Evaluation of the therapeutic value of conventional transpedal lymphography for the treatment of inguinal lymphatic fistulas after lymphadenectomy

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Vogl, Katrin Eichler, Tatjana Gruber-Rouh This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8673450/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Purpose To evaluate therapeutic effectiveness and safety of lipiodol-based conservative transpedal lymphangiography in sealing persistent inguinal lymphatic fistulas after lymphadenectomy, and to determine whether therapeutic success is influenced by the amount of injected Lipiodol or the volume of lymphatic drainage. Materials and Methods From January 2003 to June 2023, 184 patients underwent lymphangiography. Of these, 35 patients (24 male, 11 female; aged 24 to 87 years) met inclusion criteria (age ≥ 18 years, persistent lymphatic leakage after inguinal lymphadenectomy (> 3 weeks), following unsuccessful conservative management) and were subsequently included for statistical analysis. Lipiodol lymphangiography was performed via transpedal lymphatic vessel cannulation. Data collected included: age, sex, underlying disease, drainage volume before lymphangiography Lipiodol amount, procedural details, time to fistula closure, imaging follow-ups, technical success, therapeutic success and its correlation with the volume of lymphatic leakage and the volume of the applied iodised oil, complications, and additional interventions. Statistical analysis utilised the Wilcoxon–Mann–Whitney test (significance at p ≤ 0.05). Results Therapeutic success was achieved in 22 patients (62.86%) without complications, with a mean resolution time of 7.13 days. 13 patients (37.14%) required additional interventions. No significant correlation was found between therapeutic success and either the amount of Lipiodol used (p = 0.51) or drainage volume (p = 0.82). Conclusion Lipiodol-based lymphangiography is an effective and safe treatment for inguinal lymphatic fistulas. The lack of association therapeutic outcome with Lipiodol or drainage volume appears to be more related to anatomical and disease-specific factors, suggesting individualized patient assessment is warranted. lymphangiography Lymphatic Intervention Lipiodol Postoperative Lymphatic Leakage Inguinal Lymphatic Fistula Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 BACKGROUND Iodised oil-based conventional lymphangiography is a diagnostic imaging technique used to obtain detailed images of the lymphatic system and evaluating conditions like lymphatic fistulas, lymphovenous malformations, lymphatic obstructions, through the injection of an oily contrast agent [ 1 – 3 ]. Lipiodol, an iodised oil derived from poppy seeds- Papaver somniferum var, has evolved from a diagnostic contrast agent to a therapeutic tool by enabling the successful closure of lymphatic leaks [ 4 – 13 ]. Its mechanism of action is based on the accumulation of Lipiodol at leak sites, physically obstructing lymph flow and triggering a mild sterile inflammatory response leading to fibrosis, thereby occluding the leaking lymphatic vessels in the long term [ 14 ]. This dual diagnostic and therapeutic capability is a distinct advantage over conventional imaging methods. Lastly, in those cases where lymphatic leakage cannot be controlled via medical treatment, consisting of a low-fat, medium-chain triglyceride diet [ 15 ], somatostatin treatment or local treatment such as bed rest, elevation of the extremity and compression bandages, lymphatic drainage [ 16 , 17 ], vacuum therapy [ 18 ], lymphangiography is a proven as a minimally invasive method for the treatment of lymphatic leakage comparing to the surgical treatment, which is associated with relatively high complication and mortality rates of up to 38% and 25% respectively, and does not promise complete closure of the fistula [ 19 , 20 ]. The comparability of studies regarding the therapeutic effect of conventional lymphangiography is limited due to the analysis of different patient groups, on the one hand, and, on the other hand, due to the different volume ranges of lymphatic drainage. Systematic research in homogeneous patient cohorts, particularly regarding postoperative inguinal lymphatic fistulas, is rare. To address this gap, the intention of the study was to evaluate therapeutic effectiveness and safety of lipiodol-based conservative lymphangiography in sealing persistent inguinal lymphatic fistulas after lymphadenectomy and to assess whether there is a correlation between therapeutic success and the amount of injected Lipiodol and the volume of lymphatic drainage accordingly. METHODS Patient population Between January 2003 and June 2023, 184 patients were treated with lymphangiography in our department. After applying inclusion and exclusion criteria, 35 patients with lymphatic fistula formation in the inguinal region were further recorded and analysed (Fig. 1 ). Patients’ underlying disease, age, sex, daily lymphatic drainage volume in ml before the lymphangiography procedure, the amount of Lipiodol administered, technical success, whether X-Ray/CT performed after lymphangiography, clinical success, time to resolution, complications and additional interventions are summarised in Table 1 . The cohort comprised 11 female (31.4%) and 24 male (68.6%) patients, with a median age of 71 years. The age range was from 24 to 87 years, with a mean of 67.2 years. One of the main reasons for lymphatic leakage was prior inguinal lymphadenectomy for diagnosis of cutaneous malignant melanoma (82.85%, n = 29) (Fig. 2 ). Table 1 Patient Characteristics and Outcomes of Lymphatic Intervention Patient no. and underlying disease Age Sex Daily Drain Output (mL) Amount of Lipiodol administered (mL) Technical Success X-Ray/CT performed after lymphography Clinical Success Time to resolution Complication Additional intervention 1/ macrophage activation syndrome 24 m 50 9 Yes X-Ray No Not available No Surgery 2/ cutaneous malignant melanoma 71 m 50 6 Yes X-Ray No Not available No Yes, further course is not available 3/ cutaneous malignant melanoma 43 w 100 8 Yes X-Ray No Not available No Yes, further course is not available 4/ cutaneous malignant melanoma 47 m 100 9 Yes CT Yes 2 No No 5/ cutaneous malignant melanoma 66 w 100 9 Yes X-Ray No Not available No Yes, further course is not available 6/ cutaneous malignant melanoma 70 w 100 18 Yes X-Ray Yes 2 No No 7/ cutaneous malignant melanoma 77 m 100 9 Yes X-Ray Yes 7 No No 8/ cutaneous malignant melanoma 77 m 100 12 Yes X-Ray No Not available No Radiotherapy 9/ Merkel cell carcinoma 80 w 100 8 Yes X-Ray Yes 4 No No 10/ cutaneous malignant melanoma 87 w 100 8 Yes X-Ray Yes 7 No No 11/ cutaneous malignant melanoma 57 m 120 9 Yes X-Ray Yes 2 No No 12/ cutaneous malignant melanoma 80 w 120 4 Yes X-Ray Yes 2 No No 13/ B-cell lymphoma 51 m 125 8 Yes X-Ray Yes 35 No No 14/ cutaneous malignant melanoma 51 m 150 8 Yes X-Ray No Not available No Radiotherapy 15/ cutaneous malignant melanoma 75 m 150 9 Yes X-Ray Yes 1 No No 16/ cutaneous malignant melanoma 82 m 150 12 Yes X-Ray Yes 11 No No 17/ cutaneous malignant melanoma 68 m 170 10 Yes X-Ray Yes 2 No No 18/ cutaneous malignant melanoma 62 w 200 9 Yes X-Ray Yes 2 No No 19/ Merkel cell carcinoma 79 m 200 9 Yes X-Ray No Not available No Surgery 20/ cutaneous malignant melanoma 81 m 200 9 Yes X-Ray No Not available No Radiotherapy 21/ cutaneous malignant melanoma 36 w 250 6 Yes X-Ray Yes 18 No No 22/ cutaneous malignant melanoma 66 m 250 9 Yes X-Ray Yes 10 No No 23/ cutaneous malignant melanoma 76 m 250 6 Yes