Residual nephrogenic rests affects the long-term prognosis of Wilms tumor with bilateral nephrogenic rests

Residual nephrogenic rests affects the long-term prognosis of Wilms tumor with bilateral nephrogenic rests | 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 Residual nephrogenic rests affects the long-term prognosis of Wilms tumor with bilateral nephrogenic rests Xiaofeng Chang, Jinghao Yan, Shen Yang, Hong Qin, Wei Yang, Yang Yang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6667545/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Aug, 2025 Read the published version in Pediatric Surgery International → Version 1 posted 7 You are reading this latest preprint version Abstract Background/Objectives The progression of nephrogenic rests (NRs) can lead to the development of Wilms tumor (WT). To explore the factors affecting the poor prognosis associated with WT combined with bilateral NRs. Methods : We retrospectively analyzed the clinical data of patients with WT combined bilateral NRs admitted to our center from January 2008 to December 2022. The enrolled patients were divided into two groups according to whether they had residual NRs at the end of standard therapy or not. The overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier method, and prognostic risk factors were determined using univariate and multivariate cox analysis. Results : A total of 57 patients were finally enrolled in this study, of which 23 patients in the non-residual NRs group and 34 patients in the residual NRs group. In the residual NRs group, there were ultimately 15 patients (44.1%) experienced recurrence and 3 patients dead (recurrence of WT). In the non-residual NRs group, 1 patient (4.3%) experienced recurrence (P < 0.01). The difference of EFS between the two groups was significant (P<0.01). Univariate and multivariate cox analysis revealed that residual NRs was the risk factor of EFS within WT combined with bilateral NRs. Conclusion : The residual NRs increased the risk of recurrence and led the poor prognosis. Future multi-center prospective studies may need to further assess the conditions of patients with residual NRs to guide further treatment. bilateral nephrogenic rests Wilms’ tumor residual prognosis risk factor Figures Figure 1 Figure 2 1. Introduction Persistence of nephrogenic blastema beyond 36-week gestation results in what has been labeled a nephrogenic rests (NRs)(Beckwith et al. 1990 ). NRs is defined as “a focus of abnormally persistent nephrogenic cells, retaining cells that can be induced to form a Wilms tumor (WT) (Hennigar et al. 2001 ). Although NRs can have variable progression to sclerosis, dormancy, or hyperplasia, neoplastic transformation is a known complication. Approximately 90–100% of bilateral Wilms tumors (BWT) are associated with NRs(Beckwith 1998 ). However, it is currently unclear how residual NRs affect the long-term prognosis of WT with bilateral NRs. Previous studies have reported cases of transformation from cystic lesions to WT(Sandberg et al. 2020 ). Thus, we retrospectively analyzed the clinical characteristics and outcomes of WT with bilateral NRs, and investigated the prognostic risk factors among these patients. 2. Materials and Methods Patient population This study retrospectively analyzed the clinical data of children who had WT with bilateral NRs admitted to our center from January 2008 to December 2022. All patients were diagnosed with BWT or uWT + bilateral NRs upon initial presentation, through radiological or histological assessment. The residual NRs group refers to patients with stable NRs in the residual or contralateral kidneys found on contrast-enhanced computed tomography (CECT) conducted at the end of BWT standard therapy, when compared to the CECT performed at the initial diagnosis. Residual NRs comprises three types: Perilobar NRs (PLNRs), intralobar NRs (ILNRs), and mixed. Lesions are typically less than 1.75 cm in diameter and do not exhibit spherical growth. The group of non-residual NRs refers to patients in whom radiological assessments at the end of standard therapy consistently demonstrate the absence of NRs in the residual kidney or contralateral kidney(Simanovsky et al. 2016 ). The radiological definition of NRs is characterized by plaquelike, ovoid, lenticular with a diameter of ≤ 1.75 cm, which grow intrarenally and do not extend beyond the confines of the kidney(Sandberg et al. 2020 ). NRs hypoenhance compared to the adjacent renal parenchyma. PLNRs are located along the periphery of the renal lobe and are triangular or elliptical in shape. The lesion usually conforms to or bulges the renal cortex boundary and is uniform in signal intensity/attenuation with relative hypoenhancement compared to adjacent renal parenchyma at CECT(Rohrschneider et al. 1998 ). ILNRs are variable in location, but are usually found at the corticomedullary junction or medulla. The shape is also variable, but often is more elliptical or spherical. The radiological characteristics of WT are characterized by inhomogeneous, spherical, exophytic, and larger than 1.75 cm in maximal diameter(Sandberg et al. 2020 ). We excluded patients with diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) because this entity has a very distinct imaging appearance with a rind of abnormal nephrogenic tissue that surrounds the renal cortex like a mantle while preserving the reniform shape(Perlman et al. 2006 ). All patients underwented surgical treatment at our institution, and postoperative histological confirmed the diagnosis of WT with NRs. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013), and obtained approval from institutional ethical review board of Beijing Children’s Hospital ([2024]-E-043-R). As retrospective analysis, waiver of informed consent was granted by institutional review board. Clinical and Radiology Patient demographics, clinical data and outcomes (tumor recurrence, survival) were evaluated. Summarized the radiographic diagnosis at the end of standard therapy to evaluate whether there was NRs in residual or contralateral kidney. All radiological assessment for this retrospective review were reviewed independently by a pediatric radiologist with 20 years of experience and a senior radiology resident (postgraduate year 5); discrepancies were resolved by consensus before comparative analysis with pathology reports. This imaging review was performed blinded to the institutional report and institutional and central pathologic evaluations. In patients with multiple renal lesions, the radiology reviewers attempted to identify the index (i.e., pathologically evaluated) lesion in the kidney using the description of the treating surgeon in the operative note. Radiological assessment included contrast-enhanced computed tomography (CECT) and ultrasound. Treatment and Followup The standard therapy for WT combined with bilateral NRs were neoadjuvant chemotherapy, surgery, chemotherapy, and/or radiotherapy, excluding any form of maintenance chemotherapy. Modalities of surgery include radical nephrectomy (RN) and nephron-sparing surgery (NSS). The chemoradiotherapeutic protocols mainly referred to the International Society of Pediatric Oncology (SIOP) 2001–2016(Sudour-Bonnange et al. 2024 ) or Children's Oncology Group (COG) AREN0534(Ehrlich et al. 2017 ). Histological classification was conducted according to the SIOP 2016 protocol(Vujanic et al. 2018 ). The patients were reviewed every 3 monthly for the first 3 years postoperative, then semi-annually for 3–5 years. Routine examinations were as follow: abdominal ultrasonography, CECT of abdominal and CT of lung. Follow-up was conducted by out-patient consultation or over the phone. Relapse was defined as the recurrence of WT in situ or contralateral kidney, or distant metastasis confirmed via histopathology. Event-free survival (EFS) was defined as survival without recurrence. Overall survival (OS) was defined as the period of survival or till the last follow-up after WT detection. Statistical analysis Statistical analyses were performed using R software. Continuous variables were presented as means with standard deviations or medians and interquartile ranges if the normality hypothesis test rejected the null hypothesis of a normal distribution. Variables between groups were compared through Chi-square test or Fisher exact test. OS and EFS were calculated using the Kaplan-Meier methods. Univariate and multivariate cox proportional hazards regression model were used to assess the risk factors of prognosis of WT with bilateral NRs. All statistical results were reported as two-tailed P values, and < 0.05 was considered statistical significance. 