A case of cubital tunnel syndrome due to bone metastasis of lung cancer confirmed by 18 F-FDG PET/CT

A case of cubital tunnel syndrome due to bone metastasis of lung cancer confirmed by 18 F-FDG PET/CT | 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 A case of cubital tunnel syndrome due to bone metastasis of lung cancer confirmed by 18 F-FDG PET/CT Haopeng Ni, Haiying Zhou, Donghe Chen, Zhenfeng Liu, Vishnu Goutham Kota, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4933767/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Lung adenocarcinoma can metastasize to other parts of the body. Solitary metastasis to the elbow is rare; elbow metastasis presenting with the initial symptom of pain is extremely rare. Methods and results We report a 67-year-old female presented to our hospital with an eight- month history of progressively swelling and pain in her elbow. An MR scan revealed a possible malignant lesion. A subsequent 18 F-FDG PET/CT scan revealed cancer of the lower lobe of the right lung with metastasis to the mediastinal lymph nodes and elbow joint. The clinical diagnosis was pulmonary malignant tumor elbow metastasis, with ulnar nerve entrapment syndrome. A biopsy of elbow soft tissue was performed to confirm metastasis of lung adenocarcinoma. The patient refused to target-specific drug treatment for economic reasons. After six months, the patient was lost to follow up. Conclusions Our findings confirm that 18 F-FDG PET/CT is an excellent method that has potential as a diagnostic modality for examination of a malignant or locally aggressive elbow lesion. PET/CT FDG lung adenocarcinoma metastasis elbow joint Figures Figure 1 Figure 2 Figure 3 Background Lung adenocarcinoma can metastasize to other parts of the body including the lymph nodes, liver, bones[ 1 ], parotid gland[ 2 ], kidney[ 3 ], brain, thyroid[ 4 ]. Solitary metastasis to the elbow is rare; and elbow metastasis presenting with the initial symptom of pain is even more rare. In this report, we report a patient with metastatic adenocarcinoma arising in the elbow originating from primary lung adenocarcinoma. Case presentation A 67-year-old female presented with swelling and pain in her left elbow, which had persisted for eight months. No cough, sputum, hemoptysis, chest stuffiness, fever, or hoarseness were present. A previous X-ray examination showed no abnormal signs. She was advised to take nonsteroidal anti-inflammatory drugs (NSAIDs) and tramadol hydrochloride tablets, but these provided no significant pain relief. Due to the pain, she had endured poor sleep for nearly one month, and her weight had decreased by at least 5 kg in the past six months. She had numbness and paralysis in her left ring finger and little finger. The function of finger extension was limited. Chest radiographs indicated an enlarged cardiac shadow, with a cardiothoracic ratio of around 0.58. Examination of tumor markers revealed the following: CA 15 − 3, 61.5 U/mL and CA 125, 176.9 U/mL. X-ray and Magnetic Resonance Imaging (MRI) examinations were performed due to the suspicion of an infection or acute synovitis of the elbow. The X-ray showed abnormal bone density in the distal humerus and proximal ulna, while MRI revealed bone destruction and abnormal signals on the upper ulna, olecranon, and capitellum with visible soft tissue masses (Fig. 1 ). These results strongly suggested a malignant lesion. Due to the malignancy indications, an 18 F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography ( 18 F-FDG PET/CT) scan was performed to investigate primary or metastatic systemic involvement, which revealed an irregular mass with spiny margins was observed in the lower lobe of the right lung, showing unevenly increased FDG metabolism (Fig. 2 ). Multiple enlarged and calcified lymph nodes in the mediastinum (zones 2R, 4R, and 6–7) and the right hilar also demonstrated increased FDG metabolism, indicating possible lymph node metastasis. Additionally, soft tissue masses were detected in the left ulnar-radial joint and upper elbow joint, accompanied by abnormal bone density and increased FDG metabolism, suggesting a malignant lesion. The clinical diagnosis was pulmonary malignant tumor with elbow metastasis and ulnar nerve entrapment syndrome. To make a definitive diagnosis, a biopsy of the left soft tissue elbow lesion was performed under ultrasound guidance. Pathological examination confirmed lung adenocarcinoma with metastatic invasion (Fig. 3 ). Findings on transbronchial lung biopsy also supported this diagnosis. The patient refused to target-specific drug treatment for economic reasons. Pain relief was achieved with an intravenous injection of Technetium [ 99m Tc] Methylenediphosphonate Injection ( 99m Tc-MDP). After six months, the patient was lost to follow up. Discussion and Conclusions The first step in treatment is to accurately diagnose the lesion. Tumors of the elbow are rare, malignant