X-Ray Yes 2 No No 24/ Merkel cell carcinoma 78 m 250 8 Yes X-Ray No Not available No Yes, further course is not available 25/ cutaneous malignant melanoma 80 m 250 9 Yes X-Ray Yes 6 No No 26/ cutaneous malignant melanoma 80 w 250 9 Yes X-Ray Yes 6 No No 27/ Kaposi's sarcoma 47 m 300 9 Yes X-Ray Yes 2 No No 28/ cutaneous malignant melanoma 66 w 300 5 Yes X-Ray Yes 2 No No 29/ cutaneous malignant melanoma 80 m 325 9 Yes X-Ray No Not available No Radiotherapy 30/ cutaneous malignant melanoma 49 m 400 14 Yes X-Ray Yes 2 No No 31/ cutaneous malignant melanoma 68 m 400 8 Yes X-Ray Yes 25 No No 32/ cutaneous malignant melanoma 75 w 400 9 Yes X-Ray No Not available No Radiotherapy 33/ cutaneous malignant melanoma 70 m 500 10 Yes X-Ray Yes 7 No No 34/ cutaneous malignant melanoma 76 m 500 8 Yes X-Ray No Not available No Radiotherapy 35/ cutaneous malignant melanoma 77 m 500 5 Yes X-Ray No Not available No Surgery Lymphangiography procedure All 35 patients underwent the same procedure. Following the disinfection of the feet (using Kodan®, Schülke & Mayr GmbH, Norderstedt, Germany), 2 ml of mepivacaine hydrochloride (Scandicaine® 1%, Astra Zeneca GmbH, Wedel, Germany) and 2 ml of methylene blue dye (Patent Blue V, Guerbet GmbH, Sulzbach, Germany) were injected into the subcutaneous tissues of the first to third interdigital spaces (Fig. 3 ). After the pedal lymphatic vessels had been adequately coloured, which took around 15 minutes, the patient was placed on an examination table of the X-ray radioscopic system Siemens Axiom Artis MP (Siemens, Forchheim, Germany). The foot was then disinfected again and covered with a sterile fenestrated drape. Following this step, a local anesthetic (Scandicaine®) was injected subcutaneously, and a longitudinal 2 cm skin incision was made on the dorsum of the foot. The lymphatic vessels were carefully dissected free. Using a special spring-loaded needle with a stylet, the most visible lymphatic vessel was cannulated. Adhesive stripes were used to anchor the needle and infusion line. Using a syringe pump with an injection speed of 6–8 ml/h, Lipiodol was injected at a rate of up to 1 ml/10 kg body weight per foot, up to a maximum volume of 20 ml of iodised oil (48% iodised glycerol ester, Lipiodol® Ultra-Fluid, Guerbet GmbH, Sulzbach, Germany). To monitor the flow of Lipiodol through the lymphatic vessels and to rule out inadvertent venous injection, fluoroscopy was performed. As soon as a fistula was visible or 20 ml of Lipiodol had been injected, the materials were removed, and the incision was carefully disinfected and sutured. The sutures could be removed 10 to 12 days after the procedure. At the end of the procedure, a fluoroscopy of the hip and groin region is usually performed at the surgical site (Fig. 4 ). The lymphatic fistula was visualized within 24 hours of lymphangiography using X-ray or CT imaging to monitor lymph drainage and rule out further complications (Fig. 5 ). If the lymphatic fistula did not close after lymphangiography, either surgical intervention or radiation therapy was performed. Technical Success The technical success of conventional lymphangiography was characterized by the effective administration of contrast agents, with the aim of clearly visualizing the lymphatic system and all associated lymphatic abnormalities using X-ray images. Clinical Outcome Assessment Therapeutic success was defined as complete closure of the inguinal lymph fistula after lymphangiography without the need for further surgical or radiotherapeutic interventions. Additionally, the interval between the day of lymphangiography and the day of fistula closure, whether X-ray or CT was performed after lymphangiography, and whether surgical intervention and/or radiation therapy was performed in the case of a persistent lymphatic fistula were recorded in an Excel (2011) spreadsheet. Safety was assessed by the complications following lymphangiography, including but not limited to contrast leakage, wound infection, allergic reactions, embolic events, or other adverse events. Using the Wilcoxon-Mann-Whitney U test was measured the correlation between the lymphatic leakage amount and therapeutic success, as well as the injected volume of Lipiodol and therapeutic success. A p-value ≤ 0.05 was considered statistically significant. The statistical analysis was performed using the software BiAS version 11.12 (epsilon-Verlag GbR, Frankfurt am Main, Germany). RESULTS Patient Clinical Information Conventional lymphangiography was performed in all 35 patients. Before the procedure, the average daily volume of lymphatic drainage was 217.43 ml/day. The mean median value was 200 ml/day. Drainage volumes varied considerably, ranging from 50 ml/day to 500 ml/day. The amount of Lipiodol administered varied between 4 ml and 18 ml, averaging 8.77 ml. The median value was 9 ml. Clinical Outcomes In all 35 patients, the fistula site was identified and radiologically documented, resulting in a technical success rate of 100%. In 22 cases, corresponding to a therapeutic success rate of 62.86%, complete closure of the lymphatic fistula was achieved after conventional lymphangiography without the need for further surgical or radiotherapeutic interventions. The 22 clinically successful patients had an average daily lymph fistula volume of 212.95 ml/day prior to the procedure (Fig. 6 ). An average of 9 ml of Lipiodol was used, with amounts ranging from 4 to 18 ml. Only in these 22 patients was possible to assess the time between the day of lymphangiography and the day the lymph fistula closed. This time ranged from 1 to 35 days, with an average closure time of 7.13 days. Most of these patients (17) had malignant melanoma as their underlying disease. All clinically successful patients underwent an X-ray the day after lymphangiography, except for one patient who had a CT scan instead. No complications occurred in any of these 22 patients. Three of the remaining 13 patients underwent surgery based on the lymphographic findings, while six (17.14%) received radiation therapy to completely close the lymph fistula. Sufficient information on the subsequent course of the remaining four patients (11.43%) was not available. The six patients who received radiotherapy had a mean age of 73.3 years (range: 51–81 years) and a mean lymphatic fistula volume of 279.16 ml (range: 150–500 ml). Each of these patients had malignant melanoma. On average, 9.16 ml of Lipiodol was used, with a range of 8 to 12 ml. The success of the therapy was independent of the amount of lymphatic drainage and the amount of Lipiodol administered. The Wilcoxon-Mann-Whitney U test, used for statistical analysis, showed no difference in the distribution of the amount of Lipiodol administered and the therapeutic effect of lymphangiography (p = 0.51). Similarly, the daily amount of lymphatic drainage had no significant effect on the success rate of the therapy (p = 0.82). DISCUSSION Conventional lymphangiography was found to be safe and in most cases therapeutically effective. Current literature is mainly limited to the studies [ 4 – 9 ], which focus on different lymphatic flow locations, such as chylothorax, chylous ascites, thoracic and inguinal lymphatic fistulas, pelvic lymphatic fistulas, abdominal and peripheral lymphatic fistulas, thoracic, abdominal and peripheral lymphoceles, or cervical lymphoceles. While the total number of patients in most of these studies is 22 or fewer [ 6 – 8 ], only three studies report populations of 355 [ 9 ], 64 [ 5 ], and 43 patients [ 4 ], respectively. The technical success rate lymphangiography, defined