3. Results 3.1. Subsection Clinical characteristics Following screening, a total of 57 patients were enrolled in this study, of which 34 in the residual NRs group and 23 in the non-residual NRs group. In the residual group, there are 9 patients with uWT + bilateral NRs, and 25 patients with BWT + bilateral NRs. The non-residual NRs group consists entirely of BWT with bilateral NRs. The focus is that they showed no signs of NRs in the radiological assessment at the end of standard therapy. No anaplasia components were found in all patients. The baseline data of the two groups are shown in Table 1 . Treatment schedule and outcome The residual NRs group consisted of 21 patients (61.7%) who underwent bilateral NSS, with 11 cases experienced tumor recurrence; 4 patients (11.8%) received NSS + RN, of which 1 patient recurred; 9 patients (26.5%) only underwent unilateral surgery (6 cases of RN, 3 cases of NSS), with 3 cases experienced recurrence. In the residual NRs group, there were ultimately 3 patients died of recurrence WT (Fig. 1). The non-residual NRs group consisted of 15 patients (65.3%) who underwent bilateral NSS without recurrence; 8 cases (34.7%) received NSS + RN, with 1 patient experienced recurrence. None of the patients died in the group of non-residual NRs (Fig. 1). The recurrence distribution of two groups was significantly different, and the recurrence of the residual NRs group was more than those in the non-residual NRs group (P < 0.01). There was no statistically significant difference of the remaining clinical indicators between the two groups (Table 1 ). The overall 5-year OS of the whole cohort was 94.4% (95% CI 91.2–97.6%), while the EFS was 71.2% (95% CI 65.1–77.3%). According to the Kaplan-Meier curve, we found that no significant difference in OS (P = 0.99, the median survival time of the residual NRs group was 84.0 [50.0; 157.0] months, the no-residual NRs group was 81 [49; 139] months) between the two groups; however, there was a significance difference in EFS (P<0.05, the median time of the residual NRs group was 47.0 [15.0; 91.0] months, the non-residual NRs group was 75 [37.0; 139] months) (Fig. 2). Prognostic risk factors among the patients with WT with bilateral NRs According to survival analysis, the patients with WT combined with bilateral NRs exhibited favorable OS, but there was a significant decline in EFS. Thus, we further explored the prognostic risk factors of EFS among the whole cohort. As shown in Table 2 , univariate and multivariate cox analysis revealed that age (HR 1.046, P<0.01; HR 1.041, P<0.01, respectively), residual NRs (HR 12.491, P<0.05; HR 11.887, P<0.05, respectively) were substantial predictors of poor EFS.This section may be divided by subheadings. It should provide a concise and precise description of the experimental results, their interpretation, as well as the experimental conclusions that can be drawn. 4. Discussion NRs was first proposed and described in 1961(HOU and HOLMAN 1961). The histological classification of NRs is divided into perilobar and intralobular, classified as unifocal, multifocal, or diffuse, and categorized into sclerosing, obsolete, dormant or hyperplastic(Fialkowski et al. 2023 ). NRs was a precancerous proliferative process associated with a high risk of developing WT(Perlman et al. 2006 ). DHPLN represented a specific type of NRs(Beckwith et al. 1990 ). According to the prospective study published by COG in 2022, the therapeutic objective of DHPLN was to reduce the incidence of WT through standard chemotherapy(Ehrlich et al. 2022 ). However, the clinical features and radiology manifestations of WT combined with bilateral NRs were different from those of DHPLN. Therefore, our study had excluded DHPLN through radiological assessment prior to the inclusion of patients. NRs may progress to WT due to as yet unknown molecular factors(Sarkany et al. 2023 ). Through previous studies, we have applied the histological diagnosis of NRs for radiological assessment(van der Beek et al. 2025 ). Through radiological assessment, we defined whether exhibited NRs and found that the recurrence risk of WT in the residual group was significantly higher than that in the non-residual group. This further confirmed that NRs could develop into WT. In our study, 93.7% patients (15/16) who underwent a combination of surgery, chemotherapy, and radiotherapy for relapsed WT achieved long-term survival. Three deceased patients received only one treatment modality each (chemotherapy, radiotherapy, or radiofrequency ablation) after recurrence. This indicates that a multimodal treatment approach, which includes surgery combined with chemotherapy and radiotherapy (especially complete surgical resection), can significantly improve the survival outcomes for patients after relapse. Although there is no statistical difference in OS between the residual NRs group and the non-residual NRs group, all three patient deaths were caused by tumor recurrence in the residual NRs group., and none had distant metastasis at the time of initial diagnosis. One patient who expired initially underwent unilateral RN (low risk histology, LRH), with residual NRs present on the contralateral side, and recurrence (hingh risk histology, HRH) occurred on the residual NRs side after 4 years. The recurrence in five patients originated from the kidneys with residual NRs, and the pathological results after recurrence showed HRH (with the primary tumor being of intermediate risk histology, IRH). These suggested that WT after recurrence could transition from L/IRH to HRH, increasing treatment difficulty and affecting long-term prognosis. Among the recurrence cases, there were 8 (50.0%, 8/16) cases belonging to the HRH, all of which predominantly exhibited blastemal after chemotherapy, without anaplasia components. This may be related to the low incidence of anaplasia components in the Asian population(Oue et al. 2014 ). Surgical intervention in the early stages, aimed at ensuring complete resection of NRs while ensuring NSS, contributed positively to the survival prognosis of the patients. To reduce the risk of recurrence, patients with WT combined with residual NRs may require further treatment in the future. In our study, two patients in the residual NRs group underwented intensified chemotherapy or extended chemotherapy duration due to NRs and achieved long-term EFS. In a small-scale study involving patients with WT combined NRs, Ortiz confirmed that maintenance chemotherapy is an effective strategy for reducing the recurrence of NRs(Ortiz et al. 2019 ). SIOP and COG maintenance chemotherapy regimens for VA (Vincristine + Actinomycin D) have similarities and differences. However, the aforementioned studies have not assessed the status of NRs, the chemotherapeutic responsiveness following maintenance chemotherapy, and the endpoints of treatment. Therefore, the treatment approach for patients with NRs remained unclear. When the isolated NRs is fully resected in the nephrectomy specimen, the recurrence risk of WT is 3.3% versus 33.3% when the isolated NRs is not fully resected(Brown et al. 2023 ). Non-randomized studies on DHPLN suggest that combined surgical interventions counld reduce the development of BWT(Perlman et al. 2006 ). The challenge faced by clinicians is that RN may not be warranted or beneficial in WT with bilateral NRs. Therefore, we believe that the treatment of NRs should initially involve an assessment of the feasibility of achieving NSS. The patients may not require maintenance chemotherapy if they achieve complete resection of NRs through NSS. The patients who were unable to achieve complete resection through NSS need to receive maintenance chemotherapy or other treatments(Friesenbichler et al. 2018 ). Our research also found that the risk of tumor recurrence is higher for patients who are older. Therefore, during the treatment process, it was necessary to closely monitor the changes in residual NRs for patients in the older age groups; if there was an increase in volume, surgical removal should be considered.