Recurrent thymic carcinoma treated with anterior median thoracotomy, innominate vein replacement for superior vena cava, and iodide implantation: A case report and review of the literature

Recurrent thymic carcinoma treated with anterior median thoracotomy, innominate vein replacement for superior vena cava, and iodide implantation: A case report and review of the literature | 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 Recurrent thymic carcinoma treated with anterior median thoracotomy, innominate vein replacement for superior vena cava, and iodide implantation: A case report and review of the literature Zhong zheng Chen, Wen dong Qu, Xing shu Zhang, Yong xiang Song This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3991636/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 Thymic neuroendocrine tumors are rare malignant tumors with neuroendocrine functions located in the anterior mediastinum thymic region. They exhibit a high degree of malignancy and can early invade surrounding fat,pericardium, pleura, major blood vessels, and lungs,posing a significant risk of recurrence.Here, we report a case of recurrent thymic cancer treated with complete surgical resection, replacement of the innominate vein, superior vena cava formation, and iodine ion insertion.A 51-year-old male diagnosed with stage lllA malignant thymoma in November 2021, accompanied by lymph node metastasis,involving the peripheral left lung.The patient underwent six cycles of adjuvant immunotherapy with pembrolizumab and cisplatin plus etoposide, along with one course of radiotherapy postoperatively.Subsequently, the patient received regular immunotherapy and follow-up at our hospital. In October 2023,chest CT revealed tumor recurrence, with infiltration into the pericardium, bilateral innominate veins, superior vena cava, and brachiocephalic artery.Subsequently, the patient underwent a midline thoracotomy for extensive resection of recurrent thymic tumor,enlargement of pericardial resection, left innominate vein-to-right atrial artificial grafting,superior vena cava formation,and iodine-125radioisotope brachytherapy.Aggressive surgical intervention combined with adjuvant therapy is an essential treatment modality for locally advanced thymic cancer involving the superior vena cava and surrounding blood vessels. Neuroendocrine tumors of the thymus (NETT) Surgical resection Thymic carcinoma superior vena cava chemotherapy immunotherapy Figures Figure 1 Figure 2 Figure 3 Background Neuroendocrine tumors of the thymus (NETT) are rare malignant tumors with neuroendocrine functions, located in the anterior mediastinum thymic region. The origin of these tumors is not yet clear. According to the 2004 World Health Organization(WHO) classification, NETT is an epithelial tumor that is either entirely or predominantly composed of neuroendocrine cells.Therefore, the presence of a few neuroendocrine differentiation clusters in thymic carcinoma does not belong to NETT. In the 2015 WHO classification, NETT is divided into low-grade typical carcinoid, intermediate-grade atypical carcinoid,high-grade large cell neuroendocrine carcinoma,and small cell neuroendocrine carcinoma [ 1 ] . Thymic carcinoma is highly malignant and can invade surrounding fat, pericardium, pleura, major blood vessels, and lungs at an early stage [ 2 ] . According to the literature [ 3 – 4 ] , 40.0–60.0% of thymic carcinoma patients are already in stage Masaoka Ill at the time of diagnosis. For such locally advanced patients, there is currently no unified treatment strategy. However, several studies [ 3 – 6 ] advocate for complete resection of the lesion and invaded surrounding tissues and organs to improve patient prognosis. In this study, the authors discuss the treatment approach for a case of recurrent thymic carcinoma in our hospital, which involved complete surgical resection, replacement of the innominate vein, formation of the superior vena cava, and iodine ion placement, focusing on locally advanced thymic carcinoma invading the superior vena cava. Case presentation A 51-year-old male with no previous medical history, no smoking history,and no history of chronic lung disease.The patient presented to an external hospital (a large tertiary hospital) on November 30, 2021, with the chief complaint of "discovered anterior mediastinal mass with lymph node metastasis for 7days." Chest three-dimensional computed tomography (CT) revealed a mass shadow in the anterior superior mediastinum. Further positron emission tomography / computed tomography(PET/CT )examination at Zunyi Medical University Affiliated Hospital on November 23,2021, indicated an anterior mediastinal mass with increased metabolism,suggesting malignant lesions,with enlargement of mediastinal lymph nodes 3a and 6, indicating possible metastasis. After excluding relevant surgical contraindications, the patient underwent "thoracoscopic resection of anterior mediastinal tumor and wedge resection of the left upper lobe of the lung" on December 2, 2021.Postoperative pathology revealed (anterior mediastinum) neuroendocrine carcinoma (NEC, G3) with necrosis, tumor invasion into the lung parenchyma, and > 20 mitotic figures/10 high-power fields. Lymph nodes in the hilum showed no metastatic carcinoma (0/1).Immunohistochemistry results were positive for CK, Syn, CgA, CD56, and Ki-67(40%), and negative for S-100.Pathological diagnosis:Masaoka stage IVa.Postoperative follow-up chest CT showed partial loss of the left upper lobe of the lung,with a small amount of pneumonia and localized lung consolidation.Postoperative diagnosis:T3NOMO stage IIIA, based on the 8th edition of the American Joint Committee on Cancer (AJCC) staging system.The patient received 6 cycles of chemotherapy postoperatively[Specific chemotherapy regimen:Carboplatin + Etoposide,Palbociclib injection 200mg intravenous infusion on day 0,Carboplatin injection (Qilu)600mg intravenous infusion on day 1, Etoposide injection 180mg intravenous infusion from day 1 to day 3]. The patient also underwent one course of radiotherapy [Specific radiotherapy regimen: Total irradiation dose of the lesion was 50Gy, with a single dose of 2Gy,administered twice daily, five times a week (Monday to Friday), for a total of 25 sessions (fx)].Subsequently, the patient received regular immunotherapy at our hospital [Specific regimen:Palbociclib 200mg intravenous infusion]. Following that,regular chest CT follow-ups were conducted. On October 25, 2023, the patient underwent a chest CT review,which showed enlarged lymph nodes in the anterior superior mediastinum, indicating multiple lymph node metastases and narrowing of the adjacent superior vena cava. There was partial loss of the left upper lobe of the lung, with a small amount of chronic inflammation. There was a small amount of fluid accumulation in the anterior mediastinum and thickening of the left local pleura.Compared to the previous chest CT, there was a significant increase in the size of the anterior superior mediastinal lymph nodes.Consideration of recurrent metastasis of thymic carcinoma. Clinical diagnosis of the patient: Stage IVB, T3N2M1a.Preoperative comprehensive examinations: Abdominal CT, abdominal and pelvic ultrasound, and brain CT scan showed no evidence of other tumorous lesions. Serum tumor markers CEA,CA19-9, AFP, and β-hCG were within the normal range. 