similarly to our study as the successful injection of Lipiodol into lymphatic vessels with the aim of clearly visualising the lymphatic system and all associated lymphatic abnormalities using fluoroscopy, ranges in other studies from 86% to 100% [ 4 – 9 ]. In cases where lymphangiography failed and where the fistula site could not be identified and radiologically confirmed, the reasons were mainly fragile lymphatic vessels, disturbances in contrast medium outflow, or lymphoedema [ 7 , 21 ]. Whereas the therapeutic success rate ranges between 51% and 75% and is defined by the authors similarly to our study as complete closure of the lymph fistula after lymphangiography without the need for further surgical or radiotherapeutic interventions [ 4 – 9 ]. In this study was evaluated the therapeutic value of conventional lymphangiography on a homogeneous patient group with exclusively persistent inguinal lymph fistulas after lymphadenectomy. Despite differences in the patient population with other abovementioned studies, the technical success rate of 100% and the therapeutic success rate of 62.86% in our study correlate with those others, proving that conventional lymphangiography is effective in a significant proportion of cases in sealing persistent inguinal lymphatic fistulas after lymphadenectomy in addition to being an efficient diagnostic tool. Additionally, in both our work and the studies listed above, there were no complications (including, but not limited to, contrast leakage, wound infection, allergic reactions, embolic events or other adverse events), which proves the safety of this treatment. Interestingly, the total time from the day of lymphangiography to the day of fistula closure ranged from approximately 1 day to 4 weeks, which correlates well with our results of 1 day to 5 weeks. Furthermore, the median value (7.13 days) is nearly identical to the values ​​reported by Kortes et al [ 6 ] and Pan et al [ 9 ] (5 days; other authors did not report the median). Additional therapies used in the other studies for clinically unsuccessful patients included surgical interventions, immediate or delayed sclerotherapy, pleurosclerosis, and peritoneovenous shunt. While in our study almost half of the unsuccessful patients received radiotherapy (6 out of 13) and another third (4 out of 13) underwent surgery, lymphangiography was helpful in the planning of surgery due to the visualisation of the lymphatic defect. The Wilcoxon-Mann-Whitney U test in our study indicated that there is no correlation between the injected lipiodol and therapeutic success (p = 0.51). Gruber-Rouh et al reached the same conclusion [ 5 ], while other studies did not investigate such a correlation. However, Pan et al [ 9 ] found that a significantly higher volume of Lipiodol was injected in patients with chylothorax than in those with inguinal lymph fistula (p = 0.007). Therefore, the patient population could be one reason for the absence of such a correlation. The results regarding the correlation between daily lymphatic drainage volume and therapeutic success rate are contradictory. In the study by Gruber-Rouh et al [ 5 ], considering patients with a lymphatic drainage volume of less than 200 ml/day (instead of the original range of 10 to 1000 ml/day) would impact the success rate, which would be 96.8% instead of 70.3%. But even in patients with more than 200 ml/day, the therapeutic success rate was 58.1%. The same result regarding the correlation between drainage volume and therapeutic success came from Alejandre-Lafont et al [ 4 ] where occlusion occurred in 70% of patients with a lymphatic drainage volume of less than 500 ml/day, while the success rate dropped to 35% with a lymphatic drainage volume of more than 500 ml/day. In contrast, in the study by Kortes et al [ 6 ] occlusion was only observed in patients whose outflow volume exceeded 1,000 ml/day. Pan et al [ 9 ] report that a drainage volume greater than 500 ml/day correlates with treatment failure (p = 0.025). However, this correlation is based on a total of 258 patients (258 of 355 were treated with lymphangiography only), and they had various clinical diagnoses of lymphatic leaks. Out of the total cohort, only 134 patients had inguinal fistulas, with their drainage volume ranging from 200 to 400 ml per day and averaging 300 ml per day; thus, the general statement about the overall patient population does not apply exclusively to those with inguinal lymphatic fistulas. Our patients fall within almost the same drainage volume range (50 to 500 ml) and have an average of 217.43 ml/day. Most importantly, the average volume of lymph leakage in clinically successful patients was 212.95 ml/day, while for the 13 clinically unsuccessful patients it was 225 ml/day. These results suggest that the baseline severity of the lymph leak, as measured by the daily fistula volume, is not always a reliable predictor of therapeutic success in patients with less than 500 ml/day. This supports that the therapeutic effect is independent of the volume of lymphatic drainage at the time of intervention. The specific patient group contributes to this finding, as our study focused exclusively on patients with inguinal fistulas. This lack of association may indicate that other factors, such as the precise anatomical features of the leak or the underlying disease process, could have a more decisive influence on the effectiveness of lymphangiography. Despite the lack of a significant relationship between lymphatic drainage volume and therapeutic success (p = 0.82), the result of our statistical analysis (62.86%) is nearly identical to that of patients with inguinal lymphatic fistulas in the study by Pan et al (62.2%) [ 9 ] and that of the various patients in the study by Alejandre-Lafont et al (70%) [ 4 ]. Furthermore, it is acknowledged that if the daily fistula volume in our study were higher than 500 ml/day, this could lead to the correlation proposed by Alejandre-Lafont et al [ 4 ]. The limitations of the present study lie in the absence of a prospective follow-up study, as retrospective analyses have such constraints as long-term outcomes after discharge or later complications are not always fully recorded. Additionally, the present study focuses solely on transpedal lymphangiography and not intranodal method. Lastly, there is a lack of data recording other variables in clinically unsuccessful patients, such as the time interval between additional intervention and complete fistula closure and specific complications after radiotherapy or surgical intervention in this context. CONCLUSIONS In conclusion, conventional lipiodol-based lymphangiography is effective and safe as an adjunct to conservative treatments. The lack of association between Lipiodol, or drainage volume, and outcome suggests that therapeutic success may depend more on anatomical and disease-specific factors, which underscores the necessity for a more individualised approach when selecting patients and planning subsequent interventions. Abbreviations m male f female CT computed tomography n number p probability value Declarations Funding: This study was not supported by any funding. 2. Availability of data and materials: All data generated or analysed during this study are included in this published article. 3. Ethical approval: All procedures performed in studies involving human participants 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. Since this study was a retrospective audit of anonymized patient records, formal retrospective consent was not required. The study was approved by the local ethics committee (University Hospital Frankfurt am Main, No. 2023 − 1444) and conducted in accordance with EU data protection regulations. 