Advanced Management of Refractory Bronchopleural Fistula in Pulmonary Osteosarcoma Metastasis: Individualized Application of Interventional Therapy

Advanced Management of Refractory Bronchopleural Fistula in Pulmonary Osteosarcoma Metastasis: Individualized Application of Interventional Therapy | 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 Research Article Advanced Management of Refractory Bronchopleural Fistula in Pulmonary Osteosarcoma Metastasis: Individualized Application of Interventional Therapy Yuyue Jiang, Qiyuan Bao, Nannan Yang, Qungang Shan, Zhiyuan Wu, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6662992/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 Bronchopleural fistula is a life-threatening complication of pulmonary metastasis of osteosarcoma with limited therapeutic options. This study aimed to evaluate the efficacy and safety of interventional occlusion for the treatment of refractory bronchopleural fistula. Methods Data of 21 patients with bronchopleural fistula associated with pulmonary metastasis of osteosarcoma between January 2019 and December 2023 were analyzed retrospectively. Technical success, clinical success and survival were evaluated. Results All 21 patients (25 years ± 11, 14 men) received interventional therapy and underwent a total of 27 interventional embolization treatments, of which 21 (77.8%) were successfully embolized with coils and n-Butyl Cyanoacrylate (NBCA) and the instantaneous drainage speed decreased from a preoperative median of 365 ml/min (range: 60–1800) to a postoperative median of 20 ml/min (range: 0–100). 14 (66.7%) reported varying degrees of improvement in their respiratory symptoms, and nearly half of them reached the level of cure, which means that the drainage tube is no longer needed and the lungs are significantly enlarged. 3 patients (14.3%) experienced coughing out of embolization coils. 1 patient (4.7%) experienced postoperative hemoptysis (50ml) but received prompt and effective treatment. Conclusion Individualized interventional therapy, primarily including the use of coils and NBCA for embolization, is an effective and safe method for treating bronchopleural fistula associated with pulmonary metastases from osteosarcoma. Bronchopleural fistula Osteosarcoma Interventional embolization Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Osteosarcoma, acknowledged for its aggressive nature and proclivity toward metastasis, is frequently characterized by the manifestation of pulmonary metastases, presenting a prevalent clinical challenge[ 1 , 2 ]. Pulmonary metastasis is not only associated with significantly compromised patient survival rates but is often accompanied by the emergence of bronchopleural fistula (BPF), resulting in heightened therapeutic complexities and hindrances to recovery[ 3 , 4 ]. Particularly, intractable thoracic infections triggered by BPF can be fatal, impacting overall survival time[ 5 ]. Patients with pulmonary metastases from osteosarcoma often undergo treatment involving chemoradiation and antiangiogenic therapy, which can impact the healing process of BPF and even lead to the development of BPF [ 6 , 7 ]. This may pose challenges to the closure of fistulous openings, necessitating further investigation into their combined therapeutic effects with interventional occlusion techniques. In this regard, significant promise and distinct advantages are demonstrated by interventional occlusion techniques. Interventional embolization therapy is a widely utilized method in the medical field for treating vascular diseases[ 8 ]. In this technique, the combined application of coil and n-Butyl Cyanoacrylate (NCBA) has brought forth new advancements and possibilities[ 9 , 10 ]. The coil occupies abnormal vascular spaces in a controlled manner, while the NCBA adhesive, serving as a biocompatible material, reinforces the position of the coil. This enhancement aims to improve treatment efficacy and reduce the risk of complications[ 11 ]. Recent research indicates significant potential for this combined application technique in the treatment of airway-related diseases[ 12 , 13 ]. This paper investigated a clinical study utilizing interventional embolization techniques in the treatment of BPF induced by pulmonary metastasis of osteosarcoma. Through a comprehensive analysis of clinical cases and research outcomes, the aim was to delineate the efficacy, safety, and long-term prognosis associated with this emerging therapeutic approach, furnishing a deeper understanding and robust evidence base for clinical practice. Materials and methods Patients In this study, we retrospectively analyzed the medical records of all patients with refractory BPF treated by interventional occlusion coils and NBCA at our hospital from January 2019 to December 2023. The selection process could be seen in Figure 1A. A total of 21 patients were included in this study and 7 patients were excluded. Clinical data encompassing demographic details, confirmed diagnostic reports of osteosarcoma and pulmonary metastasis, imaging evidence validating the presence of BPF, comprehensive treatment history, and documented informed consent were meticulously reviewed and analyzed. Patient data, including sex, age, fistula location, etiology, surgical history, radiation and chemotherapy situation, alongside other clinical conditions, were documented and analyzed. The specific information could be found in Table 1. Procedure The decision to perform interventional occlusion was made by orthopedic surgeons, pulmonologists, thoracic surgeons and interventional radiologists during consultations in the interventional department. Informed patient consent was obtained from conscious patients or the immediate family of unconscious patients. The entire clinical course was shown in Figure 1B. The patient underwent surgery under general anesthesia. Patient positioning was adjusted so that the fistula was located at the lowest point to facilitate the aggregation of NBCA glue (n-Butyl Cyanoacrylate; BEIJING Compon Medical Devices, CHINA). Conventional imaging studies could identify the suspected location of a fistula, while the exact location of the fistula could be determined through bronchoscopy or bronchography during interventional procedures. Sometimes, intraoperative adjustments to the patient's position were necessary based on the confirmed location. Central bronchopleural fistulas could be directly observed under bronchoscopy (Figure 2), while peripheral or complex fistulas often required the injection of contrast agent through a catheter (MPA1, 4F, 100cm; Cordis, USA) guided by X-ray to observe (Figure 3). The typical fistula location could be observed as the contrast agent leaked into the thoracic cavity, known as the “smoke” phenomenon (Figure 2 and 3) or resembling “bubble shadows” (Figure 4). For situations involving multiple fistulas, a balloon occlusion test could be employed to occlude superior bronchial segments to identify the responsible bronchial segment (Figure 4). After temporarily occluding the suspected lobar bronchus using a balloon (7 F; Fogarty Ewards Lifesciences, USA), the quantitative assessment of gas drainage speed was determined through a negative pressure chest drainage bottle. If the speed decreased, it indicated the presence of a BPF in that lung lobe. If there was no decrease, it suggested that the BPF was located in another lung lobe or that there were