tumors of the elbow are extremely rare[ 5 ], which can easily result in delayed treatment. Malignant tumors presenting with elbow pain and swelling have multiple differential diagnoses. For instance, intra-neural Ewing’s sarcoma can be diagnosed by CT guided biopsy[ 6 ]. Pigmented villonodular synovitis, which can also cause pain and swelling, is mainly diagnosed by MRI and needs to be considered in the differential diagnosis[ 7 ]. Therefore, when encountered with elbow mass, radiological and clinicopathologic examinations need to be combined. MR imaging takes more advantageous than CT for evaluating soft tissue tumor margins in the elbow[ 8 ]. Meanwhile, 18 F-FDG PET/CT has shown good accuracy in detecting metastasis detection, especially in lung cancer metastasis. By providing comprehensive imaging and facilitating precise diagnosis, 18 F-FDG PET/CT plays a crucial role in the timely and effective management of such complex cases. It is well known that more than half of all cancers metastasize to the skeleton, making it the third most frequent site of metastatic spread after the lungs and the liver[ 9 ]. An epidemiological investigation conducted in this matter has revealed that of the 1.2 million new cases of cancer each year in the USA and about 300,000 of these will eventually develop a bone metastasis[ 10 ]. Lung cancer ranks third in its ability to cause bone metastasis, following breast and prostate cancers, with a post-mortem incidence of about 30%[ 11 ]. The spine, pelvis, ribs, skull, and proximal long bones are most frequently affected, while the upper limb is least affected, with 10–15% of cases [ 10 , 12 ]. When the upper limb is impacted by metastasis, particularly in the elbow region, the ulnar nerve can become compressed, leading to cubital tunnel syndrome (CuTS). Therefore, the presence of any inflammation, mass, or obstruction in this region can cause the compression of the ulnar nerve in this area and as mentioned above, this phenomenon is termed as the CuTS. CuTS, the second most common compressive neuropathy of the upper extremity after carpal tunnel syndrome, is defined by the compression of the ulnar nerve at the elbow[ 13 ]. The ulnar nerve may be entrapped at several locations in the upper arm, but the most common are the Arcade of Struthers, the medial intramuscular septum, the cubital tunnel retinaculum (flexor carpi ulnaris aponeurosis), and the deep flexor-pronator aponeurosis. Normally, lung adenocarcinomas do not metastasize to the upper limbs, but when they do, they can cause rare conditions like CuTS. Also, an acro-metastasis is a sign of extremely advanced metastatic cancer and in such conditions, it is highly likely that multiple metastases would be found elsewhere. There are very few papers which discuss lung cancer spread to the carpal bones. So far, only Lederer et al., in 1990, and Song and Yao and Antenucci et.al in 2012, have described a metastasis to the upper limb from lung cancer and in most of those, it is the carpal bones that get affected by the metastasis[ 10 , 14 ]. Therefore, when the source of elbow masses causing CuTS is unclear, 18 F-FDG PET/CT can effectively diagnose both primary and metastatic lesions. For lung adenocarcinoma and non-small cell lung cancer (NSCLC), current therapeutic strategies include chemotherapy, radiotherapy, and targeted therapy. If the patient’s prognosis is deemed to be poor, the main therapeutic approach is pain alleviation and improving the quality of life. Radical resection or total elbow arthroplasty after tumor resection needs to be critically evaluated for patient benefit[ 15 ]. Our findings highlight the potential of 18 F-FDG PET/CT as an excellent diagnostic modality for examining malignant or locally aggressive lesions in the elbow. The detailed imaging provided by 18 F-FDG PET/CT not only identified the primary lung adenocarcinoma but also detected metastasis to the mediastinal lymph nodes and elbow joint. This comprehensive evaluation underscores the utility of 18 F-FDG PET/CT in accurately diagnosing and staging malignancies, facilitating early and precise treatment planning. By revealing the full scope of metastatic spread, 18 F-FDG PET/CT plays a pivotal role in the staging of lung cancer, directly influencing the choice of therapeutic strategies. Accurate clinical staging is essential for tailoring treatments, such as surgery, chemotherapy, or radiation, to the patient's specific condition, ensuring the appropriate choice of therapeutic measures while avoiding both unnecessary interventions and missed opportunities for radical treatment. Furthermore, early and precise detection of metastatic sites can improve prognosis by enabling timely and targeted interventions. The ability of 18 F-FDG PET/CT to provide a holistic view of the disease also aids in monitoring treatment response and detecting recurrences, ultimately contributing to better patient