Comparison of Ultrasound Visibility and Retrieval Success of Two Ultrasound-Visible Clips in Targeted Axillary Dissection After Neoadjuvant Chemotherapy

Comparison of Ultrasound Visibility and Retrieval Success of Two Ultrasound-Visible Clips in Targeted Axillary Dissection After Neoadjuvant Chemotherapy | 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 Comparison of Ultrasound Visibility and Retrieval Success of Two Ultrasound-Visible Clips in Targeted Axillary Dissection After Neoadjuvant Chemotherapy Naomi Sakamoto, Hiroki Matsui, Eisuke Fukuma This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8962245/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 5 You are reading this latest preprint version Abstract Background Targeted axillary dissection (TAD) is a less invasive alternative to axillary lymph node dissection (ALND) for patients with clinically node-positive breast cancer who convert to node-negative status after neoadjuvant chemotherapy (NAC). However, the effect of preoperative ultrasound visibility of different clip types on TAD outcomes remains unclear. Methods We conducted a single-center retrospective cohort study of patients with biopsy-proven axillary node-positive breast cancer who underwent NAC followed by TAD between August 2017 and December 2024. Two ultrasound-visible clips, the UltraCor™ Twirl™ (Twirl) and HydroMARK™, were evaluated. Outcomes included ultrasound visibility, clipped node retrieval success, localization techniques, and false-negative rate (FNR). Results Twenty-nine patients were included (Twirl, n = 15; HydroMARK, n = 14). Ultrasound visibility was higher with Twirl than with HydroMARK (86.7% versus 64.3%; p = 0.330). All Twirl cases underwent combined wire and dye-guided localization, whereas HydroMARK cases used multiple localization techniques. Retrieval success reached 100% with Twirl and 78.6% with HydroMARK (p = 0.199). When clips were visible on ultrasound, retrieval rates were high for both clips at 100% for Twirl and 88.9% for HydroMARK (p = 0.850). When clips were not clearly visible, Twirl maintained 100% retrieval compared with 60.0% for HydroMARK (p = 0.895). Among patients who underwent scheduled ALND, the FNR of TAD was 0% (0/6). Conclusions Preoperative ultrasound visibility of the clip was associated with successful clip-based TAD. Twirl showed more consistent ultrasound visibility and retrieval success than HydroMARK, which suggests that Twirl may be a more reliable clip for routine clinical practice. breast cancer breast tissue marker ultrasound visibility targeted axillary dissection wire localization Figures Figure 1 Figure 2 Introduction Although axillary lymph node dissection (ALND) has historically been the standard approach in breast surgery, it carries substantial risks, including lymphedema, shoulder dysfunction, and sensory disturbance, and is associated with reduced quality of life [ 1 , 2 ]. For patients with clinically node-negative disease, sentinel lymph node biopsy (SLNB) has largely replaced ALND because it provides comparable overall survival, disease-free survival, and regional control [ 3 ]. However, optimal axillary management after neoadjuvant chemotherapy (NAC) remains under investigation, particularly for patients who are clinically node-positive before NAC. In this group, ALND is often still performed even when nodal status converts to clinically node-negative after NAC, because SLNB has shown false-negative rates (FNRs) exceeding 10% [ 4 – 6 ]. Targeted axillary dissection (TAD), which involves marking the metastatic node before NAC and removing the marked node together with the sentinel lymph node after NAC, has been introduced to address this limitation. Reported FNRs for TAD range from 2% to 7% [ 7 – 9 ], supporting omission of ALND when nodal pathologic complete response (pCR) is confirmed [ 10 ]. In addition, emerging data from the NSABP B-51/RTOG 1304 trial suggest that regional nodal irradiation can also be safely omitted in patients who achieve nodal pCR after NAC [ 11 ]. Therefore, accurate axillary assessment after NAC has become increasingly important. Various techniques for TAD have been reported, with retrieval rates of marked nodes ranging from 61% to 100% [ 12 – 21 ]. This variability likely reflects differences in the type of definitive marker used, such as radioisotopes [ 13 ], magnetic markers [ 14 ], radiofrequency identification tags [ 15 ], electromagnetic reflectors [ 16 ], visual markers such as black ink [ 17 ], and metallic clips [ 18 , 19 ]. It also reflects differences in the timing of definitive marker placement, either before NAC as a one-step approach or after NAC as a two-step approach in which the definitive marker is placed adjacent to a clip inserted before NAC, as well as differences in localization methods, including wires [ 18 , 19 ], marker-specific detection probes [ 13 – 16 ], direct visualization of black ink [ 17 ], and intraoperative ultrasound [ 20 , 21 ]. However, no consensus has been established regarding the optimal combination of marker type, timing, and localization method. Among the various TAD techniques, metallic clips are widely used in clinical practice. However, ultrasound visibility of these clips after NAC has not been systematically evaluated or consistently reported. One reason is that clipped nodes that are not detectable on imaging are often excluded or not described in study results [ 12 ]. In a systematic review by de Wild et al., identification rates of clipped nodes on imaging, most commonly ultrasound, were reported in only 23 of 41 studies and ranged from 49% to 100% [ 12 ]. Only a limited number of studies have evaluated ultrasound visibility across different clip designs. Reported visibility rates for the HydroMARK™ clip range from 22.2% (2/9) [ 22 ] to 83.3% (25/30) [ 19 ], whereas rates for the UltraCor™ Twirl™ (Twirl) clip range from 86.7% (26/30) [ 23 ] to 100% (233/233) [ 24 ]. However, direct clinical comparisons focused on ultrasound-visible clips in real-world TAD settings remain scarce. Therefore, this study aimed to describe the characteristics of patients who underwent TAD using two widely used ultrasound-visible clips in Japan, HydroMARK and Twirl, with a focus on preoperative ultrasound visibility, clipped node retrieval rates, localization techniques, and FNRs. Additional analyses compared retrieval success between cases in which the clip was visible on ultrasound and those in which it was not. These analyses also evaluated supplemental localization methods used when the clip was not clearly visible on preoperative ultrasound and documented technical issues encountered during localization procedures. Patients and Methods Study design This single-center retrospective cohort study compared two types of ultrasound-visible clips, Twirl (Medicon Co., Ltd., Osaka, Japan) and HydroMARK (Devicor Medical Japan, Tokyo, Japan), and evaluated associated clinicopathologic findings in patients with axillary lymph node-positive breast cancer who underwent surgery after NAC. Setting The study took place at Kameda Medical Hospital in Japan between August 2017 and December 2024. The institutional workflow included baseline imaging with mammography, ultrasound, magnetic resonance imaging, and positron emission tomography/computed tomography; axillary re-evaluation with targeted ultrasound and fine-needle aspiration of suspicious nodes; placement of an ultrasound-visible clip in cytology-proven metastatic nodes; NAC using anthracycline- and/or taxane-based regimens, with anti-human epidermal growth factor receptor 2 (HER2) therapy added for HER2-overexpressing tumors; response assessment of both nodal and primary tumors according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) [ 25 ]; preoperative skin marking; TAD; and pathologic evaluation. Participants The study included patients who underwent NAC followed by surgery with TAD between August 2017 and December 2024. Eligible patients were women aged 18 years or older with clinical T1–3/N1–2a breast cancer and cytology-confirmed metastatic axillary nodes. Patients with progressive disease on post-NAC axillary assessment based on RECIST 1.1 criteria were excluded because they were not considered candidates for TAD and instead underwent ALND. Exposures The exposure of interest was the clip type used for TAD: HydroMARK versus Twirl. Outcomes The primary outcomes were preoperative ultrasound visibility of the clip and successful intraoperative retrieval of the clipped lymph node. Secondary outcomes included the FNR of TAD in patients who subsequently underwent ALND and the localization techniques used. Other variables Collected variables included patient age, clinical stage and nodal status, histologic type, and hormone receptor and HER2 status. Hormone receptor positivity was defined as an Allred score of 3 or higher. HER2 positivity was defined as immunohistochemistry 3 + or immunohistochemistry 2 + with fluorescence in situ hybridization amplification. Additional variables included the number of metastatic nodes on imaging, clinical response to NAC, type of surgery, number of clipped nodes, number of nodes removed by TAD and/or ALND, identification of the sentinel lymph node tracer within the clipped node, pathologic findings, and calendar period of clip placement. Procedural details for clipped node localization were also recorded, including supplemental approaches used when the clip was not clearly visible on preoperative ultrasound and any technical issues encountered during localization. Data sources and measurement All data were obtained from the electronic medical record. Ultrasound examinations used commercially available high-frequency linear-array transducers from multiple vendors according to routine institutional practice. Two reviewers independently assessed preoperative ultrasound clip visibility: a breast sonographer and a breast surgeon, each with more than 10 years of experience. Disagreements were resolved by consensus. Clip visibility was graded on a four-level scale: Excellent, the entire clip