A Randomized Controlled Trial of Dual-Localization Using Ureteral Catheter and Methylene Blue for Intraductal Breast Lesions

A Randomized Controlled Trial of Dual-Localization Using Ureteral Catheter and Methylene Blue for Intraductal Breast Lesions | 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 A Randomized Controlled Trial of Dual-Localization Using Ureteral Catheter and Methylene Blue for Intraductal Breast Lesions Xinchou Wang, Yiyue Hu, Xieling Peng, xueqing zhou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9653887/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 Precise localization of non-palpable intraductal breast lesions is essential for successful excision. This study evaluated a dual-localization technique combining preoperative ureteral catheter placement with intraoperative methylene blue injection. Methods In this prospective three-arm RCT, 90 patients with ductoscopy-confirmed lesions were randomized to Conventional Surgery Group, MB Staining Group, Cannulation-Assisted Group. Primary outcomes were operative time and resection volume. Results Baseline characteristics were comparable. The dual-localization group had significantly shorter operative time (38.66 ± 7.07 min) and smaller resection volume (1.71 ± 1.05 cm³) versus methylene blue alone and conventional groups (p < 0.001). No catheter-related complications occurred. Conclusion The dual-localization technique significantly improves surgical precision, reduces operative time, and minimizes tissue excision without increasing complications, offering a promising advancement for managing intraductal lesions. Trial Registration This trial has been submitted for retrospective registration to the Chinese Clinical Trial Registry (ChiCTR) (Submission ID: 299472). intraductal breast lesion methylene blue ureteral catheter breast-conserving surgery randomized controlled trial Figures Figure 1 Background Pathological nipple discharge (PND) is defined as spontaneous, persistent, unilateral, watery, serous, or bloody fluid emanating from a single duct [1] .It is a common clinical manifestation of breast disease, accounting for approximately 4.8–7.4% of presentations % [2] . The most frequent etiology of PND is an intraductal occupying lesion, which includes entities such as intraductal papilloma, papillomatosis, and ductal carcinoma in situ [3] . Due to their frequently small size (often <1 cm in diameter) and occult nature, intraductal lesions are seldom palpable on clinical physical examination. Consequently, diagnostic imaging is essential. Among available techniques, fiberoptic ductoscopy (FDS) currently offers the highest diagnostic accuracy for identifying intraductal abnormalities in patients with nipple discharge [4] .Surgical excision remains the cornerstone of both definitive treatment and histopathological diagnosis for these lesions [5-7] . Standard surgical approaches range from conventional segmental resection to FDS-assisted excision of the involved ductal system. FDS provides direct visualisation of the intraductal lesion, thereby enabling precise, targeted endoscopic intervention [8] . A significant intraoperative challenge remains the accurate and sustained localization of the affected duct and the subsequent complete excision of the pathological segment. Current surgical protocols are effective for patients undergoing intervention either immediately or within 24 hours following FDS. However, a common clinical dilemma arises when surgery is delayed beyond this 24-hour window. In such cases, cessation of discharge or the presence of multi-duct discharge can obscure the identity of the offending duct, leading to potential surgical delays or necessitating repeat ductoscopic procedures for re-identification. Therefore, there is a compelling need to develop reliable methods for pre-operative duct marking that remain effective over longer periods and facilitate clear intraoperative guidance. To address this unmet need, we introduced a novel technique utilizing pre-operative ureteral catheter placement for duct localization, combined with intraoperative methylene blue dye instillation for visual tracing, to facilitate the surgical resection of intraductal lesions. We conducted a comparative analysis against both a methylene blue-only group and a conventional segmental resection group. This study aims to evaluate a more efficient, patient-friendly surgical approach that enhances operative precision, improves safety, and ultimately offers a more effective therapeutic outcome. Methods 2.1 Ethical Approval and Informed Consent This study was reviewed and approved by the Medical Ethics Committee of Guilin Maternity and Child Health Care Hospital (Approval No.2024-010-KY; Date of Approval:2024-03-08). All methods were performed in accordance with the relevant guidelines and regulations (Declaration of Helsinki). Informed consent was obtained from all individual participants included in the study.Written informed consent was obtained from all individual participants included in this study prior to their enrollment 2.2 Patient Characteristics A total of 90 patients were enrolled, including those identified with intraductal lesions via ductoscopy at our hospital between July 2024 and August 2025, as well as patients referred to our institution for surgery following ductoscopy-confirmed intraductal lesions at other hospitals. The inclusion and exclusion criteria were as follows: Inclusion Criteria: 1. Female patients with intraductal lesions identified by ductoscopy; 2. No palpable breast mass upon clinical examination; 3. No previous surgical treatment for the condition; 4. Absence of severe cardiac, pulmonary, hepatic, renal, or other organ dysfunction; 5. Willing and able to comply with follow-up requirements. Exclusion Criteria: 1. Presence of severe systemic disease (e.g., cardiac, pulmonary, hepatic, or renal) contraindicating surgery; 2. Patients without nipple discharge who were diagnosed with intraductal lesions via ductoscopy; 3. Inability to comply with follow-up protocols; 4. History of radiotherapy or chemotherapy within the past month. 