Two-Stage Surgical Management of a Giant Pediatric Chordoma of theCraniocervical Junction (C0-C3): A Case Report

Two-Stage Surgical Management of a Giant Pediatric Chordoma of theCraniocervical Junction (C0-C3): A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Two-Stage Surgical Management of a Giant Pediatric Chordoma of theCraniocervical Junction (C0-C3): A Case Report Alexey Shkarubo, Alexandr Kuleshov, Ilia Chernov, Anton Nazarenko, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9263452/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Background The surgical management of skull base and craniocervical junction (CCJ) chordomas remains a formidable challenge in modern neurosurgery. Various anterior and posterior approaches are currently employed for the resection of these tumors. Case Presentation: We present a rare clinical case of a three-year-old patient with a three-month history of headaches, progressive weakness in all extremities, and gait disturbance caused by giant chordoma extending from the clivus to the C1–C3 vertebrae. The surgical strategy involved a two-stage procedure: initial posterior craniocervical stabilization followed by tumor resection via a transoral approach. Results Subtotal resection of the tumor was achieved. Postoperatively, the patient's presenting tetraparesis demonstrated near-complete regression. The patient was discharged on the 14th postoperative day. Conclusion This case illustrates that advancements in neurosurgical techniques and accumulated clinical experience now enable the surgical treatment of extremely complex pathologies of the craniocervical junction, even in very young pediatric patients, and can ensure a high quality of life. This report details the surgical strategy and discusses the rationale for a staged approach in the management of giant pediatric chordomas. Chordoma Transoral approach Craniocervical junction Pediatric neurosurgery Skull base surgery Case report Figures Figure 1 Figure 2 Figure 3 Introduction At the current level of neurosurgical advancement, the treatment of patients with chordomas of the craniocervical junction remains a complex challenge, feasible only for multidisciplinary teams in high-volume tertiary centers with extensive experience. The infiltrative and destructive growth pattern of chordomas, with their propensity to involve the craniocervical junction and upper cervical spine, creates significant difficulties in selecting an optimal surgical approach and achieving gross-total resection, which is critical for ensuring long-term progression-free survival. For ventrally located tumors, approaches through natural anatomical corridors (transnasal or transoral) are often the most viable options [ 1 – 4 ]. However, the C1-C2 vertebral complex located along this path can obstruct adequate exposure of the tumor, and its resection inevitably necessitates subsequent stabilization of the craniocervical junction via occipitospondylodesis or C0/1-C2/3 fixation (anterior or posterior) [ 5 , 6 ]. While such procedures are well-established in the management of adult patients, the surgical treatment of children with craniocervical junction chordomas presents unique and distinct challenges. Objective To present a clinical case of a three-year-old patient with a giant chordoma of the craniocervical junction and C1–C3 vertebrae, managed with a two-stage surgical strategy. Case Presentation Patient Information A 3-year, 11-month-old male presented with a three-month history of headaches, progressive weakness in all extremities, and gait disturbance. Past medical history was unremarkable, with no family history of similar conditions. Clinical Findings Neurological examination revealed left-sided tongue deviation, tetraparesis (muscle strength 1–2/5 on the MRC scale), and neurogenic bladder dysfunction. Diagnostic Assessment Magnetic resonance imaging (MRI) identified a giant tumor involving the clivus, craniocervical junction, and the C1-C3 vertebrae, causing significant compression of the brainstem (Fig. 1 ). Based on imaging findings, the presumptive diagnosis was chordoma. Therapeutic Intervention Therapeutic Intervention Given the tumor's ventral location relative to the brainstem, an anteroposterior surgical trajectory was deemed optimal. As the tumor had also destroyed the ventral C1-C2 complex, its resection was necessary to access the intraspinal tumor components, which would inevitably result in craniocervical instability. A two-stage procedure was planned. Stage 1: Posterior Stabilization. Occipitospondylodesis was performed using a patient-specific titanium implant (Fig. 2 ). Due to the patient's young age and the consequent thinness of the occipital bone, bicortical screws were utilized. Computational modeling of the custom stabilization construct is shown in Fig. 2 . Stage 2: Tumor Resection. Two weeks after the first stage, the patient underwent a transoral subtotal resection of the tumor. A