multiple lobes involved. Initially, under imaging guidance, a chest drainage tube (7-10 F, AREON MEDICAL DEVICES, USA) connected to a negative pressure suction device (Thopaz Medela, CH) was placed into the cavity caused by the fistula. Pleurodesis agents was injected, and the negative pressure suction intensity was adjusted to 5 cmH 2 O or 10 cmH 2 O. The instantaneous drainage speed was observed, and if there was a significant reduction, continued follow-up observation was conducted. If no obvious improvement was observed, it was considered an indication for interventional occlusion. After identifying the responsible fistula, a microcatheter (PT 2 , 0.014’,185 cm; BostonScientific, USA) was used to implant a spring coil (Interlock, 3-6 mm [diameter], 12-20 cm [length]; BostonScientific, USA) into the implicated bronchus. If there were multiple fistulas, multiple spring coils could be implanted simultaneously to occlude different locations. After implanting the spring coil, NBCA glue (n-Butyl Cyanoacrylate; BEIJING Compon Medical Devices, CHINA) was directly injected. For central bronchopleural fistulas, the occlusion situation of the fistula could be directly observed under bronchoscopy, revealing the injected spring coils and significant glue accumulation. After occlusion, an instantaneous decrease in negative pressure drainage speed was observed (often reducing to below 20 ml/min), indicating effective occlusion. Pleurodesis agents were injected again to consolidate treatment. If the instantaneous drainage speed remained ≥ 100 ml/min, it indicated incomplete occlusion or the presence of other fistulas, requiring localization and continued occlusion. Follow-up All patients were given active support care and symptomatic therapy after the interventional embolization. Detailed physical examinations, including pulmonary auscultation and observation of chest morphology, were conducted. Additionally, periodic chest X-rays or CT scans were performed to evaluate the closure status of BPF and treatment effectiveness. Follow-up was conducted through the analysis of telephone communication and electronic medical records. Definitions Technical success was defined as successful closure of the BFA using coils and NBCA during the interventional procedure, with no evident residual leak or re-opening. Clinical success was defined as a significant improvement of the patient's symptoms, including alleviation of respiratory distress, significant reduction in pleural drainage volume and residual cavity. Statistical analysis SPSS version 27.0 (SPSS Inc., USA) was used for data analysis. Categorical variables were presented as numbers followed by percentages. Continuous variables were presented as the mean ± standard deviation (normality of distribution verified by the Shapiro-Wilk test); otherwise, the median and range would be reported. Survival data was were analyzed using the Kaplan-Meier method. The change in variables over time was analyzed by paired t-test for data with normal distribution. P < 0.05 was defined as the level of statistical significance. Results A total of 21 patients with BPF (14 males and 7 females) who underwent interventional embolization with coils and NBCA were included. The mean age was 25 ± 11 years (standard deviation). They had all been diagnosed with osteosarcoma. The primary lesions of osteosarcoma in 13 patients were located in the femur while others in the radius (n = 3), tibia (n = 3), rib (n = 1), and humerus (n = 1), respectively. The median time from diagnosis of osteosarcoma to the detection of lung metastasis was 12 (range: 3 - 83) months, followed by a median of 20 (range: 1 - 55) months before the appearance of BFA. The location of bronchopleural fistula predominantly occurred in the right lung (64.3%), consistent with previous research findings[14]. Fourteen patients underwent partial pulmonary resection. All of them received chemotherapy and antiangiogenic drug therapy, with six patients receiving both radiation and chemotherapy. The detailed clinical characteristics were shown in Table 1. Following the CT diagnosis identifying BFA, all of them initially received the placement of chest drainage tube, yet none of their symptoms improved effectively. After a median of 1 (range: 1 - 24) months, all of them underwent embolization procedures utilizing coils and NBCA under the intervention of interventional radiologists, with a technical success rate of 77.8%. The location of the fistula was identified through injection of contrast agent or balloon occlusion test. Figure 5A illustrated the complexity of fistula locations and cavity types. While 22.2% failed to achieve successful embolization due to the inability to clearly identify the fistula location during operation (14.8%) and the cough of the post-operative coil spring (7.4%). The patients whose fistulas were successfully occluded experienced a decrease in instantaneous drainage volume from a preoperative median of 365 ml/min (range: 60 – 1800) to a postoperative median of 20 ml/min (range: 0 – 100) (Figure 5B). During the intervention involving coil embolization and NBCA injection, patients tolerated the procedure well, with no incidents of airway rupture, choking, or laryngeal edema. 14 patients (66.7%) reported varying degrees of improvement in their respiratory symptoms. Specifically, 6 patients (28.6%) reached a level of cure (complete removal of drainage tubes, significant improvement in lung capacity, and significant symptom relief), while 8 patients (38.1%) experienced improvement (unable to completely remove drainage tubes, still requiring them for survival, but with symptom alleviation). Four patients (19.1%) underwent a second embolization due to due to the discovery of new fistulas after the initial embolization, while one patient (4.8%) underwent a third embolization. Notably, all patients received consistent conventional chemotherapy, radiation or anti-angiogenic medication for metastases throughout surgery and follow-up. During the follow-up period, three patients (14.3%) experienced coughing out of embolization coils during the postoperative observation. One patient (4.7%) experienced postoperative hemoptysis (approximately 50ml) two days after the surgery; however, symptoms eased following emergency treatment. After treatment, all patients experienced complications such as coughing and chest tightness, which were effectively alleviated through symptomatic management. 15 patients died during the follow-up period. All patients were divided into three groups based on treatment and prognosis: the “technical failure and no improvement” group, the “improvement” group, and the “cure” group. Analysis of the survival data for the three groups showed that the survival time of the “cure” group was significantly better than that of the other two groups ( p = 0.02) (Figure 5C). Discussion Bronchopleural fistula is an abnormal connection between the bronchus and the pleura, presenting symptoms such as difficulty breathing, coughing, and hemoptysis[ 4 , 15 ]. Air leaks due to BPF are associated with high morbidity (up to 57% for resectional surgery or pneumonia) and significant mortality (16–72%)[ 15 – 18 ]. Though infrequent, bronchopleural fistula poses a clinical challenge due to limited treatment options and less favorable outcomes[ 14 , 19 ]. The complexity of pulmonary tumors coupled with the patient's compromised health often restricts the use of traditional conservative treatments like chest tube drainage and more invasive surgical procedures in bronchopleural fistula management. Asamura et al.