2.3 Methods Patients were randomized into one of three groups using a random number table(n = 30 per group): Conventional Surgery Group, MB Staining Group, Cannulation-Assisted Group. All patients initially underwent ductoscopy for lesion identification. Group-specific localization procedures were performed preoperatively, followed by scheduled surgical resection. The detailed operative protocols for each group were as follows: Conventional Surgery Group: Surgical resection was performed based on the estimated depth and trajectory of the lesion assessed during ductoscopy. A standard breast segmentectomy was conducted accordingly. MB Staining Group: A 0.5 mL solution of 0.1% methylene blue was injected into the pathological duct. The stained duct and a 1–2 cm margin of surrounding breast tissue were excised down to the posterior glandular fascia. Cannulation-Assisted Group: Immediately following ductoscopy, a ureteral catheter (Oukai Medical Devices Co., Ltd., standard F3 type) was inserted into the affected duct orifice and secured with a sterile transparent dressing. During surgery, 0.5 mL of 0.1% methylene blue was injected through the catheter to mark the target duct. The stained duct and a perimeter of 1–2 cm of adjacent breast tissue were resected down to the posterior glandular margin (see Figure 1 for schematic illustration). 2.4 Outcome Measures All patients were followed up for 3 months postoperatively. The following surgical parameters were compared among the three groups: operative duration, volume of excised tissue, pathological confirmation rate, 24-hour postoperative pain score (Numerical Rating Scale, NRS), length of hospital stay, incidence of postoperative complications (e.g., breast deformity, nipple retraction), and breast ultrasound findings at 3 months. Additional metrics specific to the cannulation-assisted group included: the time interval (in days) from ureteral catheter placement to surgery, patient comfort level after catheter insertion assessed by the General Comfort Questionnaire (GCQ), incidence of catheter dislodgement, occurrence of catheter-related breast infection, and the number of ductoscopic procedures performed. 2.5 Statistical Analysis Statistical analyses were performed using SPSS software (version 26.0). Normally distributed continuous data were expressed as mean ± standard deviation (SD) and compared among the three groups using one-way ANOVA. If overall significance was detected (P < 0.05), post hoc pairwise comparisons were conducted using Tukey’s test. Categorical data were summarized as numbers (n) and percentages, and compared using the Chi-square test or Fisher’s exact test, as appropriate. All tests were two-sided, with a significance level set at α = 0.05. Results 3.1. Baseline Characteristics and Postoperative Pathological Outcomes A total of 90 female patients were enrolled in the study: 30 were assigned to the Conventional Surgery Group, 30 to the Methylene Blue Staining Group, and 30 to the Cannulation-Assisted Group. The mean age of the patients was 44.12 ± 8.11 years. There were 39 cases of left-sided nipple discharge, 46 cases of right-sided discharge, and 5 cases of bilateral discharge (P = 0.665). Discharge characteristics included yellow serous secretion (64 cases), watery secretion (6 cases), milky secretion (1 case), and bloody secretion (19 cases), with no significant differences among the three groups (P = 0.166). Postoperative pathological examination revealed 3 cases of breast cancer, 66 cases of intraductal papilloma, and 21 cases of atypical hyperplasia (P = 0.128). There were no statistically significant differences in demographic or clinical characteristics among the three groups (P > 0.05) (Table 1 ). Data from patients with a pathological diagnosis of breast cancer—such as length of hospital stay, operative time, postoperative pain scores, and volume of excised tissue—were excluded from statistical analysis of secondary outcomes. As one case of breast cancer was identified in each group, 29 patients per group were included in the subsequent comparative analyses. Table 1 Baseline characteristics. Clinical characteristic Conventional Surgery Group MB Staining Group Cannulation-Assisted Group P/Sum Mean age (SD),years 44.41 ± 8.58 44.10 ± 7.29 44.26 ± 6.31 0.961 Color of discharge Yellow 24 18 22 64 Bloody 5 10 4 19 Clear 1 1 4 6 Milky 0 1 0 1 Distributions of the lesions Left 15 14 10 39 Righ 14 15 17 46 Both 1 1 3 5 Pathological diagnoses result Intraductal Papillomatosis 20 19 27 66 Breast cancer 1 1 1 3 Atypical hyperplasia 9 10 2 21 3.2. Intraoperative Outcomes The Cannulation-Assisted Group demonstrated a significantly lower volume of excised tissue and shorter operative time compared to both the Methylene Blue Staining Group and the Conventional Surgery Group, with statistical significance (as shown in Table 2 ). No statistically significant difference was observed in operative time between the Methylene Blue Staining Group and the Conventional Surgery Group (p = 0.143). Table 2 Comparison of intraoperative indexes between the three groups. Volume of resected tissue Mean volume (SD), cm3 Conventional Surgery Group MB Staining Group Cannulation-Assisted Group p 14.68 ± 4.89 8.58 ± 3.64 1.71 ± 1.05 0.000 Duration of surgery Mean duration (SD), min 51.10 ± 9.05 49.28 ± 12.63 38.66 ± 7.07 0.000 3.3. Postoperative Outcomes The Cannulation-Assisted Group showed significantly lower postoperative pain scores compared to both the Methylene Blue Staining Group and the Conventional Surgery Group, with a statistically significant difference (p < 0.05). However, no significant difference was observed in the length of hospital stay among the three groups (Table 3 ). At the 3-month follow-up, ultrasound examination revealed hypoechoic areas suggestive of fluid collection in 13 patients in the Conventional Surgery Group, 7 in the Methylene Blue Staining Group, and 6 in the Cannulation-Assisted Group (p > 0.05). No nipple retraction or breast deformity was observed in either the Methylene Blue Staining Group or the Cannulation-Assisted Group. In contrast, 4 patients in the Conventional Surgery Group developed nipple retraction or skin traction deformity, indicating a statistically significant difference in cosmetic outcomes among the groups. Table 3 Comparison of postoperative indices between the three groups. Hospital stay Mean day (SD), days Conventional Surgery Group MB Staining Group Cannulation-Assisted Group p 5.07 ± 1.93 4.55 ± 2.01 4.52 ± 2.60 0.566 Postoperative Pain Assessment,Mean point (SD), points 2.24 ± 0.79 1.69 ± 0.47 0.79 ± 0.56 0.000 Postoperative-3-month follow-up ultrasound abnormal numbers 13 7 6 0.095 Breast contour deformity numbers 4 0 0 0.015 3.4 Complications No medical complications—such as poor wound healing, hematoma requiring intervention, persistent nipple discharge, surgical site infection, or secondary hemorrhage—were observed in any of the patients. Due to the short follow-up period, no definitive conclusions regarding long-term recurrence can be drawn at this time. Discussion In recent years, various preoperative localization and tracing techniques have been employed for the excision of intraductal lesions identified via ductoscopy. These include methylene blue staining, ductoscopy-guided localization, guidewire