tracheostomy was performed prior to the procedure. The diagnosis of chordoma was confirmed by histopathological examination. Follow-up and Outcomes The postoperative course was uneventful. Enteral feeding was initiated on postoperative day 5, and the tracheostomy was removed on day 7. Neurological examination showed significant improvement, with tetraparesis regressing to a muscle strength of 4/5. The patient was discharged in satisfactory condition on the 14th postoperative day. At the follow-up examination 5 months after surgery, further positive dynamics were noted, with limb strength improving to 5/5. There are no signs of continued tumor growth on the control MRI scan. Discussion Pediatric patients with chordomas of the craniocervical junction and upper cervical spine represent a particularly severe cohort. Due to the plasticity of neural structures, pronounced clinical symptoms develop relatively quickly, but typically only when the tumor has already reached large or giant sizes. This significantly complicates radical resection and diminishes the chances of patient recovery. In such situations, the primary goals become ensuring brainstem decompression and achieving the maximal safe tumor resection. These objectives are hindered by the tumor's propensity for infiltrative growth among major vessels and cranial nerves in close proximity to vital brainstem structures. An anatomically justified approach in cases like the one we present is the transoral route. Despite its long history in neurosurgery, it is routinely employed only in high-volume tertiary centers due to the technical complexity of such procedures and the necessity for specific expertise not only from the surgeon but also from intensivists and anesthesiologists. Consequently, the management strategy for these patients varies significantly between institutions. We accumulated extensive experience, having treated 896 patients with chordomas of various locations between 1985 and 2025. Of these, 522 patients had skull base tumors operated via transnasal, transoral, or combined approaches. Extracranial (transoral, n = 43; combined transoral and transnasal, n = 8) tumor resection with preliminary craniocervical stabilization was performed in 51 cases; however, the current three-year-old patient is the youngest to undergo this procedure. The literature describes no more than 250 similar operations, with the largest published series authored by David Choi and Alan Crockard [ 1 , 2 ]. Currently, our standard protocol for such patients involves a two-stage management strategy: initial posterior decompression and stabilization, followed by transoral tumor resection after an interval of 2–3 weeks. This strategy has replaced single-session procedures due to their excessive duration (up to 11–14 hours) and the need for intraoperative patient repositioning [ 7 , 8 ]. Given the tumor's anatomical location, gross-total or near-total resection using various approaches is achieved in no more than 80% of cases [ 9 – 13 ]. In our presented case, the tumor was also removed subtotally. Nevertheless, the primary surgical objective was met: effective decompression of the brainstem and upper cervical spinal cord. This resulted in a markedly positive impact on the patient's neurological status, with near-complete regression of tetraparesis and no postoperative complications, the reported frequency of which reaches 30% in the literature [ 9 ]. In treating patients of such a young age, the choice of surgical approach is paramount. Based on our institutional experience and the tumor's topographical anatomy, we selected the transoral approach. Its application in children is associated with increased technical difficulties due to the smaller surgical field and consequently reduced space for instrumentation. However, this anterior midline approach provides optimal exposure of ventrally located tumors, allowing for effective brainstem decompression. Another critical consideration is the extent of bone resection (and thus, growth plate involvement) and the selection of a craniocervical stabilization method that accounts for the patient's existing anatomy and future growth potential. Numerous stabilization techniques for the craniocervical junction have been developed and are applied for various pathologies in this region [ 6 ]. Many of these systems can be personalized. In our clinical case, a patient-specific implant for occipitospondylodesis was manufactured, tailored to the individual anatomy and the thin occipital bone, which necessitated the use of bicortical screw fixation. Conclusion Advancements in neurosurgical techniques, technology, and the accumulation of clinical experience now enable the surgical treatment of extremely complex pathologies of the craniocervical junction, even in very young pediatric patients, and can ensure a high quality of life. The primary remaining challenges concern the long-term consequences on spinal growth and child