Hypoparathyroidism is one of the most common complications after total or completion thyroidectomy. The reported incidence rate of hypoparathyroidism in the literature is highly variable. Data that ...provide a better understanding of the magnitude of this postoperative complication are warranted and can provide a stepping stone for further collaborations that aim to reduce complication rates and establish uniform treatment protocols.
To evaluate the incidence of postoperative, persistent hypoparathyroidism after total or completion thyroidectomy in patients who were referred to university hospital centers and assess the association of different definitions with the incidence of hypoparathyroidism.
This retrospective multicenter cohort study conducted throughout 2016 in 7 Dutch university hospital centers included 200 patients who were undergoing a total or completion thyroidectomy. Data analysis was conducted in January 2021.
We report on the incidence of persistent hypoparathyroidism, defined as the need for active vitamin D with or without calcium supplementation longer than 1 year after surgery.
A total of 200 patients (143 women 71.5%; mean IQR age, 49.0 37.0-62.0 years) were included and 30 patients (15.0%) developed persistent hypoparathyroidism. The incidence of persistent hypoparathyroidism varied between 14.5% (calcium and active vitamin D 1 year postsurgery) to 28.5% (calcium and/or active vitamin D 6 months postsurgery) depending on the definition used.
In this cohort study, the risk of persistent hypoparathyroidism after total or completion thyroidectomy was 15% in patients who were referred to university hospital centers. The high rate of persistent hypoparathyroidism warrants efforts to reduce this complication rate. There is discrepancy in the definition and treatment of persistent hypoparathyroidism, and use of uniform evidence-based treatment guidelines enables comparison of interventions.
Thyroid neoplasia is common and requires appropriate clinical workup with imaging and fine-needle aspiration (FNA) biopsy to evaluate for cancer. Yet, up to 20% of thyroid nodule FNA biopsies will be ...indeterminate in diagnosis based on cytological evaluation. Genomic approaches to characterize the malignant potential of nodules showed initial promise but have provided only modest improvement in diagnosis. Here, we describe a method using metabolic analysis by desorption electrospray ionization mass spectrometry (DESI-MS) imaging for direct analysis and diagnosis of follicular cell-derived neoplasia tissues and FNA biopsies. DESI-MS was used to analyze 178 tissue samples to determine the molecular signatures of normal, benign follicular adenoma (FTA), and malignant follicular carcinoma (FTC) and papillary carcinoma (PTC) thyroid tissues. Statistical classifiers, including benign thyroid versus PTC and benign thyroid versus FTC, were built and validated with 114,125 mass spectra, with accuracy assessed in correlation with clinical pathology. Clinical FNA smears were prospectively collected and analyzed using DESI-MS imaging, and the performance of the statistical classifiers was tested with 69 prospectively collected clinical FNA smears. High performance was achieved for both models when predicting on the FNA test set, which included 24 nodules with indeterminate preoperative cytology, with accuracies of 93% and 89%. Our results strongly suggest that DESI-MS imaging is a valuable technology for identification of malignant potential of thyroid nodules.
Abstract
Background
The impact of multifocality and bilaterality on recurrence in patients with low-risk papillary thyroid cancer (PTC) is relevant when considering patients for a de-escalated ...treatment strategy: hemithyroidectomy instead of total thyroidectomy followed with or without radioactive iodine. This study aims to analyze contralateral tumor probability in patients treated for low-risk PTC and assess multifocality and bilaterality as possible predictors for recurrence.
Methods
Patients with low-risk PTC treated with total thyroidectomy followed with or without radioactive iodine in the Netherlands between 2005 and 2015 were included in this study. Patients were identified from the Netherlands Comprehensive Cancer Organization (IKNL) and linked with the nationwide network and registry of Pathology in the Netherlands (PALGA). Contralateral tumor probability and recurrence were assessed.
Results
Of 791 included patients, 41.8% (331 of 791) had multifocal disease, with 68.9% (228 of 331) of those patients having bilateral disease. The contralateral tumor probability after hemithyroidectomy was 24.6% (150 of 610) for patients with unifocal disease and 43.1% (78 of 181) for patients with multifocal disease. We found a higher trend of recurrence in patients with bilateral disease, regardless of multifocality: in patients with contralateral disease after precompletion diagnosed unifocal disease 7.3% (11 of 150) had recurrent disease, and patients without contralateral disease after precompletion diagnosed multifocal disease 1.9% (2 per 103) had recurrence. Cox regression analysis showed that bilaterality (hazard ratio = 3.621, 95% confidence interval = 1.548 to 8.471) was the sole statistically significant risk factor for recurrence.
Conclusion
Low recurrence rates are found in patients with either multifocal or bilateral disease with low-risk PTC. Bilaterality should be taken into account when considering these patients for de-escalated treatment strategy.