localization, and ductoscopy-assisted needle localization. Ductoscopy, with its integrated cold light source, allows rough quadrant localization of the lesion. By estimating the distance from the light source to the nipple or the depth of the scope insertion, the surgeon can approximate the tumor location and perform a traditional segmentectomy based on the presumed duct trajectory. However, light scattering through thick skin reduces the accuracy of visual distance estimation, and depth assessment remains challenging. Furthermore, intraoperative traction and exposure can displace the initial landmarks, leading to imprecise excision, often resulting in excessively large resections, increased surgical difficulty, lower pathological yield, and prolonged operative time. Methylene blue staining significantly improves the rate of accurate duct excision and facilitates postoperative recovery. It also reduces operative time, blood loss, and complication rates compared to conventional segmentectomy. However, its major drawback is dye diffusion, which often leads to extensive staining of surrounding tissues, obscuring the surgical field and potentially resulting in excessive tissue dissection or incomplete lesion removal, thereby compromising pathological assessment [ 9 ] .Moreover, this technique relies heavily on the presence of nipple discharge during surgery to identify the affected duct; absence of discharge may lead to misidentification or failed localization. Guidewire localization offers precise targeting, improves excision accuracy, and enhances the detection rate of early-stage breast cancers. Nevertheless, it carries risks of duct injury and false tract formation, in addition to problems such as wire displacement, dislodgement, and higher costs [ 10 ] . Ductoscopy-assisted needle localization helps by lifting the needle to tense the peri-ductal tissue, facilitating identification and dissection of the target duct. This reduces unnecessary tissue removal and minimizes patient anxiety associated with blind excision or missed lesions. It provides an accurate and effective approach for non-palpable intraductal lesions. However, the rigidity of the needle limits access to sharply angled or branching ducts, potentially leading to missed diagnoses. The method is also costly and carries risks of needle migration or dislodgement, particularly for lesions in terminal ducts [ 1 ] In summary, each of these localization techniques has distinct advantages and limitations. Tailoring the choice of method to individual patient profiles can improve excision accuracy, shorten operative time, and reduce collateral tissue damage. Nonetheless, each method possesses inherent drawbacks. The approach of inserting a localization catheter immediately after initial ductoscopy circumvents many of these limitations, and our clinical study supports its feasibility and advantages. The cannulation-assisted group demonstrated significantly shorter operative time, smaller excision volume, and lower postoperative pain scores compared to both the conventional and methylene blue–only groups. This can be attributed to the preoperative insertion of a localization catheter during active nipple discharge, enabling rapid and precise intraoperative targeting. Injection of methylene blue through the indwelling catheter followed by guided excision reduced diffusion and minimized removal of healthy tissue. The reduced operative time and limited resection extent likely contributed to diminished postoperative pain. No significant difference was observed in the length of hospital stay among the three groups, likely because the management of benign intraductal lesions follows a relatively standardized pathway. Preoperative preparation, surgical intervention, and postoperative monitoring are protocol-driven, generally resulting in a consistent hospitalization duration of approximately five days. In this study, a standard No. 3 ureteral catheter (diameter: 1 mm) was used for preoperative duct cannulation. This catheter is rigid yet flexible, with a rounded tip that minimizes duct perforation risk, and is cost-effective. Among the 30 patients in the cannulation-assisted group, the indwelling time ranged from 1 to 4 days. There were no instances of catheter dislodgement or infection, and the comfort score was 0.55 ± 0.51, indicating good patient tolerance. The most common complications associated with ductoscopy are nipple bleeding and duct rupture [ 11 ] , Repeated procedures in a short interval increase these risks. The cannulation-assisted group showed a statistically significant reduction in the number of ductoscopies performed compared to the conventional segmentectomy group (p = 0.011), indicating that catheter insertion during the initial ductoscopy effectively reduces the need for repeated examinations. Additionally, in clinical practice, some patients experience cessation of discharge after the initial ductoscopy either while awaiting surgery or during the procedure. In such cases, surgeons must either perform an approximate resection based on initial findings or abort the surgery and repeat ductoscopy. Blind resection increases the risk of incomplete excision and breast deformity, whereas repeat ductoscopy adds time, cost, and potential patient dissatisfaction, possibly leading to patient–physician conflicts. Conclusion The combination of preoperative ureteral catheter localization and intraoperative methylene blue staining demonstrates high targeting accuracy, minimized glandular tissue damage, favorable cosmetic outcomes, and a low complication rate. This approach offers particular clinical value in accurately localizing lesions in patients whose surgery is delayed beyond the immediate post-ductoscopy period, thereby avoiding repeat procedures and reducing operative uncertainty. It is a promising and clinically recommendable technique for improving surgical precision and patient outcomes in the management of intraductal lesions. Declarations Funding This work was supported by the Self-funded Research Project of Guangxi Health Commission (Year 2024), China, entitled "Application of Ureteral Catheter Localization Combined with Intraoperative Methylene Blue Staining in Precise Resection of Pathologic Mammary Ducts" [Contract No.: Z-C20241548]. The funding body played no role in the study design, data collection, analysis, interpretation, or manuscript preparation. Author Contribution PXL,HYY and WXC wrote the main manuscript text and prepared figures 1-3. All authors reviewed the manuscript Data Availability The de-identified datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. References Yang WS, Zhang Y, Wang HL et al (2023) A retrospective study of ductoscopy combined