outcomes. In this case, the use of 18 F-FDG PET/CT facilitated the diagnosis of ulnar nerve entrapment syndrome secondary to bone metastasis of lung cancer, guiding the clinical management of the patient's symptoms and highlighting its impact on the staging, treatment, and prognosis of lung cancer. Teaching Points : Clinicians should maintain a high index of suspicion for metastatic disease in patients with lung adenocarcinoma presenting with atypical symptoms, such as elbow pain and swelling, especially when accompanied by neurological deficits like ulnar nerve entrapment. Prompt imaging with modalities such as 18F-FDG PET/CT is essential for accurate diagnosis and timely intervention. Given the rarity of elbow metastasis from lung adenocarcinoma, further research is needed to better understand the mechanisms and clinical characteristics of such metastases. This could lead to improved diagnostic strategies and more effective treatment options for managing metastatic lung cancer involving uncommon sites like the upper limb. Abbreviations NSAIDs nonsteroidal anti-inflammatory drugs CuTS Cubital tunnel syndrome 18 F-FDG PET/CT 18 F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography MRI Magnetic Resonance Imaging 99m Tc-MDP 99m Technetium Methylenediphosphonate Declarations Conflict of interest None. Ethics approval and consent to participate The study protocols were approved by the Medical Ethics Committee of the First Affiliated Hospital of the College of Medicine, Zhejiang University Consent for publication Written informed consent was obtained from the patient for publication of clinical details and clinical images. Upon request, a copy of the consent form is available for review by the Editor of this journal Availability of data and materials section The dataset supporting the conclusions of this article is included with the article. Competing interests The author declares that they have no competing interests. Funding The study was funded by the Zhejiang Traditional Chinese Medicine Research Program (grant number 2016ZA124, 2017ZB057), Zhejiang Medicine and Hygiene Research Program (grant number 2016KYB101, 2015KYA100), and National Natural Science Foundation of China (the grant number 81702135). The funding bodies had no role in the design of the study; in collection, analysis, and interpretation of data; and in drafting the manuscript. Author contributions HL, SAA and ZF L designed the study, performed data collection, analyzed the results, HP N and HY Z drafted the manuscript. DH C, VGK, MHAHA, AHAHA, and SHAE took part to the patient therapy as Registrars. The author has read and approved the final manuscript. Acknowledgements Not Applicable. References Lin C-Y, Hua-Tzu HY-FH. Lung cancer with solitary bone metastasis in the radius. Clin Nucl Med. 2009;34:684–5. Imauchi Y, Nakashima M, Nigauri T. Metastasis of lung adenocarcinoma to parotid lymph node as initial clinical manifestation. Eur Arch Otorhinolaryngol. 2001;258:155–6. Sawada T, Takahashi H, Hasatani K, Yoshida I, Oyama O, Inoue R, et al. Tumor-to-tumor metastasis: Report of an autopsy case of lung adenocarcinoma metastasizing to renal cell carcinoma. Intern Med. 2009;48:1525–9. Miyakawa M, Sato K, Hasegawa M, Nagai A, Sawada T, Tsushima T, et al. Severe thyrotoxicosis induced by thyroid metastasis of lung adenocarcinoma: A case report and review of the literature. Thyroid. 2001;11:883–8. Bruguera JANR. Primary tumors of the elbow: a review of the Leeds Regional Bone Tumour Registry. Orthopedics. 1998;21:551–3. Mohan AT, Park DH, Jalgaonkar A, Alorjani M, Aston W, Briggs T. Intra-neural Ewing’s sarcoma of the upper limb mimicking a peripheral nerve tumour. A report of 2 cases. J Plast Reconstr Aesthetic Surg. 2011;64:e153–6. Tang K, Zheng X, Lin J, Wang L. Diffuse-Type Tenosynovial Giant Cell Tumor of the Shoulder Evaluated by FDG PET/CT. Clin Nucl Med. 2019;44:310–2. Steinbach LS, Anderson SPD. MR imaging of musculoskeletal tumors in the elbow region. Magn Reson Imaging Clin N Am. 1997;5:619–53. Hage WD, Aboulafia AJ, Aboulafia DM. Incidence, location, and diagnostic evaluation of metastatic bone disease. Orthop Clin North Am. 2000;31:515–28. Rinonapoli G, Caraffa A, Antenucci R. Lung cancer presenting as a metastasis to the carpal bones: a case report. J Med Case Rep. 2012;6:384. Schlappack OK, Baur M, Steger G, Dittrich C, Moser K. The clinical course of lung metastases from breast cancer. Klinische Wochenschrift. 1988;66:790–5. Silverberg E, Cancer. statistics. 1986. CA Cancer J Clin. 1986;36:9–25. Palmer BA, Hughes TB. Cubital Tunnel Syndrome. J Hand Surg. 2010;35:153–63. Song Y, Yao J. Trapezial metastasis as the first indication of primary non-small cell carcinoma of the lung. J Hand Surg Am. 2012;37:1242–4. Casadei R, De Paolis M, Drago G, Romagnoli C, Donati D. Total elbow arthroplasty for primary and metastatic tumor. Orthopaedics and Traumatology: Surgery and Research. 