The landscape of patients with end-stage renal disease is changing with the increasing availability of kidney transplantation. In the near future, a less aggressive approach to treat secondary ...hyperparathyroidism might be beneficial. We report outcomes of parathyroidectomy for end-stage renal disease–related hyperparathyroidism comparing the outcomes of limited, subtotal, and total parathyroidectomy.
We performed a retrospective analysis of prospectively collected data. Patients were divided into 3 parathyroidectomy subgroups: limited (<3 glands removed), subtotal (3–3.5 glands), and total (4 glands) parathyroidectomy. Primary outcome was serum levels of parathyroid hormone. Secondary endpoints were serum levels of calcium, phosphate, and alkaline phosphatase, postoperative complications, and persistent or recurrent disease rates.
In total, 195 patients were included for analysis of whom 13.8% underwent limited parathyroidectomy, 46.7% subtotal parathyroidectomy, and 39.5% total parathyroidectomy. Preoperative parathyroid hormone levels (pg/mL) were 471 (210–868), 1,087 (627–1,795), and 1,070 (475–1,632) for the limited, subtotal, and total parathyroidectomy groups, respectively (P < .001). A decrease in serum parathyroid hormone was seen in all groups; however, postoperative levels remained greater in the limited parathyroidectomy group compared to the subtotal and total parathyroidectomy groups (P < .001). Serum calcium, phosphate, and alkaline phosphatase levels decreased in all groups to within the reference range. In the limited parathyroidectomy group, persistent disease and recurrence occurred more frequently (P = .02 and P = .07, respectively).
Subtotal parathyroidectomy is the optimal strategy in an era with an increasing availability of kidney transplantation and improved regimens of dialysis. In this changing practice, the approach to parathyroid surgery, however, might shift to a less aggressive and patient-tailored approach.
Whereas distal cholangiocarcinoma (DC) is treated by pancreatoduodenectomy (PD), consensus is lacking on treatment of mid-bile duct carcinoma (mid-BDC) without involvement of the pancreatic head. ...Both PD or a local resection (LR) of the extrahepatic bile duct with lymphadenectomy are being used. The aim of this study was to compare outcomes after PD and LR for mid-BDC and, for reference, PD for DC.
Retrospective monocenter study including consecutive patients who underwent LR for mid-BDC (LR), PD for mid-BDC (PD-mid) and PD for DC (PD-distal) between 2000 and 2016. Clinicopathologic characteristics, postoperative outcomes and survival were compared.
A total of 184 patients were included (LR, 22; PD-mid, 38; PD-distal, 124). Postoperative mortality was 0% following LR, 5% (2/22) for PD-mid and 3% (4/124) for PD-distal, p = 0.542. Major complications occurred in 5/22 patients (23%), 19/39 (50%) and 46/124 (37%) respectively, p = 0.103 (LR versus PD-mid, p = 0.038).
Tumor size, differentiation grade and resection margin status were comparable across groups. Median number of resected lymph nodes was 5 (range 3–7), 9 (7–14) and 12 (8–16) respectively, p < 0.001. Median overall survival was 46 months (95%CI 10–82), 19 months. (95%CI 11–27), and 29 months (95%CI 23–35) respectively, p = 0.39 (LR versus PD-mid, p = 0.20). Disease-free survival also did not differ.
LR is an acceptable treatment for selected patients with mid-BDC, showing less morbidity and comparable survival despite smaller lymph node retrieval.
The gene CDC73 (previously known as HRPT2) encodes the protein parafibromin. Biallelic mutation of CDC73 is strongly associated with malignancy in parathyroid tumors. Heterozygous germline mutations ...cause hyperparathyroidism jaw tumor syndrome,which is associated with a high life-time risk of parathyroid carcinoma. Therefore loss of parafibromin expression by immunohistochemistry may triage genetic testing for hyperparathyroidism jaw tumor syndrome and be associated with malignant behavior in atypical parathyroid tumors. We share our experience that parafibromin-negative parathyroid tumors show distinctive morphology. We searched our institutional database for parathyroid tumors demonstrating complete loss of nuclear expression of parafibromin with internal positive controls. Forty-three parafibromin-negative tumors from 40 (5.1%) of 789 patients undergoing immunohistochemistry were identified. Thirty-three (77%) were external consultation cases; the estimated incidence in unselected tumors was 0.19%. Sixteen (37.2%) fulfilled World Health Organization 2017 criteria for parathyroid carcinoma and 63% had serum calcium greater than 3mmol/L. One of 27 (3.7%) noninvasive but parafibromin-negative tumors subsequently metastasized. Parafibromin-negative patients were younger (mean, 36 vs. 63 y; P<0.001) and had larger tumors (mean, 3.04 vs. 0.62 g; P<0.001). Not all patients had full testing, but 26 patients had pathogenic CDC73 mutation/deletions confirmed in tumor (n=23) and/or germline (n=16). Parafibromin-negative tumors demonstrated distinctive morphology including extensive sheet-like rather than acinar growth, eosinophilic cytoplasm, nuclear enlargement with distinctive coarse chromatin, perinuclear cytoplasmic clearing, a prominent arborizing vasculature, and, frequently, a thick capsule. Microcystic change was found in 21 (48.8%). In conclusion, there are previously unrecognized morphologic clues to parafibromin loss/CDC73 mutation in parathyroid tumors which, given the association with malignancy and syndromic disease, are important to recognize.