development, which necessitate lifelong dynamic follow-up and the continued accumulation of clinical experience. Abbreviations CCJ Craniocervical junction MRI Magnetic resonance imaging Declarations Funding No funding Competing Interests The authors have no relevant financial or non-financial interests to disclose. Declarations of interest: none Ethics approval The approval of the Burdenko neurosurgery center local ethics committee has been received. Consent to participate Informed consent was obtained from all individual participants included in the study. Written Consent for publication was obtained from all individual participants. Research was conducted in accordance with the Declaration of Helsinki The authors affirm that human research participants provided informed consent for publication of the images № 1 and №3 Data and material are not available Code availability - no Clinical trial number: not applicable Author Contributions A.S. - final edit A.K. - final edit I.C. - wrote the main manuscript text A.N. - final edit V.P. - prepared literature review I.L. - prepared literature review M.K. - prepared parient data O.R. prepared figures 1-3 All authors reviewed the manuscript. References Choi D, Crockard HA. Evolution of transoral surgery: three decades of change in patients, pathologies, and indications. Neurosurgery. 2013;73:296–303. 10.1227/01.neu.0000430324.24623.10 . discussion 303-4. Choi D, Melcher R, Harms J, Crockard A. Outcome of 132 Operations in 97 Patients With Chordomas of the Craniocervical Junction and Upper Cervical Spine. Neurosurgery. 2010;66:59–65. 10.1227/01.NEU.0000362000.35742.3D . Shkarubo AN, Chernov IV, Andreev DN. Transoral Removal of Ventrally Located Meningiomas of the Craniovertebral Junction. World Neurosurg. 2019;124:e387–94. 10.1016/j.wneu.2018.12.103 . Shkarubo AN, Kuleshov AA, Chernov IV, Vetrile MS. Transoral Decompression and Anterior Stabilization of Atlantoaxial Joint in Patients with Basilar Impression and Chiari Malformation Type I: A Technical Report of 2 Clinical Cases. World Neurosurg 2017;102:181–90. 10.1016/j.wneu.2017.02.113 Maugeri R, Bonosi L, Brunasso L, Costanzo R, Santi S, Signorelli F, Iacopino DG, Visocchi M. Not Every Size Fits All: Surgical Corridors for Clival and Cervical Chordomas—A Systematic Review of the Literature and Illustrative Cases. J Clin Med. 2024;13:5052. 10.3390/jcm13175052 . Chernov IV, Shkarubo AN, Konovalov NA, Andreev DN, Kaprovoy SV, Starostenko DA, Milovanova OA, Kalinin PL. Techniques of stabilization of the craniovertebral junction. Russ J Neurosurg. 2025;27:120–9. Shkarubo AN, Andreev DN, Konovalov NA, Lubnin AY, Zelenkov PV, Turkin AM, Kadashev BA, Sidorkin DV, Voronina IA, Koval’ KV. Karnaukhov V V. The algorithm for surgical treatment of skull base tumors invading the craniovertebral junction. Vopr neirokhirurgii Im NN Burdenko. 2016;80:21. 10.17116/neiro201680221-34 . Shkarubo AN, Andreev DN, Konovalov NA, Zelenkov PV, Lubnin AJ, Chernov IV, Koval KV. Surgical Treatment of Skull Base Tumors, Extending to Craniovertebral Junction. World Neurosurg. 2017;99:47–58. 10.1016/j.wneu.2016.11.147 . Chernov IV, Shkarubo AN, Konyashin DA, Andreev DN. Transoral approach in surgery for chordomas extending into craniovertebral junction: a systematic review of the literature. Burdenko’s J Neurosurg. 2024;88:111. 10.17116/neiro202488031111 . Sen C, Shrivastava R, Anwar S, Triana A. Lateral Transcondylar Approach for Tumors at the Anterior Aspect of the Craniovertebral Junction. Neurosurgery. 2010;66:A104–12. 10.1227/01.NEU.0000365930.95389.60 . Passeri T, Champagne P-O, Giammattei L, Abbritti R, Cartailler J, Calugaru V, Feuvret L, Guichard J-P, Polivka M, Adle-Biassette H, Mammar H, Bresson D, Herman P, Mandonnet E, George B, Froelich S. Management strategies in clival and craniovertebral junction chordomas: a 29-year experience. J Neurosurg. 2022;1–13. 10.3171/2022.8.JNS221621 . Almefty K, Pravdenkova S, Colli BO, Al-Mefty O, Gokden M. Chordoma and chondrosarcoma: Similar, but quite different, skull base tumors. Cancer. 2007;110:2467–77. 10.1002/cncr.23073 . Colli BO, Al-Mefty O. Chordomas of the skull base: follow-up review and prognostic factors. Neurosurg Focus. 2001;10:1–11. 10.3171/foc.2001.10.3.2 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 10 Apr, 2026 Reviews received at journal 09 Apr, 2026 Reviewers agreed at journal 09 Apr, 2026 Reviewers agreed at journal 09 Apr, 2026 Reviewers agreed at journal 08 Apr, 2026 Reviewers agreed at journal 07 Apr, 2026 Reviews received at journal 07 Apr, 2026 Reviewers agreed at journal 07 Apr, 2026 Reviewers agreed at journal 07 Apr, 2026 Reviewers agreed at journal 07 Apr, 2026 Reviewers invited by journal 07 Apr, 2026 Editor assigned by journal 05 Apr, 2026 Submission checks completed at journal 05 Apr, 2026 First submitted to journal 30 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9263452","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":621072560,"identity":"81048597-dba4-41e4-b5ac-8b8648543e94","order_by":0,"name":"Alexey