1.2 Operation The surgical approach was determined based on the patient's medical history and imaging findings, as discussed in a multidisciplinary treatment (MDT) consultation. Considering the patient's history and imaging manifestations, recurrent thymic carcinoma was suspected, with involvement of the pericardium,bilateral brachiocephalic veins, superior vena cava, and brachiocephalic trunk. The surgery involved vascular replacement, extensive pericardial resection, left brachiocephalic vein-right atrium bypass, superior vena cava reconstruction, and iodine-125 radioactive seed implantation for close-range treatment. Routine anesthesia intubation and sterile draping were performed,and a mid-sternal incision was made.Intraoperatively, the tumor was observed in the anterior upper mediastinum, slightly to the right,measuring 4.1x4.0x4.2 cm, solid in consistency, firmly adherent to the surface of the pericardium, and located anterior to the aortic arch. The upper pole of the tumor was positioned between the right brachiocephalic vein and the brachiocephalic trunk,with its right margin closely adjacent to the superior vena cava and its left margin invading the left brachiocephalic vein. The tumor completely encased the initial segment of the brachiocephalic vein,extending posteriorly along the brachiocephalic trunkto the descending aorta. The tumor extended inferiorly to the level of the lower border of the aortic arch,involving the pericardium in this region. The tumor capsule appeared uneven, suggesting possible invasion of the pleura. The tumor also invaded the base of the heart (measuring approximately 5.0x4.8x5.2 cm). The right pleura was opened, and upon entering the right pleural cavity, it was observed that the right lung was not affected. The left pleura showed localized adhesions and was not entered.During the surgery, the visible primary lesion, the surrounding involved tissues, the invaded pleura,pericardium, superior vena cava, and left brachiocephalic vein were all resected. The artificial blood vessel was anastomosed end-to-end with the left brachiocephalic vein and the right atrial end. The left brachiocephalic vein was excised, and the artificial blood vessel was grafted. The tumor was further dissected towards the upper right region, revealing the bilateral superior thymic veins, which were completely freed and resected, along with the branches of multiple thymic veins. The proximal ends were occluded with vascular clips, and the distal ends were divided using an ultrasonic scalpel. The thymus, along with the surrounding tissue, was completely excised.The tumor was then pulled towards the upper right region, ensuring full mobilization of the right phrenic nerve, vagus nerve, and trachea. The relationshipbetween the tumor and the right brachiocephalic vein from its origin to the mid-segment of the superior vena cava was found to be tight. After careful dissection using scissors, the tumor involving the base of the superior vena cava was partially occluded with a side-wall vascular clamp, and the tumor and a portion of the vascular wall of the superior vena cava were resected. The tumor tissue was removed, and 5-0suture was used for vascular closure. The side wall of the superior vena cava was continuously sutured using the clamps, and superior vena cava reconstruction was performed. lodine-125 radioactive seeds were implanted in the area of the tumor in the anterior mediastinum. Hemostasis was achieved, and two drainage tubes were placed in the right pleural cavity and the anterior mediastinal region through the bilateral rib arches. The sternum was closed with steel wire sutures, and the chest was closed layer by layer.The operation was completed. 1.3 Histopathological and immunohistochemical Postoperative pathological findings: (anterior mediastinum) atypical carcinoid tumor (approximately 5 mitoses/10 high-power fields,hot spot area Ki-67proliferation index approximately 40%+);additional specimens from (anterior mediastinum) adipose tissue and (left margin) showed no evidence of tumor tissue.Lymph nodes around the mass (3/3), lymph nodes from the 2nd and 4th groups (2/2), and cervical lymph node (1/1)showed tumor metastasis,while mediastinal lymph nodes (0/2) showed no tumor metastasis (Fig. 3 ).Immunohistochemical findings:Tumor cells positive for CK (+++), Vimentin (scattered +),ATRX (+++), CD56(+++), Syn (+++), CgA (++), P53(scattered weak to moderate intensity +), SSTR2 (occasional +), Ki-67 (approximately 40%+in hot spot area), C7 (-). Discussion The most common type of primary thymic carcinoma is squamous cell carcinoma, with some rare subtypes including basaloid carcinoma,mucoepidermoid carcinoma,lymphoepithelioma-like carcinoma,clear cell carcinoma, sarcomatoid carcinoma, and neuroendocrine tumors [ 7 ] .NETT is extremely rare and was first reported by Rosai et al. in 197,including 8 patients [ 8 ] . Currently, only over 500 cases have been reported domestically and internationally [ 9 – 13 ] . In the 2015 WHO classification of thymic tumors,thymic neuroendocrine tumors are divided into 5 subtypes: typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, thymic carcinoma combined with large cell neuroendocrine carcinoma, small cell carcinoma, and thymic carcinoma combined with small cell carcinoma.This study summarizes over 500 cases of thymic neuroendocrine tumors reported in the literature. The average age of onset for patients is 57years, with a