(Fialkowski et al. 2023 ). These treatment measures for WT combined with bilateral NRs needed to be further validated in our future clinical trials. It was highly challenging to differentiate between WT and NRs through radiology and biopsy(van der Beek et al. 2022 ). The SIOP developed the UMBRELLA treatment protocol that favors radiology assessment with contrast-enhanced abdominopelvic magnetic resonance imaging (MRI)(Watson et al. 2020 ). The loss of chromosome 22 and mutations in WT-1 can also be considered early events, as they were found in both NRs and WT(Mdzin et al. 2011 ). Our study was a retrospective analysis spanning a 15-year period, during which genetic testing and access to contrast-enhanced MRI were very limited, hence our patient cohort had minimal exposure to these diagnostic modalities. Therefore, our diagnostic approach involves initial evaluation using CECT and ultrasound. To ensure accuracy, we utilized mutual verification between CECT and ultrasound for both diagnosis and follow-up. At the same time, the final histological results also supported our radiological assessment method. However MRI has shown to be equivalent to CECT in diagnostic performance for WT, it provides both qualitative and quantitative information while CT only provides qualitative information. In addition, MRI distributions can aid in the assessment of chemotherapy response(Watson et al. 2020 ). MRI may have advantages in assessing the developmental stages of NRs. With the increased availability of MRI, we plan to use contrast - enhanced MRI throughout the entire treatment period to evaluate the status of residual NRs and chemotherapeutic responsiveness in future research. This approach will more accurately assess the efficacy and endpoint of treating NRs. Limitations should be considered in this study. First, since it was a retrospective study from single center, problems such as the loss of clinical data exist, and the sample included spanned a long period, during which the treatment regimen for WT combined with bilateral NRs has been developing, it may be hard to be analyzed separately. Second, the retrospective cases lacking MRI and genetic analysis results indicate that it is impossible to understand the origin of NRs and the changes in chemotherapy response. In the future, prospective multicenter clinical studies on treatment protocols for WT with bilateral NRs should be developed. 5. Conclusions Our study revealed that WT with residual NRs increased the risk of recurrence and poor prognosis. Patients with residual NRs may require further treatment after the completion of treatment for WT. However, further verifcation of this conclusion was needed by multicenter prospective study. Declarations Author Contributions: Xiaofeng Chang, Jinghao Yan and Shen Yang contributed to the conceptu-alization and writing of the manuscript. Hong Qin, Wei Yang, Yang Yang, Yanchao Qu and Jianguo Zhang were responsible for data curation, formal analysis, funding acquisition, and validation. Hongcheng Song, and Huanmin Wang were responsible for methodology, project administration and final approval of the manuscript. All the authors have reviewed the manuscript. Funding: This work was supported by the High-level Clinical Specialty Construction Project of the Public Hospital in the Capital Region of Inner Mongolia Autonomous Region(2023SGGZ0038). Institutional Review Board Statement: The authors would like to thank all patients and their families for participating in this study. This work was supported by the High-level Clinical Spe-cialty Construction Project of the Public Hospital in the Capital Region of Inner Mongolia Au-tonomous Region(2023SGGZ0038). Informed Consent Statement: None of the authors has any financial or other support or any fi-nancial or professional relationship that may pose a competing interest. Data Availability Statement: A dataset supporting the conclusions of this study is included in this article. The datasets used or analyzed during the current study are available from the corre-sponding author upon reasonable request. Acknowledgments: The authors have reviewed and edited the output and take full responsibility for the content of this publication.” Conflicts of Interest: The authors declare no conflicts of interest. 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(2022) Kidney preservation and wilms tumor development in children with diffuse hyperplastic perilobar nephroblastomatosis: a report from the children's oncology group study aren0534. Ann Surg Oncol 29:3252-3261 doi:10.1245/s10434-021-11266-6 Fialkowski E, Sudour-Bonnange H, Vujanic GM et al. (2023) The varied spectrum of nephroblastomatosis, nephrogenic rests, and wilms tumors: review of current definitions and challenges of the field. Pediatr Blood Cancer 70 Suppl 2:e30162 doi:10.1002/pbc.30162 Friesenbichler W, Krizmanich W, Lakatos K et al. (2018) Outcome of two patients with bilateral nephroblastomatosis/wilms tumour treated with an add-on 13-cis retinoic acid therapy - case report. Pediatr Hemat Oncol 35:218-224 doi:10.1080/08880018.2018.1515284 Hennigar RA, O'Shea PA, Grattan-Smith JD (2001) Clinicopathologic features of nephrogenic rests and nephroblastomatosis. 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Lancet Child Adolesc 4:232-241 doi:10.1016/S2352-4642(19)30340-2 Tables Table 1 Baseline of patients of WT with bilateral NRs residual NRs( N =34) non-residual NRs( N =23) P Sex (n, %) Male 22(64.7) 11(47.8) 0.75 Female 12(35.3) 12(52.1) Age (median, IQR) 12(9.0,29.0) 14(8.0,22.0) 0.10 Associated with other malformations 1 (n, %) 0.47 Yes 13(38.2) 12(52.1) No 21(61.7) 11(47.8) Symptom (n, %) 0.34 Abdominal mass 24(70.6) 15(65.3) Hematuria 3(8.8) 5(21.7) Others 7(20.6) 3(12.0) Distant metastasis (n, %) 0.50 Yes 2(5.9) 0(0.0) No 32(94.1) 23(100.0) Neoadjuvant chemotherapy (n, %) 0.15 Yes 30(88.3) 16(69.6) No 4(11.7) 7(30.4) Preoperative puncture (n, %) 0.22 Yes 6(17.6) 1(4.4) No 28(82.4) 22(95.6) Surgery (n, %) 0.66 NSS (bilateral) 21(61.7) 15(65.3) RN+NSS 4(11.7) 8(34.7) RN (unilateral) 6(17.6) 0 NSS (unilateral) 3(9.0) 0 Stage (n, %) 0.40 Ⅰ 2(5.9) 3(13.0) Ⅱ 23(67.7) 16(69.6) Ⅲ 7(20.5) 4(17.4) Ⅳ 2(5.9) 0(0.0) Histology (n, %) 0.06 Cystic partially differentiated nephroblastoma 1(1.5) 5(10.8) Mixed type 7(10.3) 13(28.3) Mesenchymal 36(52.9) 18(39.1) Blastemal 2(2.9) 4(8.7) Epithelial 6(8.8) 5(10.9) Blastemal after chemotherapy (n, %) 7(10.3) 1(2.1) Unknow(no surgery) 9(13.3) 0(0.0) Histology dichotomous (n, %) L-IRH 44(86.2) 43(97.7) HRH 7(13.8) 1(2.3) Surgical margin (n, %) 0.30 Negative 12(35.3) 7(30.4) Positive 22(64.7) 16(69.6) Recurrent (n, %) ＜ 0.01 Yes 15(44.1) 1(4.3) No 19(55.9) 22(95.7) Bold indicates statistical signifcance, NRs: nephrogenic rests, IQR: interquartile range, RN: radical nephrectomy, NSS: nephron-sparing surgery, L-IRH: low-intermediate risk histology, HRH: high risk histology, Other malformations 1 : Denys-Drash syndrome (DDS), Wilms' tumor-Aniridia-Genitourinary anomalies-mental retardation syndrome (WARG), Beckwith-Wiedemann syndrome (BWS) Table 2 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table22024.11.21.doc Cite Share Download PDF Status: Published Journal Publication published 03 Aug, 2025 Read the published version in Pediatric Surgery International → Version 1 posted Editorial decision: Revision requested 15 Jun, 2025 Reviews received at journal 23 May, 2025 Reviewers agreed at journal 19 May, 2025 Reviewers invited by journal 19 May, 2025 Editor assigned by journal 16 May, 2025 Submission checks completed at journal 15 May, 2025 First submitted to journal 14 May, 2025 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6667545","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":458973841,"identity":"9c958a7b-2840-4c9a-b994-e194f979d258","order_by":0,"name":"Xiaofeng Chang","email":"","orcid":"","institution":"Capital Medical University, National Center for Children’s Health","correspondingAuthor":false,"prefix":"","firstName":"Xiaofeng","middleName":"","lastName":"Chang","suffix":""},{"id":458973842,"identity":"79ecc258-a9f2-47a4-bebb-3d99f0a37b38","order_by":1,"name":"Jinghao Yan","email":"","orcid":"","institution":"Capital Medical 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jianguo","middleName":"","lastName":"Zhang","suffix":""},{"id":458973852,"identity":"6d1ef6cd-3f8f-4016-92cd-967c68838260","order_by":8,"name":"Hongcheng Song","email":"","orcid":"","institution":"Capital Medical