4. Consent for publication: For this type of study consent for publication is not required. 5. Competing interests: The authors declare that they have no conflict of interest. Authors’ contributions: The corresponding author declares that the authors have read the manuscript and they all gave permission to submit the work in its current version. TV contributed to the collection of data. KE was involved into data validation. TGR has made substantial contributions to the conception and the design of the study, and the revision of this article. CW administered the study, was involved in data curation, analysis and interpretation of data, drafting the article. All authors read and approved the final manuscript. Acknowledgements: 1. Not applicable. 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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-8673450","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":580636436,"identity":"a7383154-9332-416b-8de9-f90c70ca76e4","order_by":0,"name":"Christian Wolfram","email":"data:image/png;base64,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","orcid":"https://orcid.org/0009-0003-2236-3814","institution":"Universitätsklinikum Frankfurt: Klinikum der Johann Wolfgang Goethe-Universitat Frankfurt","correspondingAuthor":true,"prefix":"","firstName":"Christian","middleName":"","lastName":"Wolfram","suffix":""},{"id":580636437,"identity":"005f8f82-08f6-4e53-bcb6-a9972972a4a4","order_by":1,"name":"Thomas J. Vogl","email":"","orcid":"","institution":"Universitätsklinikum Frankfurt: Klinikum der Johann Wolfgang Goethe-Universitat Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"J.","lastName":"Vogl","suffix":""},{"id":580636438,"identity":"c5f91d98-988e-496b-8374-664e05119a1d","order_by":2,"name":"Katrin Eichler","email":"","orcid":"","institution":"Universitätsklinikum Frankfurt: Klinikum der Johann Wolfgang Goethe-Universitat Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Katrin","middleName":"","lastName":"Eichler","suffix":""},{"id":580636439,"identity":"531d4ee6-73a4-488f-8573-18ba2f29d144","order_by":3,"name":"Tatjana Gruber-Rouh","email":"","orcid":"","institution":"Universitätsklinikum Frankfurt: Klinikum der Johann Wolfgang Goethe-Universitat Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Tatjana","middleName":"","lastName":"Gruber-Rouh","suffix":""}],"badges":[],"createdAt":"2026-01-22 22:25:47","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8673450/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8673450/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101751713,"identity":"0fb51e93-40ef-4000-86bd-60525357dfd9","added_by":"auto","created_at":"2026-02-03 10:22:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2553656,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart of patient selection.\u003c/strong\u003e Flow diagram illustrating the selection of patients treated with lymphangiography between January 2003 and June 2023 (n = 184). Inclusion criteria were age ≥ 18 years (range: 19–87 years), presence of a lymphatic fistula for at least 3 weeks, and unsuccessful conservative treatment (immobilisation and dietary adjustments). A distinction was made between monopedal and bipedal lymphangiography. Of the 184 patients, 84 were treated with monopedal lymphangiography. The diagnosis was categorised as inguinal lymph fistula, lymphocele, chylous ascites, chylothorax, and chylopericardium. Of these, 39 patients suffered from inguinal lymph fistulas. Exclusion criteria were incomplete medical records or the lack of a follow-up examination prior to the evaluation of the results. Only 4 were excluded from the statistical evaluation, while the other 35 patients underwent successful lymphangiography. This resulted in a sample size of 35 patients who were included in the final analysis.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8673450/v1/d43794f9f1e0bbb1f065a7fa.png"},{"id":101459437,"identity":"b0b377a9-0d68-4ee8-b16b-ca11424a4fdc","added_by":"auto","created_at":"2026-01-30 01:29:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":5820669,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOverview of Diagnoses Causing Inguinal Lymphatic Leakage. \u003c/strong\u003eBar chart displaying the underlying diagnoses in 35 patients with inguinal lymphatic leakage.\u003cstrong\u003e \u003c/strong\u003eMost lymphatic leakage cases in the study cohort were due to prior inguinal lymphadenectomy for cutaneous malignant melanoma (82.9%, n = 29), followed by Merkel cell carcinoma (8.6%, n = 3). Less common causes included macrophage activation syndrome (2.9%, n = 1), Kaposi’s sarcoma (2.9%, n = 1), and B-cell lymphoma (2.9%, n = 1).\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8673450/v1/00c04bc49d865b4012638610.png"},{"id":101459434,"identity":"d55f1905-116f-41bb-8fff-451237c1dc01","added_by":"auto","created_at":"2026-01-30 01:29:44","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":299920,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSubcutaneous Injection of Methylene Blue in Preparation for lymphangiography. \u003c/strong\u003eA 42-year-old female patient with lymphatic fistula after inguinal lymphadenectomy. Documentation of the injection of mepivacaine hydrochloride methylene blue dye into the subcutaneous tissues of the first to third interdigital spaces.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8673450/v1/131d935cfd97ba73914082a7.png"},{"id":101459433,"identity":"42d12b0f-bfc3-421d-a816-ed269f518f73","added_by":"auto","created_at":"2026-01-30 01:29:44","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2119953,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTracking of contrast fluid flow via fluoroscopy.\u003c/strong\u003e A 46-year-old male patient with lymphatic fistula after inguinal lymphadenectomy. Documentation of the accumulation of iodized oil in the region of the lymphatic fistula and flow into the drainage immediately after the lymphangiography.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8673450/v1/a96a9f0906c4e08a51600418.png"},{"id":101751694,"identity":"459d9e4d-f35d-4907-8c47-5848cad65d18","added_by":"auto","created_at":"2026-02-03 10:22:37","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":4044690,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eX-Ray 24 hours after intervention. \u003c/strong\u003eA 82-year-old male patient with lymphatic fistula after inguinal lymphadenectomy. Documentation of the visualisation of the lymphatic fistula 24 hours after the lymphangiography.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-8673450/v1/62fe733ba15ba8ca79e8dc69.png"},{"id":101459436,"identity":"2dce273f-9555-4bb6-99b9-af305dacc07d","added_by":"auto","created_at":"2026-01-30 01:29:44","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":3973208,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDaily Drainage Output in Clinically Successful Patients Prior to lymphangiography.\u003c/strong\u003e Box plot depicting daily lymph fistula drainage volumes in 22 clinically successful patients prior to lymphangiography. The mean drainage volume was 212.95 millilitres per day (ml/day) (indicated by the ‘×’ symbol), with a median value of 185 ml/day. The interquartile range extended from 115 ml/day to 262.5 ml/day, and the overall range was 100 to 500 ml/day.