male-to-female ratio of 2.5:1. Male patients are more common, and the average diameter of the tumor is 7.3 cm. Some patients experience symptoms such as chest tightness, chest pain, shortness of breath, and respiratory distress, while others are asymptomatic and the tumor is detected during physical examination as a mediastinal mass.This case involves a 51-year-old male with a tumor diameter of 4.1x4.0x4.2cm. A mediastinal mass was detected during a physical examination,consistent with the literature reports.In approximately one-third of patients, NETT presents as an asymptomatic mass in the anterior mediastinum. It rarely occurs in the middle or posterior mediastinum. NETT can exhibit local invasiveness, leading to displacement or compression of the chest structures. The reported median size is approximately 8cm. Patients may experience symptoms and signs such as cough, chest pain,shortness of breath, or superior vena cava obstruction. Additionally,at the time of diagnosis, up to 62% of patients may have mediastinal lymph node metastasis, while distant metastasis occurs in 20–30% of patients, most commonly affecting the bones, lungs,and liver [ 14 ] . Surgery is the primary treatment method for NETT, and complete resection is crucial .Literature indicates that RO resection improves patient survival [ 15 – 16 ] . Crona et al. demonstrated 100% 5- year and 10- year survival rates in 3patients who underwent RO resection, whereas mixed group patients had a 5- year survival rate of 76% and a 10- year survival rate of 32%. Sullivan ' s study showed an average survival of 109 months for surgically resected patients compared to 38 months for patients who underwent debulking procedures only.Although complete resection is ideal, in certain patients, even partial resection may offer better survival outcomes compared to no surgery at all .In cases of disease recurrence, surgery is only necessary when the disease is considered resectable .Currently, median sternotomy has been the standard approach, but video - assisted thoracoscopic surgery ( VATS ) through intercostal incisions is becoming increasingly common .The guidelines from the European and Japanese Lung Cancer Societies ( JLCS ) for thymic tumors, including thymic carcinoma and NETT, allow experienced surgeons to use VATS for stage I and Il tumors [ 17 , 18 ] . Further technological advancements, such as VATS using subxiphoid approach instead of intercostal incisions, and the use of robotic surgery, have demonstrated the potential benefits of thymectomy .Despite these advancements, the choice of surgical approach still depends on factors such as tumor size, extent of local structural damage, available equipment, and surgeon preferences and experience. The principle of achieving clear resection margins with minimal morbidity remains crucial . The patient was initially diagnosed with stage IIIB mediastinal tumor. The first surgery was performed using video-assisted thoracoscopic surgery (VATS) to remove the mediastinal mass. After surgery, the patient underwent six cycles of chemotherapy and one course of radiation therapy. Additionally, the patient received pembrolizumab as adjuvant immunotherapy. We have two concerns regarding this treatment plan: 1. For locally advanced mediastinal tumors that have invaded lung tissue, can VATS completely remove the lesion and achieve R0 resection? 2. There is controversy between the National Comprehensive Cancer Network(NCCN) and domestic guidelines regarding the recommendation of immunotherapy for adjuvant treatment of thymoma [ 19 – 22 ] . Currently, clinical trials both domestically and internationally have primarily focused on using immunotherapy after platinum-based chemotherapy failure [ 23 – 24 ] . Whether the combination of chemotherapy and immunotherapy can prolong the progression-free survival (PFS) and overall survival (OS) of patients with thymic cancer is not yet known. After the patient's tumor recurrence was detected in our hospital, it was discussed in a MDT meeting. Considering the short disease-free survival after the previous surgery and adjuvant radiation therapy, preoperative imaging results showed tumor invasion surrounding the pericardium, innominate vein, and superior vena cava. Intraoperatively, the tumor was found to be closely adhering to the right margin of the superior vena cava, and significant bleeding occurred during the dissection. The possibility of artificial vessel replacement in the superior vena cava was evaluated to ensure unobstructed cerebral venous return during the replacement surgery. Therefore, a left innominate vein-right atrium artificial vessel bypass was performed as a preliminary procedure to reduce the risk of cerebral edema caused by impaired cerebral venous return. During the continued exploration, it was observed that the tumor pedicle involved less than one-third of the wall of the superior vena cava, and it was evaluated as feasible to perform superior vena cava reconstruction, which could achieve complete tumor resection. After the completion of the reconstructive surgery, the area of superior vena cava reconstruction was significantly narrowed, but the establishment of the left innominate vein bypass effectively relieved the blood reflux resistance caused by the stenosis in that area.lodine particle placement was performed after tumor resection to serve as a preventive radiation therapy and to ensure complete tumor dissection and reduce the risk of bleeding and implantation metastasis.In this case, the patient chose a median sternotomy for the procedure. Conclusion NETT is extremely rare. For locally advanced patients with involvement of the superior vena cava and surrounding blood vessels, aggressive surgical intervention should be pursued along with adjuvant therapies to improve patient prognosis. Currently, early diagnosis followed by complete surgical resection remains the best option for prolonging patient survival. The diversification of chemotherapy regimens and the development of novel agents in the treatment of NETTs, including kinase inhibitors, mTOR inhibitors, radiopharmaceutical therapy, and immunotherapy, may potentially improve the prognosis of patients with more advanced NETs. Abbreviations World Health Organization(WHO) Neuroendocrine tumors of the thymus (NETT) Computed tomography (CT) Positron emission tomography / computed tomography（PET/CT ） Neuroendocrine carcinoma (NEC） American Joint Committee on Cancer (AJCC) Multidisciplinary treatment (MDT) Video - assisted thoracoscopic surgery ( VATS ) Japanese Lung Cancer Societies ( JLCS ) National Comprehensive Cancer Network(NCCN) Progression-free survival (PFS) Overall survival (OS) Declarations Consent A written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review. Availability of date and materials No datasets were generated or analysed during the current study. Acknowledgements Not applicable. Funding None. Author information Zhong-zheng Chen and wen-dong Qu contributed equally to this work. Yong-xiang Song is corresponding authors. Authors and Affiliations Affiliated Hospital of Zunyi Medical College,China Zhong-zheng chen,Wen-dong Qu,Xing-shu Zhang,Yong-xiang Song. Contributions CZZ collected the data, conceptualized the study, reviewed and edited the initial manuscript. SYX as the chief surgeon, QWD as the first assistant to participate in the patient's operation, drafted, reviewed and revised the manuscript.ZXS prepared figures 1-3.All authors read and approved the final manuscript. Corresponding authors Correspondence to Yong-xiang Song Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. 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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-3991636","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":276100718,"identity":"cedf8acd-7531-4a7d-b1c8-9ac085ff06ab","order_by":0,"name":"Zhong zheng Chen","email":"","orcid":"","institution":"Affiliated Hospital of Zunyi Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhong","middleName":"zheng","lastName":"Chen","suffix":""},{"id":276100719,"identity":"6d786edb-1164-4021-ae6a-a37df7aed432","order_by":1,"name":"Wen dong Qu","email":"","orcid":"","institution":"Affiliated Hospital of Zunyi Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wen","middleName":"dong","lastName":"Qu","suffix":""},{"id":276100720,"identity":"382dcc24-e3f3-4904-b0a2-117b04a14570","order_by":2,"name":"Xing shu Zhang","email":"","orcid":"","institution":"Affiliated Hospital of Zunyi Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xing","middleName":"shu","lastName":"Zhang","suffix":""},{"id":276100721,"identity":"4ed95eb7-d09c-42e7-9e93-be677901bb45","order_by":3,"name":"Yong xiang Song","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYDADfmbGBoMPBjZ2xCk/AMSS7c0HCmcUpCUTr8XgzLGEzzwfDjE2EFIt3957+PWHmjt2DTdyDDfbGBxgZmA/fHQDPi0GZ86lWRw49iy5cUaOsXGOwR0+Bp60tBt4tUjkmBkcYDuczAxkALU8Y2aQ4DHDq0V+BkjLv8PJbBI55r8tDA4zNhDSwnAjx/jBwbbDdjw8xxKMGYjRYnDmjBnD2b7DCRLszQcMewzSktkI+UW+vcf4Q8W3w/b2QPMNfvyxseNnP3wMv8MYGNgkgERiA5xLQDkIMH8AEvZEKBwFo2AUjIKRCgDmWlJ0e2fsJAAAAABJRU5ErkJggg==","orcid":"","institution":"Affiliated Hospital of Zunyi Medical College","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Yong","middleName":"xiang","lastName":"Song","suffix":""}],"badges":[],"createdAt":"2024-02-26 18:06:49","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3991636/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3991636/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":52107271,"identity":"013c2476-ddb7-47b9-84f5-f68c5a82aecd","added_by":"auto","created_at":"2024-03-06 19:53:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":636894,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTime-lapse computer tomography (CT) imaging of the\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003echest of the patient with thymoma. \u003c/strong\u003e(A)white arrow indicates right brachiocephalic vein.(B) white arrow indicates brachiocephalic trunk.(C) white arrow indicates superior vena cava, red arrow indicates left brachiocephalic vein.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3991636/v1/650fbd48d374e8ae6df7d913.png"},{"id":52107270,"identity":"e674f37a-2a0e-4a23-b10c-d25c4261dac0","added_by":"auto","created_at":"2024-03-06 19:53:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1835516,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIntraoperative Imaging \u003c/strong\u003e(A)the white icon indicates the area where the tumor invades the brachiocephalic vein.(B)the white icon represents the reconstructed superior vena cava, the black icon represents the brachiocephalic trunk, and the blue icon represents the artificial blood vessel graft from the brachiocephalic vein to the right atrium.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3991636/v1/bcfc1798dab813610da52343.png"},{"id":52107273,"identity":"cdc4b574-128f-4dd7-946d-2e88617ee7c3","added_by":"auto","created_at":"2024-03-06 19:53:48","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":556165,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eH \u0026amp; E stain shows the histology of the malignant thymoma.\u003c/strong\u003e This was evidenced by the presence of a mixture of plump epithelial cells with both vesicular nuclei and distinct nucleoli and small lymphocytes(magnification = 200X).\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-3991636/v1/388240334b5a68860b6f5bf8.png"},{"id":52223076,"identity":"408fccab-844b-478c-b67f-7ce2959a878c","added_by":"auto","created_at":"2024-03-08 04:40:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3280187,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3991636/v1/f206fce5-38a1-4e72-abf1-3886a8068c04.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Recurrent thymic carcinoma treated with anterior median thoracotomy, innominate vein replacement for superior vena cava, and iodide implantation: A case report and review of the literature","fulltext":[{"header":"Background","content":"\u003cp\u003eNeuroendocrine tumors of the thymus (NETT) are rare malignant tumors with neuroendocrine functions, located in the anterior mediastinum thymic region. The origin of these tumors is not yet clear. According to the 2004 World Health Organization(WHO) classification, NETT is an epithelial tumor that is either entirely or predominantly composed of neuroendocrine cells.Therefore, the presence of a few neuroendocrine differentiation clusters in thymic carcinoma does not belong to NETT. In the 2015 WHO classification, NETT is divided into low-grade typical carcinoid, intermediate-grade atypical carcinoid,high-grade large cell neuroendocrine carcinoma,and small cell neuroendocrine carcinoma \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Thymic carcinoma is highly malignant and can invade surrounding