with immediate methylene blue staining in nipple discharge diseases[J]. Sci Rep 13(1):19344 Montroni I, Santini D, Zucchini G et al (2010) Nipple discharge: is its significance as a risk factor for breast cancer fully understood? Observational study including 915 consecutive patients who underwent selective duct excision[J]. Breast Cancer Res Treat 123(3):895–900 Lesetedi C, Rayne S, Kruger D et al (2017) Indicators of breast cancer in patients undergoing microdochectomy for a pathological nipple discharge in a middle-income country[J]. J Surg Res 220:336–340 Filipe MD, Patuleia S, Vriens MR et al (2021) Meta-analysis and cost-effectiveness of ductoscopy, duct excision surgery and MRI for the diagnosis and treatment of patients with pathological nipple discharge[J]. Breast Cancer Res Treat 186(2):285–293 Makineli S, van Wijnbergen J, Vriens MR et al (2023) Role of duct excision surgery in the treatment of pathological nipple discharge and detection of breast carcinoma: systematic review[J]. BJS Open, 7(4) Su X, Lin Q, Cui C et al (2017) Non-calcified ductal carcinoma in situ of the breast: comparison of diagnostic accuracy of digital breast tomosynthesis, digital mammography, and ultrasonography[J]. Breast Cancer 24(4):562–570 Collins LC, Schnitt SJ (2008) Papillary lesions of the breast: selected diagnostic and management issues[J]. Histopathology 52(1):20–29 Panzironi G, Pediconi F, Sardanelli F (2019) Nipple discharge: The state of the art[J]. BJR Open 1(1):20180016 Zhu X, Xing C, Jin T et al (2011) A randomized controlled study of selective microdochectomy guided by ductoscopic wire marking or methylene blue injection[J]. Am J Surg 201(2):221–225 Zhou Y, Liang Y, Zhang J et al (2021) Evaluation of Carbon Nanoparticle Suspension and Methylene Blue Localization for Preoperative Localization of Nonpalpable Breast Lesions: A Comparative Study[J]. Front Surg 8:757694 Valdes EK, Boolbol SK, Cohen JM et al (2016) Clinical Experience With Mammary Ductoscopy[J]. Ann Surg Oncol 23(Suppl 5):9015–9019 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9653887","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":637541681,"identity":"8a4607e9-0e69-4431-b906-b6ae263f8dc6","order_by":0,"name":"Xinchou Wang","email":"","orcid":"","institution":"Guilin Maternal and Child Health Care Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xinchou","middleName":"","lastName":"Wang","suffix":""},{"id":637541682,"identity":"36196414-b7d1-4b27-ac83-8e3663bfe590","order_by":1,"name":"Yiyue Hu","email":"","orcid":"","institution":"Guilin Maternal and Child Health Care Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yiyue","middleName":"","lastName":"Hu","suffix":""},{"id":637541683,"identity":"15f93e28-e54f-491d-9611-cd674add2af2","order_by":2,"name":"Xieling Peng","email":"","orcid":"","institution":"Qingyuan People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xieling","middleName":"","lastName":"Peng","suffix":""},{"id":637541684,"identity":"ed9feda4-4fa0-4d83-b972-4cd3f4e151e7","order_by":3,"name":"xueqing zhou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzElEQVRIiWNgGAWjYBACPiBmZmCQAFEHDnz4QYQWNoQWtsSDM3uI1wICPMaHOdiI0cLee/h1YZuFvcHxnA+HGXgY5PnFDhDQwnMuzXpmmwSzZM/bDYcLLBgMZ85OIKBFIsfMmLdNgo1fInfD4Rk8DAkGt4nUwgNkPDjMw0acFuPHQC0S/BI5DERq4TljxsxzTsJAsueZATCQJQj7hZ+9x/gzT1kdMMSSH3/48MNGnl+agBaw2yA0WKUEQeUgwPwBScsoGAWjYBSMAkwAAN3hOypCApZmAAAAAElFTkSuQmCC","orcid":"","institution":"The People's Hospital of Pingshan Shenzhen","correspondingAuthor":true,"prefix":"","firstName":"xueqing","middleName":"","lastName":"zhou","suffix":""}],"badges":[],"createdAt":"2026-05-08 12:09:00","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9653887/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9653887/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109269515,"identity":"1a120bc8-5654-4684-818e-69e07ca7b01c","added_by":"auto","created_at":"2026-05-14 13:29:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":498168,"visible":true,"origin":"","legend":"\u003cp\u003eSurgical procedure of cannulation-assisted methylene blue staining for intraductal lesion resection.\u003cbr\u003e\nA: Injection of methylene blue through the indwelling catheter to delineate the target duct;\u003cbr\u003e\nB: Excision of the stained duct and surrounding tissue along its trajectory;\u003cbr\u003e\nC: Intraoperative verification of the resected specimen;\u003cbr\u003e\nD: Postoperative appearance of the surgical incision.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9653887/v1/8d8a35296430429c5f03c065.png"},{"id":109269517,"identity":"9aa2af16-fff2-4062-9ae8-a99bc110217b","added_by":"auto","created_at":"2026-05-14 13:29:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":932611,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9653887/v1/685a38b6-e757-443e-8520-9617cba85a2e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Randomized Controlled Trial of Dual-Localization Using Ureteral Catheter and Methylene Blue for Intraductal Breast Lesions","fulltext":[{"header":"Background","content":"\u003cp\u003ePathological nipple discharge (PND) is defined as spontaneous, persistent, unilateral, watery, serous, or bloody fluid emanating from a single duct\u003csup\u003e[1]\u003c/sup\u003e.It is a common clinical manifestation of breast disease, accounting for approximately 4.8–7.4% of presentations %\u003csup\u003e[2]\u003c/sup\u003e. The most frequent etiology of PND is an intraductal occupying lesion, which includes entities such as intraductal papilloma, papillomatosis, and ductal carcinoma in situ \u003csup\u003e[3]\u003c/sup\u003e. Due to their frequently small size (often \u0026lt;1 cm in diameter) and occult nature, intraductal lesions are seldom palpable on clinical physical examination. Consequently, diagnostic imaging is essential. Among available techniques, fiberoptic ductoscopy (FDS) currently offers the highest diagnostic accuracy for identifying intraductal abnormalities in patients with nipple discharge \u003csup\u003e[4]\u003c/sup\u003e.Surgical excision remains the cornerstone of both definitive treatment and histopathological diagnosis for these lesions \u003csup\u003e[5-7]\u003c/sup\u003e. Standard surgical approaches range from conventional segmental resection to FDS-assisted excision of the involved ductal system. FDS provides direct visualisation of the intraductal lesion, thereby enabling precise, targeted endoscopic intervention\u003csup\u003e[8]\u003c/sup\u003e. A significant intraoperative challenge remains the accurate and sustained localization of the affected duct and the subsequent complete excision of the pathological segment. Current surgical protocols are effective for patients undergoing intervention either immediately or within 24 hours following FDS. However, a common clinical dilemma arises when surgery is delayed beyond this 24-hour window. In such cases, cessation of discharge or the presence of multi-duct discharge can obscure the identity of the offending duct, leading to potential surgical delays or necessitating repeat ductoscopic procedures for re-identification. Therefore, there is a compelling need to develop reliable methods for pre-operative duct marking that remain effective over longer periods and facilitate clear intraoperative guidance.