[ 20 ] conducted a 28-year study involving 52 patients with lung cancer-related bronchopleural fistula. They found that wider resection such as pneumonectomy, residual carcinomatous tissue at the bronchial stump, preoperative irradiation, and diabetes were the main risk factors for the occurrence of bronchopleural fistula. Additionally, they observed that the treatment outcomes were unsatisfactory. Chemotherapy and anti-angiogenic drugs worsen this situation by affecting the natural healing of the body's tissues. Unfortunately, the pulmonary metastases commonly associated with osteosarcoma heighten the likelihood of bronchopleural fistula occurrence[ 14 , 20 ]. This may arise from lung resection surgery or the metastatic tumors themselves. Our team's experience suggests that sarcomas are more prone to triggering bronchopleural fistulas compared to epithelial cancers. Moreover, bronchopleural fistulas induced by peripheral tumors often occur in the secondary bronchial areas, which further complicates the challenges of interventional treatments guided by bronchoscopy[ 21 ]. Published reports have described the use of polyethylene glycol, fibrin glues, autologous blood products, gel foam, silver nitrate, and stenting among other techniques[ 15 ]. Abramian O et al.[ 14 ] described two separate cases where they used ethanol for therapeutic closure of bronchopleural fistulas. Baden W et al.[ 22 ] reported a case of a 2-year-old patient where coil spring intervention was utilized to seal a pneumonia-related bronchopleural fistula. And Katoch CD et al.[ 23 ] reported the use of a biological glue intervention for sealing in 25 patients with bronchopleural fistula, most of whom had benign lung diseases. Considering the rapid advancement of interventional occlusion techniques and the complexity of bronchopleural fistulas associated with pulmonary metastases of osteosarcoma, we proposed a personalized application of interventional therapy. This involved the combined application of occlusion coils and NBCA (N-butyl cyanoacrylate) for targeted intervention. When using NBCA glue alone for occlusion, the glue tends to flow easily and does not adhere well to the fistula. On the other hand, when using a coil alone for occlusion, gaps within the coil may allow gas to still pass through the fistula. Innovatively, we used a combination of coil and NBCA glue to occlude the fistula. The NBCA glue can fill the gaps within the coil, and it adheres more effectively and for a longer duration to the fistula and the diseased bronchus, enhancing its efficacy. The combined use of both methods results in a more thorough and effective occlusion of the fistula. Our research conducted a systematic review analyzing clinical data of bronchopleural fistula formation post-pulmonary metastasis in osteosarcoma, treated through interventional occlusion. The results highlighted this as a safe, effective, and promising treatment option with potential for further development. Specifically, this treatment approach demonstrated high operability, achieving an 77.8% technical success rate in the interventional embolization procedure. 66.7% of patients experienced varying degrees of improvement in their symptoms, and surprisingly, almost half of them achieved a level of cure, characterized by the absence of continued drainage tube requirement and significant lung re-expansion. These achievements were particularly valuable for patients with osteosarcoma who have already developed pulmonary metastases. More importantly, the survival time of patients was significantly improved by interventional embolization. Despite a single instance of minor hemoptysis (50ml) post-treatment, which was adequately managed, and the resolution of other complications like cough and chest pain through symptomatic treatment, overall, this treatment approach was minimally traumatic for patients. It was particularly suitable for individuals with pulmonary metastasis from osteosarcoma, often characterized by compromised health conditions. However, during the follow-up period, we still observed three patients experiencing coughing out of spring coils. These complications underscored the importance of closely monitoring and managing potential post-operative complications. Despite encouraging results, our study is limited by its retrospective nature and relatively small sample size. Thus, future exploration in larger, prospective cohorts is necessary to delve into the long-term outcomes and durability of embolization intervention, providing a more comprehensive understanding. Conclusion In conclusion, for intractable bronchopleural fistulas associated with pulmonary metastases of osteosarcoma, the individualized interventional embolization with coil and NBCA is a safe, effective, and promising therapeutic approach with broad application prospects. Abbreviations NBCA, n-Butyl Cyanoacrylate BPF, bronchopleural fistula CT, Computed tomography Declarations Ethics approval and consent to participate This study adhered strictly to the Principles of the Helsinki Declaration. The use of clinical data has been approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Approval number: 2025 − 173, NCT06927596). Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Funding This study was founded by National Natural Science Foundation of China (82272089 to ZM. W), Famous Medical Studio Project of Huangpu District of Shanghai (2023MY02 to ZM. W) and Key discipline of Shanghai Health System (2024ZDXK0060 to J.L). Author Contribution Zhongmin Wang, Weibin Zhang and Wei Huang designed the study and drafted the manuscript. Yuyue Jiang, Qiyuan Bao and Nannan Yang collected the clinical data and performed the statistical analysis. Qungang Shan, Zhiyuan Wu, Xiaoyi Ding and Jian Lu participated in the operation and supervised the study. All authors read and approved the final manuscript. Acknowledgement We wish to acknowledge Yingjie Chen from West China Hospital of Sichuan University for his help about manuscript writing. At the same time, we thank the patients who participated in this study. Availability of data and materials All data generated or analyzed during this study are included in this published article. References Ritter J, Bielack SS. Osteosarcoma. Annals of Oncology. 2010;21 Suppl 7:vii320-5. Sueyoshi T, Jono H, Shinriki S, Ota K, Ota T, Tasaki M, et al. Therapeutic approaches targeting midkine suppress tumor growth and lung metastasis in osteosarcoma. Cancer Letters. 2012;316:23-30. Giritsky AS, Etcubanas E, Mark JB. Pulmonary resection in children with metastatic osteogenic sarcoma: improved survival with surgery, chemotherapy, and irradiation. Journal of Thoracic and Cardiovascular Surgery. 1978;75:354-62. Cannella M, Cornelis F, Descat E, Ferron S, Carteret T, Castagnède H, et al. Bronchopleural fistula after radiofrequency ablation of lung tumours. Cardiovascular and Interventional Radiology. 2011;34 Suppl 2:S171-4. Khan JH, Rahman SB, McElhinney DB, Harmon AL, Anthony JP, Hall TS, et al. Management Strategies for Complex Bronchopleural Fistula. 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Thoracic and Cardiovascular Surgeon. 2003;51:106-8. Park JD BI, Park KS, Kim SJ, Jeon MH, Hong JM. Fluoroscopy-Guided Treatment of a Bronchopleural Fistula with a Platinum Vascular Occlusion Coil and N-butly-2-cyanoacrylate (NBCA): A Case Report. J Korean Soc Radiol. 