Shkarubo","email":"","orcid":"","institution":"Burdenko Neurosurgery Institute","correspondingAuthor":false,"prefix":"","firstName":"Alexey","middleName":"","lastName":"Shkarubo","suffix":""},{"id":621072562,"identity":"d2124c8b-e925-4e0d-bab2-7dc788a97d08","order_by":1,"name":"Alexandr Kuleshov","email":"","orcid":"","institution":"Central Scientific Research Institute of Traumatology and Orthopedics","correspondingAuthor":false,"prefix":"","firstName":"Alexandr","middleName":"","lastName":"Kuleshov","suffix":""},{"id":621072564,"identity":"6e641da6-e00e-416e-9d71-983d523fa732","order_by":2,"name":"Ilia Chernov","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAqElEQVRIiWNgGAWjYBACNgYeCIMfiA+QpkWygVgtDDAtBsSqZ+BjP3vwceUOm8TNt9sfHmDcc5gIh/HkJRuePZOWuO3OGaBFz4jRIsFjJtnYdtjY7EYO0C8HiNNi/hOkxXhG+gOitZgxArXIGUgkGBCphSfHGOiwNDmJGzkGBxIOpBPWIt9+xvBjY5sND/+M9McfPhywJqwFFSSQqmEUjIJRMApGAXYAADkNN7j9gX0bAAAAAElFTkSuQmCC","orcid":"","institution":"Burdenko Neurosurgery Institute","correspondingAuthor":true,"prefix":"","firstName":"Ilia","middleName":"","lastName":"Chernov","suffix":""},{"id":621072568,"identity":"4a0da960-616e-4978-a7c0-bfc3ccf20dc6","order_by":3,"name":"Anton Nazarenko","email":"","orcid":"","institution":"Central Scientific Research Institute of Traumatology and Orthopedics","correspondingAuthor":false,"prefix":"","firstName":"Anton","middleName":"","lastName":"Nazarenko","suffix":""},{"id":621072569,"identity":"3b44846b-b4e7-48fb-9a92-5fa23bed862c","order_by":4,"name":"Viktor Pertsukov","email":"","orcid":"","institution":"Burdenko Neurosurgery Institute","correspondingAuthor":false,"prefix":"","firstName":"Viktor","middleName":"","lastName":"Pertsukov","suffix":""},{"id":621072571,"identity":"58aedf9e-2208-4767-a1dd-aa3dca227321","order_by":5,"name":"Igor Lisyanskiy","email":"","orcid":"","institution":"Central Scientific Research Institute of Traumatology and Orthopedics","correspondingAuthor":false,"prefix":"","firstName":"Igor","middleName":"","lastName":"Lisyanskiy","suffix":""},{"id":621072572,"identity":"995bf096-5c1b-4c74-992e-dc0fd17b4fce","order_by":6,"name":"Maria Kapyrina","email":"","orcid":"","institution":"Central Scientific Research Institute of Traumatology and Orthopedics","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"","lastName":"Kapyrina","suffix":""},{"id":621072575,"identity":"48b24688-2767-47eb-b817-a4307857526c","order_by":7,"name":"Olga Rastvorova","email":"","orcid":"","institution":"Burdenko Neurosurgery Institute","correspondingAuthor":false,"prefix":"","firstName":"Olga","middleName":"","lastName":"Rastvorova","suffix":""}],"badges":[],"createdAt":"2026-03-30 07:10:55","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9263452/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9263452/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106871218,"identity":"fdef34c3-4066-4881-a635-0f5ffb393620","added_by":"auto","created_at":"2026-04-14 09:44:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1092640,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA – T2-weighted MRI, sagittal view. B – T2-weighted MRI, axial view. C – T1-weighted contrast-enhanced MRI, sagittal view.\u003c/strong\u003e \u003cem\u003eThe imaging reveals a giant chordoma causing severe compression of the brainstem structures.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-9263452/v1/e1bb51a3702cad07b3b98bf5.png"},{"id":107480173,"identity":"691c5a2b-487b-47f5-ba11-f125c9929aeb","added_by":"auto","created_at":"2026-04-22 02:06:02","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":901225,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient-specific stabilization system in lateral, posterior and anterior view.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-9263452/v1/3abab1f61d909e6f271e2a2c.png"},{"id":106871219,"identity":"7c789c8a-0b9f-4a56-9027-64c1e9f8561e","added_by":"auto","created_at":"2026-04-14 09:44:54","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1080748,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePostoperative CT and MRI on day 6. A – CT, sagittal view. B - T1-weighted contrast-enhanced MRI, sagittal view, C - T1-weighted contrast-enhanced MRI, axial view, D - \u0026nbsp;T2-weighted MRI, frontal view. \u003c/strong\u003e\u003cem\u003eThe images demonstrate adequate brainstem decompression and residual tumor fragments in the parastem region.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-9263452/v1/fe03a9eaa3586a8ea6179fd0.png"},{"id":107482290,"identity":"7e03836a-9421-4265-ae49-a923652cd228","added_by":"auto","created_at":"2026-04-22 02:23:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3906947,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9263452/v1/3327548d-6da2-4eba-af90-634a9dca4832.