\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-8673450/v1/a4298bc84c36a9c23feccf8f.png"},{"id":101755060,"identity":"a15f7f71-9b1f-4ec6-83ae-144ccd782398","added_by":"auto","created_at":"2026-02-03 10:48:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":21896570,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8673450/v1/6d8a15cd-2825-4ccc-aa2a-b4422c5db9cb.pdf"}],"financialInterests":"","formattedTitle":"Evaluation of the therapeutic value of conventional transpedal lymphography for the treatment of inguinal lymphatic fistulas after lymphadenectomy","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eIodised oil-based conventional lymphangiography is a diagnostic imaging technique used to obtain detailed images of the lymphatic system and evaluating conditions like lymphatic fistulas, lymphovenous malformations, lymphatic obstructions, through the injection of an oily contrast agent [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Lipiodol, an iodised oil derived from poppy seeds- Papaver somniferum var, has evolved from a diagnostic contrast agent to a therapeutic tool by enabling the successful closure of lymphatic leaks [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Its mechanism of action is based on the accumulation of Lipiodol at leak sites, physically obstructing lymph flow and triggering a mild sterile inflammatory response leading to fibrosis, thereby occluding the leaking lymphatic vessels in the long term [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This dual diagnostic and therapeutic capability is a distinct advantage over conventional imaging methods. Lastly, in those cases where lymphatic leakage cannot be controlled via medical treatment, consisting of a low-fat, medium-chain triglyceride diet [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], somatostatin treatment or local treatment such as bed rest, elevation of the extremity and compression bandages, lymphatic drainage [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], vacuum therapy [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], lymphangiography is a proven as a minimally invasive method for the treatment of lymphatic leakage comparing to the surgical treatment, which is associated with relatively high complication and mortality rates of up to 38% and 25% respectively, and does not promise complete closure of the fistula [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe comparability of studies regarding the therapeutic effect of conventional lymphangiography is limited due to the analysis of different patient groups, on the one hand, and, on the other hand, due to the different volume ranges of lymphatic drainage. Systematic research in homogeneous patient cohorts, particularly regarding postoperative inguinal lymphatic fistulas, is rare.\u003c/p\u003e \u003cp\u003eTo address this gap, the intention of the study was to evaluate therapeutic effectiveness and safety of lipiodol-based conservative lymphangiography in sealing persistent inguinal lymphatic fistulas after lymphadenectomy and to assess whether there is a correlation between therapeutic success and the amount of injected Lipiodol and the volume of lymphatic drainage accordingly.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient population\u003c/h2\u003e \u003cp\u003eBetween January 2003 and June 2023, 184 patients were treated with lymphangiography in our department. After applying inclusion and exclusion criteria, 35 patients with lymphatic fistula formation in the inguinal region were further recorded and analysed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Patients\u0026rsquo; underlying disease, age, sex, daily lymphatic drainage volume in ml before the lymphangiography procedure, the amount of Lipiodol administered, technical success, whether X-Ray/CT performed after lymphangiography, clinical success, time to resolution, complications and additional interventions are summarised in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The cohort comprised 11 female (31.4%) and 24 male (68.6%) patients, with a median age of 71 years. The age range was from 24 to 87 years, with a mean of 67.2 years. One of the main reasons for lymphatic leakage was prior inguinal lymphadenectomy for diagnosis of cutaneous malignant melanoma (82.85%, n\u0026thinsp;=\u0026thinsp;29) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \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\u003ePatient Characteristics and Outcomes of Lymphatic Intervention\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient no. and underlying disease\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDaily Drain Output (mL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAmount of Lipiodol administered (mL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTechnical Success\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray/CT performed after lymphography\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eClinical Success\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTime to resolution\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eComplication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAdditional intervention\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1/ macrophage activation syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot available\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot available\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eYes, further course is not available\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ew\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot available\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eYes, further course is not available\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ew\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot available\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eYes, further course is not available\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ew\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot available\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9/ Merkel cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ew\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ew\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ew\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13/ B-cell lymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot available\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ew\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19/ Merkel cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot available\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot available\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ew\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e22/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e23/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24/ Merkel cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot available\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eYes, further course is not available\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e26/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ew\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27/ Kaposi's sarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e28/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ew\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e29/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e325\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot available\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e31/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e32/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ew\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot available\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e33/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e34/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot available\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e35/ cutaneous malignant melanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003em\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX-Ray\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNot available\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eLymphangiography procedure\u003c/h3\u003e\n\u003cp\u003eAll 35 patients underwent the same procedure. Following the disinfection of the feet (using Kodan\u0026reg;, Sch\u0026uuml;lke \u0026amp; Mayr GmbH, Norderstedt, Germany), 2 ml of mepivacaine hydrochloride (Scandicaine\u0026reg; 1%, Astra Zeneca GmbH, Wedel, Germany) and 2 ml of methylene blue dye (Patent Blue V, Guerbet GmbH, Sulzbach, Germany) were injected into the subcutaneous tissues of the first to third interdigital spaces (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). After the pedal lymphatic vessels had been adequately coloured, which took around 15 minutes, the patient was placed on an examination table of the X-ray radioscopic system Siemens Axiom Artis MP (Siemens, Forchheim, Germany). The foot was then disinfected again and covered with a sterile fenestrated drape. Following this step, a local anesthetic (Scandicaine\u0026reg;) was injected subcutaneously, and a longitudinal 2 cm skin incision was made on the dorsum of the foot. The lymphatic vessels were carefully dissected free. Using a special spring-loaded needle with a stylet, the most visible lymphatic vessel was cannulated. Adhesive stripes were used to anchor the needle and infusion line. Using a syringe pump with an injection speed of 6\u0026ndash;8 ml/h, Lipiodol was injected at a rate of up to 1 ml/10 kg body weight per foot, up to a maximum volume of 20 ml of iodised oil (48% iodised glycerol ester, Lipiodol\u0026reg; Ultra-Fluid, Guerbet GmbH, Sulzbach, Germany). To monitor the flow of Lipiodol through the lymphatic vessels and to rule out inadvertent venous injection, fluoroscopy was performed. As soon as a fistula was visible or 20 ml of Lipiodol had been injected, the materials were removed, and the incision was carefully disinfected and sutured. The sutures could be removed 10 to 12 days after the procedure. At the end of the procedure, a fluoroscopy of the hip and groin region is usually performed at the surgical site (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The lymphatic fistula was visualized within 24 hours of lymphangiography using X-ray or CT imaging to monitor lymph drainage and rule out further complications (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). If the lymphatic fistula did not close after lymphangiography, either surgical intervention or radiation therapy was performed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eTechnical Success\u003c/h3\u003e\n\u003cp\u003eThe technical success of conventional lymphangiography was characterized by the effective administration of contrast agents, with the aim of clearly visualizing the lymphatic system and all associated lymphatic abnormalities using X-ray images.\u003c/p\u003e\n\u003ch3\u003eClinical Outcome Assessment\u003c/h3\u003e\n\u003cp\u003eTherapeutic success was defined as complete closure of the inguinal lymph fistula after lymphangiography without the need for further surgical or radiotherapeutic interventions. Additionally, the interval between the day of lymphangiography and the day of fistula closure, whether X-ray or CT was performed after lymphangiography, and whether surgical intervention and/or radiation therapy was performed in the case of a persistent lymphatic fistula were recorded in an Excel (2011) spreadsheet. Safety was assessed by the complications following lymphangiography, including but not limited to contrast leakage, wound infection, allergic reactions, embolic events, or other adverse events. Using the Wilcoxon-Mann-Whitney U test was measured the correlation between the lymphatic leakage amount and therapeutic success, as well as the injected volume of Lipiodol and therapeutic success. A p-value\u0026thinsp;\u0026le;\u0026thinsp;0.05 was considered statistically significant. The statistical analysis was performed using the software BiAS version 11.12 (epsilon-Verlag GbR, Frankfurt am Main, Germany).\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePatient Clinical Information\u003c/h2\u003e \u003cp\u003eConventional lymphangiography was performed in all 35 patients. Before the procedure, the average daily volume of lymphatic drainage was 217.43 ml/day. The mean median value was 200 ml/day. Drainage volumes varied considerably, ranging from 50 ml/day to 500 ml/day. The amount of Lipiodol administered varied between 4 ml and 18 ml, averaging 8.77 ml. The median value was 9 ml.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eClinical Outcomes\u003c/h3\u003e\n\u003cp\u003eIn all 35 patients, the fistula site was identified and radiologically documented, resulting in a technical success rate of 100%. In 22 cases, corresponding to a therapeutic success rate of 62.86%, complete closure of the lymphatic fistula was achieved after conventional lymphangiography without the need for further surgical or radiotherapeutic interventions. The 22 clinically successful patients had an average daily lymph fistula volume of 212.95 ml/day prior to the procedure (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). An average of 9 ml of Lipiodol was used, with amounts ranging from 4 to 18 ml. Only in these 22 patients was possible to assess the time between the day of lymphangiography and the day the lymph fistula closed. This time ranged from 1 to 35 days, with an average closure time of 7.13 days. Most of these patients (17) had malignant melanoma as their underlying disease. All clinically successful patients underwent an X-ray the day after lymphangiography, except for one patient who had a CT scan instead. No complications occurred in any of these 22 patients.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThree of the remaining 13 patients underwent surgery based on the lymphographic findings, while six (17.14%) received radiation therapy to completely close the lymph fistula. Sufficient information on the subsequent course of the remaining four patients (11.43%) was not available. The six patients who received radiotherapy had a mean age of 73.3 years (range: 51\u0026ndash;81 years) and a mean lymphatic fistula volume of 279.16 ml (range: 150\u0026ndash;500 ml). Each of these patients had malignant melanoma. On average, 9.16 ml of Lipiodol was used, with a range of 8 to 12 ml.\u003c/p\u003e \u003cp\u003eThe success of the therapy was independent of the amount of lymphatic drainage and the amount of Lipiodol administered. The Wilcoxon-Mann-Whitney U test, used for statistical analysis, showed no difference in the distribution of the amount of Lipiodol administered and the therapeutic effect of lymphangiography (p\u0026thinsp;=\u0026thinsp;0.51). Similarly, the daily amount of lymphatic drainage had no significant effect on the success rate of the therapy (p\u0026thinsp;=\u0026thinsp;0.82).