{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:32:08Z","timestamp":1789421528894,"version":"build-2803163510"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:00:00Z","timestamp":1609977600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:00:00Z","timestamp":1609977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Endocr Disord"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The common endocrine disorder primary hyperparathyroidism (PHPT) can be cured by surgery. Preoperative localization of parathyroid adenoma (PTA) by imaging is a prerequisite for outpatient minimally invasive parathyroidectomy (MIP). Compared to inpatient bilateral cervical exploration (BCE) which is performed if imaging is inconclusive, MIP is superior in terms of cure and complication rates and less costly. The imaging procedure F18-choline (FCH) PET\/CT outperforms Tc99m-sestaMIBI (MIBI) SPECT\/CT for PTA localization, but it is much costlier. The aim of this study is to identify the most efficient first-line imaging modality for optimal patient care in PHPT without added cost to society.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We will conduct a multicenter open diagnostic intervention randomized phase III trial comparing two diagnostic strategies in patients with PHPT: upfront FCH PET\/CT versus MIBI SPECT\/CT. The primary endpoint is the proportion of patients in whom the first-line imaging method results in successful MIP and cure. Follow-up including biological tests will be performed 1 and 6\u2009months after surgery. The main secondary endpoint is the social cost of both strategies. Other secondary endpoints are as follows: FCH PET\/CT and MIBI SPECT\/CT diagnostic performance, performance of surgical procedure and complication rate, FCH PET\/CT inter- and intra-observer variability and optimization of FCH PET\/CT procedure. Fifty-eight patients will be enrolled and randomized 1:1.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>FCH PET\/CT is a highly efficient but expensive imaging test for preoperative PTA localization and costs three to four times more than MIBI SPECT\/CT. Whether FCH PET\/CT improves patient outcomes compared to the reference standard MIBI SPECT\/CT is unknown. To justify its added cost, FCH PET\/CT-guided parathyroid surgery should lead to improved patient management, resulting in higher cure rates and fewer BCEs and surgical complications.<\/jats:p>\n                <jats:p>In the previous phase II APACH1 study, we showed that second-line FCH PET\/CT led to a cure in 88% of patients with negative or inconclusive MIBI SPECT\/CT. BCE could be avoided in 75% of patients and surgical complication rates were low. We therefore hypothesize that upfront FCH PET\/CT would improve patient care in PHPT and that the reduction in clinical costs would offset the increase in imaging costs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04040946\">NCT04040946<\/jats:ext-link>, registered August 1, 2019.\u00a0<\/jats:p>\n                <jats:p><jats:bold>Protocol version<\/jats:bold><\/jats:p>\n                <jats:p>Version 2.1 dated from 2020\/04\/23.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12902-020-00667-5","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T14:03:57Z","timestamp":1610028237000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Upfront F18-choline PET\/CT versus Tc99m-sestaMIBI SPECT\/CT guided surgery in primary hyperparathyroidism: the randomized phase III diagnostic trial APACH2"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0791-9899","authenticated-orcid":false,"given":"Elske","family":"Quak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Lasne Cardon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"Ciappuccini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charline","family":"Lasnon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vianney","family":"Bastit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Le Henaff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Lireux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gauthier","family":"Foucras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Jaudet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Berchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Michel","family":"Grellard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Lequesne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Clarisse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Bardet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"key":"667_CR1","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/S0140-6736(17)31430-7","volume":"391","author":"JP Bilezikian","year":"2018","unstructured":"Bilezikian JP, Bandeira L, Khan A, Cusano NE. Hyperparathyroidism. Lancet. 