fat, pericardium, pleura, major blood vessels, and lungs at an early stage \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. According to the literature \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e, 40.0\u0026ndash;60.0% of thymic carcinoma patients are already in stage Masaoka Ill at the time of diagnosis. For such locally advanced patients, there is currently no unified treatment strategy. However, several studies \u003csup\u003e[\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e advocate for complete resection of the lesion and invaded surrounding tissues and organs to improve patient prognosis. In this study, the authors discuss the treatment approach for a case of recurrent thymic carcinoma in our hospital, which involved complete surgical resection, replacement of the innominate vein, formation of the superior vena cava, and iodine ion placement, focusing on locally advanced thymic carcinoma invading the superior vena cava.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 51-year-old male with no previous medical history, no smoking history,and no history of chronic lung disease.The patient presented to an external hospital (a large tertiary hospital) on November 30, 2021, with the chief complaint of \u0026quot;discovered anterior mediastinal mass with lymph node metastasis for 7days.\u0026quot; Chest three-dimensional computed tomography (CT) revealed a mass shadow in the anterior superior mediastinum. Further positron emission tomography / computed tomography(PET/CT )examination at Zunyi Medical University Affiliated Hospital on November 23,2021, indicated an anterior mediastinal mass with increased metabolism,suggesting malignant lesions,with enlargement of mediastinal lymph nodes 3a and 6, indicating possible metastasis. After excluding relevant surgical contraindications, the patient underwent \u0026quot;thoracoscopic resection of anterior mediastinal tumor and wedge resection of the left upper lobe of the lung\u0026quot; on December 2, 2021.Postoperative pathology revealed (anterior mediastinum) neuroendocrine carcinoma (NEC, G3) with necrosis, tumor invasion into the lung parenchyma, and \u0026gt;\u0026thinsp;20 mitotic figures/10 high-power fields. Lymph nodes in the hilum showed no metastatic carcinoma (0/1).Immunohistochemistry results were positive for CK, Syn, CgA, CD56, and Ki-67(40%), and negative for S-100.Pathological diagnosis:Masaoka stage IVa.Postoperative follow-up chest CT showed partial loss of the left upper lobe of the lung,with a small amount of pneumonia and localized lung consolidation.Postoperative diagnosis:T3NOMO stage IIIA, based on the 8th edition of the American Joint Committee on Cancer (AJCC) staging system.The patient received 6 cycles of chemotherapy postoperatively[Specific chemotherapy regimen:Carboplatin\u0026thinsp;+\u0026thinsp;Etoposide,Palbociclib injection 200mg intravenous infusion on day 0,Carboplatin injection (Qilu)600mg intravenous infusion on day 1, Etoposide injection 180mg intravenous infusion from day 1 to day 3]. The patient also underwent one course of radiotherapy [Specific radiotherapy regimen: Total irradiation dose of the lesion was 50Gy, with a single dose of 2Gy,administered twice daily, five times a week (Monday to Friday), for a total of 25 sessions (fx)].Subsequently, the patient received regular immunotherapy at our hospital [Specific regimen:Palbociclib 200mg intravenous infusion]. Following that,regular chest CT follow-ups were conducted. On October 25, 2023, the patient underwent a chest CT review,which showed enlarged lymph nodes in the anterior superior mediastinum, indicating multiple lymph node metastases and narrowing of the adjacent superior vena cava. There was partial loss of the left upper lobe of the lung, with a small amount of chronic inflammation. There was a small amount of fluid accumulation in the anterior mediastinum and thickening of the left local pleura.Compared to the previous chest CT, there was a significant increase in the size of the anterior superior mediastinal lymph nodes.Consideration of recurrent metastasis of thymic carcinoma. Clinical diagnosis of the patient: Stage IVB, T3N2M1a.Preoperative comprehensive examinations: Abdominal CT, abdominal and pelvic ultrasound, and brain CT scan showed no evidence of other tumorous lesions. Serum tumor markers CEA,CA19-9, AFP, and \u0026beta;-hCG were within the normal range.\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003e\u003cstrong\u003e1.2 Operation\u003c/strong\u003e The surgical approach was determined based on the patient\u0026apos;s medical history and imaging findings, as discussed in a multidisciplinary treatment (MDT) consultation. Considering the patient\u0026apos;s history and imaging manifestations, recurrent thymic carcinoma was suspected, with involvement of the pericardium,bilateral brachiocephalic veins, superior vena cava, and brachiocephalic trunk. The surgery involved vascular replacement, extensive pericardial resection, left brachiocephalic vein-right atrium bypass, superior vena cava reconstruction, and iodine-125 radioactive seed implantation for close-range treatment. Routine anesthesia intubation and sterile draping were performed,and a mid-sternal incision was made.Intraoperatively, the tumor was observed in the anterior upper mediastinum, slightly to the right,measuring 4.1x4.0x4.2 cm, solid in consistency, firmly adherent to the surface of the pericardium, and located anterior to the aortic arch. The upper pole of the tumor was positioned between the right brachiocephalic vein and the brachiocephalic trunk,with its right margin closely adjacent to the superior vena cava and its left margin invading the left brachiocephalic vein. The tumor completely encased the initial segment of the brachiocephalic vein,extending posteriorly along the brachiocephalic trunkto the descending aorta. The tumor extended inferiorly to the level of the lower border of the aortic arch,involving the pericardium in this region. The tumor capsule appeared uneven, suggesting possible invasion of the pleura. The tumor also invaded the base of the heart (measuring approximately 5.0x4.8x5.2 cm). The right pleura was opened, and upon entering the right pleural cavity, it was observed that the right lung was not affected. The left pleura showed localized adhesions and was not entered.During the surgery, the visible primary lesion, the surrounding