2009;61:375-8. Cagirici U, Cetin Y, Cakan A, Samancilar O, Veral A, Askar FZ. Experimental use of N-butyl cyanoacrylate tissue adhesive on lung parenchyma after pulmonary resection. Thoracic and Cardiovascular Surgeon. 2007;55:180-1. Abramian O, Rosenheck J, Taddeo-Kolman D, Bowen F, Boujaoude Z, Abouzgheib W. Therapeutic closure of bronchopleural fistulas using ethanol. Therapeutic Advances in Respiratory Disease. 2021;15:17534666211044411. Lois M, Noppen M. Bronchopleural fistulas: an overview of the problem with special focus on endoscopic management. Chest. 2005;128:3955-65. Lazarus DR, Casal RF. Persistent air leaks: a review with an emphasis on bronchoscopic management. Journal of Thoracic Disease. 2017;9:4660-70. Salmon CJ, Ponn RB, Westcott JL. Endobronchial vascular occlusion coils for control of a large parenchymal bronchopleural fistula. Chest. 1990;98:233-4. Pierson DJ, Horton CA, Bates PW. Persistent bronchopleural air leak during mechanical ventilation. A review of 39 cases. Chest. 1986;90:321-3. Baumann MH, Sahn SA. Medical management and therapy of bronchopleural fistulas in the mechanically ventilated patient. Chest. 1990;97:721-8. Asamura H, Naruke T, Tsuchiya R, Goya T, Kondo H, Suemasu K. Bronchopleural fistulas associated with lung cancer operations. Univariate and multivariate analysis of risk factors, management, and outcome. Journal of Thoracic and Cardiovascular Surgery. 1992;104:1456-64. Westcott JL, Volpe JP. Peripheral bronchopleural fistula: CT evaluation in 20 patients with pneumonia, empyema, or postoperative air leak. Radiology. 1995;196:175-81. Baden W, Hofbeck M, Warmann SW, Schaefer JF, Sieverding L. Interventional closure of a bronchopleural fistula in a 2 year old child with detachable coils. BMC Pediatrics. 2022;22:250. Katoch CD, Chandran VM, Bhattacharyya D, Barthwal MS. Closure of bronchopleural fistula by interventional bronchoscopy using sealants and endobronchial devices. Med J Armed Forces India. 2013;69:326-9. Table Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table.docx 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-6662992","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":494992240,"identity":"d9b2d3e1-0608-4050-946c-c53e0b3e6de4","order_by":0,"name":"Yuyue Jiang","email":"","orcid":"","institution":"Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197, Ruijin 2nd Road, Shanghai","correspondingAuthor":false,"prefix":"","firstName":"Yuyue","middleName":"","lastName":"Jiang","suffix":""},{"id":494992241,"identity":"2d803639-f235-4b21-bf6a-6d9a1eff31a1","order_by":1,"name":"Qiyuan 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10:08:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6662992/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6662992/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88527505,"identity":"c314ef4e-7e50-430a-ae16-5e144b668652","added_by":"auto","created_at":"2025-08-07 10:39:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":287528,"visible":true,"origin":"","legend":"\u003cp\u003eThe inclusion criteria (A) and clinical course (B) of the whole study.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6662992/v1/1aa0537f69a7f64b6c9efb8a.png"},{"id":88527497,"identity":"1b5cb74f-f4c5-4963-a858-17e74d86eb6a","added_by":"auto","created_at":"2025-08-07 10:39:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":248240,"visible":true,"origin":"","legend":"\u003cp\u003eA 29-year-old man diagnosed with lung metastasis of osteosarcoma developed a huge cavity in the thoracic cavity after undergoing partial lung resection surgery (\u003cstrong\u003eA\u003c/strong\u003e, white asterisk). \u003cstrong\u003e(B) \u003c/strong\u003eDuring surgery, significant defects in the bronchial wall were observed through the bronchoscope, suggesting a central bronchopleural fistula. \u003cstrong\u003e(C)\u003c/strong\u003e Under image guidance, the injection of a small amount of contrast agent allowed the observation of leakage into the thoracic cavity, referred to as the “smoke” phenomenon (black arrow), to determine the location of the fistula. The previously placed thoracic negative pressure drainage tube could also be observed (white arrow). \u003cstrong\u003e(D)\u003c/strong\u003e One controllable embolization spring coil, along with NBCA, was injected (black arrow). \u003cstrong\u003e(E)\u003c/strong\u003e Reconstructed CT scan images revealed the position of the spring coil. \u003cstrong\u003e(F) \u003c/strong\u003eA repeated bronchoscopy examination clearly revealed the placement of the spring coil, with the reflective material being NBCA.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6662992/v1/3d43f626daa2dc4334eb064f.png"},{"id":88527495,"identity":"a9e0e3ec-a154-4718-b33f-b58caa3a6823","added_by":"auto","created_at":"2025-08-07 10:39:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":240149,"visible":true,"origin":"","legend":"\u003cp\u003eA 10-year-old woman diagnosed with lung metastasis of osteosarcoma experienced spontaneous pneumothorax \u003cstrong\u003e(A)\u003c/strong\u003e after undergoing partial lung resection surgery. Despite conservative treatment, a persistent cavity (\u003cstrong\u003eB\u003c/strong\u003e, white asterisk) remains, suggesting a peripheral bronchopleural fistula. After confirming the location of the fistula with contrast agent \u003cstrong\u003e(C)\u003c/strong\u003e, a spring coil and NBCA were injected \u003cstrong\u003e(D)\u003c/strong\u003e.\u003cstrong\u003e (E)\u003c/strong\u003e Upon reexamination one month later, the spring coil position was stable. \u003cstrong\u003e(F) \u003c/strong\u003eIn a follow-up examination one and a half years later, the cavity was completely gone, and the lung had re-expanded to fill the thoracic cavity.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6662992/v1/524065b613667428366f603c.png"},{"id":88527507,"identity":"7d72a596-5732-410c-9548-aa999ba44d97","added_by":"auto","created_at":"2025-08-07 10:39:13","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":253159,"visible":true,"origin":"","legend":"\u003cp\u003eA 12-year-old woman, diagnosed with lung metastasis of osteosarcoma, underwent local ablation treatment, leading to the formation of a cavity \u003cstrong\u003e(A)\u003c/strong\u003e.\u003cstrong\u003e(B)\u003c/strong\u003e Through balloon and contrast agent tests, the location of the superior bronchial segment of the fistula was determined. \u003cstrong\u003e(C) \u003c/strong\u003eFollowing the injection of contrast agent, “bubble shadows” were visible. \u003cstrong\u003e(D) \u003c/strong\u003eEventually, four springs and NBCA were injected. \u003cstrong\u003e(E) \u003c/strong\u003eUpon reexamination one month later, the springs were securely in place. \u003cstrong\u003e(F) \u003c/strong\u003eA year later, in another follow-up examination, lung expansion was observed, and the spring coil had shifted closer to the thoracic wall.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6662992/v1/161edd62a621b91bbaf5cd32.png"},{"id":88527492,"identity":"562124e4-0ae4-441f-a794-fa5496867d13","added_by":"auto","created_at":"2025-08-07 10:39:13","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":140501,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A) \u003c/strong\u003eAn alluvial diagram of bronchopleural fistula-related pulmonary cavities. \u003cstrong\u003e(B)\u003c/strong\u003e Change of the instantaneous drainage speed before and after the occlusion. \u003cstrong\u003e(C) \u003c/strong\u003eSurvival analysis of three groups of patients with different therapeutic effects. Survival data were analyzed using Kaplan-Meier Method.