Postoperative follow-up of papillary thyroid cancer includes serial serum thyroglobulin levels. This study aimed to determine whether stimulated thyroglobulin levels measured in the early ...postoperative period can accurately quantify the risk of recurrence in papillary thyroid cancer.
We undertook a cohort study of patients who underwent total thyroidectomy for papillary thyroid cancer ≥10 mm in the period 2000 to 2016 with complete biochemical data. All patients had a postoperative stimulated thyroglobulin measured within 3 months after total thyroidectomy. Structural recurrence was defined as disease detected on imaging and confirmed on histology. Biochemical disease was defined as patients with stimulated serum thyroglobulin ≥1 ng/mL with no evidence of structural disease.
This study included 502 patients with a mean age of 50 years and median tumor diameter of 20 mm. Median follow-up was 18 months. Stimulated postoperative thyroglobulin was measured before radioiodine-ablation and was categorized into 3 groups: (1) 219 (44%) patients had thyroglobulin <1 ng/mL; (2) 55 (11%) had 1ng/mL ≤ thyroglobulin <2 ng/mL; and (3) 228 (45%) had thyroglobulin ≥2 ng/mL. The structural recurrence rate for each group was 5%, 2%, and 30%, respectively (P < .0001).
In patients undergoing total thyroidectomy for papillary thyroid cancer, early postoperative stimulated thyroglobulin accurately quantifies the risk of structural disease recurrence.
In addition to biochemical cure, clinical benefits after surgery for primary aldosteronism depend on the magnitude of decrease in blood pressure (BP) and use of antihypertensive medications with a ...subsequent decreased risk of cardiovascular and/or cerebrovascular morbidity and drug-induced adverse effects.
To evaluate the change in BP and use of antihypertensive medications within an international cohort of patients who recently underwent surgery for primary aldosteronism.
A cohort study was conducted across 16 referral medical centers in Europe, the United States, Canada, and Australia. Patients who underwent unilateral adrenalectomy for primary aldosteronism between January 2010 and December 2016 were included. Data analysis was performed from August 2017 to June 2018. Unilateral disease was confirmed using computed tomography, magnetic resonance imaging, and/or adrenal venous sampling. Patients with missing or incomplete preoperative or follow-up data regarding BP or corresponding number of antihypertensive medications were excluded.
Clinical success was defined based on postoperative BP and number of antihypertensive medications. Cure was defined as normotension without antihypertensive medications, and clear improvement as normotension with lower or equal use of antihypertensive medications. In patients with preoperative normotensivity, improvement was defined as postoperative normotension with lower antihypertensive use. All other patients were stratified as no clear success because the benefits of surgery were less obvious, mainly owing to postoperative, persistent hypertension. Clinical outcomes were assessed at follow-up closest to 6 months after surgery.
On the basis of inclusion and exclusion criteria, a total of 435 patients (84.6%) from a cohort of 514 patients who underwent unilateral adrenalectomy were eligible. Of these patients, 186 (42.3%) were women; mean (SD) age at the time of surgery was 50.7 (11.4) years. Cure was achieved in 118 patients (27.1%), clear improvement in 135 (31.0%), and no clear success in 182 (41.8%). In the subgroup classified as no clear success, 166 patients (91.2%) had postoperative hypertension. However, within this subgroup, the mean (SD) systolic and diastolic BP decreased significantly by 9 (22) mm Hg (P < .001) and 3 (15) mm Hg (P = .04), respectively. Also, the number of antihypertensive medications used decreased from 3 (range, 0-7) to 2 (range, 0-6) (P < .001). Moreover, in 75 of 182 patients (41.2%) within this subgroup, the decrease in systolic BP was 10 mm Hg or greater.
In this study, for most patients, adrenalectomy was associated with a postoperative normotensive state and reduction of antihypertensive medications. Furthermore, a significant proportion of patients with postoperative, persistent hypertension may benefit from adrenalectomy given the observed clinically relevant and significant reduction of BP and antihypertensive medications.