2016;102:459–65. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-4933767","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":346971701,"identity":"f4342680-e7bd-4f58-98dd-79f35948c0d7","order_by":0,"name":"Haopeng Ni","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Haopeng","middleName":"","lastName":"Ni","suffix":""},{"id":346971704,"identity":"17575765-9d19-4132-9c75-8c58aeed62fa","order_by":1,"name":"Haiying Zhou","email":"","orcid":"","institution":"The Chinese University of Hong Kong","correspondingAuthor":false,"prefix":"","firstName":"Haiying","middleName":"","lastName":"Zhou","suffix":""},{"id":346971705,"identity":"9f4de40d-95c1-4b57-9194-f86f49254bcc","order_by":2,"name":"Donghe Chen","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Donghe","middleName":"","lastName":"Chen","suffix":""},{"id":346971706,"identity":"77b4b662-f1cf-497c-a019-c1eb63405509","order_by":3,"name":"Zhenfeng Liu","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Zhenfeng","middleName":"","lastName":"Liu","suffix":""},{"id":346971707,"identity":"34135b60-edc5-4966-824f-a77024b26d99","order_by":4,"name":"Vishnu Goutham Kota","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Vishnu","middleName":"Goutham","lastName":"Kota","suffix":""},{"id":346971708,"identity":"d8c74a25-1d3d-4014-b1f2-1e65dd929801","order_by":5,"name":"Mohamed Hasan Abdulla","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"Hasan","lastName":"Abdulla","suffix":""},{"id":346971709,"identity":"5a237be5-4482-4558-a455-6a7488beeed2","order_by":6,"name":"Ali Hasan Abdulla","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ali","middleName":"Hasan","lastName":"Abdulla","suffix":""},{"id":346971710,"identity":"680393f4-136a-47f5-a358-c65007068b26","order_by":7,"name":"Sohaib Hasan Ezzi","email":"","orcid":"","institution":"Nahda University in Beni Suef","correspondingAuthor":false,"prefix":"","firstName":"Sohaib","middleName":"Hasan","lastName":"Ezzi","suffix":""},{"id":346971711,"identity":"6ea0b0eb-dda2-4fcf-90f3-ef7c18f3798e","order_by":8,"name":"Sahar Ahmed Abdalbary","email":"","orcid":"","institution":"Nahda University in Beni Suef","correspondingAuthor":false,"prefix":"","firstName":"Sahar","middleName":"Ahmed","lastName":"Abdalbary","suffix":""},{"id":346971712,"identity":"115a48df-6ded-420e-95f3-8551a6c90c8a","order_by":9,"name":"Hui Lu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAs0lEQVRIiWNgGAWjYBACAwbGxgMMFQzMII4EsVoaDjCcIU0LA8MBxjYIhzgt5hLJDYd559WxGxxgPnibh8Euj6AWyxmJQC3b2JgNDrAlW/MwJBcTdtgNsBYeoBYeM2kehgOJDcRpmSMB1ML/jRQtDQYgW9iI1HLmYcPBOccSmCUPsxlbzjFIJkLL8fSHD97U1CXzHW9+eONNhR1hLTCQDIlMA2LVA4EdCWpHwSgYBaNgpAEAjaM5/McVJkwAAAAASUVORK5CYII=","orcid":"","institution":"Zhejiang University","correspondingAuthor":true,"prefix":"","firstName":"Hui","middleName":"","lastName":"Lu","suffix":""}],"badges":[],"createdAt":"2024-08-18 14:29:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4933767/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4933767/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66565562,"identity":"099d9a31-4de8-4fdd-b033-b798ea976e1c","added_by":"auto","created_at":"2024-10-14 10:39:12","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":274878,"visible":true,"origin":"","legend":"\u003cp\u003eThe X-ray showed abnormal bone density in the distal humerus and proximal ulna (A). The MRI showed bone destruction and abnormal signals on the upper ulna, olecranon, and capitellum with visible soft tissue masses. T1WI showed a low signal (B), T2WI showed a high signal (C), and contrast-enhanced lesions showed significant uneven enhancement (D).\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4933767/v1/9f25f277a1918d766ab98b95.jpg"},{"id":66565473,"identity":"39af7649-3403-427a-a0b3-13b7877249ef","added_by":"auto","created_at":"2024-10-14 10:39:05","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":303180,"visible":true,"origin":"","legend":"\u003cp\u003eAn \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT scan showed there was an irregular mass in the lower lobe of the right lung with a spiculated margin, which surrounded the segmental bronchus and pulled the pleura. Patchy shadows were seen in the distal bronchus, and FDG metabolism increased unevenly, suggesting a malignant lesion (lung cancer) with possible obstructive changes (A). There was an irregular mass surrounding the bronchial opening in the middle lobe of the right lung. FDG metabolism increased slightly, suggesting possible multi-center malignant lesions, please confirm with tracheoscope. There was a lesion close to the right oblique cleft pleura, and there were multiple fine knots on the right oblique cleft pleura. FDG metabolism was not increased, and a close follow-up was recommended (B). Multiple\u0026nbsp;enlarged lymph nodes with calcification were seen in the mediastinal (2R, 4R, 6-7 area) and right lung portal. FDG metabolism was increased, and the possibility of lymph node metastasis was considered (C). There was a soft tissue mass accompanied by abnormal bone density in the upper segment of the left ulnar and elbow joint. FDG metabolism was increased, suggesting a malignant lesion (D).