\u003c/p\u003e\n\u003cp\u003eTo address this unmet need, we introduced a novel technique utilizing pre-operative ureteral catheter placement for duct localization, combined with intraoperative methylene blue dye instillation for visual tracing, to facilitate the surgical resection of intraductal lesions. We conducted a comparative analysis against both a methylene blue-only group and a conventional segmental resection group. This study aims to evaluate a more efficient, patient-friendly surgical approach that enhances operative precision, improves safety, and ultimately offers a more effective therapeutic outcome.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003e2.1 Ethical Approval and Informed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was reviewed and approved by the Medical Ethics Committee of Guilin Maternity and Child Health Care Hospital (Approval No.2024-010-KY; Date of Approval:2024-03-08). All methods were performed in accordance with the relevant guidelines and regulations (Declaration of Helsinki). Informed consent was obtained from all individual participants included in the study.Written informed consent was obtained from all individual participants included in this study prior to their enrollment\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2 Patient Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;A total of 90 patients were enrolled, including those identified with intraductal lesions via ductoscopy at our hospital between July 2024 and August 2025, as well as patients referred to our institution for surgery following ductoscopy-confirmed intraductal lesions at other hospitals. The inclusion and exclusion criteria were as follows:\u003c/p\u003e\n\u003cp\u003eInclusion Criteria:\u003c/p\u003e\n\u003cp\u003e1. Female patients with intraductal lesions identified by ductoscopy;\u003c/p\u003e\n\u003cp\u003e2. No palpable breast mass upon clinical examination;\u003c/p\u003e\n\u003cp\u003e3. No previous surgical treatment for the condition;\u003c/p\u003e\n\u003cp\u003e4. Absence of severe cardiac, pulmonary, hepatic, renal, or other organ dysfunction;\u003c/p\u003e\n\u003cp\u003e5. Willing and able to comply with follow-up requirements.\u003c/p\u003e\n\u003cp\u003eExclusion Criteria:\u003c/p\u003e\n\u003cp\u003e1. Presence of severe systemic disease (e.g., cardiac, pulmonary, hepatic, or renal) contraindicating surgery;\u003c/p\u003e\n\u003cp\u003e2. Patients without nipple discharge who were diagnosed with intraductal lesions via ductoscopy;\u003c/p\u003e\n\u003cp\u003e3. Inability to comply with follow-up protocols;\u003c/p\u003e\n\u003cp\u003e4. History of radiotherapy or chemotherapy within the past month.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients were randomized into one of three groups using a random number table(n = 30 per group): Conventional Surgery Group, MB Staining Group, Cannulation-Assisted Group. All patients initially underwent ductoscopy for lesion identification. Group-specific localization procedures were performed preoperatively, followed by scheduled surgical resection. The detailed operative protocols for each group were as follows:\u003c/p\u003e\n\u003cp\u003eConventional Surgery Group: Surgical resection was performed based on the estimated depth and trajectory of the lesion assessed during ductoscopy. A standard breast segmentectomy was conducted accordingly.\u003c/p\u003e\n\u003cp\u003eMB Staining Group: A 0.5 mL solution of 0.1% methylene blue was injected into the pathological duct. The stained duct and a 1\u0026ndash;2 cm margin of surrounding breast tissue were excised down to the posterior glandular fascia.\u003c/p\u003e\n\u003cp\u003eCannulation-Assisted Group: Immediately following ductoscopy, a ureteral catheter (Oukai Medical Devices Co., Ltd., standard F3 type) was inserted into the affected duct orifice and secured with a sterile transparent dressing. During surgery, 0.5 mL of 0.1% methylene blue was injected through the catheter to mark the target duct. The stained duct and a perimeter of 1\u0026ndash;2 cm of adjacent breast tissue were resected down to the posterior glandular margin (see Figure 1 for schematic illustration).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003e2.4 Outcome Measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients were followed up for 3 months postoperatively. The following surgical parameters were compared among the three groups: operative duration, volume of excised tissue, pathological confirmation rate, 24-hour postoperative pain score (Numerical Rating Scale, NRS), length of hospital stay, incidence of postoperative complications (e.g., breast deformity, nipple retraction), and breast ultrasound findings at 3 months.\u003c/p\u003e\n\u003cp\u003eAdditional metrics specific to the cannulation-assisted group included: the time interval (in days) from ureteral catheter placement to surgery, patient comfort level after catheter insertion assessed by the General Comfort Questionnaire (GCQ), incidence of catheter dislodgement, occurrence of catheter-related breast infection, and the number of ductoscopic procedures performed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.5 Statistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using SPSS software (version 26.0). Normally distributed continuous data were expressed as mean \u0026plusmn; standard deviation (SD) and compared among the three groups using one-way ANOVA. If overall significance was detected (P \u0026lt; 0.05), post hoc pairwise comparisons were conducted using Tukey\u0026rsquo;s test. Categorical data were summarized as numbers (n) and percentages, and compared using the Chi-square test or Fisher\u0026rsquo;s exact test, as appropriate. All tests were two-sided, with a significance level set at \u0026alpha; = 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Baseline Characteristics and Postoperative Pathological Outcomes\u003c/h2\u003e \u003cp\u003eA total of 90 female patients were enrolled in the study: 30 were assigned to the Conventional Surgery Group, 30 to the Methylene Blue Staining Group, and 30 to the Cannulation-Assisted Group. The mean age of the patients