scholarly journals Ultrasound elastography score and strain index in different parathyroid lesions

2019 ◽  
Vol 8 (12) ◽  
pp. 1579-1590
Author(s):  
Bekir Cakir ◽  
F Neslihan Cuhaci Seyrek ◽  
Oya Topaloglu ◽  
Didem Ozdemir ◽  
Ahmet Dirikoc ◽  
...  
Keyword(s):  
Parathyroid Adenoma ◽  
Ultrasound Elastography ◽  
Parathyroid Hyperplasia ◽  
Strain Index ◽  
Median Serum ◽  
Parathyroid Adenomas ◽  
Parathyroid Lesions ◽  
Atypical Parathyroid Adenoma ◽  
Thyroid Parenchyma ◽  
Parathyroid Lesion

Background Despite significant improvement in imaging quality and advanced scientific knowledge, it may still sometimes be difficult to distinguish different parathyroid lesions. The aims of this prospective study were to evaluate parathyroid lesions with ultrasound elastography and to determine whether strain index can help to differentiate parathyroid lesions. Methods Patients with biochemically confirmed hyperparathyroidism and localised parathyroid lesions in ultrasonography were included. All patients underwent B-mode US and USE examination. Ultrasound elastography scores and strain index of lesions were determined. Strain index was defined as the ratio of strain of the thyroid parenchyma to the strain of the parathyroid lesion. Results Data of 245 lesions of 230 patients were analysed. Histopathologically, there were 202 (82.45%) parathyroid adenomas, 26 (10.61%) atypical parathyroid adenomas, and 17 (6.94%) cases of parathyroid hyperplasia. Median serum Ca was significantly higher in atypical parathyroid adenoma patients than parathyroid hyperplasia patients (P = 0.019) and median PTH was significantly higher in APA compared to PA patients (P < 0.001). In 221 (90.2%) of the parathyroid lesions, USE score was 1 or 2. The median SI of atypical parathyroid adenomas was significantly higher than parathyroid adenomas and hyperplasia lesions (1.5 (0.56–4.86), 1.01 (0.21–8.43) and 0.91 (0.26–2.02), respectively, P = 0.003). Conclusion Our study revealed that SI of parathyroid lesions as well as serum calcium, parathyroid hormone levels, and B-mode US features may help to predict the atypical parathyroid adenoma. Ultrasound elastography can be used to differentiate among parathyroid lesions and guide a surgical approach.

scholarly journals Atypical parathyroid adenomas as a rare cause of primary hyperparathyroidism - in an academic institution experience

2021 ◽  
Author(s):  
Grzegorz Kowalski ◽  
Grzegorz Buła ◽  
Adam Bednarczyk ◽  
Agata Gawrychowska ◽  
Jacek Gawrychowski
Keyword(s):  
Retrospective Study ◽  
Primary Hyperparathyroidism ◽  
Parathyroid Adenoma ◽  
Parathyroid Carcinoma ◽  
Clinical Presentation ◽  
Parathyroid Hyperplasia ◽  
Endocrine Surgery ◽  
Parathyroid Adenomas ◽  
Multiple Gland Disease ◽  
Atypical Parathyroid Adenoma

Abstract BACKGROUND Primary hyperparathyroidism (PHPT) is caused by benign and malignant conditions. Most commonly by typical adenoma/single gland disease (PA) - this is 80-85% cases of PHPT. Parathyroid hyperplasia or multiple gland disease accounts for 10-15% of cases of PHPT. Atypical parathyroid adenoma (APA) and carcinoma (PC) - very rare conditions - are both responsible for PHPT in approximately 0,5 - 1,5% of cases. OBJECTIVES To estimate occurrence of atypical parathyroid adenoma, parathyroid carcinoma and parathyroid hyperplasia along with characterize them based on their etiology, clinical presentation, diagnosis and treatment METHODS We performed a retrospective study and enrolled 1,019 patients with primary hyperparathyroidism undergoing parathyroidectomy at academic Department of General and Endocrine Surgery between 1983 and 2018. RESULTS Out of 1,019 cases of primary hyperparathyroidism, 850 (83.4%) cases were due to typical parathyroid adenoma (PA), 135 (13.2%) cases were due to parathyroid hyperplasia, 29 (2.8%) cases were due to parathyroid carcinoma (PC), and 5 (0.5%) cases were due to atypical parathyroid adenoma (APA).