2018;391:168\u201378.","journal-title":"Lancet."},{"key":"667_CR2","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1097\/SLA.0b013e318208fed9","volume":"253","author":"R Udelsman","year":"2011","unstructured":"Udelsman R, Lin Z, Donovan P. The superiority of minimally invasive parathyroidectomy based on 1650 consecutive patients with primary hyperparathyroidism. Ann Surg. 2011;253:585\u201391.","journal-title":"Ann Surg"},{"key":"667_CR3","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1148\/radiol.2019182122","volume":"291","author":"R Yeh","year":"2019","unstructured":"Yeh R, Tay YD, Tabacco G, Dercle L, Kuo JH, Bandeira L, et al. Diagnostic performance of 4D CT and Sestamibi SPECT\/CT in localizing parathyroid adenomas in primary hyperparathyroidism. Radiology. 2019;291:469\u201376.","journal-title":"Radiology"},{"key":"667_CR4","doi-asserted-by":"publisher","first-page":"2012","DOI":"10.2967\/jnumed.108.054858","volume":"49","author":"DR Neumann","year":"2008","unstructured":"Neumann DR, Obuchowski NA, Difilippo FP. Preoperative 123I\/99mTc-sestamibi subtraction SPECT and SPECT\/CT in primary hyperparathyroidism. J Nucl Med. 2008;49:2012\u20137.","journal-title":"J Nucl Med"},{"key":"667_CR5","doi-asserted-by":"publisher","first-page":"1762","DOI":"10.1007\/s00259-018-3980-9","volume":"45","author":"M Beheshti","year":"2018","unstructured":"Beheshti M, Hehenwarter L, Paymani Z, Rendl G, Imamovic L, Rettenbacher R, et al. (18) F-Fluorocholine PET\/CT in the assessment of primary hyperparathyroidism compared with (99m)Tc-MIBI or (99m)Tc-tetrofosmin SPECT\/CT: a prospective dual-centre study in 100 patients. Eur J Nucl Med Mol Imaging. 2018;45:1762\u201371.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"667_CR6","doi-asserted-by":"publisher","first-page":"e491","DOI":"10.1097\/RLU.0000000000001845","volume":"42","author":"N Thanseer","year":"2017","unstructured":"Thanseer N, Bhadada SK, Sood A, Mittal BR, Behera A, Gorla AKR, et al. Comparative effectiveness of ultrasonography, 99mTc-Sestamibi, and 18F-Fluorocholine PET\/CT in detecting parathyroid adenomas in patients with primary hyperparathyroidism. Clin Nucl Med. 2017;42:e491\u20137.","journal-title":"Clin Nucl Med"},{"key":"667_CR7","first-page":"359","volume":"35","author":"G Akbaba","year":"2012","unstructured":"Akbaba G, Berker D, Isik S, Aydin Y, Ciliz D, Peksoy I, et al. A comparative study of pre-operative imaging methods in patients with primary hyperparathyroidism: ultrasonography, 99mTc sestamibi, single photon emission computed tomography, and magnetic resonance imaging. J Endocrinol Investig. 2012;35:359\u201364.","journal-title":"J Endocrinol Investig"},{"key":"667_CR8","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1245\/s10434-011-1870-5","volume":"19","author":"K Cheung","year":"2012","unstructured":"Cheung K, Wang TS, Farrokhyar F, Roman SA, Sosa JA. A meta-analysis of preoperative localization techniques for patients with primary hyperparathyroidism. Ann Surg Oncol. 2012;19:577\u201383.","journal-title":"Ann Surg Oncol"},{"key":"667_CR9","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.2967\/jnumed.107.040428","volume":"48","author":"WC Lavely","year":"2007","unstructured":"Lavely WC, Goetze S, Friedman KP, Leal JP, Zhang Z, Garret-Mayer E, et al. Comparison of SPECT\/CT, SPECT, and planar imaging with single- and dual-phase (99m)Tc-sestamibi parathyroid scintigraphy. J Nucl Med. 2007;48:1084\u20139.","journal-title":"J Nucl Med"},{"key":"667_CR10","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1097\/RLU.0b013e31823362e5","volume":"37","author":"R Ciappuccini","year":"2012","unstructured":"Ciappuccini R, Morera J, Pascal P, Rame J-P, Heutte N, Aide N, et al. Dual-phase 99mTc sestamibi scintigraphy with neck and thorax SPECT\/CT in primary hyperparathyroidism: a single-institution experience. Clin Nucl Med. 2012;37:223\u20138.","journal-title":"Clin Nucl Med"},{"key":"667_CR11","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.ejso.2016.09.016","volume":"43","author":"M Hocevar","year":"2017","unstructured":"Hocevar M, Lezaic L, Rep S, Zaletel K, Kocjan T, Sever MJ, et al. Focused parathyroidectomy without intraoperative parathormone testing is safe after pre-operative localization with (18) F-Fluorocholine PET\/CT. Eur J Surg Oncol. 