University, National Center for Children’s Health","correspondingAuthor":false,"prefix":"","firstName":"Hongcheng","middleName":"","lastName":"Song","suffix":""},{"id":458973853,"identity":"28b546d9-aa4f-4af2-9548-5026f2d5a498","order_by":9,"name":"Huanmin Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYJACZijJ+JiB4QBpWpiNSdTCwMAmTZQWg+NnD78ubLPL023nPVZdUHOHgb+9O4Hh5w48Ws7kpVnPbEsuNjvMl3Z7xrFnDBJnzm5g7D2DW4vZgRwzY9425sRth3nMbvM2HGYwkMjdwMzYhkfL+TcgLfVgLcXEabmRY/yYt+0wWAszUVrsb7wxY+Y5dxykxVh6xrHDPCC/HOzFo0WyP8f4M09ZdeK282cMPxfUHJbjb+/d+OAnHi1AwCaBzOMBEQfwagDG5AcCCkbBKBgFo2CkAwBMS1JV86pw6QAAAABJRU5ErkJggg==","orcid":"","institution":"Capital Medical University, National Center for Children’s Health","correspondingAuthor":true,"prefix":"","firstName":"Huanmin","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2025-05-14 23:38:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6667545/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6667545/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00383-025-06142-3","type":"published","date":"2025-08-03T16:21:20+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":83279898,"identity":"3596b0da-7d10-4c18-87f9-dad15c6a2dbf","added_by":"auto","created_at":"2025-05-22 10:06:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":344843,"visible":true,"origin":"","legend":"\u003cp\u003eClinical treatment process of patients with WT complicated by bilateral NRs\u003c/p\u003e\n\u003cp\u003e1 2 patients distant metastasis\u003c/p\u003e\n\u003cp\u003e2 Due to family reasons, only received tumor radiofrequency ablation at other hospital after the recurrence, which unfortunately led to the patient's death and showed a histological change from L-IRH to HRH.\u003c/p\u003e\n\u003cp\u003eS Patients received surgery after the recurrence.\u003c/p\u003e\n\u003cp\u003eR Patients received radiotherapy after the recurrence.\u003c/p\u003e\n\u003cp\u003eC Patients were treated with chemotherapy after the recurrence.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6667545/v1/a09edfd859ed115a45392665.png"},{"id":83279902,"identity":"18861795-8184-4fdd-9bc0-cf67e26f0c19","added_by":"auto","created_at":"2025-05-22 10:06:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":830619,"visible":true,"origin":"","legend":"\u003cp\u003eOS and EFS of patients with WT complicated by bilateral NRs\u003c/p\u003e\n\u003cp\u003eA. OS of WT complicated by bilateral NRs patients\u003c/p\u003e\n\u003cp\u003eB. EFS of WT complicated by bilateral NRs patients\u003c/p\u003e","description":"","filename":"F2.png","url":"https://assets-eu.researchsquare.com/files/rs-6667545/v1/a7840e6d2120943937792c00.png"},{"id":88268257,"identity":"db262d2e-77e0-4fc0-8c25-859486093893","added_by":"auto","created_at":"2025-08-04 16:50:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1924468,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6667545/v1/1fc4abf1-d480-4aff-afa0-012841fc534f.pdf"},{"id":83279908,"identity":"55adf8f9-4ce9-4daf-b9e1-8f62c0f12e3a","added_by":"auto","created_at":"2025-05-22 10:06:31","extension":"doc","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":56832,"visible":true,"origin":"","legend":"","description":"","filename":"Table22024.11.21.doc","url":"https://assets-eu.researchsquare.com/files/rs-6667545/v1/c125202909939c756be08134.doc"}],"financialInterests":"No competing interests reported.","formattedTitle":"Residual nephrogenic rests affects the long-term prognosis of Wilms tumor with bilateral nephrogenic rests","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003ePersistence of nephrogenic blastema beyond 36-week gestation results in what has been labeled a nephrogenic rests (NRs)(Beckwith et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e1990\u003c/span\u003e). NRs is defined as \u0026ldquo;a focus of abnormally persistent nephrogenic cells, retaining cells that can be induced to form a Wilms tumor (WT) (Hennigar et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2001\u003c/span\u003e). Although NRs can have variable progression to sclerosis, dormancy, or hyperplasia, neoplastic transformation is a known complication. Approximately 90\u0026ndash;100% of bilateral Wilms tumors (BWT) are associated with NRs(Beckwith \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1998\u003c/span\u003e). However, it is currently unclear how residual NRs affect the long-term prognosis of WT with bilateral NRs. Previous studies have reported cases of transformation from cystic lesions to WT(Sandberg et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Thus, we retrospectively analyzed the clinical characteristics and outcomes of WT with bilateral NRs, and investigated the prognostic risk factors among these patients.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cp\u003e \u003cb\u003ePatient population\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThis study retrospectively analyzed the clinical data of children who had WT with bilateral NRs admitted to our center from January 2008 to December 2022. All patients were diagnosed with BWT or uWT\u0026thinsp;+\u0026thinsp;bilateral NRs upon initial presentation, through radiological or histological assessment. The residual NRs group refers to patients with stable NRs in the residual or contralateral kidneys found on contrast-enhanced computed tomography (CECT) conducted at the end of BWT standard therapy, when compared to the CECT performed at the initial diagnosis. Residual NRs comprises three types: Perilobar NRs (PLNRs), intralobar NRs (ILNRs), and mixed. Lesions are typically less than 1.75 cm in diameter and do not exhibit spherical growth. The group of non-residual NRs refers to patients in whom radiological assessments at the end of standard therapy consistently demonstrate the absence of NRs in the residual kidney or contralateral kidney(Simanovsky et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). The radiological definition of NRs is characterized by plaquelike, ovoid, lenticular with a diameter of \u0026le;\u0026thinsp;1.75 cm, which grow intrarenally and do not extend beyond the confines of the kidney(Sandberg et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). NRs hypoenhance compared to the adjacent renal parenchyma. PLNRs are located along the periphery of the renal lobe and are triangular or elliptical in shape. The lesion usually conforms to or bulges the renal cortex boundary and is uniform in signal intensity/attenuation with relative hypoenhancement compared to adjacent renal parenchyma at CECT(Rohrschneider et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e1998\u003c/span\u003e). ILNRs are variable in location, but are usually found at the corticomedullary junction or medulla. The shape is also variable, but often is more elliptical or spherical. The radiological characteristics of WT are characterized by inhomogeneous, spherical, exophytic, and larger than 1.75 cm in maximal diameter(Sandberg et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). We excluded patients with diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) because this entity has a very distinct imaging appearance with a rind of abnormal nephrogenic tissue that surrounds the renal cortex like a mantle while preserving the reniform shape(Perlman et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). All patients underwented surgical treatment at our institution, and postoperative histological confirmed the diagnosis of WT with NRs. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013), and obtained approval from institutional ethical review board of Beijing Children\u0026rsquo;s Hospital ([2024]-E-043-R). As retrospective analysis, waiver of informed consent was granted by institutional review board.\u003c/p\u003e \u003cp\u003e \u003cb\u003eClinical and Radiology\u003c/b\u003e \u003c/p\u003e \u003cp\u003ePatient demographics, clinical data and outcomes (tumor recurrence, survival) were evaluated.\u003c/p\u003e \u003cp\u003eSummarized the radiographic diagnosis at the end of standard therapy to evaluate whether there was NRs in residual or contralateral kidney. All radiological assessment for this retrospective review were reviewed independently by a pediatric radiologist with 20 years of experience and a senior radiology resident (postgraduate year 5); discrepancies were resolved by consensus before comparative analysis with pathology reports. This imaging review was performed blinded to the institutional report and institutional and central pathologic evaluations. In patients with multiple renal lesions, the radiology reviewers attempted to identify the index (i.e., pathologically evaluated) lesion in the kidney using the description of the treating surgeon in the operative note. Radiological assessment included contrast-enhanced computed tomography (CECT) and ultrasound.