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eConventional lymphangiography was found to be safe and in most cases therapeutically effective. Current literature is mainly limited to the studies [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], which focus on different lymphatic flow locations, such as chylothorax, chylous ascites, thoracic and inguinal lymphatic fistulas, pelvic lymphatic fistulas, abdominal and peripheral lymphatic fistulas, thoracic, abdominal and peripheral lymphoceles, or cervical lymphoceles. While the total number of patients in most of these studies is 22 or fewer [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], only three studies report populations of 355 [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], 64 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and 43 patients [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], respectively. The technical success rate lymphangiography, defined similarly to our study as the successful injection of Lipiodol into lymphatic vessels with the aim of clearly visualising the lymphatic system and all associated lymphatic abnormalities using fluoroscopy, ranges in other studies from 86% to 100% [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In cases where lymphangiography failed and where the fistula site could not be identified and radiologically confirmed, the reasons were mainly fragile lymphatic vessels, disturbances in contrast medium outflow, or lymphoedema [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Whereas the therapeutic success rate ranges between 51% and 75% and is defined by the authors similarly to our study as complete closure of the lymph fistula after lymphangiography without the need for further surgical or radiotherapeutic interventions [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In this study was evaluated the therapeutic value of conventional lymphangiography on a homogeneous patient group with exclusively persistent inguinal lymph fistulas after lymphadenectomy. Despite differences in the patient population with other abovementioned studies, the technical success rate of 100% and the therapeutic success rate of 62.86% in our study correlate with those others, proving that conventional lymphangiography is effective in a significant proportion of cases in sealing persistent inguinal lymphatic fistulas after lymphadenectomy in addition to being an efficient diagnostic tool. Additionally, in both our work and the studies listed above, there were no complications (including, but not limited to, contrast leakage, wound infection, allergic reactions, embolic events or other adverse events), which proves the safety of this treatment. Interestingly, the total time from the day of lymphangiography to the day of fistula closure ranged from approximately 1 day to 4 weeks, which correlates well with our results of 1 day to 5 weeks. Furthermore, the median value (7.13 days) is nearly identical to the values ​​reported by Kortes et al [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and Pan et al [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] (5 days; other authors did not report the median). Additional therapies used in the other studies for clinically unsuccessful patients included surgical interventions, immediate or delayed sclerotherapy, pleurosclerosis, and peritoneovenous shunt. While in our study almost half of the unsuccessful patients received radiotherapy (6 out of 13) and another third (4 out of 13) underwent surgery, lymphangiography was helpful in the planning of surgery due to the visualisation of the lymphatic defect.\u003c/p\u003e \u003cp\u003eThe Wilcoxon-Mann-Whitney U test in our study indicated that there is no correlation between the injected lipiodol and therapeutic success (p\u0026thinsp;=\u0026thinsp;0.51). Gruber-Rouh et al reached the same conclusion [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], while other studies did not investigate such a correlation. However, Pan et al [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] found that a significantly higher volume of Lipiodol was injected in patients with chylothorax than in those with inguinal lymph fistula (p\u0026thinsp;=\u0026thinsp;0.007). Therefore, the patient population could be one reason for the absence of such a correlation. The results regarding the correlation between daily lymphatic drainage volume and therapeutic success rate are contradictory. In the study by Gruber-Rouh et al [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], considering patients with a lymphatic drainage volume of less than 200 ml/day (instead of the original range of 10 to 1000 ml/day) would impact the success rate, which would be 96.8% instead of 70.3%. But even in patients with more than 200 ml/day, the therapeutic success rate was 58.1%. The same result regarding the correlation between drainage volume and therapeutic success came from Alejandre-Lafont et al [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] where occlusion occurred in 70% of patients with a lymphatic drainage volume of less than 500 ml/day, while the success rate dropped to 35% with a lymphatic drainage volume of more than 500 ml/day. In contrast, in the study by Kortes et al [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] occlusion was only observed in patients whose outflow volume exceeded 1,000 ml/day. Pan et al [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] report that a drainage volume greater than 500 ml/day correlates with treatment failure (p\u0026thinsp;=\u0026thinsp;0.025). However, this correlation is based on a total of 258 patients (258 of 355 were treated with lymphangiography only), and they had various clinical diagnoses of lymphatic leaks. Out of the total cohort, only 134 patients had inguinal fistulas, with their drainage volume ranging from 200 to 400 ml per day and averaging 300 ml per day; thus, the general statement about the overall patient population does not apply exclusively to those with inguinal lymphatic fistulas. Our patients fall within almost the same drainage volume range (50 to 500 ml) and have an average of 217.43 ml/day. Most importantly, the average volume of lymph leakage in clinically successful patients was 212.95 ml/day, while for the 13 clinically unsuccessful patients it was 225 ml/day. These results suggest that the baseline severity of the lymph leak, as measured by the daily fistula volume, is not always a reliable predictor of therapeutic success in patients with less than 500 ml/day. This supports that the therapeutic effect is independent of the volume of lymphatic drainage at the time of intervention.\u003c/p\u003e \u003cp\u003eThe specific patient group contributes to this finding, as our study focused exclusively on patients with inguinal fistulas. This lack of association may indicate that other factors, such as the precise anatomical features of the leak or the underlying disease process, could have a more decisive influence on the effectiveness of lymphangiography. Despite the lack of a significant relationship between lymphatic drainage volume and therapeutic success (p\u0026thinsp;=\u0026thinsp;0.82), the result of our statistical analysis (62.86%) is nearly identical to that of patients with inguinal lymphatic fistulas in the study by Pan et al (62.2%) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and that of the various patients in the study by Alejandre-Lafont et al (70%) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Furthermore, it is acknowledged that if the daily fistula volume in our study were higher than 500 ml/day, this could lead to the correlation proposed by Alejandre-Lafont et al [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe limitations of the present study lie in the absence of a prospective follow-up study, as retrospective analyses have such constraints as long-term outcomes after discharge or later complications are not always fully recorded. Additionally, the present study focuses solely on transpedal lymphangiography and not intranodal method. Lastly, there is a lack of data recording other variables in clinically unsuccessful patients, such as the time interval between additional intervention and complete fistula closure and specific complications after radiotherapy or surgical intervention in this context.