clearly visualized and distinguishable from surrounding axillary tissue; Good, part of the clip visualized and distinguishable; Fair, a structure suggestive of the clip seen with low confidence; and Poor, clip not identified. For analysis, Excellent and Good were classified as visible (Fig. 1 ), and Fair and Poor as not clearly visible (Fig. 2 ). Successful retrieval was defined as intraoperative confirmation of the clip within excised nodal tissue using ultrasound and/or specimen radiography. The FNR of TAD was calculated in patients who subsequently underwent ALND and was defined as the proportion with negative TAD but pathologically positive nodes at ALND. Axillary pCR was defined as ypN0, counting isolated tumor cells as node-negative ypN0(i+) and breast pCR as ypT0/is. Baseline axillary assessment and clip placement Ultrasound criteria for fine-needle aspiration of suspicious nodes included focal or diffuse cortical thickening greater than 3 mm, loss of the fatty hilum, or round or irregular morphology. When more than two nodes appeared suspicious, two nodes or the most abnormal nodes were sampled. Clips were inserted into cytology-proven metastatic nodes, either two nodes or the largest node when multiple nodes were positive. Preoperative ultrasound was repeated every 2–3 months to evaluate clip visibility or displacement and to monitor response to NAC. Localization and TAD procedures During surgery, ultrasound-guided localization used one or a combination of the following techniques: fluorescence-guided localization, wire localization, or dye-guided localization. For fluorescence-guided localization, indocyanine green at a volume of 0.1–0.2 mL was injected into the clipped node and visualized with a Photodynamic Eye™ camera (Hamamatsu Photonics, Shizuoka, Japan). Wire localization used a reverse-wire set consisting of a 21-gauge × 90-mm introducer needle and a 0.25-mm × 230-mm reverse wire (Hakko Co., Nagano, Japan). Dye-guided localization used methyl violet or pyoktanin at a volume of 0.1–0.2 mL. When wire localization was combined with fluorescence- or dye-guided localization, indocyanine green or dye was injected through the wire introducer to avoid additional puncture. SLNB used subareolar injection of technetium-99m on the day before surgery and patent blue dye on the day of surgery after induction of general anesthesia. TAD included resection of the clipped node, followed by SLNB and biopsy of any palpable nodes. When the clip was not clearly visible on preoperative ultrasound, supplemental localization approaches were applied. Surgeons reviewed insertion-time computed tomography and ultrasound images to identify the most plausible hyperechoic focus corresponding to the clipped node. When preoperative ultrasound findings remained inconclusive, intraoperative fluoroscopy was performed at the discretion of the surgeon after induction of anesthesia, followed by repeat targeted ultrasound. Breast surgeons with more than 10 years of experience in interventional procedures and breast surgery performed fine-needle aspiration, clip placement, preoperative clip localization, and TAD. Pathologic evaluation Series 1, from August 2017 to January 2020, included patients who underwent TAD followed by planned ALND. Series 2, from February 2020 to December 2024, used intraoperative frozen section analysis for TAD nodes. ALND was performed when clipped node retrieval failed or when frozen section results were positive or suspicious. ALND was omitted when frozen section results were negative, according to an intraoperative frozen section-driven selective approach. All TAD nodes underwent re-evaluation on permanent sections. Clipped nodes were serially sectioned at 2-mm intervals, whereas other nodes were sectioned once per node. When clipped node retrieval during TAD was unsuccessful, the clipped node was identified and removed from the ALND specimen using ultrasound or specimen radiography. Study size The study included all eligible patients with biopsy-proven node-positive breast cancer who received NAC followed by TAD during the study period and provided informed consent to participate. No a priori sample size calculation was performed. Quantitative variables and statistical methods Continuous variables were summarized as mean ± standard deviation, and categorical variables as counts and percentages. Between-group comparisons used the Student’s t-test for continuous variables and the chi-square test for categorical variables. Additional analysis and case description Retrieval success rates of clipped lymph nodes were compared between cases in which the clip was classified as visible and those in which it was classified as not clearly visible on preoperative ultrasound. Ethics This study was approved by the Institutional Review Board of our hospital (IRB No. 24–158). Patient consent was obtained using an opt-out method in accordance with institutional policy. Results Participants During the study period, 29 eligible patients who consented to participate in the study were included in the analysis, with 15 in the Twirl group and 14 in the HydroMARK group. No patients met exclusion criteria after enrollment. Descriptive data The two groups showed no significant differences in age, clinical stage, histologic type, hormone receptor and HER2 status, number of suspicious lymph nodes, or nodal and primary tumor response to NAC based on RECIST 1.1 assessment (Table 1 ). Primary outcome data were available for all 29 patients. No clip displacement was observed on the initial preoperative ultrasound assessment. Evaluation of later displacement remained limited because nodal shrinkage after NAC reduced detectability. Table 1 Baseline clinicopathological characteristics Age, mean (SD) Twirl (n = 15) HydroMARK (n = 14) p value 57.6 (14.39) 50.9 (8.77) 0.147 Clinical T stage (cT), n (%) 0.625 cT1 3 (20.0) 5 (35.7) cT2 11 (73.3) 8 (57.1) cT3 1 (6.7) 1 (7.1) Clinical stage (cStage), n (%) 0.358 IIA 2 (13.3) 5 (35.7) IIB 12 (80.0) 8 (57.1) IIIA 1 (6.7) 1 (7.1) Histological type, n (%) 0.366 Invasive ductal carcinoma 12 (80.0) 13 (92.9) Invasive lobular carcinoma 1 (6.7) 1 (7.1) Invasive micropapillary carcinoma 2 (13.3) 0 (0.0) HR/HER2 status, n (%) 0.907 HR+/HER2− 5 (33.3) 5 (35.7) HR+/HER2+ 4 (26.7) 5 (35.7) HR−/HER2+ 2 (13.3) 1 (7.1) HR−/HER2− 4 (26.7) 3 (21.4) Number of metastatic nodes on imaging, n (%) 0.326 1 5 (33.3) 5 (35.7) ≤ 2 5 (33.3) 8 (57.1) 3 1 (6.7) 0 (0.0) ≥ 4 4 (26.7) 1 (7.1) Nodal response, n (%) 0.206 Complete response 10 (66.7) 13 (92.9) Partial response 4 (26.7) 1 (7.1) Stable disease 1 (6.7) 0 (0.0) Progressive disease 0 (0.0) 0 (0.0) Primary tumor response, n (%) 0.809 Complete response 6 (40.0) 4 (28.6) Partial response 8 (53.3) 9 (64.3) Stable disease 1 (6.7) 1 (7.1) Progressive disease 0 (0.0) 0 (0.0) HR , hormone receptor; HER2 , human epidermal growth factor receptor 2 The groups also showed no significant differences in type of breast surgery, number of clipped lymph nodes, or rates of nodal and breast pCR (Table 2 ). The mean number of nodes removed by TAD was 3.93 ± 1.33 in the Twirl group and 4.64 ± 1.39 in the HydroMARK group (p = 0.173). The mean number removed by ALND was 9.90 ± 5.59 and 11.36 ± 4.36, respectively (p = 0.480). Sentinel lymph node tracer identification within the clipped node occurred in 60.0% and 69.2% of cases, respectively (p = 0.910). The rate of ALND differed significantly between groups (p < 0.001). Table 2 Clinicopathological characteristics and TAD outcomes according to clip type Type of breast surgery, n (%) Twirl (n = 15) HydroMARK (n = 14) p value 1.000 Mastectomy 9 (60.0) 9 (64.3) Breast-conserving surgery 6 (40.0) 5 (35.7) Axillary surgical procedure, n (%) < 0.001 TAD with planned ALND 0 (0.0) 13 (92.9) TAD only 5 (33.3) 0 (0.0) IFS-driven selective ALND 10 (66.7) 1 (7.1) Number of clipped nodes, n (%) 0.285 One 14 (93.3) 10 (71.4) Two 1 (6.7) 4 (28.6) US visibility of the clipped node, n (%) 0.330 Visible 13 (86.7) 9 (64.3) Not clearly visible 2 (13.3) 5 (35.7) Localization methods, n (%) 0.083 Fluorescence 0 (0.0) 2 (14.3) Wire + fluorescence 0 (0.0) 2 (14.3) Wire + dye 15 (100.0) 10 (71.4) Clipped node retrieval, n (%) 0.199 Success 15 (100.0) 11 (78.6) Failure 0 (0.0) 3 (21.4) Average number of lymph nodes removed, mean (SD) TAD total 3.93 (1.33) 4.64 (1.39) 0.173 Clipped node 1.07 (0.26) 1.29 (0.47) 0.127 SLN 2.60 (1.72) 3.14 (1.75) 0.407 Palpable node 0.40 (0.83) 0.14 (0.36) 0.296 ALND 9.90 (5.59) 11.36 (4.36) 0.480 SLN tracer in the clipped node, n (%) 9 (60.0) 10 (69.2) 0.910 Pathological results of TAD, n (%) IFS not performed 0 (0.0) 13 (92.9) < 0.001 IFS positive or suspicious 8 (53.3) 1 (7.1) IFS negative 7 (46.7) 0 (0.0) Permanent pathology positive 10 (66.7) 8 (57.1) 0.885 Permanent pathology negative 5 (33.3) 6 (42.9) Pathological response to NAC, n (%) Nodal pCR 5 (33.3) 6 (42.9) 0.885 Breast pCR 4 (26.7) 6 (42.9) 0.224 US, ultrasound; TAD, targeted axillary dissection; ALND, axillary lymph node dissection; IFS, intraoperative frozen section; SLN, sentinel lymph node; NAC, neoadjuvant chemotherapy; pCR, pathological complete response. HydroMARK clips were used mainly during Series 1, when scheduled ALND was routine. In contrast, all Twirl clips were used during Series 2, when an intraoperative frozen section-driven selective ALND strategy was applied. Among 16 intraoperative frozen section cases, eight positive and one suspicious case proceeded to intraoperative ALND. Two of seven cases with negative frozen section results showed metastasis in the TAD node on permanent sections. Preoperative ultrasound visibility The proportion of patients with clips visible on preoperative ultrasound was higher in the Twirl group than in the HydroMARK group, at 86.7% (13/15) versus 64.3% (9/14), respectively. However, this difference did not reach statistical significance (p = 0.330; Table 2 ). Clipped node retrieval success The Twirl clip showed a higher clipped node retrieval success rate than the HydroMARK clip, with successful retrieval in 100% (15/15) versus 