was 44.12\u0026thinsp;\u0026plusmn;\u0026thinsp;8.11 years. There were 39 cases of left-sided nipple discharge, 46 cases of right-sided discharge, and 5 cases of bilateral discharge (P\u0026thinsp;=\u0026thinsp;0.665). Discharge characteristics included yellow serous secretion (64 cases), watery secretion (6 cases), milky secretion (1 case), and bloody secretion (19 cases), with no significant differences among the three groups (P\u0026thinsp;=\u0026thinsp;0.166). Postoperative pathological examination revealed 3 cases of breast cancer, 66 cases of intraductal papilloma, and 21 cases of atypical hyperplasia (P\u0026thinsp;=\u0026thinsp;0.128). There were no statistically significant differences in demographic or clinical characteristics among the three groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eData from patients with a pathological diagnosis of breast cancer\u0026mdash;such as length of hospital stay, operative time, postoperative pain scores, and volume of excised tissue\u0026mdash;were excluded from statistical analysis of secondary outcomes. As one case of breast cancer was identified in each group, 29 patients per group were included in the subsequent comparative analyses.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical characteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConventional Surgery Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMB Staining Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCannulation-Assisted Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP/Sum\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean age (SD),years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.41\u0026thinsp;\u0026plusmn;\u0026thinsp;8.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.10\u0026thinsp;\u0026plusmn;\u0026thinsp;7.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44.26\u0026thinsp;\u0026plusmn;\u0026thinsp;6.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.961\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eColor of discharge\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYellow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBloody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClear\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMilky\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eDistributions of the lesions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRigh\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBoth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003ePathological diagnoses result\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraductal Papillomatosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtypical hyperplasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Intraoperative Outcomes\u003c/h2\u003e \u003cp\u003eThe Cannulation-Assisted Group demonstrated a significantly lower volume of excised tissue and shorter operative time compared to both the Methylene Blue Staining Group and the Conventional Surgery Group, with statistical significance (as shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). No statistically significant difference was observed in operative time between the Methylene Blue Staining Group and the Conventional Surgery Group (p\u0026thinsp;=\u0026thinsp;0.143).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of intraoperative indexes between the three groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVolume of resected tissue Mean volume (SD), cm3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConventional Surgery Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMB Staining Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCannulation-Assisted Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.68\u0026thinsp;\u0026plusmn;\u0026thinsp;4.89\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.58\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.71\u0026thinsp;\u0026plusmn;\u0026thinsp;1.05\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of surgery\u003c/p\u003e \u003cp\u003eMean duration (SD), min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e51.10\u0026thinsp;\u0026plusmn;\u0026thinsp;9.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e49.28\u0026thinsp;\u0026plusmn;\u0026thinsp;12.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e38.66\u0026thinsp;\u0026plusmn;\u0026thinsp;7.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Postoperative Outcomes\u003c/h2\u003e \u003cp\u003eThe Cannulation-Assisted Group showed significantly lower postoperative pain scores compared to both the Methylene Blue Staining Group and the Conventional Surgery Group, with a statistically significant difference (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, no significant difference was observed in the length of hospital stay among the three groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAt the 3-month follow-up, ultrasound examination revealed hypoechoic areas suggestive of fluid collection in 13 patients in the Conventional Surgery Group, 7 in the Methylene Blue Staining Group, and 6 in the Cannulation-Assisted Group (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). No nipple retraction or breast deformity was observed in either the Methylene Blue Staining Group or the Cannulation-Assisted Group. In contrast, 4 patients in the Conventional Surgery Group developed nipple retraction or skin traction deformity, indicating a statistically significant difference in cosmetic outcomes among the groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of postoperative indices between the three groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHospital stay\u003c/p\u003e \u003cp\u003eMean day (SD), days\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConventional Surgery Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMB Staining Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCannulation-Assisted Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.07\u0026thinsp;\u0026plusmn;\u0026thinsp;1.93\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.55\u0026thinsp;\u0026plusmn;\u0026thinsp;2.01\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.52\u0026thinsp;\u0026plusmn;\u0026thinsp;2.60\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.566\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative Pain Assessment,Mean point (SD), points\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative-3-month follow-up ultrasound abnormal numbers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.095\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast contour deformity numbers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Complications\u003c/h2\u003e \u003cp\u003eNo medical complications\u0026mdash;such as poor wound healing, hematoma requiring intervention, persistent nipple discharge, surgical site infection, or secondary hemorrhage\u0026mdash;were observed in any of the patients. Due to the short follow-up period, no definitive conclusions regarding long-term recurrence can be drawn at this time.