involved tissues, the invaded pleura,pericardium, superior vena cava, and left brachiocephalic vein were all resected. The artificial blood vessel was anastomosed end-to-end with the left brachiocephalic vein and the right atrial end. The left brachiocephalic vein was excised, and the artificial blood vessel was grafted. The tumor was further dissected towards the upper right region, revealing the bilateral superior thymic veins, which were completely freed and resected, along with the branches of multiple thymic veins. The proximal ends were occluded with vascular clips, and the distal ends were divided using an ultrasonic scalpel. The thymus, along with the surrounding tissue, was completely excised.The tumor was then pulled towards the upper right region, ensuring full mobilization of the right phrenic nerve, vagus nerve, and trachea. The relationshipbetween the tumor and the right brachiocephalic vein from its origin to the mid-segment of the superior vena cava was found to be tight. After careful dissection using scissors, the tumor involving the base of the superior vena cava was partially occluded with a side-wall vascular clamp, and the tumor and a portion of the vascular wall of the superior vena cava were resected. The tumor tissue was removed, and 5-0suture was used for vascular closure. The side wall of the superior vena cava was continuously sutured using the clamps, and superior vena cava reconstruction was performed. lodine-125 radioactive seeds were implanted in the area of the tumor in the anterior mediastinum. Hemostasis was achieved, and two drainage tubes were placed in the right pleural cavity and the anterior mediastinal region through the bilateral rib arches. The sternum was closed with steel wire sutures, and the chest was closed layer by layer.The operation was completed.\u003cbr\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.3 Histopathological and immunohistochemical\u003c/strong\u003e Postoperative pathological findings: (anterior mediastinum) atypical carcinoid tumor (approximately 5 mitoses/10 high-power fields,hot spot area Ki-67proliferation index approximately 40%+);additional specimens from (anterior mediastinum) adipose tissue and (left margin) showed no evidence of tumor tissue.Lymph nodes around the mass (3/3), lymph nodes from the 2nd and 4th groups (2/2), and cervical lymph node (1/1)showed tumor metastasis,while mediastinal lymph nodes (0/2) showed no tumor metastasis (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).Immunohistochemical findings:Tumor cells positive for CK (+++), Vimentin (scattered +),ATRX (+++), CD56(+++), Syn (+++), CgA (++), P53(scattered weak to moderate intensity +), SSTR2 (occasional +), Ki-67 (approximately 40%+in hot spot area), C7 (-).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe most common type of primary thymic carcinoma is squamous cell carcinoma, with some rare subtypes including basaloid carcinoma,mucoepidermoid carcinoma,lymphoepithelioma-like carcinoma,clear cell carcinoma, sarcomatoid carcinoma, and neuroendocrine tumors \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.NETT is extremely rare and was first reported by Rosai et al. in 197,including 8 patients \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCurrently, only over 500 cases have been reported domestically and internationally\u003csup\u003e[\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. In the 2015 WHO classification of thymic tumors,thymic neuroendocrine tumors are divided into 5 subtypes: typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, thymic carcinoma combined with large cell neuroendocrine carcinoma, small cell carcinoma, and thymic carcinoma combined with small cell carcinoma.This study summarizes over 500 cases of thymic neuroendocrine tumors reported in the literature. The average age of onset for patients is 57years, with a male-to-female ratio of 2.5:1. Male patients are more common, and the average diameter of the tumor is 7.3 cm. Some patients experience symptoms such as chest tightness, chest pain, shortness of breath, and respiratory distress, while others are asymptomatic and the tumor is detected during physical examination as a mediastinal mass.This case involves a 51-year-old male with a tumor diameter of 4.1x4.0x4.2cm. A mediastinal mass was detected during a physical examination,consistent with the literature reports.In approximately one-third of patients, NETT presents as an asymptomatic mass in the anterior mediastinum. It rarely occurs in the middle or posterior mediastinum. NETT can exhibit local invasiveness, leading to displacement or compression of the chest structures. The reported median size is approximately 8cm. Patients may experience symptoms and signs such as cough, chest pain,shortness of breath, or superior vena cava obstruction. Additionally,at the time of diagnosis, up to 62% of patients may have mediastinal lymph node metastasis, while distant metastasis occurs in 20\u0026ndash;30% of patients, most commonly affecting the bones, lungs,and liver \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSurgery is the primary treatment method for NETT, and complete resection is crucial .Literature indicates that RO resection improves patient survival \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Crona et al. demonstrated 100% 5- year and 10- year survival rates in 3patients who underwent RO resection, whereas mixed group patients had a 5- year survival rate of 76% and a 10- year survival rate of 32%. Sullivan ' s study showed an average survival of 109 months for surgically resected patients compared to 38 months for patients who underwent debulking procedures only.Although complete resection is ideal, in certain patients, even partial resection may offer better survival outcomes compared to no surgery at all .In cases of disease recurrence, surgery is only necessary when the disease is considered resectable .Currently, median sternotomy has been the standard approach, but video - assisted thoracoscopic surgery ( VATS ) through intercostal incisions is becoming increasingly common .The guidelines from the European and Japanese Lung Cancer Societies ( JLCS ) for thymic tumors, including thymic carcinoma and NETT, allow experienced surgeons to use VATS for stage I and Il tumors \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. Further technological advancements, such as VATS using subxiphoid approach instead of intercostal incisions, and the use of robotic surgery, have demonstrated the potential benefits of thymectomy .Despite these advancements, the choice of surgical approach still depends on factors such as tumor size, extent of local structural damage, available equipment, and surgeon preferences and experience. The principle of achieving clear resection margins with minimal morbidity remains crucial .