78.6% (11/14), respectively. However, this difference did not reach statistical significance (p = 0.199; Table 2 ). False-negative rate Scheduled ALND was performed only in the HydroMARK group. In this subgroup, the FNR of TAD was 0% (0/6). Localization and supplemental localization approaches Localization modalities differed between groups (p = 0.083; Table 2 ). All Twirl cases underwent combined wire and dye-guided localization (15/15). HydroMARK cases used fluorescence-guided localization alone (2/14), fluorescence-guided plus wire localization (2/14), or dye-guided plus wire localization (10/14). Supplemental localization approaches were applied in seven cases in which the clip was not clearly visible on preoperative ultrasound, including two Twirl cases and five HydroMARK cases. Targeting based on reference to insertion-time computed tomography and ultrasound images to identify the most plausible hyperechoic focus was performed in all seven cases. In the Twirl group, fluoroscopy was attempted in two cases, successfully identified the clip, and enabled subsequent ultrasound targeting. In the HydroMARK group, fluoroscopy was attempted in two cases but did not depict the clip. Technical issues during localization procedures Among 27 cases that used wire localization, three (11%) had wire withdrawal or wire cutting. In two of these cases (66.7%), surgeons achieved successful clipped node retrieval using intraoperative ultrasound and dye-guided visualization. No allergic reactions to dye or uncontrolled bleeding occurred. Retrieval success according to preoperative ultrasound visibility Retrieval success was higher when the clip was visible on preoperative ultrasound than when it was not clearly visible, at 95.4% (21/22) versus 71.4% (5/7), respectively, although the difference did not reach statistical significance (p = 0.269). Twirl showed consistently higher retrieval success than HydroMARK under both visibility conditions. When the clip was visible, retrieval success reached 100% (13/13) with Twirl and 88.9% (8/9) with HydroMARK (p = 0.850). When the clip was not clearly visible on preoperative ultrasound, Twirl achieved 100% retrieval success (2/2), whereas HydroMARK achieved 60.0% (3/5; p = 0.895). Discussion In this single-center retrospective cohort of patients who underwent TAD after NAC, clips were visible on preoperative ultrasound in 86.7% (13/15) of Twirl cases versus 64.3% (9/14) of HydroMARK cases (p = 0.330). Retrieval success reached 100% (15/15) with Twirl and 78.6% (11/14) with HydroMARK (p = 0.199). Although these outcomes favored the Twirl clip, the differences did not reach statistical significance. Several studies have reported high ultrasound visibility for the Twirl clip. Portnow et al. [ 26 ] found that Twirl achieved the highest visibility scores among several markers in animal tissue models. In clinical settings, Lim et al. [ 22 ] reported an ultrasound visibility rate of 92% (12/13) for Twirl. Lee et al. [ 24 ] reported persistent visibility on follow-up ultrasound in all Twirl cases, with 85.0% (198/233) well visualized with high confidence and 15.0% (35/233) moderately well visualized, and none poorly visualized. Kim et al. [ 23 ] also reported better ultrasound visibility for Twirl than for the UltraClip™ dual-trigger breast tissue marker (BARD®, Tempe, AZ, USA), at 86.7% (26/30) versus 72.4% (21/29), respectively (p = 0.209). In the present study, Twirl remained visible in 86.7% (13/15) of cases, showing a higher tendency toward ultrasound detectability than HydroMARK at 64.3% (9/14). Previous reports suggest that the larger profile and distinctive shape of the Twirl clip improve differentiation from surrounding axillary fat and fibrous tissue [ 22 , 23 ]. In contrast, reported ultrasound visibility rates for HydroMARK range from 22.2% (2/9) to 83.3% (25/30) in TAD settings [ 19 , 22 ]. Hydrogel resorption over time and chemotherapy-associated nodal shrinkage may reduce ultrasound detectability [ 18 , 21 , 23 ]. Regarding clipped node retrieval, Twirl showed a higher success rate than HydroMARK at 100% versus 78.6%, although the difference did not reach statistical significance (p = 0.199). When the clip was visible on ultrasound, retrieval rates were high with both markers, at 88.9% (8/9) for HydroMARK and 100% (13/13) for Twirl. This pattern indicates that clip visibility on ultrasound supports high retrieval accuracy regardless of clip type, consistent with prior reports [ 20 , 22 , 23 , 27 ]. In the subgroup with clips not clearly visible on ultrasound, retrieval reached 60.0% (3/5) with HydroMARK and 100% (2/2) with Twirl. Twirl maintained high retrieval performance despite limited ultrasound visibility because supplemental localization methods remained effective. Intraoperative fluoroscopic detection followed by targeted ultrasound enabled reliable identification and removal of Twirl-marked nodes. HydroMARK did not show fluoroscopic visibility, likely related to its smaller metallic component, approximately 2 mm compared with about 4 mm for Twirl, which limited the effectiveness of backup localization strategies. Previous studies have described wire-related complications during TAD, including wire displacement and fracture [ 12 , 19 ]. Wire-related issues occurred in 11% (3/27) of cases in the present study. Even in these cases, combining intraoperative ultrasound with visualization of injected dye enabled successful clipped node retrieval in 66.7% (2/3). These findings suggest that a localization strategy that integrates dye injection and intraoperative ultrasound in addition to wire localization can preserve a high retrieval rate despite wire-related complications. In this study, the FNR of TAD was 0% (0/6) among HydroMARK cases that underwent scheduled ALND. Although the sample size was small, this result aligns with previously reported FNRs for TAD, which range from 2% to 7% [ 7 – 9 ], and supports the reliability of clip-guided TAD after NAC. Multiple TAD techniques have been described, but no direct head-to-head comparisons exist, and most centers choose an approach based on regulatory constraints, availability, cost, and workflow. Clip-based wire localization remains non-radioactive, low-cost, and widely adopted as a practical and accessible method. Prior studies that evaluated the individual clips examined here reported retrieval rates of 89.7% (26/29) to 100% (13/13) for Twirl [ 22 , 23 ] and 77.8% (7/9) to 96% (226/235) for HydroMARK [ 19 – 22 ]. The direct comparison in this study provides side-by-side clinical data for these two clips. Although differences did not reach statistical significance, the favorable trends observed with Twirl compared with HydroMARK may help guide clip selection in routine clinical practice. These findings suggest that Twirl may provide more consistent performance than HydroMARK for TAD in everyday clinical settings. This study has several limitations. First, the single-center retrospective design and small sample size of 29 patients limit statistical power and generalizability. Second, clip type varied by calendar period, with HydroMARK used earlier and Twirl used later, which introduces potential temporal confounding. The clip choice did not depend on patient characteristics, which likely reduced but did not eliminate this effect. In addition, the use of multiple localization methods in the HydroMARK group may have influenced comparisons between clips. Third, ultrasound-based assessment of clip visibility depends on equipment, imaging settings, and patient factors such as body habitus and axillary depth, which creates inherent variability in ultrasound-based evaluations. Fourth, long-term follow-up data, including axillary recurrence and survival outcomes, were not available, and future studies with longer follow-up are needed. These findings indicate that, within a non-radioactive, clip-based TAD workflow, Twirl provides more consistent ultrasound visibility and retrieval success than HydroMARK. Clip selection should also consider institutional experience and device availability, and larger multicenter studies should confirm these results. Declarations Compliance with Ethical Standards Conflict of interest The authors declare no conflicts of interest. Ethical approval All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This retrospective study was approved by the Institutional Review Board of our hospital (IRB No. 24-158). Informed consent Patient consent was obtained using an opt-out method in accordance with institutional policy. Funding This research received no external funding. Acknowledgments The authors thank the ultrasound technologists, radiology staff, and operating room staff for their technical support, and colleagues who assisted with administrative aspects of the study. Data Availability Statement The datasets generated and/or analyzed during this study are not publicly available because of privacy and ethical restrictions but are available from the corresponding author on reasonable request. Author Contributions All authors made substantial contributions to the work reported, including the conception and design of the study, data acquisition, and analysis and interpretation of data. All authors participated in drafting the article or revising it critically for important intellectual content, approved the final version to be published, agreed on the journal to which the article has been submitted, and agree to be accountable for all aspects of the work. Specifically, N.S. and H.M. contributed to the conceptualization and study design. H.M. performed the formal data analysis. N.S. and E.F. collected the data. E.F. provided supervision. All authors contributed to manuscript drafting and revision. All authors have read and approved the final manuscript. References Mansel RE, Fallowfield L, Kissin M, Goyal A, Newcombe RG, Dixon JM, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. 