Do patients with atypical parathyroid adenoma need a close follow-up?

2021 ◽  
Author(s):  
Federica Saponaro ◽  
Elena Pardi ◽  
Laura Mazoni ◽  
Simona Borsari ◽  
Liborio Torregrossa ◽  
...  
Keyword(s):  
Parathyroid Adenoma ◽  
Serum Calcium ◽  
Good Prognosis ◽  
Histopathological Diagnosis ◽  
Symptomatic Disease ◽  
Asymptomatic Patients ◽  
Parathyroid Adenomas ◽  
Relevant Role ◽  
Atypical Parathyroid Adenoma

Abstract Context Atypical parathyroid adenomas (APAs) are neoplasms with uncertain malignant potential but lack unequivocal histological signs of malignancy. Objective To retrospectively evaluate the clinical and biochemical profiles of patients with APA, the outcome after parathyroidectomy (PTX), and the presence of CDC73 germline and somatic mutations. Design Monocentric study on consecutive patients undergoing PTX for primary hyperparathyroidism (PHPT) between June 2000 and December 2020. Patients Fifty-eight patients with a confirmed histopathological diagnosis of APA. Age and sex-matched controls with parathyroid adenoma (PA) were also included. Results Fifty-four patients had sporadic PHPT and four familial isolated hyperparathyroidism (FIHP). Thirty-four patients (59%) had a symptomatic disease. Serum calcium and PTH levels were significantly higher in symptomatic compared to asymptomatic patients (P=0.048 and 0.008, respectively). FIHP patients were younger than the sporadic counterpart (30±17yr vs. 55±13 yrs). APA patients had significantly higher serum calcium and PTH levels and lower 25(OH)D concentration, BMD and T-score at 1/3 distal radius compared to those with PA. Four of 56 APA patients displayed a CDC73 germline mutation. No somatic CDC73 mutation was identified in 24 tumor specimens. The mean follow-up after surgery was of 60±56.4 months. All but six patients (90%), five with apparently sporadic PHPT and one with FIHP, were cured after surgery. Conclusions The large majority of patients with APA, despite a moderate/severe phenotype, have a good prognosis. Germline CDC73 mutation-positive patients had a higher rate of persistent/recurrent disease. CDC73 gene alterations do not seem to have a relevant role in the tumorigenesis of sporadic APA.

scholarly journals 2D-Shear Wave Elastography in the Evaluation of Parathyroid Lesions in Patients with Hyperparathyroidism

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Ioana Golu ◽  
Ioan Sporea ◽  
Lavinia Moleriu ◽  
Anca Tudor ◽  
Marioara Cornianu ◽  
...  
Keyword(s):  
Parathyroid Adenoma ◽  
Shear Wave ◽  
Thyroid Tissue ◽  
Shear Wave Elastography ◽  
Study Groups ◽  
Tertiary Hyperparathyroidism ◽  
A Value ◽  
Parathyroid Lesions ◽  
The Mean ◽  
Thyroid Parenchyma

Background and Aims. 2D-shear wave elastography (2D-SWE) is a relatively new elastographic technique. The aim of the present study is to determine the values of the elasticity indexes (EI) measured by 2D-SWE in parathyroid benign lesions (adenomas or hyperplasia) and to establish if this investigation is helpful for the preoperative identification of the parathyroid adenoma. Material and Methods. The study groups were represented by 22 patients with primary or tertiary hyperparathyroidism, diagnosed by specific tests, and 43 healthy controls, in whom the thyroid parenchyma was evaluated, in order to compare the EI of the thyroid tissue with those of the parathyroid lesions. Results. The mean EI measured by 2D-SWE in the parathyroid lesions was 10.2 ± 4.9 kPa, significantly lower than that of the normal thyroid parenchyma (19.5 ± 7.6 kPa; p=0.007), indicating soft tissue. For a cutoff value of 12.5 kPa, the EI assessed by 2D-SWE had a sensitivity of 93% and a specificity of 86% (AUC = 0.949; p<0.001) for predicting parathyroid lesions. Conclusion. A value lower than 12.5 kPa for the mean EI measured by 2D-SWE can be used to confirm that the lesion/nodule is a parathyroid adenoma.