\u003c/p\u003e \u003cp\u003e \u003cb\u003eTreatment and Followup\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe standard therapy for WT combined with bilateral NRs were neoadjuvant chemotherapy, surgery, chemotherapy, and/or radiotherapy, excluding any form of maintenance chemotherapy. Modalities of surgery include radical nephrectomy (RN) and nephron-sparing surgery (NSS). The chemoradiotherapeutic protocols mainly referred to the International Society of Pediatric Oncology (SIOP) 2001\u0026ndash;2016(Sudour-Bonnange et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2024\u003c/span\u003e) or Children's Oncology Group (COG) AREN0534(Ehrlich et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Histological classification was conducted according to the SIOP 2016 protocol(Vujanic et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). The patients were reviewed every 3 monthly for the first 3 years postoperative, then semi-annually for 3\u0026ndash;5 years. Routine examinations were as follow: abdominal ultrasonography, CECT of abdominal and CT of lung. Follow-up was conducted by out-patient consultation or over the phone. Relapse was defined as the recurrence of WT in situ or contralateral kidney, or distant metastasis confirmed via histopathology. Event-free survival (EFS) was defined as survival without recurrence. Overall survival (OS) was defined as the period of survival or till the last follow-up after WT detection.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eStatistical analyses were performed using R software. Continuous variables were presented as means with standard deviations or medians and interquartile ranges if the normality hypothesis test rejected the null hypothesis of a normal distribution. Variables between groups were compared through Chi-square test or Fisher exact test. OS and EFS were calculated using the Kaplan-Meier methods. Univariate and multivariate cox proportional hazards regression model were used to assess the risk factors of prognosis of WT with bilateral NRs. All statistical results were reported as two-tailed \u003cem\u003eP\u003c/em\u003e values, and \u0026lt;\u0026thinsp;0.05 was considered statistical significance.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Subsection\u003c/h2\u003e \u003cp\u003eClinical characteristics\u003c/p\u003e \u003cp\u003eFollowing screening, a total of 57 patients were enrolled in this study, of which 34 in the residual NRs group and 23 in the non-residual NRs group. In the residual group, there are 9 patients with uWT\u0026thinsp;+\u0026thinsp;bilateral NRs, and 25 patients with BWT\u0026thinsp;+\u0026thinsp;bilateral NRs. The non-residual NRs group consists entirely of BWT with bilateral NRs. The focus is that they showed no signs of NRs in the radiological assessment at the end of standard therapy. No anaplasia components were found in all patients. The baseline data of the two groups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eTreatment schedule and outcome\u003c/p\u003e \u003cp\u003eThe residual NRs group consisted of 21 patients (61.7%) who underwent bilateral NSS, with 11 cases experienced tumor recurrence; 4 patients (11.8%) received NSS\u0026thinsp;+\u0026thinsp;RN, of which 1 patient recurred; 9 patients (26.5%) only underwent unilateral surgery (6 cases of RN, 3 cases of NSS), with 3 cases experienced recurrence. In the residual NRs group, there were ultimately 3 patients died of recurrence WT (Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eThe non-residual NRs group consisted of 15 patients (65.3%) who underwent bilateral NSS without recurrence; 8 cases (34.7%) received NSS\u0026thinsp;+\u0026thinsp;RN, with 1 patient experienced recurrence. None of the patients died in the group of non-residual NRs (Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eThe recurrence distribution of two groups was significantly different, and the recurrence of the residual NRs group was more than those in the non-residual NRs group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). There was no statistically significant difference of the remaining clinical indicators between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe overall 5-year OS of the whole cohort was 94.4% (95% CI 91.2\u0026ndash;97.6%), while the EFS was 71.2% (95% CI 65.1\u0026ndash;77.3%). According to the Kaplan-Meier curve, we found that no significant difference in OS (P\u0026thinsp;=\u0026thinsp;0.99, the median survival time of the residual NRs group was 84.0 [50.0; 157.0] months, the no-residual NRs group was 81 [49; 139] months) between the two groups; however, there was a significance difference in EFS (P\u0026lt;0.05, the median time of the residual NRs group was 47.0 [15.0; 91.0] months, the non-residual NRs group was 75 [37.0; 139] months) (Fig.\u0026nbsp;2).\u003c/p\u003e \u003cp\u003ePrognostic risk factors among the patients with WT with bilateral NRs\u003c/p\u003e \u003cp\u003eAccording to survival analysis, the patients with WT combined with bilateral NRs exhibited favorable OS, but there was a significant decline in EFS. Thus, we further explored the prognostic risk factors of EFS among the whole cohort. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, univariate and multivariate cox analysis revealed that age (HR 1.046, P\u0026lt;0.01; HR 1.041, P\u0026lt;0.01, respectively), residual NRs (HR 12.491, P\u0026lt;0.05; HR 11.887, P\u0026lt;0.05, respectively) were substantial predictors of poor EFS.This section may be divided by subheadings. It should provide a concise and precise description of the experimental results, their interpretation, as well as the experimental conclusions that can be drawn.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eNRs was first proposed and described in 1961(HOU and HOLMAN 1961). The histological classification of NRs is divided into perilobar and intralobular, classified as unifocal, multifocal, or diffuse, and categorized into sclerosing, obsolete, dormant or hyperplastic(Fialkowski et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). NRs was a precancerous proliferative process associated with a high risk of developing WT(Perlman et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). DHPLN represented a specific type of NRs(Beckwith et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e1990\u003c/span\u003e). According to the prospective study published by COG in 2022, the therapeutic objective of DHPLN was to reduce the incidence of WT through standard chemotherapy(Ehrlich et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). However, the clinical features and radiology manifestations of WT combined with bilateral NRs were different from those of DHPLN. Therefore, our study had excluded DHPLN through radiological assessment prior to the inclusion of patients.