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Systematic review of targeted axillary dissection in node-positive breast cancer treated with neoadjuvant systemic therapy: variation in type of marker and timing of placement. Br J Surg. 2024;111:znae071. Simons JM, van Nijnatten TJA, van der Pol CC, van Diest PJ, Jager A, van Klaveren D, et al. Diagnostic accuracy of radioactive iodine seed placement in the axilla with sentinel lymph node biopsy after neoadjuvant chemotherapy in node-positive breast cancer. JAMA Surg. 2022;157:991–9. Barry PA, Harborough K, Sinnett V, Heeney A, St John ER, Gagliardi T, et al. Clinical utility of axillary nodal markers in breast cancer. Eur J Surg Oncol. 2023;49:709–15. Laws A, Dillon K, Kelly BN, Kantor O, Hughes KS, Gadd MA, et al. Node-positive patients treated with neoadjuvant chemotherapy can be spared axillary lymph node dissection with wireless non-radioactive localizers. Ann Surg Oncol. 2020;27:4819–27. Weinfurtner RJ, Leon A, Calvert A, Lee MC. Ultrasound-guided radar reflector localization of axillary lymph nodes facilitates targeted axillary dissection. Clin Imaging. 2022;90:19–25. de Boniface J, Frisell J, Kuhn T, Wiklander-Brakenhielm I, Dembrower K, Nyman P, et al. False-negative rate in the extended prospective TATTOO trial evaluating targeted axillary dissection by carbon tattooing in clinically node-positive breast cancer patients receiving neoadjuvant systemic therapy. Breast Cancer Res Treat. 2022;193:589–95. Kuemmel S, Heil J, Rueland A, Seiberling C, Harrach H, Schindowski D, et al. A prospective, multicenter registry study to evaluate the clinical feasibility of targeted axillary dissection (TAD) in node-positive breast cancer patients. Ann Surg. 2022;276:e553–62. Hartmann S, Reimer T, Gerber B, Stubert J, Stengel B, Stachs A. Wire localization of clip-marked axillary lymph nodes in breast cancer patients treated with primary systemic therapy. Eur J Surg Oncol. 2018;44:1307–11. Pinto CS, Peleteiro B, Pinto CA, Osório F, Costa S, Magalhães A, et al. Initial experience with targeted axillary dissection after neoadjuvant therapy in breast cancer patients. Breast Cancer. 2022;29:709–19. Siso C, Esgueva A, Rivero J, Morales C, Miranda I, Peg V, et al. Feasibility and safety of targeted axillary dissection guided by intraoperative ultrasound after neoadjuvant treatment. Eur J Surg Oncol. 2023;49:106938. Lim GH, Teo SY, Gudi M, Ng RP, Pang J, Tan YS, et al. Initial results of a novel technique of clipped node localization in breast cancer patients postneoadjuvant chemotherapy: Skin Mark clipped Axillary nodes Removal Technique (SMART trial). Cancer Med. 2020;9:1978–85. Kim KE, Ko EY, Han BK, Ko ES, Choi JS, Kim H, et al. Comparison of the ultrasound visibility of tissue markers in metastatic lymph nodes after neoadjuvant chemotherapy in patients with breast cancer. Diagnostics (Basel). 2022;12:2424. Lee SYS, Win T, Lee YS, Teo SY. Sonographic visibility of the UltraCor™ Twirl™ tissue marker. Breast Dis. 2022;41(1):535–43. 10.3233/BD-210078 . Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47. Portnow LH, Ellie Kwak E, Senapati GM, Kwait DC, Denison CM, Giess CS, et al. Ultrasound visibility of select breast biopsy markers for targeted axillary node localization following neoadjuvant treatment: simulation using animal tissue models. Breast Cancer Res Treat. 2020;184:185–92. Banys-Paluchowski M, Gasparri ML, de Boniface J, Gentilini O, Stickeler E, Hartmann S, AXSANA Study Group, et al. Surgical management of the axilla in clinically node-positive breast cancer patients converting to clinical node negativity through neoadjuvant chemotherapy: current status, knowledge gaps, and rationale for the EUBREAST-03 AXSANA study. Cancers (Basel). 2021;13:1565. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Major Revision 22 Apr, 2026 Reviewers agreed at journal 30 Mar, 2026 Reviewers invited by journal 30 Mar, 2026 Editor assigned by journal 25 Feb, 2026 First submitted to journal 24 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8962245","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":614584003,"identity":"1e2c37c1-a735-41d3-b5af-1cf302b9902d","order_by":0,"name":"Naomi Sakamoto","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIie3RPQrCMBiA4S84uBRck0G9QlRQC0XxJg2BTB7BISC4uhYqegXdHBMKdRG7BnQoeAG9gVVEN1M3wTzbB3nJH4Dj/KSqzjEEAPg5I2lNPE4xiK8S6BaLk3di1aspgf1txubxVOcwCaASW7bxI5b0yf7IolPKKaQC0EJ9TqgBZsjsyKQZdzGSCaAotCSZopjMDmxVPlFhu0gUW5dPzJhTsuedjRGchqnw7HfJdvpMtoP60nCdXyZBo2V7sbsKkTB6rCuO5LUiewHoKmH4mpql/9RxHOdf3ABflkj+aWJyygAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-5286-5116","institution":"Kameda Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Naomi","middleName":"","lastName":"Sakamoto","suffix":""},{"id":614584004,"identity":"0bc3937e-b674-451a-988d-290f7616acdd","order_by":1,"name":"Hiroki Matsui","email":"","orcid":"","institution":"University of Tokyo: Tokyo Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Hiroki","middleName":"","lastName":"Matsui","suffix":""},{"id":614584005,"identity":"32c7c08c-371a-4cb7-8598-4e4465c23f93","order_by":2,"name":"Eisuke Fukuma","email":"","orcid":"","institution":"Kameda Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Eisuke","middleName":"","lastName":"Fukuma","suffix":""}],"badges":[],"createdAt":"2026-02-25 02:36:59","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8962245/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8962245/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105886475,"identity":"8b36eb43-b93b-4663-82a9-826fa81a73ab","added_by":"auto","created_at":"2026-04-01 07:29:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":934119,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative preoperative ultrasound images of clips classified as “visible” after neoadjuvant chemotherapy.\u003c/p\u003e\n\u003cp\u003e(a) UltraCore™ Twirl™ clip with nearly the entire clip clearly visualized.\u003c/p\u003e\n\u003cp\u003e(b) UltraCore™ Twirl™ clip with partial visualization of the clip that remained clearly distinguishable from surrounding tissue.\u003c/p\u003e\n\u003cp\u003e(c) HydroMARK™ clip with both the metallic marker and the surrounding hydrogel component clearly visualized.\u003c/p\u003e\n\u003cp\u003e(d) HydroMARK™ clip with visualization of the metallic component, allowing clear differentiation from surrounding axillary tissue.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8962245/v1/27fa7aa988f0ffba12910d70.png"},{"id":105886476,"identity":"e7a5e767-ec4a-48d2-afc4-77d8fd3e2b43","added_by":"auto","created_at":"2026-04-01 07:29:39","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":496586,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative preoperative ultrasound images of clips classified as “not clearly visible” after neoadjuvant chemotherapy.\u003c/p\u003e\n\u003cp\u003e(a) UltraCore™ Twirl™ clip showing a structure suggestive of the clip with low confidence.\u003c/p\u003e\n\u003cp\u003e(b) HydroMARK™ clip that could not be confidently identified on ultrasound.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8962245/v1/4064850802b54a2040441696.png"},{"id":105886490,"identity":"6afb2ff2-e104-4681-809e-6452ec6426df","added_by":"auto","created_at":"2026-04-01 07:29:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2662557,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8962245/v1/3ebe4ea3-62a4-4b8d-a0fa-07eb7f1b163c.pdf"}],"financialInterests":"","formattedTitle":"Comparison of Ultrasound Visibility and Retrieval Success of Two Ultrasound-Visible Clips in Targeted Axillary Dissection After Neoadjuvant Chemotherapy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAlthough axillary lymph node dissection (ALND) has historically been the standard approach in breast surgery, it carries substantial risks, including lymphedema, shoulder dysfunction, and sensory disturbance, and is associated with reduced quality of life [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. For patients with clinically node-negative disease, sentinel lymph node biopsy (SLNB) has largely replaced ALND because it provides comparable overall survival, disease-free survival, and regional control [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, optimal axillary management after neoadjuvant chemotherapy (NAC) remains under investigation, particularly for patients who are clinically node-positive before NAC. In this group, ALND is often still performed even when nodal status converts to clinically node-negative after NAC, because SLNB has shown false-negative rates (FNRs) exceeding 10% [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTargeted axillary dissection (TAD), which involves marking the metastatic node before NAC and removing the marked node together with the sentinel lymph node after NAC, has been introduced to address this limitation. Reported FNRs for TAD range from 2% to 7% [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], supporting omission of ALND when nodal pathologic complete response (pCR) is confirmed [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In addition, emerging data from the NSABP B-51/RTOG 1304 trial suggest that regional nodal irradiation can also be safely omitted in patients who achieve nodal pCR after NAC [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Therefore, accurate axillary assessment after NAC has become increasingly important.\u003c/p\u003e \u003cp\u003eVarious techniques for TAD have been reported, with retrieval rates of marked nodes ranging from 61% to 100% [\u003cspan additionalcitationids=\"CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. This variability likely reflects differences in the type of definitive marker used, such as radioisotopes [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], magnetic markers [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], radiofrequency identification tags [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], electromagnetic reflectors [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], visual markers such as black ink [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], and metallic clips [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. It also reflects differences in the timing of definitive marker placement, either before NAC as a one-step approach or after NAC as a two-step approach in which the definitive marker is placed adjacent to a clip inserted before NAC, as well as differences in localization methods, including wires [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], marker-specific detection probes [\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], direct visualization of black ink [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], and intraoperative ultrasound [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, no consensus has been established regarding the optimal combination of marker type, timing, and localization method.