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn recent years, various preoperative localization and tracing techniques have been employed for the excision of intraductal lesions identified via ductoscopy. These include methylene blue staining, ductoscopy-guided localization, guidewire localization, and ductoscopy-assisted needle localization.\u003c/p\u003e \u003cp\u003eDuctoscopy, with its integrated cold light source, allows rough quadrant localization of the lesion. By estimating the distance from the light source to the nipple or the depth of the scope insertion, the surgeon can approximate the tumor location and perform a traditional segmentectomy based on the presumed duct trajectory. However, light scattering through thick skin reduces the accuracy of visual distance estimation, and depth assessment remains challenging. Furthermore, intraoperative traction and exposure can displace the initial landmarks, leading to imprecise excision, often resulting in excessively large resections, increased surgical difficulty, lower pathological yield, and prolonged operative time.\u003c/p\u003e \u003cp\u003eMethylene blue staining significantly improves the rate of accurate duct excision and facilitates postoperative recovery. It also reduces operative time, blood loss, and complication rates compared to conventional segmentectomy. However, its major drawback is dye diffusion, which often leads to extensive staining of surrounding tissues, obscuring the surgical field and potentially resulting in excessive tissue dissection or incomplete lesion removal, thereby compromising pathological assessment\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.Moreover, this technique relies heavily on the presence of nipple discharge during surgery to identify the affected duct; absence of discharge may lead to misidentification or failed localization.\u003c/p\u003e \u003cp\u003eGuidewire localization offers precise targeting, improves excision accuracy, and enhances the detection rate of early-stage breast cancers. Nevertheless, it carries risks of duct injury and false tract formation, in addition to problems such as wire displacement, dislodgement, and higher costs \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDuctoscopy-assisted needle localization helps by lifting the needle to tense the peri-ductal tissue, facilitating identification and dissection of the target duct. This reduces unnecessary tissue removal and minimizes patient anxiety associated with blind excision or missed lesions. It provides an accurate and effective approach for non-palpable intraductal lesions. However, the rigidity of the needle limits access to sharply angled or branching ducts, potentially leading to missed diagnoses. The method is also costly and carries risks of needle migration or dislodgement, particularly for lesions in terminal ducts \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn summary, each of these localization techniques has distinct advantages and limitations. Tailoring the choice of method to individual patient profiles can improve excision accuracy, shorten operative time, and reduce collateral tissue damage. Nonetheless, each method possesses inherent drawbacks. The approach of inserting a localization catheter immediately after initial ductoscopy circumvents many of these limitations, and our clinical study supports its feasibility and advantages.\u003c/p\u003e \u003cp\u003eThe cannulation-assisted group demonstrated significantly shorter operative time, smaller excision volume, and lower postoperative pain scores compared to both the conventional and methylene blue\u0026ndash;only groups. This can be attributed to the preoperative insertion of a localization catheter during active nipple discharge, enabling rapid and precise intraoperative targeting. Injection of methylene blue through the indwelling catheter followed by guided excision reduced diffusion and minimized removal of healthy tissue. The reduced operative time and limited resection extent likely contributed to diminished postoperative pain.\u003c/p\u003e \u003cp\u003eNo significant difference was observed in the length of hospital stay among the three groups, likely because the management of benign intraductal lesions follows a relatively standardized pathway. Preoperative preparation, surgical intervention, and postoperative monitoring are protocol-driven, generally resulting in a consistent hospitalization duration of approximately five days.\u003c/p\u003e \u003cp\u003eIn this study, a standard No. 3 ureteral catheter (diameter: 1 mm) was used for preoperative duct cannulation. This catheter is rigid yet flexible, with a rounded tip that minimizes duct perforation risk, and is cost-effective. Among the 30 patients in the cannulation-assisted group, the indwelling time ranged from 1 to 4 days. There were no instances of catheter dislodgement or infection, and the comfort score was 0.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51, indicating good patient tolerance.\u003c/p\u003e \u003cp\u003eThe most common complications associated with ductoscopy are nipple bleeding and duct rupture\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e, Repeated procedures in a short interval increase these risks. The cannulation-assisted group showed a statistically significant reduction in the number of ductoscopies performed compared to the conventional segmentectomy group (p\u0026thinsp;=\u0026thinsp;0.011), indicating that catheter insertion during the initial ductoscopy effectively reduces the need for repeated examinations.\u003c/p\u003e \u003cp\u003eAdditionally, in clinical practice, some patients experience cessation of discharge after the initial ductoscopy either while awaiting surgery or during the procedure. In such cases, surgeons must either perform an approximate resection based on initial findings or abort the surgery and repeat ductoscopy. Blind resection increases the risk of incomplete excision and breast deformity, whereas repeat ductoscopy adds time, cost, and potential patient dissatisfaction, possibly leading to patient\u0026ndash;physician conflicts.