\u003c/p\u003e \u003cp\u003eNRs may progress to WT due to as yet unknown molecular factors(Sarkany et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Through previous studies, we have applied the histological diagnosis of NRs for radiological assessment(van der Beek et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Through radiological assessment, we defined whether exhibited NRs and found that the recurrence risk of WT in the residual group was significantly higher than that in the non-residual group. This further confirmed that NRs could develop into WT. In our study, 93.7% patients (15/16) who underwent a combination of surgery, chemotherapy, and radiotherapy for relapsed WT achieved long-term survival. Three deceased patients received only one treatment modality each (chemotherapy, radiotherapy, or radiofrequency ablation) after recurrence. This indicates that a multimodal treatment approach, which includes surgery combined with chemotherapy and radiotherapy (especially complete surgical resection), can significantly improve the survival outcomes for patients after relapse. Although there is no statistical difference in OS between the residual NRs group and the non-residual NRs group, all three patient deaths were caused by tumor recurrence in the residual NRs group., and none had distant metastasis at the time of initial diagnosis. One patient who expired initially underwent unilateral RN (low risk histology, LRH), with residual NRs present on the contralateral side, and recurrence (hingh risk histology, HRH) occurred on the residual NRs side after 4 years. The recurrence in five patients originated from the kidneys with residual NRs, and the pathological results after recurrence showed HRH (with the primary tumor being of intermediate risk histology, IRH). These suggested that WT after recurrence could transition from L/IRH to HRH, increasing treatment difficulty and affecting long-term prognosis. Among the recurrence cases, there were 8 (50.0%, 8/16) cases belonging to the HRH, all of which predominantly exhibited blastemal after chemotherapy, without anaplasia components. This may be related to the low incidence of anaplasia components in the Asian population(Oue et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). Surgical intervention in the early stages, aimed at ensuring complete resection of NRs while ensuring NSS, contributed positively to the survival prognosis of the patients. To reduce the risk of recurrence, patients with WT combined with residual NRs may require further treatment in the future.\u003c/p\u003e \u003cp\u003eIn our study, two patients in the residual NRs group underwented intensified chemotherapy or extended chemotherapy duration due to NRs and achieved long-term EFS. In a small-scale study involving patients with WT combined NRs, Ortiz confirmed that maintenance chemotherapy is an effective strategy for reducing the recurrence of NRs(Ortiz et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). SIOP and COG maintenance chemotherapy regimens for VA (Vincristine\u0026thinsp;+\u0026thinsp;Actinomycin D) have similarities and differences. However, the aforementioned studies have not assessed the status of NRs, the chemotherapeutic responsiveness following maintenance chemotherapy, and the endpoints of treatment. Therefore, the treatment approach for patients with NRs remained unclear. When the isolated NRs is fully resected in the nephrectomy specimen, the recurrence risk of WT is 3.3% versus 33.3% when the isolated NRs is not fully resected(Brown et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Non-randomized studies on DHPLN suggest that combined surgical interventions counld reduce the development of BWT(Perlman et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). The challenge faced by clinicians is that RN may not be warranted or beneficial in WT with bilateral NRs. Therefore, we believe that the treatment of NRs should initially involve an assessment of the feasibility of achieving NSS. The patients may not require maintenance chemotherapy if they achieve complete resection of NRs through NSS. The patients who were unable to achieve complete resection through NSS need to receive maintenance chemotherapy or other treatments(Friesenbichler et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Our research also found that the risk of tumor recurrence is higher for patients who are older. Therefore, during the treatment process, it was necessary to closely monitor the changes in residual NRs for patients in the older age groups; if there was an increase in volume, surgical removal should be considered.(Fialkowski et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). These treatment measures for WT combined with bilateral NRs needed to be further validated in our future clinical trials.\u003c/p\u003e \u003cp\u003eIt was highly challenging to differentiate between WT and NRs through radiology and biopsy(van der Beek et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). The SIOP developed the UMBRELLA treatment protocol that favors radiology assessment with contrast-enhanced abdominopelvic magnetic resonance imaging (MRI)(Watson et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). The loss of chromosome 22 and mutations in WT-1 can also be considered early events, as they were found in both NRs and WT(Mdzin et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). Our study was a retrospective analysis spanning a 15-year period, during which genetic testing and access to contrast-enhanced MRI were very limited, hence our patient cohort had minimal exposure to these diagnostic modalities. Therefore, our diagnostic approach involves initial evaluation using CECT and ultrasound. To ensure accuracy, we utilized mutual verification between CECT and ultrasound for both diagnosis and follow-up. At the same time, the final histological results also supported our radiological assessment method. However MRI has shown to be equivalent to CECT in diagnostic performance for WT, it provides both qualitative and quantitative information while CT only provides qualitative information. In addition, MRI distributions can aid in the assessment of chemotherapy response(Watson et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). MRI may have advantages in assessing the developmental stages of NRs. With the increased availability of MRI, we plan to use contrast - enhanced MRI throughout the entire treatment period to evaluate the status of residual NRs and chemotherapeutic responsiveness in future research. This approach will more accurately assess the efficacy and endpoint of treating NRs.\u003c/p\u003e \u003cp\u003eLimitations should be considered in this study. First, since it was a retrospective study from single center, problems such as the loss of clinical data exist, and the sample included spanned a long period, during which the treatment regimen for WT combined with bilateral NRs has been developing, it may be hard to be analyzed separately. Second, the retrospective cases lacking MRI and genetic analysis results indicate that it is impossible to understand the origin of NRs and the changes in chemotherapy response. In the future, prospective multicenter clinical studies on treatment protocols for WT with bilateral NRs should be developed.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eOur study revealed that WT with residual NRs increased the risk of recurrence and poor prognosis. Patients with residual NRs may require further treatment after the completion of treatment for WT. However, further verifcation of this conclusion was needed by multicenter prospective study.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e Xiaofeng Chang, Jinghao Yan and Shen Yang contributed to the conceptu-alization and writing of the manuscript. Hong Qin, Wei Yang, Yang Yang, Yanchao Qu and Jianguo Zhang were responsible for data curation, formal analysis, funding acquisition, and validation. Hongcheng Song, and Huanmin Wang were responsible for methodology, project administration and final approval of the manuscript. All the authors have reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This work was supported by the High-level Clinical Specialty Construction Project of the Public Hospital in the Capital Region of Inner Mongolia Autonomous Region(2023SGGZ0038).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutional Review Board Statement:\u0026nbsp;\u003c/strong\u003eThe authors would like to thank all patients and their families for participating in this study. This work was supported by the High-level Clinical Spe-cialty Construction Project of the Public Hospital in the Capital Region of Inner Mongolia Au-tonomous Region(2023SGGZ0038).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent Statement:\u003c/strong\u003e None of the authors has any financial or other support or any fi-nancial or professional relationship that may pose a competing interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u003c/strong\u003e A dataset supporting the conclusions of this study is included in this article. The datasets used or analyzed during the current study are available from the corre-sponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003eThe authors have reviewed and edited the output and take full responsibility for the content of this publication.