scholarly journals Genetic Alteration Profiles and Clinicopathological Associations in Atypical Parathyroid Adenoma

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xinxin Mao ◽  
Yan Wu ◽  
Shuangni Yu ◽  
Jie Chen
Keyword(s):  
Parathyroid Adenoma ◽  
De Novo ◽  
Sequencing Analysis ◽  
Sequencing Data ◽  
Genomic Alterations ◽  
Parathyroid Tumors ◽  
Formalin Fixed Paraffin ◽  
Parathyroid Adenomas ◽  
Formalin Fixed Paraffin Embedded ◽  
Atypical Parathyroid Adenoma

Genomic aberrations associated with atypical parathyroid adenoma (AA) are poorly understood. Thus, herein, we sought to expand our current understanding of the molecular basis of atypical parathyroid adenomas. We analyzed 134 samples that had been surgically obtained from parathyroid tumors, including parathyroid carcinomas, atypical parathyroid adenomas, and parathyroid adenomas. The tumors were harvested from formalin-fixed, paraffin-embedded tissues. Fifteen tumor-related genes from recently published genome sequencing data were subjected to targeted sequencing analysis, and an average sequencing depth of 500x was achieved. Sixteen (16/50, 32%) AA tumors harbored at least one of the following genomic alterations: CDC73 (12, 24%), EZH2 (4, 8%), HIC1 (1, 2%), and CDKN2A (1, 2%). Our study identified, for the first time, a relatively high frequency of genomic alterations in patients with AA in a Chinese population. This suggests that AA arises de novo, rather than developing from a parathyroid adenoma. Altogether, these findings will improve our understanding of the malignant potential of parathyroid tumors at the molecular level.

scholarly journals Clinical Behaviors of Atypical Parathyroid Adenomas

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A258-A259
Author(s):  
Sarah S Pearlstein ◽  
Kim Eric ◽  
Chomsky-Higgins Kate ◽  
Elham Khanafshar ◽  
Quan-Yang Duh
Keyword(s):  
Parathyroid Adenoma ◽  
Disease Recurrence ◽  
Neck Mass ◽  
Recurrence Rates ◽  
Parathyroid Adenomas ◽  
Long Term Follow Up ◽  
Biochemical Cure ◽  
Atypical Parathyroid Adenoma

Abstract Background: Atypical parathyroid adenoma is a rare entity that share some pathology features of parathyroid carcinoma such as fibrosis. Little is known about the clinical behavior of atypical parathyroid adenomas. Pathologically, it is defined as a hypercellular parathyroid lesion with intratumoral banding fibrosis, mitotic figures, trabecular growth and presence of tumor in the surrounding capsule but lacks unequivocal evidence of invasion, such as invasion to peritumoral vessels, perineural invasion and surrounding structures. Methods: A retrospective study of 15 consecutive patients with atypical parathyroid adenoma treated at a single center between 2010 and 2020 was performed. Patient demographics, clinical characteristics, biochemical profile, indications for surgery, preoperative localization studies, intraoperative findings, histopathological characteristics, disease recurrence or persistence and survival were collected. Results: 7 of 15 were female with a median age of 62 (IQR: 52–67). Five of the 15 patients (33%) were re-operative. No patients presented with palpable neck mass. Presentations were consistent with usual primary hyperparathyroidism. Average calcium on presentation was 11.2, and average PTH was 199. One patient had known MEN1 syndrome and one patient had family history of hyperparathyroidism but had negative genetic testing. Most patients 12/15 had correctly localizing imaging pre-operatively with the other 3 having equivocal or non-localizing studies. Two patients did not have biochemical resolution of hyperparathyroidism, both were re-operative. Of the patients with biochemical cure, 6 did not have follow up beyond 6 months, and 7 patients had long term follow up with persistent biochemical resolution and no recurrence of disease for a median of 4 years (IQR: 3.75–9.25). On review of pathology, no patients had invasive features and all patients had presence of thick fibrous bands or capsule. Conclusion: Patients with atypical adenoma have good response to surgery and low recurrence rates. Reoperation with associated scarring and fibrous bands can confound pathological findings. Our experience shows that patients found to have atypical parathyroid adenoma at their primary operation with resulting biochemical cure can be followed long-term with seemingly indolent and nonaggressive behavior.