\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4933767/v1/f6b43c98dbd9b2f8f534138f.jpg"},{"id":66565563,"identity":"f7df8e4b-3734-485e-8fc9-e7ad7e5f7fa9","added_by":"auto","created_at":"2024-10-14 10:39:12","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":144711,"visible":true,"origin":"","legend":"\u003cp\u003ePathological examination revealed lung adenocarcinoma with metastatic invasion (A, hematoxylin-eosin stain, original magnification 20x; B, hematoxylin-eosin stain, original magnification 40x). Findings on transbronchial lung biopsy supported this diagnosis.\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4933767/v1/dea54cf54dcedf8a6e28cf59.jpg"},{"id":66963301,"identity":"e602d92a-9db5-4af5-883c-c1222b265a47","added_by":"auto","created_at":"2024-10-18 13:17:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1048977,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4933767/v1/eba81377-4176-4ea4-9bfc-f59698c4a860.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A case of cubital tunnel syndrome due to bone metastasis of lung cancer confirmed by 18 F-FDG PET/CT","fulltext":[{"header":"Background","content":"\u003cp\u003eLung adenocarcinoma can metastasize to other parts of the body including the lymph nodes, liver, bones[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], parotid gland[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], kidney[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], brain, thyroid[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Solitary metastasis to the elbow is rare; and elbow metastasis presenting with the initial symptom of pain is even more rare. In this report, we report a patient with metastatic adenocarcinoma arising in the elbow originating from primary lung adenocarcinoma.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 67-year-old female presented with swelling and pain in her left elbow, which had persisted for eight months. No cough, sputum, hemoptysis, chest stuffiness, fever, or hoarseness were present. A previous X-ray examination showed no abnormal signs. She was advised to take nonsteroidal anti-inflammatory drugs (NSAIDs) and tramadol hydrochloride tablets, but these provided no significant pain relief. Due to the pain, she had endured poor sleep for nearly one month, and her weight had decreased by at least 5 kg in the past six months. She had numbness and paralysis in her left ring finger and little finger. The function of finger extension was limited. Chest radiographs indicated an enlarged cardiac shadow, with a cardiothoracic ratio of around 0.58. Examination of tumor markers revealed the following: CA 15\u0026thinsp;\u0026minus;\u0026thinsp;3, 61.5 U/mL and CA 125, 176.9 U/mL. X-ray and Magnetic Resonance Imaging (MRI) examinations were performed due to the suspicion of an infection or acute synovitis of the elbow. The X-ray showed abnormal bone density in the distal humerus and proximal ulna, while MRI revealed bone destruction and abnormal signals on the upper ulna, olecranon, and capitellum with visible soft tissue masses (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). These results strongly suggested a malignant lesion. Due to the malignancy indications, an \u003csup\u003e18\u003c/sup\u003eF-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (\u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT) scan was performed to investigate primary or metastatic systemic involvement, which revealed an irregular mass with spiny margins was observed in the lower lobe of the right lung, showing unevenly increased FDG metabolism (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Multiple enlarged and calcified lymph nodes in the mediastinum (zones 2R, 4R, and 6\u0026ndash;7) and the right hilar also demonstrated increased FDG metabolism, indicating possible lymph node metastasis. Additionally, soft tissue masses were detected in the left ulnar-radial joint and upper elbow joint, accompanied by abnormal bone density and increased FDG metabolism, suggesting a malignant lesion. The clinical diagnosis was pulmonary malignant tumor with elbow metastasis and ulnar nerve entrapment syndrome. To make a definitive diagnosis, a biopsy of the left soft tissue elbow lesion was performed under ultrasound guidance. Pathological examination confirmed lung adenocarcinoma with metastatic invasion (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Findings on transbronchial lung biopsy also supported this diagnosis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe patient refused to target-specific drug treatment for economic reasons. Pain relief was achieved with an intravenous injection of Technetium [\u003csup\u003e99m\u003c/sup\u003eTc] Methylenediphosphonate Injection (\u003csup\u003e99m\u003c/sup\u003eTc-MDP). After six months, the patient was lost to follow up.