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Two-Stage Surgical Management of a Giant Pediatric Chordoma of theCraniocervical Junction (C0-C3): A Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAt the current level of neurosurgical advancement, the treatment of patients with chordomas of the craniocervical junction remains a complex challenge, feasible only for multidisciplinary teams in high-volume tertiary centers with extensive experience. The infiltrative and destructive growth pattern of chordomas, with their propensity to involve the craniocervical junction and upper cervical spine, creates significant difficulties in selecting an optimal surgical approach and achieving gross-total resection, which is critical for ensuring long-term progression-free survival. For ventrally located tumors, approaches through natural anatomical corridors (transnasal or transoral) are often the most viable options [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, the C1-C2 vertebral complex located along this path can obstruct adequate exposure of the tumor, and its resection inevitably necessitates subsequent stabilization of the craniocervical junction via occipitospondylodesis or C0/1-C2/3 fixation (anterior or posterior) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. While such procedures are well-established in the management of adult patients, the surgical treatment of children with craniocervical junction chordomas presents unique and distinct challenges.\u003c/p\u003e\n\u003ch3\u003eObjective\u003c/h3\u003e\n\u003cp\u003eTo present a clinical case of a three-year-old patient with a giant chordoma of the craniocervical junction and C1–C3 vertebrae, managed with a two-stage surgical strategy.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003cdiv id=\"Sec4\" class=\"Section3\"\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Case Presentation","content":"\u003ch2\u003ePatient Information\u003c/h2\u003e\u003cp\u003eA 3-year, 11-month-old male presented with a three-month history of headaches, progressive weakness in all extremities, and gait disturbance. Past medical history was unremarkable, with no family history of similar conditions.\u003c/p\u003e\n\u003ch3\u003eClinical Findings\u003c/h3\u003e\n\u003cp\u003eNeurological examination revealed left-sided tongue deviation, tetraparesis (muscle strength 1\u0026ndash;2/5 on the MRC scale), and neurogenic bladder dysfunction.\u003c/p\u003e\n\u003ch3\u003eDiagnostic Assessment\u003c/h3\u003e\n\u003cp\u003eMagnetic resonance imaging (MRI) identified a giant tumor involving the clivus, craniocervical junction, and the C1-C3 vertebrae, causing significant compression of the brainstem (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Based on imaging findings, the presumptive diagnosis was chordoma.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eTherapeutic Intervention\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eTherapeutic Intervention\u003c/div\u003e \u003cp\u003eGiven the tumor's ventral location relative to the brainstem, an anteroposterior surgical trajectory was deemed optimal. As the tumor had also destroyed the ventral C1-C2 complex, its resection was necessary to access the intraspinal tumor components, which would inevitably result in craniocervical instability. A two-stage procedure was planned.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStage 1: Posterior Stabilization.\u003c/b\u003e Occipitospondylodesis was performed using a patient-specific titanium implant (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Due to the patient's young age and the consequent thinness of the occipital bone, bicortical screws were utilized. Computational modeling of the custom stabilization construct is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eStage 2: Tumor Resection.\u003c/b\u003e Two weeks after the first stage, the patient underwent a transoral subtotal resection of the tumor. A tracheostomy was performed prior to the procedure. The diagnosis of chordoma was confirmed by histopathological examination.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eFollow-up and Outcomes\u003c/h2\u003e \u003cp\u003eThe postoperative course was uneventful. Enteral feeding was initiated on postoperative day 5, and the tracheostomy was removed on day 7. Neurological examination showed significant improvement, with tetraparesis regressing to a muscle strength of 4/5. The patient was discharged in satisfactory condition on the 14th postoperative day. At the follow-up examination 5 months after surgery, further positive dynamics were noted, with limb strength improving to 5/5. There are no signs of continued tumor growth on the control MRI scan.