Multiple concurrent atypical parathyroid adenomas: a rare occurrence

2020 ◽  
Vol 13 (5) ◽  
pp. e234421
Author(s):  
Jack Faulkner ◽  
Kiran Varadharajan ◽  
Natasha Choudhury
Keyword(s):  
Parathyroid Adenoma ◽  
Vascular Invasion ◽  
Parathyroid Carcinoma ◽  
Postoperative Recovery ◽  
Rare Entity ◽  
Rare Occurrence ◽  
First Case ◽  
Parathyroid Adenomas ◽  
Atypical Parathyroid Adenoma ◽  
Histological Characteristics

We present a case of an 80-year-old patient with three concurrent multiple atypical parathyroid adenomas. The patient was managed with bilateral parathyroid exploration and concurrent parathyroidectomy. Postoperative recovery was uneventful. Atypical parathyroid adenomas are a rare entity that are clinically difficult to distinguish from parathyroid carcinoma. Histological characteristics are similar however atypical adenomas lack complete capsular or vascular invasion and cannot be considered malignant. All reported cases of atypical parathyroid adenoma are solitary lesions. We present the first case of multiple concurrent atypical parathyroid adenomas.

scholarly journals An Interesting Case of Life-Threatening Hypercalcemia Secondary to Atypical Parathyroid Adenoma versus Parathyroid Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Ankur Mishra ◽  
David Newman
Keyword(s):  
Parathyroid Adenoma ◽  
Serum Calcium ◽  
Parathyroid Carcinoma ◽  
Interesting Case ◽  
High Serum ◽  
En Bloc ◽  
Severe Hypercalcemia ◽  
Parathyroid Adenomas ◽  
Life Threatening ◽  
Atypical Parathyroid Adenoma

Context.Severe hypercalcemia is a life-threatening condition. Atypical parathyroid adenoma and parathyroid carcinomas are uncommon causes which can be difficult to differentiate.Objective.We report a case of a 36-year-old male with very high serum calcium due to a possible atypical parathyroid adenoma versus parathyroid carcinoma.Case Illustration.A serum calcium level of 23.2 mg/dl was noted on admission. He was initially treated with IV hydration, pamidronate, and salmon calcitonin to lower his calcium levels. He also underwent a surgical en bloc resection of parathyroid mass. Pathology showed a mixed picture consistent with possible atypical adenoma versus parathyroid carcinoma. However, due to the possible involvement of the recurrent laryngeal nerve, parathyroid carcinoma was more likely. Also after operation the patient developed hungry bones syndrome and his calcium was replaced vigorously. He continues to be on calcium, vitamin D, and calcitriol supplementation.Results.A review of the literature was conducted to identify previous studies pertaining to parathyroid adenomas and parathyroid cancer.Conclusion.We thereby conclude that hypercalcemia requires very careful monitoring especially after operation. Also it can be very difficult to distinguish between atypical parathyroid adenomas and parathyroid carcinomas as in our case and no clear cut guidelines yet exist to differentiate the two based on histology.

scholarly journals Atypical Parathyroid Adenoma in a Young Man

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A182-A182
Author(s):  
Elizabeth R Bowen ◽  
Joseph Stephen Dillon
Keyword(s):  
Parathyroid Hormone ◽  
Parathyroid Adenoma ◽  
Mitotic Activity ◽  
Parathyroid Carcinoma ◽  
Sudden Onset ◽  
Lytic Lesion ◽  
Brown Tumor ◽  
Adjacent Structures ◽  
Parathyroid Adenomas ◽  
Atypical Parathyroid Adenoma