\u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eThe first step in treatment is to accurately diagnose the lesion. Tumors of the elbow are rare, malignant tumors of the elbow are extremely rare[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], which can easily result in delayed treatment. Malignant tumors presenting with elbow pain and swelling have multiple differential diagnoses. For instance, intra-neural Ewing\u0026rsquo;s sarcoma can be diagnosed by CT guided biopsy[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Pigmented villonodular synovitis, which can also cause pain and swelling, is mainly diagnosed by MRI and needs to be considered in the differential diagnosis[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Therefore, when encountered with elbow mass, radiological and clinicopathologic examinations need to be combined. MR imaging takes more advantageous than CT for evaluating soft tissue tumor margins in the elbow[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Meanwhile, \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT has shown good accuracy in detecting metastasis detection, especially in lung cancer metastasis. By providing comprehensive imaging and facilitating precise diagnosis, \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT plays a crucial role in the timely and effective management of such complex cases.\u003c/p\u003e \u003cp\u003eIt is well known that more than half of all cancers metastasize to the skeleton, making it the third most frequent site of metastatic spread after the lungs and the liver[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. An epidemiological investigation conducted in this matter has revealed that of the 1.2\u0026nbsp;million new cases of cancer each year in the USA and about 300,000 of these will eventually develop a bone metastasis[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Lung cancer ranks third in its ability to cause bone metastasis, following breast and prostate cancers, with a post-mortem incidence of about 30%[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The spine, pelvis, ribs, skull, and proximal long bones are most frequently affected, while the upper limb is least affected, with 10\u0026ndash;15% of cases [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. When the upper limb is impacted by metastasis, particularly in the elbow region, the ulnar nerve can become compressed, leading to cubital tunnel syndrome (CuTS). Therefore, the presence of any inflammation, mass, or obstruction in this region can cause the compression of the ulnar nerve in this area and as mentioned above, this phenomenon is termed as the CuTS. CuTS, the second most common compressive neuropathy of the upper extremity after carpal tunnel syndrome, is defined by the compression of the ulnar nerve at the elbow[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The ulnar nerve may be entrapped at several locations in the upper arm, but the most common are the Arcade of Struthers, the medial intramuscular septum, the cubital tunnel retinaculum (flexor carpi ulnaris aponeurosis), and the deep flexor-pronator aponeurosis. Normally, lung adenocarcinomas do not metastasize to the upper limbs, but when they do, they can cause rare conditions like CuTS. Also, an acro-metastasis is a sign of extremely advanced metastatic cancer and in such conditions, it is highly likely that multiple metastases would be found elsewhere. There are very few papers which discuss lung cancer spread to the carpal bones. So far, only Lederer et al., in 1990, and Song and Yao and Antenucci et.al in 2012, have described a metastasis to the upper limb from lung cancer and in most of those, it is the carpal bones that get affected by the metastasis[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Therefore, when the source of elbow masses causing CuTS is unclear, \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT can effectively diagnose both primary and metastatic lesions.\u003c/p\u003e \u003cp\u003eFor lung adenocarcinoma and non-small cell lung cancer (NSCLC), current therapeutic strategies include chemotherapy, radiotherapy, and targeted therapy. If the patient\u0026rsquo;s prognosis is deemed to be poor, the main therapeutic approach is pain alleviation and improving the quality of life. Radical resection or total elbow arthroplasty after tumor resection needs to be critically evaluated for patient benefit[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur findings highlight the potential of \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT as an excellent diagnostic modality for examining malignant or locally aggressive lesions in the elbow. The detailed imaging provided by \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT not only identified the primary lung adenocarcinoma but also detected metastasis to the mediastinal lymph nodes and elbow joint. This comprehensive evaluation underscores the utility of \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT in accurately diagnosing and staging malignancies, facilitating early and precise treatment planning.