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe combination of preoperative ureteral catheter localization and intraoperative methylene blue staining demonstrates high targeting accuracy, minimized glandular tissue damage, favorable cosmetic outcomes, and a low complication rate. This approach offers particular clinical value in accurately localizing lesions in patients whose surgery is delayed beyond the immediate post-ductoscopy period, thereby avoiding repeat procedures and reducing operative uncertainty. It is a promising and clinically recommendable technique for improving surgical precision and patient outcomes in the management of intraductal lesions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003e This work was supported by the Self-funded Research Project of Guangxi Health Commission (Year 2024), China, entitled \"Application of Ureteral Catheter Localization Combined with Intraoperative Methylene Blue Staining in Precise Resection of Pathologic Mammary Ducts\" [Contract No.: Z-C20241548]. The funding body played no role in the study design, data collection, analysis, interpretation, or manuscript preparation.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003ePXL,HYY and WXC wrote the main manuscript text and prepared figures 1-3. All authors reviewed the manuscript\u003c/p\u003e\n\u003ch3\u003eData Availability\u003c/h3\u003e\n\u003cp\u003eThe de-identified datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eYang WS, Zhang Y, Wang HL et al (2023) A retrospective study of ductoscopy combined with immediate methylene blue staining in nipple discharge diseases[J]. Sci Rep 13(1):19344\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMontroni I, Santini D, Zucchini G et al (2010) Nipple discharge: is its significance as a risk factor for breast cancer fully understood? Observational study including 915 consecutive patients who underwent selective duct excision[J]. Breast Cancer Res Treat 123(3):895\u0026ndash;900\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLesetedi C, Rayne S, Kruger D et al (2017) Indicators of breast cancer in patients undergoing microdochectomy for a pathological nipple discharge in a middle-income country[J]. J Surg Res 220:336\u0026ndash;340\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFilipe MD, Patuleia S, Vriens MR et al (2021) Meta-analysis and cost-effectiveness of ductoscopy, duct excision surgery and MRI for the diagnosis and treatment of patients with pathological nipple discharge[J]. Breast Cancer Res Treat 186(2):285\u0026ndash;293\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMakineli S, van Wijnbergen J, Vriens MR et al (2023) Role of duct excision surgery in the treatment of pathological nipple discharge and detection of breast carcinoma: systematic review[J]. BJS Open, 7(4)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSu X, Lin Q, Cui C et al (2017) Non-calcified ductal carcinoma in situ of the breast: comparison of diagnostic accuracy of digital breast tomosynthesis, digital mammography, and ultrasonography[J]. Breast Cancer 24(4):562\u0026ndash;570\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollins LC, Schnitt SJ (2008) Papillary lesions of the breast: selected diagnostic and management issues[J]. Histopathology 52(1):20\u0026ndash;29\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePanzironi G, Pediconi F, Sardanelli F (2019) Nipple discharge: The state of the art[J]. BJR Open 1(1):20180016\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu X, Xing C, Jin T et al (2011) A randomized controlled study of selective microdochectomy guided by ductoscopic wire marking or methylene blue injection[J]. Am J Surg 201(2):221\u0026ndash;225\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou Y, Liang Y, Zhang J et al (2021) Evaluation of Carbon Nanoparticle Suspension and Methylene Blue Localization for Preoperative Localization of Nonpalpable Breast Lesions: A Comparative Study[J]. Front Surg 8:757694\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValdes EK, Boolbol SK, Cohen JM et al (2016) Clinical Experience With Mammary Ductoscopy[J]. Ann Surg Oncol 23(Suppl 5):9015\u0026ndash;9019\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"intraductal breast lesion, methylene blue, ureteral catheter, breast-conserving surgery, randomized controlled trial","lastPublishedDoi":"10.21203/rs.3.rs-9653887/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9653887/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePrecise localization of non-palpable intraductal breast lesions is essential for successful excision. This study evaluated a dual-localization technique combining preoperative ureteral catheter placement with intraoperative methylene blue injection.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this prospective three-arm RCT, 90 patients with ductoscopy-confirmed lesions were randomized to Conventional Surgery Group, MB Staining Group, Cannulation-Assisted Group. Primary outcomes were operative time and resection volume.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eBaseline characteristics were comparable. The dual-localization group had significantly shorter operative time (38.66\u0026thinsp;\u0026plusmn;\u0026thinsp;7.07 min) and smaller resection volume (1.71\u0026thinsp;\u0026plusmn;\u0026thinsp;1.05 cm\u0026sup3;) versus methylene blue alone and conventional groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No catheter-related complications occurred.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe dual-localization technique significantly improves surgical precision, reduces operative time, and minimizes tissue excision without increasing complications, offering a promising advancement for managing intraductal lesions.\u003c/p\u003e\u003ch2\u003eTrial Registration\u003c/h2\u003e \u003cp\u003eThis trial has been submitted for retrospective registration to the Chinese Clinical Trial Registry (ChiCTR) (Submission ID: 299472).\u003c/p\u003e","manuscriptTitle":"A Randomized Controlled Trial of Dual-Localization Using Ureteral Catheter and Methylene Blue for Intraductal Breast Lesions","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-14 13:29:22","doi":"10.21203/rs.3.rs-9653887/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":"897c63a4-1dc2-47f7-9be7-58dcbd667011","owner":[],"postedDate":"May 14th, 2026","published":true,"recentEditorialEvents":[{"type":"editorAssigned","content":"","date":"2026-05-14T12:50:49+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-05-14T12:49:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"Breast Cancer Research and Treatment","date":"2026-05-08T12:00:43+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-14T13:29:22+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-14 13:29:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9653887","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9653887","identity":"rs-9653887","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}