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-6662992/v1/8cccf882c5bec53bc6dd61bb.png"},{"id":96917603,"identity":"36443754-9dda-4de1-97d6-5338ad8e4422","added_by":"auto","created_at":"2025-11-27 14:10:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1708417,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6662992/v1/a28b0e23-088e-417d-a2e6-0db0447f476b.pdf"},{"id":88527491,"identity":"b3d9d120-fb16-4a23-ba57-ae303a5bf256","added_by":"auto","created_at":"2025-08-07 10:39:12","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":26004,"visible":true,"origin":"","legend":"","description":"","filename":"Table.docx","url":"https://assets-eu.researchsquare.com/files/rs-6662992/v1/3f03aaf3936ba59bad6cca06.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Advanced Management of Refractory Bronchopleural Fistula in Pulmonary Osteosarcoma Metastasis: Individualized Application of Interventional Therapy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOsteosarcoma, acknowledged for its aggressive nature and proclivity toward metastasis, is frequently characterized by the manifestation of pulmonary metastases, presenting a prevalent clinical challenge[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Pulmonary metastasis is not only associated with significantly compromised patient survival rates but is often accompanied by the emergence of bronchopleural fistula (BPF), resulting in heightened therapeutic complexities and hindrances to recovery[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Particularly, intractable thoracic infections triggered by BPF can be fatal, impacting overall survival time[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePatients with pulmonary metastases from osteosarcoma often undergo treatment involving chemoradiation and antiangiogenic therapy, which can impact the healing process of BPF and even lead to the development of BPF [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This may pose challenges to the closure of fistulous openings, necessitating further investigation into their combined therapeutic effects with interventional occlusion techniques. In this regard, significant promise and distinct advantages are demonstrated by interventional occlusion techniques.\u003c/p\u003e\u003cp\u003eInterventional embolization therapy is a widely utilized method in the medical field for treating vascular diseases[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In this technique, the combined application of coil and n-Butyl Cyanoacrylate (NCBA) has brought forth new advancements and possibilities[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The coil occupies abnormal vascular spaces in a controlled manner, while the NCBA adhesive, serving as a biocompatible material, reinforces the position of the coil. This enhancement aims to improve treatment efficacy and reduce the risk of complications[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Recent research indicates significant potential for this combined application technique in the treatment of airway-related diseases[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis paper investigated a clinical study utilizing interventional embolization techniques in the treatment of BPF induced by pulmonary metastasis of osteosarcoma. Through a comprehensive analysis of clinical cases and research outcomes, the aim was to delineate the efficacy, safety, and long-term prognosis associated with this emerging therapeutic approach, furnishing a deeper understanding and robust evidence base for clinical practice.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, we retrospectively analyzed the medical records of all patients with refractory BPF treated by interventional occlusion coils and NBCA at our hospital from January 2019 to December 2023. The selection process could be seen in Figure 1A. A total of 21 patients were included in this study and 7 patients were excluded.\u003c/p\u003e\n\u003cp\u003eClinical data encompassing demographic details, confirmed diagnostic reports of osteosarcoma and pulmonary metastasis, imaging evidence validating the presence of BPF, comprehensive treatment history, and documented informed consent were meticulously reviewed and analyzed. Patient data, including sex, age, fistula location, etiology, surgical history, radiation and chemotherapy situation, alongside other clinical conditions, were documented and analyzed. The specific information could be found in Table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProcedure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe decision to perform interventional occlusion was made by orthopedic surgeons, pulmonologists, thoracic surgeons and interventional radiologists during consultations in the interventional department. Informed patient consent was obtained from conscious patients or the immediate family of unconscious patients. The entire clinical course was shown in Figure 1B.\u003c/p\u003e\n\u003cp\u003eThe patient underwent surgery under general anesthesia. Patient positioning was adjusted so that the fistula was located at the lowest point to facilitate the aggregation of NBCA glue (n-Butyl Cyanoacrylate; BEIJING Compon Medical Devices, CHINA). Conventional imaging studies could identify the suspected location of a fistula, while the exact location of the fistula could be determined through bronchoscopy or bronchography during interventional procedures. Sometimes, intraoperative adjustments to the patient\u0026apos;s position were necessary based on the confirmed location. Central bronchopleural fistulas could be directly observed under bronchoscopy (Figure 2), while peripheral or complex fistulas often required the injection of contrast agent through a catheter (MPA1, 4F, 100cm; Cordis, USA) guided by X-ray to observe (Figure 3). The typical fistula location could be observed as the contrast agent leaked into the thoracic cavity, known as the \u0026ldquo;smoke\u0026rdquo; phenomenon (Figure 2 and 3) or resembling \u0026ldquo;bubble shadows\u0026rdquo; (Figure 4). For situations involving multiple fistulas, a balloon occlusion test could be employed to occlude superior bronchial segments to identify the responsible bronchial segment (Figure 4). After temporarily occluding the suspected lobar bronchus using a balloon (7 F; Fogarty Ewards Lifesciences, USA), the quantitative assessment of gas drainage speed was determined through a negative pressure chest drainage bottle. If the speed decreased, it indicated the presence of a BPF in that lung lobe. If there was no decrease, it suggested that the BPF was located in another lung lobe or that there were multiple lobes involved.