\u003c/p\u003e \u003cp\u003eBy revealing the full scope of metastatic spread, \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT plays a pivotal role in the staging of lung cancer, directly influencing the choice of therapeutic strategies. Accurate clinical staging is essential for tailoring treatments, such as surgery, chemotherapy, or radiation, to the patient's specific condition, ensuring the appropriate choice of therapeutic measures while avoiding both unnecessary interventions and missed opportunities for radical treatment. Furthermore, early and precise detection of metastatic sites can improve prognosis by enabling timely and targeted interventions. The ability of \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT to provide a holistic view of the disease also aids in monitoring treatment response and detecting recurrences, ultimately contributing to better patient outcomes.\u003c/p\u003e \u003cp\u003eIn this case, the use of \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT facilitated the diagnosis of ulnar nerve entrapment syndrome secondary to bone metastasis of lung cancer, guiding the clinical management of the patient's symptoms and highlighting its impact on the staging, treatment, and prognosis of lung cancer.\u003c/p\u003e \u003cp\u003e \u003cb\u003eTeaching Points\u003c/b\u003e:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eClinicians should maintain a high index of suspicion for metastatic disease in patients with lung adenocarcinoma presenting with atypical symptoms, such as elbow pain and swelling, especially when accompanied by neurological deficits like ulnar nerve entrapment. Prompt imaging with modalities such as 18F-FDG PET/CT is essential for accurate diagnosis and timely intervention.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eGiven the rarity of elbow metastasis from lung adenocarcinoma, further research is needed to better understand the mechanisms and clinical characteristics of such metastases. This could lead to improved diagnostic strategies and more effective treatment options for managing metastatic lung cancer involving uncommon sites like the upper limb.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNSAIDs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enonsteroidal anti-inflammatory drugs\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCuTS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCubital tunnel syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e \u003csup\u003e18\u003c/sup\u003eF-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography\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 \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003csup\u003e99m\u003c/sup\u003eTc-MDP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e \u003csup\u003e99m\u003c/sup\u003eTechnetium Methylenediphosphonate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocols were approved by the Medical Ethics Committee of\u0026nbsp;the First Affiliated Hospital of the College of Medicine, Zhejiang University\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of clinical details and clinical images. Upon request, a copy of the consent form is available for review by the Editor of this journal\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials section\u003c/strong\u003e\u003c/p\u003e\n\u003ch3\u003eThe dataset supporting the conclusions of this article is included with the article.\u003c/h3\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author declares that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was funded by\u0026nbsp;the\u0026nbsp;Zhejiang Traditional Chinese Medicine Research Program (grant number 2016ZA124, 2017ZB057), Zhejiang Medicine and Hygiene Research Program (grant number 2016KYB101, 2015KYA100), and National Natural Science Foundation of China (the grant number 81702135). The funding bodies had no role in the design of the study; in\u0026nbsp;collection, analysis, and interpretation of data;\u0026nbsp;and in\u0026nbsp;drafting\u0026nbsp;the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHL, SAA and ZF L designed the study, performed data collection, analyzed the results, HP N and HY Z drafted the manuscript. DH C, VGK, MHAHA, AHAHA, and SHAE took part to the patient therapy as Registrars. The author has read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLin C-Y, Hua-Tzu HY-FH. Lung cancer with solitary bone metastasis in the radius. Clin Nucl Med. 2009;34:684\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eImauchi Y, Nakashima M, Nigauri T. Metastasis of lung adenocarcinoma to parotid lymph node as initial clinical manifestation. Eur Arch Otorhinolaryngol. 