Abstract Patient is a 38-year-old man who developed sudden onset of pain in the upper left arm while carrying a case of water. The pain recurred periodically over the next few months. He presented to the emergency department where imaging showed a pathologic fracture in the proximal left humerus through a lytic lesion. Laboratory testing showed: calcium 13.8 mg/dL (8.5–10.1 mg/dL), 25-OH vitamin D 8 ng/mL (31–100 ng/mL), parathyroid hormone 1583.1 pg/mL (18.5–88 pg/mL). Neck ultrasound showed a complex nodule in the left neck measuring 4.2 x 1.7 x 2.5 cm. Subsequent biopsy of the left arm lesion showed a Brown tumor. The patient was referred to endocrinology. There was concern for parathyroid carcinoma given the elevated parathyroid hormone and large neck lesion. Technetium-99m sestamibi scan showed a 4.1 x 2.6 x 2.5 cm mass posterior to the left thyroid lobe. He subsequently underwent left hemithyroidectomy and parathyroidectomy. Pathology revealed a 3.1 cm parathyroid mass with scattered fibrous bands, foci of prominent nucleoli and foci of sheet-like trabecular and spindled architecture. It was without necrosis, lymphovascular invasion, perineural invasion, increased mitotic activity, atypical mitoses or invasion into adjacent structures. Thus, it was classified as an atypical parathyroid adenoma. Primary hyperparathyroidism is the third most common endocrine disorder, but fewer than 2% occur as a result of an atypical parathyroid adenoma. Patients with an atypical parathyroid adenoma tend to have a more dramatic clinical presentation compared to those with classic adenoma. We see higher calcium and parathyroid hormone levels. Atypical parathyroid adenomas are classified as such due to other features which place the lesion at a higher risk for malignant behavior including higher mitotic activity, adherence to adjacent structures, banding fibrosis and a growth pattern that is either solid or trabecular. In contrast to parathyroid carcinoma, atypical parathyroid adenomas do not show invasion into the surrounding tissues or lymphatic/vascular vessels, and there should be no evidence of metastatic disease. The exact definition of an atypical parathyroid adenoma varies among institutions, and recognition of the defining features (or lack thereof) necessitates an experienced endocrine pathologist. Due to their uncertain malignant potential, patients with an atypical parathyroid adenoma should undergo routine surveillance for recurrence. Routine follow-up of calcium, parathyroid hormone and imaging is indicated to detect for recurrence. A CDC73 germline mutation is associated with recurrence compared to CDC73-negative patients. Parafibromin expression is also thought to play a role although studies so far have had discrepant results.

scholarly journals Shear Wave Elastography versus Strain Elastography in Diagnosing Parathyroid Adenomas

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Laura Cotoi ◽  
Daniela Amzar ◽  
Ioan Sporea ◽  
Andreea Borlea ◽  
Dan Navolan ◽  
...  
Keyword(s):  
Parathyroid Adenoma ◽  
Shear Wave ◽  
Muscle Tissue ◽  
Thyroid Tissue ◽  
Shear Wave Elastography ◽  
Strain Ratio ◽  
Strain Elastography ◽  
Parathyroid Adenomas ◽  
The Mean ◽  
Thyroid Parenchyma

Objectives. The aim of the study was to compare elastographic means in parathyroid adenomas, using shear wave elastography and strain elastography. Methods. This prospective study examined 20 consecutive patients diagnosed with primary hyperparathyroidism and parathyroid adenoma, confirmed by biochemical assay, technetium-99 sestamibi scintigraphy, and pathology report, after parathyroid surgery. All patients were examined on conventional 2B ultrasound, 2D shear wave elastography, and strain elastography. We determined using 2D shear wave elastography (SWE) the elasticity index (EI) in parathyroid adenoma, thyroid parenchyma, and surrounding muscle and examined using strain elastography the parathyroid adenoma, and determined the strain ratio with the thyroid tissue and muscle tissue. Results. All patients had positive sestamibi scintigraphy and underwent surgery, with confirmation of parathyroid adenoma in all cases. The mean parathormone (PTH) value before surgery was 153.29 pg/ml (36.5, 464.8) and serum calcium concentration was 10.5 mg/dl (9, 11.5). We compared using 2D-SWE and strain elastography parathyroid adenoma with thyroid tissue and with surrounding muscle. The mean EI measured by SWE in parathyroid adenoma was 4.74 ± 2.74 kPa and in thyroid parenchyma was 11.718 ± 4.206 kPa (mean difference = 6.978 kPa, p<0.001), and the mean EI value in muscle tissue was 16.362 ± 3.829 kPa (mean difference = 11.622, p<0.001). Using ROC analysis, we found that an EI below 7 kPa correctly identifies parathyroid tissue. We evaluated parathyroid adenomas using strain elastography by color mapping and strain ratio as a semiquantitative measurement; however, we could not find any statistical correlation comparing the strain ratio obtained from the parathyroid adenoma with the thyroid tissue (p=0.485). Conclusion. Ultrasound elastography is a helpful tool in identifying parathyroid adenomas. A cutoff value below 7 kPa can be used in 2D-SWE. Color maps in strain elastography without adding strain ratio can be used, parathyroid adenoma being identified as score 1 in the Rago criteria.