2017;43:133\u20137.","journal-title":"Eur J Surg Oncol"},{"key":"667_CR12","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1007\/s00259-017-3911-1","volume":"45","author":"E Quak","year":"2018","unstructured":"Quak E, Blanchard D, Houdu B, Le RY, Ciappuccini R, Lireux B, et al. F18-choline PET\/CT guided surgery in primary hyperparathyroidism when ultrasound and MIBI SPECT\/CT are negative or inconclusive: the APACH1 study. Eur J Nucl Med Mol Imaging. 2018;45:658\u201366.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"667_CR13","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s13550-019-0544-3","volume":"9","author":"WAM Broos","year":"2019","unstructured":"Broos WAM, Wondergem M, Knol RJJ, van der Zant FM. Parathyroid imaging with (18) F-fluorocholine PET\/CT as a first-line imaging modality in primary hyperparathyroidism: a retrospective cohort study. EJNMMI Res. 2019;9:72.","journal-title":"EJNMMI Res"},{"key":"667_CR14","doi-asserted-by":"publisher","first-page":"3561","DOI":"10.1210\/jc.2014-1413","volume":"99","author":"JP Bilezikian","year":"2014","unstructured":"Bilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C, et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the fourth international workshop. J Clin Endocrinol Metab. 2014;99:3561\u20139.","journal-title":"J Clin Endocrinol Metab"},{"key":"667_CR15","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1097\/00000542-200506000-00010","volume":"102","author":"P Auquier","year":"2005","unstructured":"Auquier P, Pernoud N, Bruder N, Simeoni M-C, Auffray J-P, Colavolpe C, et al. Development and validation of a perioperative satisfaction questionnaire. Anesthesiology. 2005;102:1116\u201323.","journal-title":"Anesthesiology."},{"key":"667_CR16","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1093\/rpd\/ncq024","volume":"139","author":"H Uusij\u00e4rvi","year":"2010","unstructured":"Uusij\u00e4rvi H, Nilsson L-E, Bjartell A, Mattsson S. Biokinetics of 18F-choline studied in four prostate cancer patients. Radiat Prot Dosim. 2010;139:240\u20134.","journal-title":"Radiat Prot Dosim"},{"key":"667_CR17","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1186\/1745-6215-13-137","volume":"13","author":"M Rodger","year":"2012","unstructured":"Rodger M, Ramsay T, Fergusson D. Diagnostic randomized controlled trials: the final frontier. Trials. 2012;13:137.","journal-title":"Trials."}],"container-title":["BMC Endocrine Disorders"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12902-020-00667-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12902-020-00667-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12902-020-00667-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T14:36:12Z","timestamp":1610030172000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcendocrdisord.biomedcentral.com\/articles\/10.1186\/s12902-020-00667-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,7]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["667"],"URL":"https:\/\/doi.org\/10.1186\/s12902-020-00667-5","relation":{},"ISSN":["1472-6823"],"issn-type":[{"value":"1472-6823","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,7]]},"assertion":[{"value":"10 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study received ethical approval from the <i>Medical Ethics Committee<\/i> South-East II in July 2019 (Reference 2019\u201335, N\u00b0 EudraCT: 2019\u2013000274-36) and from the National Agency for Medical and Health products Safety (Reference: MEDAECNAT-2019-04-00001_2019\u2013000274-36) in May 2019. All patients will give their written informed consent before any study-related assessment starts.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3"}}