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePediatric patients with chordomas of the craniocervical junction and upper cervical spine represent a particularly severe cohort. Due to the plasticity of neural structures, pronounced clinical symptoms develop relatively quickly, but typically only when the tumor has already reached large or giant sizes. This significantly complicates radical resection and diminishes the chances of patient recovery. In such situations, the primary goals become ensuring brainstem decompression and achieving the maximal safe tumor resection. These objectives are hindered by the tumor's propensity for infiltrative growth among major vessels and cranial nerves in close proximity to vital brainstem structures.\u003c/p\u003e \u003cp\u003eAn anatomically justified approach in cases like the one we present is the transoral route. Despite its long history in neurosurgery, it is routinely employed only in high-volume tertiary centers due to the technical complexity of such procedures and the necessity for specific expertise not only from the surgeon but also from intensivists and anesthesiologists. Consequently, the management strategy for these patients varies significantly between institutions.\u003c/p\u003e \u003cp\u003eWe accumulated extensive experience, having treated 896 patients with chordomas of various locations between 1985 and 2025. Of these, 522 patients had skull base tumors operated via transnasal, transoral, or combined approaches. Extracranial (transoral, n\u0026thinsp;=\u0026thinsp;43; combined transoral and transnasal, n\u0026thinsp;=\u0026thinsp;8) tumor resection with preliminary craniocervical stabilization was performed in 51 cases; however, the current three-year-old patient is the youngest to undergo this procedure. The literature describes no more than 250 similar operations, with the largest published series authored by David Choi and Alan Crockard [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCurrently, our standard protocol for such patients involves a two-stage management strategy: initial posterior decompression and stabilization, followed by transoral tumor resection after an interval of 2\u0026ndash;3 weeks. This strategy has replaced single-session procedures due to their excessive duration (up to 11\u0026ndash;14 hours) and the need for intraoperative patient repositioning [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven the tumor's anatomical location, gross-total or near-total resection using various approaches is achieved in no more than 80% of cases [\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In our presented case, the tumor was also removed subtotally. Nevertheless, the primary surgical objective was met: effective decompression of the brainstem and upper cervical spinal cord. This resulted in a markedly positive impact on the patient's neurological status, with near-complete regression of tetraparesis and no postoperative complications, the reported frequency of which reaches 30% in the literature [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn treating patients of such a young age, the choice of surgical approach is paramount. Based on our institutional experience and the tumor's topographical anatomy, we selected the transoral approach. Its application in children is associated with increased technical difficulties due to the smaller surgical field and consequently reduced space for instrumentation. However, this anterior midline approach provides optimal exposure of ventrally located tumors, allowing for effective brainstem decompression. Another critical consideration is the extent of bone resection (and thus, growth plate involvement) and the selection of a craniocervical stabilization method that accounts for the patient's existing anatomy and future growth potential. Numerous stabilization techniques for the craniocervical junction have been developed and are applied for various pathologies in this region [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Many of these systems can be personalized. In our clinical case, a patient-specific implant for occipitospondylodesis was manufactured, tailored to the individual anatomy and the thin occipital bone, which necessitated the use of bicortical screw fixation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAdvancements in neurosurgical techniques, technology, and the accumulation of clinical experience now enable the surgical treatment of extremely complex pathologies of the craniocervical junction, even in very young pediatric patients, and can ensure a high quality of life. The primary remaining challenges concern the long-term consequences on spinal growth and child development, which necessitate lifelong dynamic follow-up and the continued accumulation of clinical experience.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCCJ\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCraniocervical junction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMagnetic resonance imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003eDeclarations of interest: none\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe approval of the Burdenko neurosurgery center\u0026nbsp;local ethics committee has been received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003eWritten Consent for publication was obtained from all individual participants.