\u003c/p\u003e \u003cp\u003eAmong the various TAD techniques, metallic clips are widely used in clinical practice. However, ultrasound visibility of these clips after NAC has not been systematically evaluated or consistently reported. One reason is that clipped nodes that are not detectable on imaging are often excluded or not described in study results [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In a systematic review by de Wild et al., identification rates of clipped nodes on imaging, most commonly ultrasound, were reported in only 23 of 41 studies and ranged from 49% to 100% [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Only a limited number of studies have evaluated ultrasound visibility across different clip designs. Reported visibility rates for the HydroMARK\u0026trade; clip range from 22.2% (2/9) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] to 83.3% (25/30) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], whereas rates for the UltraCor\u0026trade; Twirl\u0026trade; (Twirl) clip range from 86.7% (26/30) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] to 100% (233/233) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. However, direct clinical comparisons focused on ultrasound-visible clips in real-world TAD settings remain scarce.\u003c/p\u003e \u003cp\u003eTherefore, this study aimed to describe the characteristics of patients who underwent TAD using two widely used ultrasound-visible clips in Japan, HydroMARK and Twirl, with a focus on preoperative ultrasound visibility, clipped node retrieval rates, localization techniques, and FNRs. Additional analyses compared retrieval success between cases in which the clip was visible on ultrasound and those in which it was not. These analyses also evaluated supplemental localization methods used when the clip was not clearly visible on preoperative ultrasound and documented technical issues encountered during localization procedures.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cp\u003eStudy design\u003c/p\u003e \u003cp\u003eThis single-center retrospective cohort study compared two types of ultrasound-visible clips, Twirl (Medicon Co., Ltd., Osaka, Japan) and HydroMARK (Devicor Medical Japan, Tokyo, Japan), and evaluated associated clinicopathologic findings in patients with axillary lymph node-positive breast cancer who underwent surgery after NAC.\u003c/p\u003e \u003cp\u003eSetting\u003c/p\u003e \u003cp\u003eThe study took place at Kameda Medical Hospital in Japan between August 2017 and December 2024. The institutional workflow included baseline imaging with mammography, ultrasound, magnetic resonance imaging, and positron emission tomography/computed tomography; axillary re-evaluation with targeted ultrasound and fine-needle aspiration of suspicious nodes; placement of an ultrasound-visible clip in cytology-proven metastatic nodes; NAC using anthracycline- and/or taxane-based regimens, with anti-human epidermal growth factor receptor 2 (HER2) therapy added for HER2-overexpressing tumors; response assessment of both nodal and primary tumors according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]; preoperative skin marking; TAD; and pathologic evaluation.\u003c/p\u003e \u003cp\u003eParticipants\u003c/p\u003e \u003cp\u003eThe study included patients who underwent NAC followed by surgery with TAD between August 2017 and December 2024. Eligible patients were women aged 18 years or older with clinical T1\u0026ndash;3/N1\u0026ndash;2a breast cancer and cytology-confirmed metastatic axillary nodes. Patients with progressive disease on post-NAC axillary assessment based on RECIST 1.1 criteria were excluded because they were not considered candidates for TAD and instead underwent ALND.\u003c/p\u003e \u003cp\u003eExposures\u003c/p\u003e \u003cp\u003eThe exposure of interest was the clip type used for TAD: HydroMARK versus Twirl.\u003c/p\u003e \u003cp\u003eOutcomes\u003c/p\u003e \u003cp\u003eThe primary outcomes were preoperative ultrasound visibility of the clip and successful intraoperative retrieval of the clipped lymph node. Secondary outcomes included the FNR of TAD in patients who subsequently underwent ALND and the localization techniques used.\u003c/p\u003e \u003cp\u003eOther variables\u003c/p\u003e \u003cp\u003eCollected variables included patient age, clinical stage and nodal status, histologic type, and hormone receptor and HER2 status. Hormone receptor positivity was defined as an Allred score of 3 or higher. HER2 positivity was defined as immunohistochemistry 3\u0026thinsp;+\u0026thinsp;or immunohistochemistry 2\u0026thinsp;+\u0026thinsp;with fluorescence in situ hybridization amplification. Additional variables included the number of metastatic nodes on imaging, clinical response to NAC, type of surgery, number of clipped nodes, number of nodes removed by TAD and/or ALND, identification of the sentinel lymph node tracer within the clipped node, pathologic findings, and calendar period of clip placement. Procedural details for clipped node localization were also recorded, including supplemental approaches used when the clip was not clearly visible on preoperative ultrasound and any technical issues encountered during localization.\u003c/p\u003e \u003cp\u003eData sources and measurement\u003c/p\u003e \u003cp\u003eAll data were obtained from the electronic medical record. Ultrasound examinations used commercially available high-frequency linear-array transducers from multiple vendors according to routine institutional practice. Two reviewers independently assessed preoperative ultrasound clip visibility: a breast sonographer and a breast surgeon, each with more than 10 years of experience. Disagreements were resolved by consensus. Clip visibility was graded on a four-level scale: Excellent, the entire clip clearly visualized and distinguishable from surrounding axillary tissue; Good, part of the clip visualized and distinguishable; Fair, a structure suggestive of the clip seen with low confidence; and Poor, clip not identified. For analysis, Excellent and Good were classified as visible (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), and Fair and Poor as not clearly visible (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSuccessful retrieval was defined as intraoperative confirmation of the clip within excised nodal tissue using ultrasound and/or specimen radiography. The FNR of TAD was calculated in patients who subsequently underwent ALND and was defined as the proportion with negative TAD but pathologically positive nodes at ALND. Axillary pCR was defined as ypN0, counting isolated tumor cells as node-negative ypN0(i+) and breast pCR as ypT0/is.\u003c/p\u003e \u003cp\u003eBaseline axillary assessment and clip placement\u003c/p\u003e \u003cp\u003eUltrasound criteria for fine-needle aspiration of suspicious nodes included focal or diffuse cortical thickening greater than 3 mm, loss of the fatty hilum, or round or irregular morphology. When more than two nodes appeared suspicious, two nodes or the most abnormal nodes were sampled. Clips were inserted into cytology-proven metastatic nodes, either two nodes or the largest node when multiple nodes were positive. Preoperative ultrasound was repeated every 2\u0026ndash;3 months to evaluate clip visibility or displacement and to monitor response to NAC.\u003c/p\u003e \u003cp\u003eLocalization and TAD procedures\u003c/p\u003e \u003cp\u003eDuring surgery, ultrasound-guided localization used one or a combination of the following techniques: fluorescence-guided localization, wire localization, or dye-guided localization. For fluorescence-guided localization, indocyanine green at a volume of 0.1\u0026ndash;0.2 mL was injected into the clipped node and visualized with a Photodynamic Eye\u0026trade; camera (Hamamatsu Photonics, Shizuoka, Japan). Wire localization used a reverse-wire set consisting of a 21-gauge \u0026times; 90-mm introducer needle and a 0.25-mm \u0026times; 230-mm reverse wire (Hakko Co., Nagano, Japan). Dye-guided localization used methyl violet or pyoktanin at a volume of 0.1\u0026ndash;0.2 mL. When wire localization was combined with fluorescence- or dye-guided localization, indocyanine green or dye was injected through the wire introducer to avoid additional puncture.\u003c/p\u003e \u003cp\u003eSLNB used subareolar injection of technetium-99m on the day before surgery and patent blue dye on the day of surgery after induction of general anesthesia. TAD included resection of the clipped node, followed by SLNB and biopsy of any palpable nodes.\u003c/p\u003e \u003cp\u003eWhen the clip was not clearly visible on preoperative ultrasound, supplemental localization approaches were applied. Surgeons reviewed insertion-time computed tomography and ultrasound images to identify the most plausible hyperechoic focus corresponding to the clipped node. When preoperative ultrasound findings remained inconclusive, intraoperative fluoroscopy was performed at the discretion of the surgeon after induction of anesthesia, followed by repeat targeted ultrasound.\u003c/p\u003e \u003cp\u003eBreast surgeons with more than 10 years of experience in interventional procedures and breast surgery performed fine-needle aspiration, clip placement, preoperative clip localization, and TAD.