scholarly journals Benign, Malignant or Something in Between: A Rapidly Developing Atypical Parathyroid Adenoma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A183-A184
Author(s):  
Albana Sykja ◽  
Ye Lynn Ko ◽  
Rajeev Raghavan ◽  
Harit Buch
Keyword(s):  
Primary Hyperparathyroidism ◽  
Parathyroid Adenoma ◽  
Parathyroid Carcinoma ◽  
Malignant Potential ◽  
Thyroid Lobe ◽  
Uncertain Malignant Potential ◽  
Parathyroid Adenomas ◽  
Atypical Parathyroid Adenoma ◽  
Left Thyroid Lobe

Abstract Introduction: Although Primary Hyperparathyroidism (PHPT) is the third most common endocrine disorder, parathyroid carcinoma and atypical parathyroid adenoma are the rarest of endocrine tumours. The true incidence of atypical parathyroid adenomas has been elusive to endocrinologists since it is not possible to differentiate clinically between parathyroid carcinoma and atypical parathyroid adenomas before histological analysis. Atypical parathyroid adenoma represents a group of an intermediate form of parathyroid neoplasms with uncertain malignant potential. The majority of patients present with hypercalcaemia, however the development of atypical adenoma in patients with known PHPT is extremely rare. Clinical Case: A 78-year-old gentleman presented at the emergency department with lethargy and slurred speech which had started 1 week ago. Blood tests revealed severe hypercalcaemia. (Ca 4.98 mmol/L, PTH 114.2 pmol/L). The patient had a background of primary hyperparathyroidism which was diagnosed due to incidental mild hypercalcaemia (Ca 2.71 mmol/L, PTH 17.57 pmol/L, 25OH-vitamin D3 55 nmol/L). 2 weeks prior to presentation to the Emergency Department calcium and PTH levels were stable. On clinical examination, he was found mildly confused with no other clinical findings. No precipitating factors were identified. Hydration with IV crystalloids commenced and bisphosphonate IV was given. In view of PHPT Cinacalcet was added to treatment (30 mg BD). While the calcium levels seemed to improve initially, (lowest level achieved Ca 3.05 mmol/L) a week later they started to rise gradually. Hypercalcaemia proved refractory to medical treatment despite concomitant use of aggressive hydration, increased cinacalcet dose, second intravenous bisphosphonate, and intravenous calcitonin. Neck U/S revealed a probable parathyroid adenoma measuring 2cm axially at the inferior pole of the left thyroid lobe. In view of the severity and refractory nature of hypercalcaemia, a PET CT was requested which identified an 18 mm soft tissue mass in the left lower neck posterior to the left thyroid lobe with moderate to intense FDG uptake. There was no evidence of increased uptake elsewhere. The patient required 2 sessions of haemodialysis to maintain calcium levels around 3.5 preoperatively. He underwent parathyroidectomy with histological findings in keeping with atypical parathyroid adenoma. Gradual reduction of calcium levels was noted post-operatively with the lowest on day 10 (1.99) when he was started on oral calcium supplementation. The patient remains under follow-up with normal calcium levels 6 months postoperatively while remains on calcium and vitamin D3 supplements. Conclusion: To our knowledge, this is the only case of a patient with known primary hyperparathyroidism and mild hypercalcaemia, to develop severe parathyroid crisis with refractory to medical management hypercalcaemia within 2 weeks. Prompt surgical intervention remains of paramount importance in the management of these patients. They should have lifelong follow up in the view of uncertain malignant potential of the atypical parathyroid adenoma.

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