\u003c/p\u003e\n\u003cp\u003eResearch was conducted in accordance with the Declaration of Helsinki\u003c/p\u003e\n\u003cp\u003eThe authors affirm that human research participants provided informed consent for publication of the images № 1 and \u0026nbsp;№3\u003c/p\u003e\n\u003cp\u003eData and material are not available\u003c/p\u003e\n\u003cp\u003eCode availability - no\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA.S. - final edit\u003c/p\u003e\n\u003cp\u003eA.K. - final edit\u003c/p\u003e\n\u003cp\u003eI.C. \u0026nbsp;- \u0026nbsp;wrote the main manuscript text\u003c/p\u003e\n\u003cp\u003eA.N. - final edit\u003c/p\u003e\n\u003cp\u003eV.P. - \u0026nbsp;prepared literature review\u003c/p\u003e\n\u003cp\u003eI.L. - \u0026nbsp;prepared literature review\u003c/p\u003e\n\u003cp\u003eM.K. - \u0026nbsp;prepared parient data\u003c/p\u003e\n\u003cp\u003eO.R. prepared figures 1-3\u003c/p\u003e\n\u003cp\u003eAll authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChoi D, Crockard HA. Evolution of transoral surgery: three decades of change in patients, pathologies, and indications. Neurosurgery. 2013;73:296\u0026ndash;303. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1227/01.neu.0000430324.24623.10\u003c/span\u003e\u003cspan address=\"10.1227/01.neu.0000430324.24623.10\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. discussion 303-4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoi D, Melcher R, Harms J, Crockard A. Outcome of 132 Operations in 97 Patients With Chordomas of the Craniocervical Junction and Upper Cervical Spine. Neurosurgery. 2010;66:59\u0026ndash;65. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1227/01.NEU.0000362000.35742.3D\u003c/span\u003e\u003cspan address=\"10.1227/01.NEU.0000362000.35742.3D\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShkarubo AN, Chernov IV, Andreev DN. Transoral Removal of Ventrally Located Meningiomas of the Craniovertebral Junction. World Neurosurg. 2019;124:e387\u0026ndash;94. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.wneu.2018.12.103\u003c/span\u003e\u003cspan address=\"10.1016/j.wneu.2018.12.103\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShkarubo AN, Kuleshov AA, Chernov IV, Vetrile MS. Transoral Decompression and Anterior Stabilization of Atlantoaxial Joint in Patients with Basilar Impression and Chiari Malformation Type I: A Technical Report of 2 Clinical Cases. \u003cem\u003eWorld Neurosurg\u003c/em\u003e 2017;102:181\u0026ndash;90. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.wneu.2017.02.113\u003c/span\u003e\u003cspan address=\"10.1016/j.wneu.2017.02.113\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaugeri R, Bonosi L, Brunasso L, Costanzo R, Santi S, Signorelli F, Iacopino DG, Visocchi M. Not Every Size Fits All: Surgical Corridors for Clival and Cervical Chordomas\u0026mdash;A Systematic Review of the Literature and Illustrative Cases. J Clin Med. 2024;13:5052. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/jcm13175052\u003c/span\u003e\u003cspan address=\"10.3390/jcm13175052\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChernov IV, Shkarubo AN, Konovalov NA, Andreev DN, Kaprovoy SV, Starostenko DA, Milovanova OA, Kalinin PL. Techniques of stabilization of the craniovertebral junction. Russ J Neurosurg. 2025;27:120\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShkarubo AN, Andreev DN, Konovalov NA, Lubnin AY, Zelenkov PV, Turkin AM, Kadashev BA, Sidorkin DV, Voronina IA, Koval\u0026rsquo; KV. Karnaukhov V V. The algorithm for surgical treatment of skull base tumors invading the craniovertebral junction. Vopr neirokhirurgii Im NN Burdenko. 2016;80:21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.17116/neiro201680221-34\u003c/span\u003e\u003cspan address=\"10.17116/neiro201680221-34\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShkarubo AN, Andreev DN, Konovalov NA, Zelenkov PV, Lubnin AJ, Chernov IV, Koval KV. Surgical Treatment of Skull Base Tumors, Extending to Craniovertebral Junction. World Neurosurg. 2017;99:47\u0026ndash;58. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.wneu.2016.11.147\u003c/span\u003e\u003cspan address=\"10.1016/j.wneu.2016.11.147\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChernov IV, Shkarubo AN, Konyashin DA, Andreev DN. Transoral approach in surgery for chordomas extending into craniovertebral junction: a systematic review of the literature. Burdenko\u0026rsquo;s J Neurosurg. 2024;88:111. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.17116/neiro202488031111\u003c/span\u003e\u003cspan address=\"10.17116/neiro202488031111\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSen C, Shrivastava R, Anwar S, Triana A. Lateral Transcondylar Approach for Tumors at the Anterior Aspect of the Craniovertebral Junction. Neurosurgery. 