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInitially, under imaging guidance, a chest drainage tube (7-10 F, AREON MEDICAL DEVICES, USA) connected to a negative pressure suction device (Thopaz Medela, CH) was placed into the cavity caused by the fistula. Pleurodesis agents was injected, and the negative pressure suction intensity was adjusted to 5 cmH\u003csub\u003e2\u003c/sub\u003eO or 10 cmH\u003csub\u003e2\u003c/sub\u003eO. The instantaneous drainage speed was observed, and if there was a significant reduction, continued follow-up observation was conducted. If no obvious improvement was observed, it was considered an indication for interventional occlusion. After identifying the responsible fistula, a microcatheter (PT\u003csup\u003e2\u003c/sup\u003e, 0.014\u0026rsquo;,185 cm; BostonScientific, USA) was used to implant a spring coil (Interlock, 3-6 mm [diameter], 12-20 cm [length]; BostonScientific, USA) into the implicated bronchus. If there were multiple fistulas, multiple spring coils could be implanted simultaneously to occlude different locations. After implanting the spring coil, NBCA glue (n-Butyl Cyanoacrylate; BEIJING Compon Medical Devices, CHINA) was directly injected. For central bronchopleural fistulas, the occlusion situation of the fistula could be directly observed under bronchoscopy, revealing the injected spring coils and significant glue accumulation. After occlusion, an instantaneous decrease in negative pressure drainage speed was observed (often reducing to below 20 ml/min), indicating effective occlusion. Pleurodesis agents were injected again to consolidate treatment. If the instantaneous drainage speed remained \u0026ge; 100 ml/min, it indicated incomplete occlusion or the presence of other fistulas, requiring localization and continued occlusion.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFollow-up\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients were given active support care and symptomatic therapy after the interventional embolization. Detailed physical examinations, including pulmonary auscultation and observation of chest morphology, were conducted. Additionally, periodic chest X-rays or CT scans were performed to evaluate the closure status of BPF and treatment effectiveness. Follow-up was conducted through the analysis of telephone communication and electronic medical records.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinitions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTechnical success was defined as successful closure of the BFA using coils and NBCA during the interventional procedure, with no evident residual leak or re-opening. Clinical success was defined as a significant improvement of the patient\u0026apos;s symptoms, including alleviation of respiratory distress, significant reduction in pleural drainage volume and residual cavity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSPSS version 27.0 (SPSS Inc., USA) was used for data analysis. Categorical variables were presented as numbers followed by percentages. Continuous variables were presented as the mean \u0026plusmn; standard deviation (normality of distribution verified by the Shapiro-Wilk test); otherwise, the median and range would be reported. Survival data was were analyzed using the Kaplan-Meier method. The change in variables over time was analyzed by paired t-test for data with normal distribution. \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 was defined as the level of statistical significance.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 21 patients with BPF (14 males and 7 females) who underwent interventional embolization with coils and NBCA were included. The mean age was 25 \u0026plusmn; 11 years (standard deviation). They had all been diagnosed with osteosarcoma. The primary lesions of osteosarcoma in 13 patients were located in the femur while others in the radius (n = 3), tibia (n = 3), rib (n = 1), and humerus (n = 1), respectively. The median time from diagnosis of osteosarcoma to the detection of lung metastasis was 12 (range: 3 - 83) months, followed by a median of 20 (range: 1 - 55) months before the appearance of BFA. The location of bronchopleural fistula predominantly occurred in the right lung (64.3%), consistent with previous research findings[14]. Fourteen patients underwent partial pulmonary resection. All of them received chemotherapy and antiangiogenic drug therapy, with six patients receiving both radiation and chemotherapy. The detailed clinical characteristics were shown in Table 1.\u003c/p\u003e\n\u003cp\u003eFollowing the CT diagnosis identifying BFA, all of them initially received the placement of chest drainage tube, yet none of their symptoms improved effectively. After a median of 1 (range: 1 - 24) months, all of them underwent embolization procedures utilizing coils and NBCA under the intervention of interventional radiologists, with a technical success rate of 77.8%. The location of the fistula was identified through injection of contrast agent or balloon occlusion test. Figure 5A illustrated the complexity of fistula locations and cavity types. While 22.2% failed to achieve successful embolization due to the inability to clearly identify the fistula location during operation (14.8%) and the cough of the post-operative coil spring (7.4%). The patients whose fistulas were successfully occluded experienced a decrease in instantaneous drainage volume from a preoperative median of 365 ml/min (range: 60 \u0026ndash; 1800) to a postoperative median of 20 ml/min (range: 0 \u0026ndash; 100) (Figure 5B). During the intervention involving coil embolization and NBCA injection, patients tolerated the procedure well, with no incidents of airway rupture, choking, or laryngeal edema.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e14 patients (66.7%) reported varying degrees of improvement in their respiratory symptoms. Specifically, 6 patients (28.6%) reached a level of cure (complete removal of drainage tubes, significant improvement in lung capacity, and significant symptom relief), while 8 patients (38.1%) experienced improvement (unable to completely remove drainage tubes, still requiring them for survival, but with symptom alleviation). Four patients (19.1%) underwent a second embolization due to due to the discovery of new fistulas after the initial embolization, while one patient (4.8%) underwent a third embolization. Notably, all patients received consistent conventional chemotherapy, radiation or anti-angiogenic medication for metastases throughout surgery and follow-up.\u003c/p\u003e\n\u003cp\u003eDuring the follow-up period, three patients (14.3%) experienced coughing out of embolization coils during the postoperative observation. One patient (4.7%) experienced postoperative hemoptysis (approximately 50ml) two days after the surgery; however, symptoms eased following emergency treatment. After treatment, all patients experienced complications such as coughing and chest tightness, which were effectively alleviated through symptomatic management. 15 patients died during the follow-up period. All patients were divided into three groups based on treatment and prognosis: the \u0026ldquo;technical failure and no improvement\u0026rdquo; group, the \u0026ldquo;improvement\u0026rdquo; group, and the \u0026ldquo;cure\u0026rdquo; group. Analysis of the survival data for the three groups showed that the survival time of the \u0026ldquo;cure\u0026rdquo; group was significantly better than that of the other two groups (\u003cem\u003ep\u003c/em\u003e = 0.02) (Figure 5C).