\u0026rdquo;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e The authors declare no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBeckwith JB (1998) Nephrogenic rests and the pathogenesis of wilms tumor: developmental and clinical considerations. Am J Med Genet 79:268-273 doi:10.1002/(sici)1096-8628(19981002)79:4\u0026lt;268::aid-ajmg7\u0026gt;3.0.co;2-i\u003c/li\u003e\n\u003cli\u003eBeckwith JB, Kiviat NB, Bonadio JF (1990) Nephrogenic rests, nephroblastomatosis, and the pathogenesis of wilms\u0026apos; tumor. Pediatr Pathol 10:1-36 doi:10.3109/15513819009067094\u003c/li\u003e\n\u003cli\u003eBrown EG, Engwall-Gill AJ, Aldrink JH et al. (2023) Unwrapping nephrogenic rests and nephroblastomatosis for pediatric surgeons: a systematic review utilizing the pico model by the apsa cancer committee. J Pediatr Surg 58:2128-2134 doi:10.1016/j.jpedsurg.2023.07.011\u003c/li\u003e\n\u003cli\u003eEhrlich P, Chi YY, Chintagumpala MM et al. (2017) Results of the first prospective multi-institutional treatment study in children with bilateral wilms tumor (aren0534): a report from the children\u0026apos;s oncology group. Ann Surg 266:470-478 doi:10.1097/SLA.0000000000002356\u003c/li\u003e\n\u003cli\u003eEhrlich PF, Tornwall B, Chintagumpala MM et al. (2022) Kidney preservation and wilms tumor development in children with diffuse hyperplastic perilobar nephroblastomatosis: a report from the children\u0026apos;s oncology group study aren0534. Ann Surg Oncol 29:3252-3261 doi:10.1245/s10434-021-11266-6\u003c/li\u003e\n\u003cli\u003eFialkowski E, Sudour-Bonnange H, Vujanic GM et al. (2023) The varied spectrum of nephroblastomatosis, nephrogenic rests, and wilms tumors: review of current definitions and challenges of the field. Pediatr Blood Cancer 70 Suppl 2:e30162 doi:10.1002/pbc.30162\u003c/li\u003e\n\u003cli\u003eFriesenbichler W, Krizmanich W, Lakatos K et al. (2018) Outcome of two patients with bilateral nephroblastomatosis/wilms tumour treated with an add-on 13-cis retinoic acid therapy - case report. Pediatr Hemat Oncol 35:218-224 doi:10.1080/08880018.2018.1515284\u003c/li\u003e\n\u003cli\u003eHennigar RA, O\u0026apos;Shea PA, Grattan-Smith JD (2001) Clinicopathologic features of nephrogenic rests and nephroblastomatosis. Adv Anat Pathol 8:276-289 doi:10.1097/00125480-200109000-00005\u003c/li\u003e\n\u003cli\u003eHOU LT, HOLMAN RL (1961) Bilateral nephroblastomatosis in a premature infant. J Pathol Bacteriol 82:249-255 doi:10.1002/path.1700820202\u003c/li\u003e\n\u003cli\u003eMdzin R, Phillips M, Edwards C et al. (2011) Perilobar nephrogenic rests and chromosome 22. Pediatr Devel Pathol 14:485-492 doi:10.2350/10-01-0781-CR.1\u003c/li\u003e\n\u003cli\u003eOrtiz MV, Fernandez-Ledon S, Ramaswamy K et al. (2019) Maintenance chemotherapy to reduce the risk of a metachronous wilms tumor in children with bilateral nephroblastomatosis. Pediatr Blood Cancer 66:e27500 doi:10.1002/pbc.27500\u003c/li\u003e\n\u003cli\u003eOue T, Koshinaga T, Okita H et al. (2014) Bilateral wilms tumors treated according to the japan wilms tumor study group protocol. Pediatr Blood Cancer 61:1184-1189 doi:10.1002/pbc.24979\u003c/li\u003e\n\u003cli\u003ePerlman EJ, Faria P, Soares A et al. (2006) Hyperplastic perilobar nephroblastomatosis: long-term survival of 52 patients. Pediatr Blood Cancer 46:203-221 doi:10.1002/pbc.20386\u003c/li\u003e\n\u003cli\u003eRohrschneider WK, Weirich A, Rieden K et al. (1998) Us, ct and mr imaging characteristics of nephroblastomatosis. Pediatr Radiol 28:435-443 doi:10.1007/s002470050378\u003c/li\u003e\n\u003cli\u003eSandberg JK, Chi YY, Smith EA et al. (2020) Imaging characteristics of nephrogenic rests versus small wilms tumors: a report from the children\u0026apos;s oncology group study aren03b2. Am J Roentgenol 214:987-994 doi:10.2214/AJR.19.22301\u003c/li\u003e\n\u003cli\u003eSarkany B, Kuthi L, Kovacs G (2023) Novel concept of wilms\u0026apos; tumor development: involvement of pluripotential cells of ureteric bud. Hum Pathol 138:34-40 doi:10.1016/j.humpath.2023.05.004\u003c/li\u003e\n\u003cli\u003eSimanovsky N, Revel-Vilk S, Weintraub M, Hiller N (2016) Association between renal cystic lesions and bilateral wilms\u0026apos; tumours. Eur Radiol 26:1665-1669 doi:10.1007/s00330-015-3976-9\u003c/li\u003e\n\u003cli\u003eSudour-Bonnange H, van Tinteren H, Ramirez-Villar GL et al. (2024) Characteristics and outcome of synchronous bilateral wilms tumour in the siop wt 2001 study: report from the siop renal tumour study group (siop-rtsg). Brit J Cancer 131:972-981 doi:10.1038/s41416-024-02799-0\u003c/li\u003e\n\u003cli\u003evan der Beek JN, Fitski M, de Krijger RR et al. (2025) Direct correlation of mr-dwi and histopathology of wilms\u0026apos; tumours through a patient-specific 3d-printed cutting guide. Eur Radiol 35:652-663 doi:10.1007/s00330-024-10959-2\u003c/li\u003e\n\u003cli\u003evan der Beek JN, Watson TA, Nievelstein R et al. (2022) Mri characteristics of pediatric renal tumors: a siop-rtsg radiology panel delphi study. J Magn Reson Imaging 55:543-552 doi:10.1002/jmri.27878\u003c/li\u003e\n\u003cli\u003eVujanic GM, Gessler M, Ooms A et al. (2018) The umbrella siop-rtsg 2016 wilms tumour pathology and molecular biology protocol. Nat Rev Urol 15:693-701 doi:10.1038/s41585-018-0100-3\u003c/li\u003e\n\u003cli\u003eWatson T, Oostveen M, Rogers H et al. (2020) The role of imaging in the initial investigation of paediatric renal tumours. Lancet Child Adolesc 4:232-241 doi:10.1016/S2352-4642(19)30340-2\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 Baseline of patients of WT with bilateral NRs\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eresidual NRs(\u003cem\u003eN\u003c/em\u003e=34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003enon-residual NRs(\u003cem\u003eN\u003c/em\u003e=23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eSex (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e22(64.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e11(47.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e12(35.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e12(52.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eAge (median, IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e12(9.0,29.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e14(8.0,22.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eAssociated with other malformations\u003csup\u003e1\u003c/sup\u003e (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e13(38.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e12(52.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e21(61.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e11(47.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eSymptom (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eAbdominal mass\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e24(70.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e15(65.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eHematuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e3(8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e5(21.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e7(20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e3(12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eDistant metastasis (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e2(5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e32(94.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e23(100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eNeoadjuvant chemotherapy (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e30(88.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e16(69.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e4(11.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e7(30.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003ePreoperative puncture (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e6(17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e1(4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e28(82.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e22(95.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eSurgery (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eNSS (bilateral)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e21(61.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e15(65.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eRN+NSS\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e4(11.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e8(34.