2010;66:A104\u0026ndash;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1227/01.NEU.0000365930.95389.60\u003c/span\u003e\u003cspan address=\"10.1227/01.NEU.0000365930.95389.60\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePasseri T, Champagne P-O, Giammattei L, Abbritti R, Cartailler J, Calugaru V, Feuvret L, Guichard J-P, Polivka M, Adle-Biassette H, Mammar H, Bresson D, Herman P, Mandonnet E, George B, Froelich S. Management strategies in clival and craniovertebral junction chordomas: a 29-year experience. J Neurosurg. 2022;1\u0026ndash;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/2022.8.JNS221621\u003c/span\u003e\u003cspan address=\"10.3171/2022.8.JNS221621\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlmefty K, Pravdenkova S, Colli BO, Al-Mefty O, Gokden M. Chordoma and chondrosarcoma: Similar, but quite different, skull base tumors. Cancer. 2007;110:2467\u0026ndash;77. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/cncr.23073\u003c/span\u003e\u003cspan address=\"10.1002/cncr.23073\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eColli BO, Al-Mefty O. Chordomas of the skull base: follow-up review and prognostic factors. Neurosurg Focus. 2001;10:1\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/foc.2001.10.3.2\u003c/span\u003e\u003cspan address=\"10.3171/foc.2001.10.3.2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Chordoma, Transoral approach, Craniocervical junction, Pediatric neurosurgery, Skull base surgery, Case report","lastPublishedDoi":"10.21203/rs.3.rs-9263452/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9263452/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe surgical management of skull base and craniocervical junction (CCJ) chordomas remains a formidable challenge in modern neurosurgery. Various anterior and posterior approaches are currently employed for the resection of these tumors.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003eWe present a rare clinical case of a three-year-old patient with a three-month history of headaches, progressive weakness in all extremities, and gait disturbance caused by giant chordoma extending from the clivus to the C1\u0026ndash;C3 vertebrae. The surgical strategy involved a two-stage procedure: initial posterior craniocervical stabilization followed by tumor resection via a transoral approach.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSubtotal resection of the tumor was achieved. Postoperatively, the patient's presenting tetraparesis demonstrated near-complete regression. The patient was discharged on the 14th postoperative day.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis case illustrates that advancements in neurosurgical techniques and accumulated clinical experience now enable the surgical treatment of extremely complex pathologies of the craniocervical junction, even in very young pediatric patients, and can ensure a high quality of life. This report details the surgical strategy and discusses the rationale for a staged approach in the management of giant pediatric chordomas.\u003c/p\u003e","manuscriptTitle":"Two-Stage Surgical Management of a Giant Pediatric Chordoma of theCraniocervical Junction (C0-C3): A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-14 09:44:50","doi":"10.21203/rs.3.rs-9263452/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-10T15:10:38+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-10T02:52:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"202208078029969385334772239715104045067","date":"2026-04-10T02:12:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"5773271473829472625703257502448245422","date":"2026-04-09T07:52:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"81868130646151494638611512876889733065","date":"2026-04-08T19:48:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"137018927849939184233705949050611640356","date":"2026-04-07T15:13:55+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-07T13:51:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"134082618117526235596908662260599056771","date":"2026-04-07T13:13:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"60198917907725664980128269496297645301","date":"2026-04-07T09:10:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"169209344898815358863744014883499694826","date":"2026-04-07T08:15:50+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-07T07:34:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-06T02:29:49+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-06T00:39:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2026-03-30T06:53:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"bfc2b0be-72cc-473c-8e39-7f7589971c4f","owner":[],"postedDate":"April 14th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-12T06:24:35+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-14 09:44:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9263452","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9263452","identity":"rs-9263452","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}