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBronchopleural fistula is an abnormal connection between the bronchus and the pleura, presenting symptoms such as difficulty breathing, coughing, and hemoptysis[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Air leaks due to BPF are associated with high morbidity (up to 57% for resectional surgery or pneumonia) and significant mortality (16\u0026ndash;72%)[\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Though infrequent, bronchopleural fistula poses a clinical challenge due to limited treatment options and less favorable outcomes[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The complexity of pulmonary tumors coupled with the patient's compromised health often restricts the use of traditional conservative treatments like chest tube drainage and more invasive surgical procedures in bronchopleural fistula management. Asamura et al.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] conducted a 28-year study involving 52 patients with lung cancer-related bronchopleural fistula. They found that wider resection such as pneumonectomy, residual carcinomatous tissue at the bronchial stump, preoperative irradiation, and diabetes were the main risk factors for the occurrence of bronchopleural fistula. Additionally, they observed that the treatment outcomes were unsatisfactory. Chemotherapy and anti-angiogenic drugs worsen this situation by affecting the natural healing of the body's tissues.\u003c/p\u003e\u003cp\u003eUnfortunately, the pulmonary metastases commonly associated with osteosarcoma heighten the likelihood of bronchopleural fistula occurrence[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. This may arise from lung resection surgery or the metastatic tumors themselves. Our team's experience suggests that sarcomas are more prone to triggering bronchopleural fistulas compared to epithelial cancers. Moreover, bronchopleural fistulas induced by peripheral tumors often occur in the secondary bronchial areas, which further complicates the challenges of interventional treatments guided by bronchoscopy[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePublished reports have described the use of polyethylene glycol, fibrin glues, autologous blood products, gel foam, silver nitrate, and stenting among other techniques[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Abramian O et al.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] described two separate cases where they used ethanol for therapeutic closure of bronchopleural fistulas. Baden W et al.[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] reported a case of a 2-year-old patient where coil spring intervention was utilized to seal a pneumonia-related bronchopleural fistula. And Katoch CD et al.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] reported the use of a biological glue intervention for sealing in 25 patients with bronchopleural fistula, most of whom had benign lung diseases.\u003c/p\u003e\u003cp\u003eConsidering the rapid advancement of interventional occlusion techniques and the complexity of bronchopleural fistulas associated with pulmonary metastases of osteosarcoma, we proposed a personalized application of interventional therapy. This involved the combined application of occlusion coils and NBCA (N-butyl cyanoacrylate) for targeted intervention. When using NBCA glue alone for occlusion, the glue tends to flow easily and does not adhere well to the fistula. On the other hand, when using a coil alone for occlusion, gaps within the coil may allow gas to still pass through the fistula. Innovatively, we used a combination of coil and NBCA glue to occlude the fistula. The NBCA glue can fill the gaps within the coil, and it adheres more effectively and for a longer duration to the fistula and the diseased bronchus, enhancing its efficacy. The combined use of both methods results in a more thorough and effective occlusion of the fistula.\u003c/p\u003e\u003cp\u003e Our research conducted a systematic review analyzing clinical data of bronchopleural fistula formation post-pulmonary metastasis in osteosarcoma, treated through interventional occlusion. The results highlighted this as a safe, effective, and promising treatment option with potential for further development. Specifically, this treatment approach demonstrated high operability, achieving an 77.8% technical success rate in the interventional embolization procedure. 66.7% of patients experienced varying degrees of improvement in their symptoms, and surprisingly, almost half of them achieved a level of cure, characterized by the absence of continued drainage tube requirement and significant lung re-expansion. These achievements were particularly valuable for patients with osteosarcoma who have already developed pulmonary metastases. More importantly, the survival time of patients was significantly improved by interventional embolization. Despite a single instance of minor hemoptysis (50ml) post-treatment, which was adequately managed, and the resolution of other complications like cough and chest pain through symptomatic treatment, overall, this treatment approach was minimally traumatic for patients. It was particularly suitable for individuals with pulmonary metastasis from osteosarcoma, often characterized by compromised health conditions. However, during the follow-up period, we still observed three patients experiencing coughing out of spring coils. These complications underscored the importance of closely monitoring and managing potential post-operative complications.\u003c/p\u003e\u003cp\u003eDespite encouraging results, our study is limited by its retrospective nature and relatively small sample size. Thus, future exploration in larger, prospective cohorts is necessary to delve into the long-term outcomes and durability of embolization intervention, providing a more comprehensive understanding.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, for intractable bronchopleural fistulas associated with pulmonary metastases of osteosarcoma, the individualized interventional embolization with coil and NBCA is a safe, effective, and promising therapeutic approach with broad application prospects.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNBCA, n-Butyl Cyanoacrylate\u003c/p\u003e\n\u003cp\u003eBPF, bronchopleural fistula\u003c/p\u003e\n\u003cp\u003eCT, Computed tomography\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eThis study adhered strictly to the Principles of the Helsinki Declaration. The use of clinical data has been approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Approval number: 2025\u0026thinsp;\u0026minus;\u0026thinsp;173, NCT06927596).\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThis study was founded by National Natural Science Foundation of China (82272089 to ZM. W), Famous Medical Studio Project of Huangpu District of Shanghai (2023MY02 to ZM. W) and Key discipline of Shanghai Health System (2024ZDXK0060 to J.L).\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eZhongmin Wang, Weibin Zhang and Wei Huang designed the study and drafted the manuscript. Yuyue Jiang, Qiyuan Bao and Nannan Yang collected the clinical data and performed the statistical analysis. Qungang Shan, Zhiyuan Wu, Xiaoyi Ding and Jian Lu participated in the operation and supervised the study. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eWe wish to acknowledge Yingjie Chen from West China Hospital of Sichuan University for his help about manuscript writing. At the same time, we thank the patients who participated in this study.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRitter J, Bielack SS. Osteosarcoma. Annals of Oncology. 2010;21 Suppl 7:vii320-5.