\u003c/p\u003e \u003cp\u003eThe patient was initially diagnosed with stage IIIB mediastinal tumor. The first surgery was performed using video-assisted thoracoscopic surgery (VATS) to remove the mediastinal mass. After surgery, the patient underwent six cycles of chemotherapy and one course of radiation therapy. Additionally, the patient received pembrolizumab as adjuvant immunotherapy. We have two concerns regarding this treatment plan: 1. For locally advanced mediastinal tumors that have invaded lung tissue, can VATS completely remove the lesion and achieve R0 resection? 2. There is controversy between the National Comprehensive Cancer Network(NCCN) and domestic guidelines regarding the recommendation of immunotherapy for adjuvant treatment of thymoma \u003csup\u003e[\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Currently, clinical trials both domestically and internationally have primarily focused on using immunotherapy after platinum-based chemotherapy failure \u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Whether the combination of chemotherapy and immunotherapy can prolong the progression-free survival (PFS) and overall survival (OS) of patients with thymic cancer is not yet known. After the patient's tumor recurrence was detected in our hospital, it was discussed in a MDT meeting. Considering the short disease-free survival after the previous surgery and adjuvant radiation therapy, preoperative imaging results showed tumor invasion surrounding the pericardium, innominate vein, and superior vena cava. Intraoperatively, the tumor was found to be closely adhering to the right margin of the superior vena cava, and significant bleeding occurred during the dissection. The possibility of artificial vessel replacement in the superior vena cava was evaluated to ensure unobstructed cerebral venous return during the replacement surgery. Therefore, a left innominate vein-right atrium artificial vessel bypass was performed as a preliminary procedure to reduce the risk of cerebral edema caused by impaired cerebral venous return. During the continued exploration, it was observed that the tumor pedicle involved less than one-third of the wall of the superior vena cava, and it was evaluated as feasible to perform superior vena cava reconstruction, which could achieve complete tumor resection. After the completion of the reconstructive surgery, the area of superior vena cava reconstruction was significantly narrowed, but the establishment of the left innominate vein bypass effectively relieved the blood reflux resistance caused by the stenosis in that area.lodine particle placement was performed after tumor resection to serve as a preventive radiation therapy and to ensure complete tumor dissection and reduce the risk of bleeding and implantation metastasis.In this case, the patient chose a median sternotomy for the procedure.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eNETT is extremely rare. For locally advanced patients with involvement of the superior vena cava and surrounding blood vessels, aggressive surgical intervention should be pursued along with adjuvant therapies to improve patient prognosis. Currently, early diagnosis followed by complete surgical resection remains the best option for prolonging patient survival. The diversification of chemotherapy regimens and the development of novel agents in the treatment of NETTs, including kinase inhibitors, mTOR inhibitors, radiopharmaceutical therapy, and immunotherapy, may potentially improve the prognosis of patients with more advanced NETs.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eWorld Health Organization(WHO)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNeuroendocrine tumors of the thymus (NETT)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eComputed tomography (CT)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePositron emission tomography / computed tomography（PET/CT\u0026nbsp;）\u003c/p\u003e\n\u003cp\u003eNeuroendocrine carcinoma (NEC）\u003c/p\u003e\n\u003cp\u003eAmerican Joint Committee on Cancer (AJCC)\u003c/p\u003e\n\u003cp\u003eMultidisciplinary treatment (MDT)\u003c/p\u003e\n\u003cp\u003eVideo - assisted thoracoscopic surgery ( VATS )\u003c/p\u003e\n\u003cp\u003eJapanese Lung Cancer Societies ( JLCS )\u003c/p\u003e\n\u003cp\u003eNational Comprehensive Cancer Network(NCCN)\u003c/p\u003e\n\u003cp\u003eProgression-free survival (PFS)\u003c/p\u003e\n\u003cp\u003eOverall survival (OS)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConsent\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of date and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZhong-zheng Chen and wen-dong Qu\u0026nbsp;contributed equally to this work.\u003c/p\u003e\n\u003cp\u003eYong-xiang Song is\u0026nbsp;corresponding authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors and Affiliations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAffiliated Hospital of Zunyi Medical College,China\u003c/p\u003e\n\u003cp\u003eZhong-zheng chen,Wen-dong Qu,Xing-shu Zhang,Yong-xiang Song.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCZZ collected the data, conceptualized the study, reviewed and edited the initial manuscript. SYX as the chief surgeon, QWD as the first assistant to participate in the patient\u0026apos;s operation, drafted, reviewed and revised the manuscript.ZXS prepared figures 1-3.All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding authors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence to Yong-xiang Song\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e方三高，李晟磊，陈岗．2015年WHO肺、胸膜、胸腺及心脏肿瘤分类( 胸腺) 解读［J］．重庆医学，2015，36: 5041-5053．\u003c/li\u003e\n \u003cli\u003eKAWASAKI H，TAIＲA N，ICHI T，et al． Weekly chemo therapy with cisplatin，vincristine，doxorubicin，and etoposide followed by surgery for thymic carcinoma［J］． EJSO，2014，40( 9) : 1151\u003c/li\u003e\n \u003cli\u003eKONDO K，MONDEN Y． Therapy for thymic epithelial tumors: a clinical study of 1，320 patients from Japan［J］．