\u003c/p\u003e \u003cp\u003ePathologic evaluation\u003c/p\u003e \u003cp\u003eSeries 1, from August 2017 to January 2020, included patients who underwent TAD followed by planned ALND. Series 2, from February 2020 to December 2024, used intraoperative frozen section analysis for TAD nodes. ALND was performed when clipped node retrieval failed or when frozen section results were positive or suspicious. ALND was omitted when frozen section results were negative, according to an intraoperative frozen section-driven selective approach. All TAD nodes underwent re-evaluation on permanent sections. Clipped nodes were serially sectioned at 2-mm intervals, whereas other nodes were sectioned once per node. When clipped node retrieval during TAD was unsuccessful, the clipped node was identified and removed from the ALND specimen using ultrasound or specimen radiography.\u003c/p\u003e \u003cp\u003eStudy size\u003c/p\u003e \u003cp\u003e The study included all eligible patients with biopsy-proven node-positive breast cancer who received NAC followed by TAD during the study period and provided informed consent to participate. No a priori sample size calculation was performed.\u003c/p\u003e \u003cp\u003eQuantitative variables and statistical methods\u003c/p\u003e \u003cp\u003eContinuous variables were summarized as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, and categorical variables as counts and percentages. Between-group comparisons used the Student\u0026rsquo;s t-test for continuous variables and the chi-square test for categorical variables.\u003c/p\u003e \u003cp\u003eAdditional analysis and case description\u003c/p\u003e \u003cp\u003eRetrieval success rates of clipped lymph nodes were compared between cases in which the clip was classified as visible and those in which it was classified as not clearly visible on preoperative ultrasound.\u003c/p\u003e \u003cp\u003eEthics\u003c/p\u003e \u003cp\u003eThis study was approved by the Institutional Review Board of our hospital (IRB No. 24\u0026ndash;158). Patient consent was obtained using an opt-out method in accordance with institutional policy.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eParticipants\u003c/p\u003e \u003cp\u003eDuring the study period, 29 eligible patients who consented to participate in the study were included in the analysis, with 15 in the Twirl group and 14 in the HydroMARK group. No patients met exclusion criteria after enrollment.\u003c/p\u003e \u003cp\u003eDescriptive data\u003c/p\u003e \u003cp\u003eThe two groups showed no significant differences in age, clinical stage, histologic type, hormone receptor and HER2 status, number of suspicious lymph nodes, or nodal and primary tumor response to NAC based on RECIST 1.1 assessment (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Primary outcome data were available for all 29 patients. No clip displacement was observed on the initial preoperative ultrasound assessment. Evaluation of later displacement remained limited because nodal shrinkage after NAC reduced detectability.\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 clinicopathological characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eAge, mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTwirl (n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHydroMARK (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.6 (14.39)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.9 (8.77)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.147\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical T stage (cT), n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.625\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (73.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical stage (cStage), n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.358\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIIA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistological type, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.366\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvasive ductal carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (92.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvasive lobular carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvasive micropapillary carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHR/HER2 status, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.907\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR+/HER2\u0026minus;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR+/HER2+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR\u0026minus;/HER2+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR\u0026minus;/HER2\u0026minus;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of metastatic nodes on imaging, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.326\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNodal response, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.206\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplete response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (92.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePartial response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStable disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgressive disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrimary tumor response, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.809\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplete response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePartial response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (53.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (64.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStable disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgressive disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003eHR\u003c/b\u003e, hormone receptor; \u003cb\u003eHER2\u003c/b\u003e, human epidermal growth factor receptor 2\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe groups also showed no significant differences in type of breast surgery, number of clipped lymph nodes, or rates of nodal and breast pCR (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The mean number of nodes removed by TAD was 3.93\u0026thinsp;\u0026plusmn;\u0026thinsp;1.33 in the Twirl group and 4.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39 in the HydroMARK group (p\u0026thinsp;=\u0026thinsp;0.173). The mean number removed by ALND was 9.90\u0026thinsp;\u0026plusmn;\u0026thinsp;5.59 and 11.36\u0026thinsp;\u0026plusmn;\u0026thinsp;4.36, respectively (p\u0026thinsp;=\u0026thinsp;0.480). Sentinel lymph node tracer identification within the clipped node occurred in 60.0% and 69.2% of cases, respectively (p\u0026thinsp;=\u0026thinsp;0.910). The rate of ALND differed significantly between groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\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\u003eClinicopathological characteristics and TAD outcomes according to clip type\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eType of breast surgery, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTwirl (n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHydroMARK (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMastectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (64.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast-conserving surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAxillary surgical procedure, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAD with planned ALND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (92.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAD only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIFS-driven selective ALND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of clipped nodes, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.285\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOne\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (93.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (71.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTwo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUS visibility of the clipped node, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.330\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisible\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (86.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (64.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot clearly visible\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLocalization methods, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.083\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFluorescence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWire\u0026thinsp;+\u0026thinsp;fluorescence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWire\u0026thinsp;+\u0026thinsp;dye\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (71.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClipped node retrieval, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.199\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuccess\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (78.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFailure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAverage number of lymph nodes removed, mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAD total\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.93 (1.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.64 (1.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.173\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClipped node\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.07 (0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.29 (0.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.127\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSLN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.60 (1.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.14 (1.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.407\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePalpable node\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.40 (0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.14 (0.