\u003c/li\u003e\n\u003cli\u003eSueyoshi T, Jono H, Shinriki S, Ota K, Ota T, Tasaki M, et al. Therapeutic approaches targeting midkine suppress tumor growth and lung metastasis in osteosarcoma. Cancer Letters. 2012;316:23-30.\u003c/li\u003e\n\u003cli\u003eGiritsky AS, Etcubanas E, Mark JB. Pulmonary resection in children with metastatic osteogenic sarcoma: improved survival with surgery, chemotherapy, and irradiation. Journal of Thoracic and Cardiovascular Surgery. 1978;75:354-62.\u003c/li\u003e\n\u003cli\u003eCannella M, Cornelis F, Descat E, Ferron S, Carteret T, Castagn\u0026egrave;de H, et al. Bronchopleural fistula after radiofrequency ablation of lung tumours. Cardiovascular and Interventional Radiology. 2011;34 Suppl 2:S171-4.\u003c/li\u003e\n\u003cli\u003eKhan JH, Rahman SB, McElhinney DB, Harmon AL, Anthony JP, Hall TS, et al. Management Strategies for Complex Bronchopleural Fistula. Asian Cardiovascular and Thoracic Annals. 2000;8:78-84.\u003c/li\u003e\n\u003cli\u003eWhelan JS, Davis LE. Osteosarcoma, Chondrosarcoma, and Chordoma. Journal of Clinical Oncology. 2018;36:188-93.\u003c/li\u003e\n\u003cli\u003eRutkowski P. Antiangiogenic agents combined with systemic chemotherapy in refractory osteosarcoma. Lancet Oncology. 2021;22:1206-7.\u003c/li\u003e\n\u003cli\u003eHu J, Albadawi H, Chong BW, Deipolyi AR, Sheth RA, Khademhosseini A, et al. Advances in Biomaterials and Technologies for Vascular Embolization. Adv Mater. 2019;31:e1901071.\u003c/li\u003e\n\u003cli\u003eSong HH, Won YD, Kim YJ. Transcatheter N-butyl cyanoacrylate embolization of pseudoaneurysms. Journal of Vascular and Interventional Radiology. 2010;21:1508-11.\u003c/li\u003e\n\u003cli\u003eHu YC, Newman CB, Dashti SR, Albuquerque FC, McDougall CG. Cranial dural arteriovenous fistula: transarterial Onyx embolization experience and technical nuances. Journal of Neurointerventional Surgery. 2011;3:5-13.\u003c/li\u003e\n\u003cli\u003eWatanabe S, Watanabe T, Urayama H. Endobronchial occlusion method of bronchopleural fistula with metallic coils and glue. Thoracic and Cardiovascular Surgeon. 2003;51:106-8.\u003c/li\u003e\n\u003cli\u003ePark JD BI, Park KS, Kim SJ, Jeon MH, Hong JM. Fluoroscopy-Guided Treatment of a Bronchopleural Fistula with a Platinum Vascular Occlusion Coil and N-butly-2-cyanoacrylate (NBCA): A Case Report. J Korean Soc Radiol. 2009;61:375-8.\u003c/li\u003e\n\u003cli\u003eCagirici U, Cetin Y, Cakan A, Samancilar O, Veral A, Askar FZ. Experimental use of N-butyl cyanoacrylate tissue adhesive on lung parenchyma after pulmonary resection. Thoracic and Cardiovascular Surgeon. 2007;55:180-1.\u003c/li\u003e\n\u003cli\u003eAbramian O, Rosenheck J, Taddeo-Kolman D, Bowen F, Boujaoude Z, Abouzgheib W. Therapeutic closure of bronchopleural fistulas using ethanol. Therapeutic Advances in Respiratory Disease. 2021;15:17534666211044411.\u003c/li\u003e\n\u003cli\u003eLois M, Noppen M. Bronchopleural fistulas: an overview of the problem with special focus on endoscopic management. Chest. 2005;128:3955-65.\u003c/li\u003e\n\u003cli\u003eLazarus DR, Casal RF. Persistent air leaks: a review with an emphasis on bronchoscopic management. Journal of Thoracic Disease. 2017;9:4660-70.\u003c/li\u003e\n\u003cli\u003eSalmon CJ, Ponn RB, Westcott JL. Endobronchial vascular occlusion coils for control of a large parenchymal bronchopleural fistula. Chest. 1990;98:233-4.\u003c/li\u003e\n\u003cli\u003ePierson DJ, Horton CA, Bates PW. Persistent bronchopleural air leak during mechanical ventilation. A review of 39 cases. Chest. 1986;90:321-3.\u003c/li\u003e\n\u003cli\u003eBaumann MH, Sahn SA. Medical management and therapy of bronchopleural fistulas in the mechanically ventilated patient. Chest. 1990;97:721-8.\u003c/li\u003e\n\u003cli\u003eAsamura H, Naruke T, Tsuchiya R, Goya T, Kondo H, Suemasu K. Bronchopleural fistulas associated with lung cancer operations. Univariate and multivariate analysis of risk factors, management, and outcome. Journal of Thoracic and Cardiovascular Surgery. 1992;104:1456-64.\u003c/li\u003e\n\u003cli\u003eWestcott JL, Volpe JP. Peripheral bronchopleural fistula: CT evaluation in 20 patients with pneumonia, empyema, or postoperative air leak. Radiology. 1995;196:175-81.\u003c/li\u003e\n\u003cli\u003eBaden W, Hofbeck M, Warmann SW, Schaefer JF, Sieverding L. Interventional closure of a bronchopleural fistula in a 2\u0026thinsp;year old child with detachable coils. BMC Pediatrics. 2022;22:250.\u003c/li\u003e\n\u003cli\u003eKatoch CD, Chandran VM, Bhattacharyya D, Barthwal MS. Closure of bronchopleural fistula by interventional bronchoscopy using sealants and endobronchial devices. Med J Armed Forces India. 2013;69:326-9.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\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":"Bronchopleural fistula, Osteosarcoma, Interventional embolization","lastPublishedDoi":"10.21203/rs.3.rs-6662992/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6662992/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eBronchopleural fistula is a life-threatening complication of pulmonary metastasis of osteosarcoma with limited therapeutic options. This study aimed to evaluate the efficacy and safety of interventional occlusion for the treatment of refractory bronchopleural fistula.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eData of 21 patients with bronchopleural fistula associated with pulmonary metastasis of osteosarcoma between January 2019 and December 2023 were analyzed retrospectively. Technical success, clinical success and survival were evaluated.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAll 21 patients (25 years\u0026thinsp;\u0026plusmn;\u0026thinsp;11, 14 men) received interventional therapy and underwent a total of 27 interventional embolization treatments, of which 21 (77.8%) were successfully embolized with coils and n-Butyl Cyanoacrylate (NBCA) and the instantaneous drainage speed decreased from a preoperative median of 365 ml/min (range: 60\u0026ndash;1800) to a postoperative median of 20 ml/min (range: 0\u0026ndash;100). 14 (66.7%) reported varying degrees of improvement in their respiratory symptoms, and nearly half of them reached the level of cure, which means that the drainage tube is no longer needed and the lungs are significantly enlarged. 3 patients (14.3%) experienced coughing out of embolization coils. 1 patient (4.7%) experienced postoperative hemoptysis (50ml) but received prompt and effective treatment.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eIndividualized interventional therapy, primarily including the use of coils and NBCA for embolization, is an effective and safe method for treating bronchopleural fistula associated with pulmonary metastases from osteosarcoma.\u003c/p\u003e","manuscriptTitle":"Advanced Management of Refractory Bronchopleural Fistula in Pulmonary Osteosarcoma Metastasis: Individualized Application of Interventional Therapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-07 10:39:08","doi":"10.21203/rs.3.rs-6662992/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":"416322d3-4e04-4bda-a5c7-101abaa9c3cf","owner":[],"postedDate":"August 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-26T13:53:49+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-07 10:39:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6662992","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6662992","identity":"rs-6662992","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}