Ann Thorac Surg，2003，76( 3) : 878\u003c/li\u003e\n \u003cli\u003eFU H，GU ZT，FANG WT，et al． Long-term survival after surgical treatment of thymic carcinoma: a retrospective analysis from the Chinese alliance for research of thymoma database［J］．Ann Surg Oncol，2016，23( 2) : 619\u003c/li\u003e\n \u003cli\u003e谷志涛，方文涛． 胸腺癌的综合治疗进展［J］．中华胸部 外科电子杂志，2017，4( 4) : 263\u003c/li\u003e\n \u003cli\u003eWEKSLEＲ B，DHUPAＲ Ｒ，PAＲIKH V，et al． Thymic carcinoma: a multivariate analysis of factors predictive of survival in 290 patients［J］．Ann Thorac Surg，2013，95( 1) : 299\u003c/li\u003e\n \u003cli\u003e石之虎，雷蕾．胸腺神经内分泌癌2例［J］．临床与验病理学杂志，2015，31( 9) : 1073 － 1074．\u003c/li\u003e\n \u003cli\u003eRosai J, Higa E. Mediastinal endocrine neoplasm, of probable thymic origin, related to carcinoid tumor. Clinicopathologic study of 8 cases. Cancer 1972;29:1061e74.\u003c/li\u003e\n \u003cli\u003eHsu CH, et al. Trends in the incidence of thymoma, thymic carcinoma, and thymic neuroendocrine tumor in the United States. PLoS One 2019;14: e0227197.\u003c/li\u003e\n \u003cli\u003eStrobel P, et al. Tumor genetics and survival of thymic neuroendocrine neoplasms: a multi-institutional clinicopathologic study. Gene Chromosome Cancer 2014;53:738e49.\u003c/li\u003e\n \u003cli\u003eBakhos CT, et al. Thymic neuroendocrine tumors and thymic carcinoma: demographics, treatment, and survival. Innovations 2020;15:468e74.\u003c/li\u003e\n \u003cli\u003eDe Jong WK, et al. Thymic epithelial tumours: a population-based study of the incidence, diagnostic procedures and therapy. Eur J Cancer 2007;44: 123e30.\u003c/li\u003e\n \u003cli\u003eJia‐Yu Tang,Hui‐Jiang Gao,Guo‐Dong Shi,et al.Development and validation of a nomogram prognostic model for patients with neuroendocrine tumors of the thymus[J].Thoracic Cancer, 2020, 11(9).\u003c/li\u003e\n \u003cli\u003eLau J, Cvasciuc T I, Simpson D, et al. Continuing challenges of primary neuroendocrine tumours of the thymus: A concise review[J]. European Journal of Surgical Oncology, 2022.07.017.\u003c/li\u003e\n \u003cli\u003eCrona J, et al. Treatment, prognostic markers and survival in thymic neuroendocrine tumours. A study from a single tertiary referral centre. Lung Cancer 2012;79:289e93.\u003c/li\u003e\n \u003cli\u003eSullivan JLMD, Weksler Bmbamd. Neuroendocrine tumors of the thymus: analysis of factors affecting survival in 254 patients. Ann Thorac Surg 2016;103:935e9.\u003c/li\u003e\n \u003cli\u003eYokoi K, et al. JLCS medical practice guidelines for thymic tumors: summary of recommendations. Jpn J Clin Oncol 2017;47:1119e22.\u003c/li\u003e\n \u003cli\u003eGirard N, et al. Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015;26:v40e55.\u003c/li\u003e\n \u003cli\u003e中国医师协会肿瘤多学科诊疗专业委员会. 中国胸腺上皮肿瘤临床诊疗指南 (2021 版)[J]. 中华肿瘤杂志，2021，43(4)：395-404.\u003c/li\u003e\n \u003cli\u003eTateo V，Manuzzi L，De Giglio A，et al. Immunobiology of thymic epithelial tumors：implications for immunotherapy with immune checkpoint inhibitors [J]. Int J Mol Sci，2020，21(23)：9056.\u003c/li\u003e\n \u003cli\u003eGiaccone G，Kim C. Durable response in patients with thymic carcinoma treated with pembrolizumab after prolonged follow-up[J]. J Thorac Oncol，2021，16(3)：483-485.\u003c/li\u003e\n \u003cli\u003eBaudin E，Caplin M，Garcia-Carbonero R，et al. Lung and thymic carcinoids：ESMO Clinical Practice Guidelines for diagnosis，treatment and follow-up[J]. Ann Oncol，2021，32(4)：439-451.\u003c/li\u003e\n \u003cli\u003eCho J，Kim HS，Ku BM，et al. Pembrolizumab for patients with refractory or relapsed thymic epithelial tumor：an open-label phase Ⅱ trial [J]. J Clin Oncol，2019，37(24)：2162-2170.\u003c/li\u003e\n \u003cli\u003eGiaccone G，Kim C，Thompson J，et al. Pembrolizumab in patients with thymic carcinoma：a single-arm，single-centre，phase 2 study[J]. Lancet Oncol，2018，19(3)：347-355.\u003c/li\u003e\n\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":"Neuroendocrine tumors of the thymus (NETT), Surgical resection, Thymic carcinoma, superior vena cava, chemotherapy, immunotherapy","lastPublishedDoi":"10.21203/rs.3.rs-3991636/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3991636/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThymic neuroendocrine tumors are rare malignant tumors with neuroendocrine functions located in the anterior mediastinum thymic region. They exhibit a high degree of malignancy and can early invade surrounding fat,pericardium, pleura, major blood vessels, and lungs,posing a significant risk of recurrence.Here, we report a case of recurrent thymic cancer treated with complete surgical resection, replacement of the innominate vein, superior vena cava formation, and iodine ion insertion.A 51-year-old male diagnosed with stage lllA malignant thymoma in November 2021, accompanied by lymph node metastasis,involving the peripheral left lung.The patient underwent six cycles of adjuvant immunotherapy with pembrolizumab and cisplatin plus etoposide, along with one course of radiotherapy postoperatively.Subsequently, the patient received regular immunotherapy and follow-up at our hospital. In October 2023,chest CT revealed tumor recurrence, with infiltration into the pericardium, bilateral innominate veins, superior vena cava, and brachiocephalic artery.Subsequently, the patient underwent a midline thoracotomy for extensive resection of recurrent thymic tumor,enlargement of pericardial resection, left innominate vein-to-right atrial artificial grafting,superior vena cava formation,and iodine-125radioisotope brachytherapy.Aggressive surgical intervention combined with adjuvant therapy is an essential treatment modality for locally advanced thymic cancer involving the superior vena cava and surrounding blood vessels.\u003c/p\u003e","manuscriptTitle":"Recurrent thymic carcinoma treated with anterior median thoracotomy, innominate vein replacement for superior vena cava, and iodide implantation: A case report and review of the literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-06 19:53:43","doi":"10.21203/rs.3.rs-3991636/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":"69c8414e-5523-40e2-bd18-fd6e46b48a12","owner":[],"postedDate":"March 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-08T04:32:06+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-06 19:53:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3991636","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3991636","identity":"rs-3991636","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}