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.296\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.90 (5.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11.36 (4.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.480\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSLN tracer in the clipped node, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (69.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.910\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePathological results of TAD, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIFS not performed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (92.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIFS positive or suspicious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (53.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIFS negative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (46.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePermanent pathology positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.885\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePermanent pathology negative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePathological response to NAC, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNodal pCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.885\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast pCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.224\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eUS, ultrasound; TAD, targeted axillary dissection; ALND, axillary lymph node dissection; IFS, intraoperative frozen section; SLN, sentinel lymph node; NAC, neoadjuvant chemotherapy; pCR, pathological complete response.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eHydroMARK clips were used mainly during Series 1, when scheduled ALND was routine. In contrast, all Twirl clips were used during Series 2, when an intraoperative frozen section-driven selective ALND strategy was applied. Among 16 intraoperative frozen section cases, eight positive and one suspicious case proceeded to intraoperative ALND. Two of seven cases with negative frozen section results showed metastasis in the TAD node on permanent sections.\u003c/p\u003e \u003cp\u003ePreoperative ultrasound visibility\u003c/p\u003e \u003cp\u003eThe proportion of patients with clips visible on preoperative ultrasound was higher in the Twirl group than in the HydroMARK group, at 86.7% (13/15) versus 64.3% (9/14), respectively. However, this difference did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.330; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eClipped node retrieval success\u003c/p\u003e \u003cp\u003eThe Twirl clip showed a higher clipped node retrieval success rate than the HydroMARK clip, with successful retrieval in 100% (15/15) versus 78.6% (11/14), respectively. However, this difference did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.199; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFalse-negative rate\u003c/p\u003e \u003cp\u003eScheduled ALND was performed only in the HydroMARK group. In this subgroup, the FNR of TAD was 0% (0/6).\u003c/p\u003e \u003cp\u003eLocalization and supplemental localization approaches\u003c/p\u003e \u003cp\u003eLocalization modalities differed between groups (p\u0026thinsp;=\u0026thinsp;0.083; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). All Twirl cases underwent combined wire and dye-guided localization (15/15). HydroMARK cases used fluorescence-guided localization alone (2/14), fluorescence-guided plus wire localization (2/14), or dye-guided plus wire localization (10/14).\u003c/p\u003e \u003cp\u003eSupplemental localization approaches were applied in seven cases in which the clip was not clearly visible on preoperative ultrasound, including two Twirl cases and five HydroMARK cases. Targeting based on reference to insertion-time computed tomography and ultrasound images to identify the most plausible hyperechoic focus was performed in all seven cases. In the Twirl group, fluoroscopy was attempted in two cases, successfully identified the clip, and enabled subsequent ultrasound targeting. In the HydroMARK group, fluoroscopy was attempted in two cases but did not depict the clip.\u003c/p\u003e \u003cp\u003eTechnical issues during localization procedures\u003c/p\u003e \u003cp\u003eAmong 27 cases that used wire localization, three (11%) had wire withdrawal or wire cutting. In two of these cases (66.7%), surgeons achieved successful clipped node retrieval using intraoperative ultrasound and dye-guided visualization. No allergic reactions to dye or uncontrolled bleeding occurred.\u003c/p\u003e \u003cp\u003eRetrieval success according to preoperative ultrasound visibility\u003c/p\u003e \u003cp\u003eRetrieval success was higher when the clip was visible on preoperative ultrasound than when it was not clearly visible, at 95.4% (21/22) versus 71.4% (5/7), respectively, although the difference did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.269). Twirl showed consistently higher retrieval success than HydroMARK under both visibility conditions. When the clip was visible, retrieval success reached 100% (13/13) with Twirl and 88.9% (8/9) with HydroMARK (p\u0026thinsp;=\u0026thinsp;0.850). When the clip was not clearly visible on preoperative ultrasound, Twirl achieved 100% retrieval success (2/2), whereas HydroMARK achieved 60.0% (3/5; p\u0026thinsp;=\u0026thinsp;0.895).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this single-center retrospective cohort of patients who underwent TAD after NAC, clips were visible on preoperative ultrasound in 86.7% (13/15) of Twirl cases versus 64.3% (9/14) of HydroMARK cases (p\u0026thinsp;=\u0026thinsp;0.330). Retrieval success reached 100% (15/15) with Twirl and 78.6% (11/14) with HydroMARK (p\u0026thinsp;=\u0026thinsp;0.199). Although these outcomes favored the Twirl clip, the differences did not reach statistical significance.\u003c/p\u003e \u003cp\u003eSeveral studies have reported high ultrasound visibility for the Twirl clip. Portnow et al. [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] found that Twirl achieved the highest visibility scores among several markers in animal tissue models. In clinical settings, Lim et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] reported an ultrasound visibility rate of 92% (12/13) for Twirl. Lee et al. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] reported persistent visibility on follow-up ultrasound in all Twirl cases, with 85.0% (198/233) well visualized with high confidence and 15.0% (35/233) moderately well visualized, and none poorly visualized. Kim et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] also reported better ultrasound visibility for Twirl than for the UltraClip\u0026trade; dual-trigger breast tissue marker (BARD\u0026reg;, Tempe, AZ, USA), at 86.7% (26/30) versus 72.4% (21/29), respectively (p\u0026thinsp;=\u0026thinsp;0.209). In the present study, Twirl remained visible in 86.7% (13/15) of cases, showing a higher tendency toward ultrasound detectability than HydroMARK at 64.3% (9/14). Previous reports suggest that the larger profile and distinctive shape of the Twirl clip improve differentiation from surrounding axillary fat and fibrous tissue [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In contrast, reported ultrasound visibility rates for HydroMARK range from 22.2% (2/9) to 83.3% (25/30) in TAD settings [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Hydrogel resorption over time and chemotherapy-associated nodal shrinkage may reduce ultrasound detectability [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRegarding clipped node retrieval, Twirl showed a higher success rate than HydroMARK at 100% versus 78.6%, although the difference did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.199). When the clip was visible on ultrasound, retrieval rates were high with both markers, at 88.9% (8/9) for HydroMARK and 100% (13/13) for Twirl. This pattern indicates that clip visibility on ultrasound supports high retrieval accuracy regardless of clip type, consistent with prior reports [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the subgroup with clips not clearly visible on ultrasound, retrieval reached 60.0% (3/5) with HydroMARK and 100% (2/2) with Twirl. Twirl maintained high retrieval performance despite limited ultrasound visibility because supplemental localization methods remained effective. Intraoperative fluoroscopic detection followed by targeted ultrasound enabled reliable identification and removal of Twirl-marked nodes. HydroMARK did not show fluoroscopic visibility, likely related to its smaller metallic component, approximately 2 mm compared with about 4 mm for Twirl, which limited the effectiveness of backup localization strategies.\u003c/p\u003e \u003cp\u003ePrevious studies have described wire-related complications during TAD, including wire displacement and fracture [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Wire-related issues occurred in 11% (3/27) of cases in the present study. Even in these cases, combining intraoperative ultrasound with visualization of injected dye enabled successful clipped node retrieval in 66.7% (2/3). These findings suggest that a localization strategy that integrates dye injection and intraoperative ultrasound in addition to wire localization can preserve a high retrieval rate despite wire-related complications.\u003c/p\u003e \u003cp\u003eIn this study, the FNR of TAD was 0% (0/6) among HydroMARK cases that underwent scheduled ALND. Although the sample size was small, this result aligns with previously reported FNRs for TAD, which range from 2% to 7% [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], and supports the reliability of clip-guided TAD after NAC.