2001;258:155\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSawada T, Takahashi H, Hasatani K, Yoshida I, Oyama O, Inoue R, et al. Tumor-to-tumor metastasis: Report of an autopsy case of lung adenocarcinoma metastasizing to renal cell carcinoma. Intern Med. 2009;48:1525\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiyakawa M, Sato K, Hasegawa M, Nagai A, Sawada T, Tsushima T, et al. Severe thyrotoxicosis induced by thyroid metastasis of lung adenocarcinoma: A case report and review of the literature. Thyroid. 2001;11:883\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBruguera JANR. Primary tumors of the elbow: a review of the Leeds Regional Bone Tumour Registry. Orthopedics. 1998;21:551\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohan AT, Park DH, Jalgaonkar A, Alorjani M, Aston W, Briggs T. Intra-neural Ewing\u0026rsquo;s sarcoma of the upper limb mimicking a peripheral nerve tumour. A report of 2 cases. J Plast Reconstr Aesthetic Surg. 2011;64:e153\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTang K, Zheng X, Lin J, Wang L. Diffuse-Type Tenosynovial Giant Cell Tumor of the Shoulder Evaluated by FDG PET/CT. Clin Nucl Med. 2019;44:310\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSteinbach LS, Anderson SPD. MR imaging of musculoskeletal tumors in the elbow region. Magn Reson Imaging Clin N Am. 1997;5:619\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHage WD, Aboulafia AJ, Aboulafia DM. Incidence, location, and diagnostic evaluation of metastatic bone disease. Orthop Clin North Am. 2000;31:515\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRinonapoli G, Caraffa A, Antenucci R. Lung cancer presenting as a metastasis to the carpal bones: a case report. J Med Case Rep. 2012;6:384.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchlappack OK, Baur M, Steger G, Dittrich C, Moser K. The clinical course of lung metastases from breast cancer. Klinische Wochenschrift. 1988;66:790\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSilverberg E, Cancer. statistics. 1986. CA Cancer J Clin. 1986;36:9\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePalmer BA, Hughes TB. Cubital Tunnel Syndrome. J Hand Surg. 2010;35:153\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSong Y, Yao J. Trapezial metastasis as the first indication of primary non-small cell carcinoma of the lung. J Hand Surg Am. 2012;37:1242\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCasadei R, De Paolis M, Drago G, Romagnoli C, Donati D. Total elbow arthroplasty for primary and metastatic tumor. Orthopaedics and Traumatology: Surgery and Research. 2016;102:459\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"PET/CT, FDG, lung adenocarcinoma, metastasis, elbow joint","lastPublishedDoi":"10.21203/rs.3.rs-4933767/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4933767/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eLung adenocarcinoma can metastasize to other parts of the body. Solitary metastasis to the elbow is rare; elbow metastasis presenting with the initial symptom of pain is extremely rare.\u003c/p\u003e\u003ch2\u003eMethods and results\u003c/h2\u003e \u003cp\u003eWe report a 67-year-old female presented to our hospital with an eight- month history of progressively swelling and pain in her elbow. An MR scan revealed a possible malignant lesion. A subsequent \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT scan revealed cancer of the lower lobe of the right lung with metastasis to the mediastinal lymph nodes and elbow joint. The clinical diagnosis was pulmonary malignant tumor elbow metastasis, with ulnar nerve entrapment syndrome. A biopsy of elbow soft tissue was performed to confirm metastasis of lung adenocarcinoma. The patient refused to target-specific drug treatment for economic reasons. After six months, the patient was lost to follow up.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOur findings confirm that \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT is an excellent method that has potential as a diagnostic modality for examination of a malignant or locally aggressive elbow lesion.\u003c/p\u003e","manuscriptTitle":"A case of cubital tunnel syndrome due to bone metastasis of lung cancer confirmed by 18 F-FDG PET/CT","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-14 10:38:23","doi":"10.21203/rs.3.rs-4933767/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"816199d1-c343-41f2-b0b5-2c635b70c1c2","owner":[],"postedDate":"October 14th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-18T13:09:15+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-14 10:38:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4933767","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4933767","identity":"rs-4933767","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}