients with pT1a‐pT4b tumours DTC who were operated between 1980 and 2016 was carried out. Results A total of 277 patients with papillary microcarcinoma pT1aN0M0 were treated by hemithyroidectomy. TTx as one‐step procedure was performed in 1114 patients compared to 867 with TTx as a two‐step procedure. Patients with papillary thyroid cancer more frequently had a TTx as one‐step procedure than follicular thyroid cancer patients (59.4% vs 47%; P < 0.001). Compared to a one‐step thyroidectomy, overall complication rate was not different compared to patients undergoing a single operation. Multivariate analysis showed that the presence of distant metastases, T‐stage and age at diagnosis were the only independent determinants for DTC‐specific survival, regardless of a one‐ or two‐time thyroidectomy. Conclusion The present study on the largest of such patient collectives provides evidence that a delayed completion operation does not affect DSS in DTC, nor does it lead to a significant increase in complication rates.

Background Postsurgical hypoparathyroidism (PH) is the most frequent complication after thyroid surgery. The aim of this systematic review and meta-analysis is to summarize a unifying definition of PH and to elucidate the best possible approach for early detection of PH. Methods A systematic review of the literature according to the PICO framework using Embase, PUBMED and the Cochrane library was carried out on 1 December 2021 followed by analysis for risk of bias, data extraction and meta-analysis. All studies addressing the definition of postoperative hypoparathyroidism and/or diagnostic approaches for early detection and diagnosis were included. Case reports, commentaries, non-English articles, book chapters and pilot studies and reviews were excluded. Results From 13 704 articles, 188 articles were eligible for inclusion and further analysis. These articles provided heterogeneous definitions of PH. Meta-analysis revealed that postoperative measurements of parathormone (PTH) levels have a higher sensitivity and specificity than intraoperative PTH measurements to predict PH after thyroid surgery. None of the timeframes analysed after surgery within the first postoperative day (POD1) was superior to predict the onset of PH. PTH levels of less than 15 pg/ml and less than 10 pg/ml are both reliable threshold levels to predict the postoperative onset of PH. A relative reduction of mean(s.d.) PTH levels from pre- to postoperative values of 73 (standard deviation 11) per cent may also be predictive for the development of PH. The estimation of calcium levels on POD1 are recommended. Conclusion PH is best defined as an undetectable or inappropriately low postoperative PTH level in the context of hypocalcaemia with or without hypocalcaemic symptoms. PTH levels should be measured after surgery within 24 h. Both threshold levels below 10 and 15 pg/ml or relative loss of PTH before/after thyroid surgery are reliable to predict the onset of PH.

Evolutionary distance allows for the determination of a high-risk group of recurrence if preoperative liver biopsy is considered.