\u003c/p\u003e \u003cp\u003eMultiple TAD techniques have been described, but no direct head-to-head comparisons exist, and most centers choose an approach based on regulatory constraints, availability, cost, and workflow. Clip-based wire localization remains non-radioactive, low-cost, and widely adopted as a practical and accessible method. Prior studies that evaluated the individual clips examined here reported retrieval rates of 89.7% (26/29) to 100% (13/13) for Twirl [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and 77.8% (7/9) to 96% (226/235) for HydroMARK [\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The direct comparison in this study provides side-by-side clinical data for these two clips. Although differences did not reach statistical significance, the favorable trends observed with Twirl compared with HydroMARK may help guide clip selection in routine clinical practice. These findings suggest that Twirl may provide more consistent performance than HydroMARK for TAD in everyday clinical settings.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, the single-center retrospective design and small sample size of 29 patients limit statistical power and generalizability. Second, clip type varied by calendar period, with HydroMARK used earlier and Twirl used later, which introduces potential temporal confounding. The clip choice did not depend on patient characteristics, which likely reduced but did not eliminate this effect. In addition, the use of multiple localization methods in the HydroMARK group may have influenced comparisons between clips. Third, ultrasound-based assessment of clip visibility depends on equipment, imaging settings, and patient factors such as body habitus and axillary depth, which creates inherent variability in ultrasound-based evaluations. Fourth, long-term follow-up data, including axillary recurrence and survival outcomes, were not available, and future studies with longer follow-up are needed.\u003c/p\u003e \u003cp\u003eThese findings indicate that, within a non-radioactive, clip-based TAD workflow, Twirl provides more consistent ultrasound visibility and retrieval success than HydroMARK. Clip selection should also consider institutional experience and device availability, and larger multicenter studies should confirm these results.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompliance with Ethical Standards\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.\u0026nbsp;This retrospective study was approved by the Institutional Review Board of our hospital (IRB No. 24-158).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient consent was obtained using an opt-out method in accordance with institutional policy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the ultrasound technologists, radiology staff, and operating room staff for their technical support, and colleagues who assisted with administrative aspects of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during this study are not publicly available because of privacy and ethical restrictions but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors made substantial contributions to the work reported, including the conception and design of the study, data acquisition, and analysis and interpretation of data. All authors participated in drafting the article or revising it critically for important intellectual content, approved the final version to be published, agreed on the journal to which the article has been submitted, and agree to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003eSpecifically, N.S. and H.M. contributed to the conceptualization and study design. H.M. performed the formal data analysis. N.S. and E.F. collected the data. E.F. provided supervision. All authors contributed to manuscript drafting and revision. All authors have read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMansel RE, Fallowfield L, Kissin M, Goyal A, Newcombe RG, Dixon JM, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst. 2006;98:599\u0026ndash;609.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDabakuyo TS, Fraisse J, Causeret S, Gouy S, Padeano MM, Loustalot C, et al. A multicenter cohort study to compare quality of life in breast cancer patients according to sentinel lymph node biopsy or axillary lymph node dissection. Ann Oncol. 2009;20:1352\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol. 2010;11:927\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoileau JF, Poirier B, Basik M, Holloway CMB, Gaboury Sideris L et al. 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Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection. J Clin Oncol. 2016;34:1072\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimons JM, van Nijnatten TJA, van der Pol CC, Luiten EJT, Koppert LB, Smidt ML. Diagnostic accuracy of different surgical procedures for axillary staging after neoadjuvant systemic therapy in node-positive breast cancer: a systematic review and meta-analysis. Ann Surg. 2019;269:432\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKirkilesis G, Constantinidou A, Kontos M. False negativity of targeted axillary dissection in breast cancer. Breast Care (Basel). 2021;16:532\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuemmel S, Heil J, Bruzas S, Breit E, Schindowski D, Harrach H, et al. Safety of targeted axillary dissection after neoadjuvant therapy in patients with node-positive breast cancer. JAMA Surg. 2023;158:807\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMamounas EP, Bandos H, White JR, Julian TB, Boughey JC, Kuerer HM, et al. Regional nodal irradiation in patients with node-positive breast cancer who become node-negative after neoadjuvant chemotherapy (NSABP B-51/RTOG 1304). N Engl J Med. 2025;392:2113\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Wild SR, Koppert LB, van Nijnatten TJA, Kooreman LFS, Vrancken Peeters MJTFD, Smidt ML, et al. Systematic review of targeted axillary dissection in node-positive breast cancer treated with neoadjuvant systemic therapy: variation in type of marker and timing of placement. 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Cancers (Basel). 2021;13:1565.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"breast-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brca","sideBox":"Learn more about [Breast Cancer](http://link.springer.com/journal/12282)","snPcode":"12282","submissionUrl":"https://www.editorialmanager.com/brca/default2.aspx","title":"Breast Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"breast cancer, breast tissue marker, ultrasound visibility, targeted axillary dissection, wire localization","lastPublishedDoi":"10.21203/rs.3.rs-8962245/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8962245/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTargeted axillary dissection (TAD) is a less invasive alternative to axillary lymph node dissection (ALND) for patients with clinically node-positive breast cancer who convert to node-negative status after neoadjuvant chemotherapy (NAC). However, the effect of preoperative ultrasound visibility of different clip types on TAD outcomes remains unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e We conducted a single-center retrospective cohort study of patients with biopsy-proven axillary node-positive breast cancer who underwent NAC followed by TAD between August 2017 and December 2024. Two ultrasound-visible clips, the UltraCor\u0026trade; Twirl\u0026trade; (Twirl) and HydroMARK\u0026trade;, were evaluated. Outcomes included ultrasound visibility, clipped node retrieval success, localization techniques, and false-negative rate (FNR).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTwenty-nine patients were included (Twirl, n\u0026thinsp;=\u0026thinsp;15; HydroMARK, n\u0026thinsp;=\u0026thinsp;14). Ultrasound visibility was higher with Twirl than with HydroMARK (86.7% versus 64.3%; p\u0026thinsp;=\u0026thinsp;0.330). All Twirl cases underwent combined wire and dye-guided localization, whereas HydroMARK cases used multiple localization techniques. Retrieval success reached 100% with Twirl and 78.6% with HydroMARK (p\u0026thinsp;=\u0026thinsp;0.199). When clips were visible on ultrasound, retrieval rates were high for both clips at 100% for Twirl and 88.9% for HydroMARK (p\u0026thinsp;=\u0026thinsp;0.850). When clips were not clearly visible, Twirl maintained 100% retrieval compared with 60.0% for HydroMARK (p\u0026thinsp;=\u0026thinsp;0.895). Among patients who underwent scheduled ALND, the FNR of TAD was 0% (0/6).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003ePreoperative ultrasound visibility of the clip was associated with successful clip-based TAD. Twirl showed more consistent ultrasound visibility and retrieval success than HydroMARK, which suggests that Twirl may be a more reliable clip for routine clinical practice.\u003c/p\u003e","manuscriptTitle":"Comparison of Ultrasound Visibility and Retrieval Success of Two Ultrasound-Visible Clips in Targeted Axillary Dissection After Neoadjuvant Chemotherapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-01 07:29:22","doi":"10.21203/rs.3.rs-8962245/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revision","date":"2026-04-23T03:43:13+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2026-03-30T12:43:18+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-30T10:14:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-25T10:10:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"Breast Cancer","date":"2026-02-24T21:35:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"breast-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brca","sideBox":"Learn more about [Breast Cancer](http://link.springer.com/journal/12282)","snPcode":"12282","submissionUrl":"https://www.editorialmanager.com/brca/default2.aspx","title":"Breast Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"229f9d3d-d4f7-4494-b1ee-c4e6f96f1166","owner":[],"postedDate":"April 1st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-04-23T07:43:37+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-01 07:29:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8962245","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8962245","identity":"rs-8962245","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}