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eIn conclusion, conventional lipiodol-based lymphangiography is effective and safe as an adjunct to conservative treatments. The lack of association between Lipiodol, or drainage volume, and outcome suggests that therapeutic success may depend more on anatomical and disease-specific factors, which underscores the necessity for a more individualised approach when selecting patients and planning subsequent interventions.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003em\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ef\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efemale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecomputed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003en\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enumber\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ep\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eprobability value\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis study was not supported by any funding.\u003c/p\u003e \u003cp\u003e2. Availability of data and materials: All data generated or analysed during this study are included in this published article.\u003c/p\u003e \u003cp\u003e3. Ethical approval: All procedures performed in studies involving human participants 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. Since this study was a retrospective audit of anonymized patient records, formal retrospective consent was not required. The study was approved by the local ethics committee (University Hospital Frankfurt am Main, No. 2023\u0026thinsp;\u0026minus;\u0026thinsp;1444) and conducted in accordance with EU data protection regulations.\u003c/p\u003e \u003cp\u003e4. Consent for publication: For this type of study consent for publication is not required.\u003c/p\u003e \u003cp\u003e5. Competing interests: The authors declare that they have no conflict of interest.\u003c/p\u003e\u003ch2\u003eAuthors\u0026rsquo; contributions:\u003c/h2\u003e \u003cp\u003eThe corresponding author declares that the authors have read the manuscript and they all gave permission to submit the work in its current version. TV contributed to the collection of data. KE was involved into data validation. TGR has made substantial contributions to the conception and the design of the study, and the revision of this article. CW administered the study, was involved in data curation, analysis and interpretation of data, drafting the article. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements:\u003c/h2\u003e \u003cp\u003e1. Not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKinmonth JB (1952) Lymphangiography in man; a method of outlining lymphatic trunks at operation. 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J Vasc Interv Radiol JVIR 27(12):1890\u0026ndash;1896. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jvir.2016.06.030\u003c/span\u003e\u003cspan address=\"10.1016/j.jvir.2016.06.030\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\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":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"cvir-endovascular","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cire","sideBox":"Learn more about [CVIR Endovascular](https://www.springer.com/journal/42155)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/cire/default.aspx","title":"CVIR Endovascular","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"lymphangiography, Lymphatic Intervention, Lipiodol, Postoperative Lymphatic Leakage, Inguinal Lymphatic Fistula","lastPublishedDoi":"10.21203/rs.3.rs-8673450/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8673450/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo evaluate therapeutic effectiveness and safety of lipiodol-based conservative transpedal lymphangiography in sealing persistent inguinal lymphatic fistulas after lymphadenectomy, and to determine whether therapeutic success is influenced by the amount of injected Lipiodol or the volume of lymphatic drainage.\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e \u003cp\u003eFrom January 2003 to June 2023, 184 patients underwent lymphangiography. Of these, 35 patients (24 male, 11 female; aged 24 to 87 years) met inclusion criteria (age\u0026thinsp;\u0026ge;\u0026thinsp;18 years, persistent lymphatic leakage after inguinal lymphadenectomy (\u0026gt;\u0026thinsp;3 weeks), following unsuccessful conservative management) and were subsequently included for statistical analysis. Lipiodol lymphangiography was performed via transpedal lymphatic vessel cannulation. Data collected included: age, sex, underlying disease, drainage volume before lymphangiography Lipiodol amount, procedural details, time to fistula closure, imaging follow-ups, technical success, therapeutic success and its correlation with the volume of lymphatic leakage and the volume of the applied iodised oil, complications, and additional interventions. Statistical analysis utilised the Wilcoxon\u0026ndash;Mann\u0026ndash;Whitney test (significance at p\u0026thinsp;\u0026le;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTherapeutic success was achieved in 22 patients (62.86%) without complications, with a mean resolution time of 7.13 days. 13 patients (37.14%) required additional interventions. No significant correlation was found between therapeutic success and either the amount of Lipiodol used (p\u0026thinsp;=\u0026thinsp;0.51) or drainage volume (p\u0026thinsp;=\u0026thinsp;0.82).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eLipiodol-based lymphangiography is an effective and safe treatment for inguinal lymphatic fistulas. The lack of association therapeutic outcome with Lipiodol or drainage volume appears to be more related to anatomical and disease-specific factors, suggesting individualized patient assessment is warranted.\u003c/p\u003e","manuscriptTitle":"Evaluation of the therapeutic value of conventional transpedal lymphography for the treatment of inguinal lymphatic fistulas after lymphadenectomy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-30 01:29:39","doi":"10.21203/rs.3.rs-8673450/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2026-01-27T16:15:46+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-26T16:06:10+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-26T06:30:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"CVIR Endovascular","date":"2026-01-23T16:19:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cvir-endovascular","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cire","sideBox":"Learn more about [CVIR Endovascular](https://www.springer.com/journal/42155)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/cire/default.aspx","title":"CVIR Endovascular","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a8325447-f9a4-4f7b-9ae6-c146cc9dc833","owner":[],"postedDate":"January 30th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T21:20:01+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-30 01:29:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8673450","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8673450","identity":"rs-8673450","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}