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eRN (unilateral)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e6(17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eNSS (unilateral)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e3(9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eStage (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eⅠ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e2(5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e3(13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eⅡ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e23(67.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e16(69.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eⅢ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e7(20.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e4(17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eⅣ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e2(5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eHistology (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eCystic partially differentiated nephroblastoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e1(1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e5(10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"6\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eMixed type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e7(10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e13(28.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eMesenchymal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e36(52.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e18(39.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eBlastemal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e2(2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e4(8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eEpithelial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e6(8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e5(10.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eBlastemal after chemotherapy (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e7(10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e1(2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eUnknow(no surgery)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e9(13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eHistology dichotomous (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eL-IRH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e44(86.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e43(97.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eHRH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e7(13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e1(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eSurgical margin (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e12(35.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e7(30.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e22(64.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e16(69.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eRecurrent (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e15(44.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e1(4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 215px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e19(55.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e22(95.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Bold indicates statistical signifcance,\u003c/p\u003e\n\u003cp\u003eNRs: nephrogenic rests,\u003c/p\u003e\n\u003cp\u003eIQR: interquartile range,\u003c/p\u003e\n\u003cp\u003eRN: radical nephrectomy,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNSS: nephron-sparing surgery,\u003c/p\u003e\n\u003cp\u003eL-IRH: low-intermediate risk histology,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHRH: high risk histology,\u003c/p\u003e\n\u003cp\u003eOther malformations\u003csup\u003e1\u003c/sup\u003e: Denys-Drash syndrome (DDS), Wilms\u0026apos; tumor-Aniridia-Genitourinary anomalies-mental retardation syndrome (WARG), Beckwith-Wiedemann syndrome (BWS)\u003c/p\u003e\n\u003cp\u003eTable 2 is available in the Supplementary Files section.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-surgery-international","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pesi","sideBox":"Learn more about [Pediatric Surgery International](http://link.springer.com/journal/383)","snPcode":"383","submissionUrl":"https://submission.nature.com/new-submission/383/3","title":"Pediatric Surgery International","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"bilateral, nephrogenic rests, Wilms’ tumor, residual, prognosis, risk factor","lastPublishedDoi":"10.21203/rs.3.rs-6667545/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6667545/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground/Objectives\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe progression of nephrogenic rests (NRs) can lead to the development of Wilms tumor (WT). To explore the factors affecting the poor prognosis associated with WT combined with bilateral NRs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: We retrospectively analyzed the clinical data of patients with WT combined bilateral NRs admitted to our center from January 2008 to December 2022. The enrolled patients were divided into two groups according to whether they had residual NRs at the end of standard therapy or not. The overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier method, and prognostic risk factors were determined using univariate and multivariate cox analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: A total of 57 patients were finally enrolled in this study, of which 23 patients in the non-residual NRs group and 34 patients in the residual NRs group. In the residual NRs group, there were ultimately 15 patients (44.1%) experienced recurrence and 3 patients dead (recurrence of WT). In the non-residual NRs group, 1 patient (4.3%) experienced recurrence (P \u0026lt; 0.01). The difference of EFS between the two groups was significant (P\u0026lt;0.01). Univariate and multivariate cox analysis revealed that residual NRs was the risk factor of EFS within WT combined with bilateral NRs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: The residual NRs increased the risk of recurrence and led the poor prognosis. Future multi-center prospective studies may need to further assess the conditions of patients with residual NRs to guide further treatment.\u003c/p\u003e","manuscriptTitle":"Residual nephrogenic rests affects the long-term prognosis of Wilms tumor with bilateral nephrogenic rests","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-22 10:06:26","doi":"10.21203/rs.3.rs-6667545/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-15T23:35:12+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-23T05:42:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"240295589485183246503799155127173501911","date":"2025-05-19T22:36:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-19T15:09:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-16T05:46:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-15T10:31:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Surgery International","date":"2025-05-14T23:22:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-surgery-international","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pesi","sideBox":"Learn more about [Pediatric Surgery International](http://link.springer.com/journal/383)","snPcode":"383","submissionUrl":"https://submission.nature.com/new-submission/383/3","title":"Pediatric Surgery International","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c8742f25-bbd2-4373-93ef-e067921650f5","owner":[],"postedDate":"May 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-04T16:42:48+00:00","versionOfRecord":{"articleIdentity":"rs-6667545","link":"https://doi.org/10.1007/s00383-025-06142-3","journal":{"identity":"pediatric-surgery-international","isVorOnly":false,"title":"Pediatric Surgery International"},"publishedOn":"2025-08-03 16:21:20","publishedOnDateReadable":"August 3rd, 2025"},"versionCreatedAt":"2025-05-22 10:06:26","video":"","vorDoi":"10.1007/s00383-025-06142-3","vorDoiUrl":"https://doi.org/10.1007/s00383-025-06142-3","workflowStages":[]},"version":"v1","identity":"rs-6667545","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6667545","identity":"rs-6667545","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}