No Clinical Efficacy of Adipose-Derived Regenerative Cells and Lipotransfer in Breast Cancer-Related Lymphedema: A double-blinded placebo-controlled phase-II trial.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a debilitating sequela affecting up to one in three breast cancer survivors. Current treatments are palliative and does not address the underlying lymphatic injury. Recently, preclinical and non-randomized studies have shown promising results using Adipose-Derived Regenerative Cells (ADRCs) and lipotransfer in alleviating BCRL through regeneration of lymphatic tissue. However no randomized controlled trial has been performed in an attempt to eliminate a placebo effect. METHODS: This randomized, double-blinded, placebo-controlled trial included patients with no-option, persistent disabling unilateral BCRL. Patients were randomly assigned in a 1:1 ratio to receive either autologous ADRCs (4.20x10 7±1.75x10 7 cells) and 30cc lipotransfer or placebo (saline) to the axilla. The primary outcome was a change in BCRL volume one year after treatment. Secondary outcomes included changes in the quality of life, indocyanine green lymphangiography stage, bioimpedance, and safety. RESULTS: Eighty patients were included, of which 39 were allocated to ADRCs and lipotransfer treatment and 41 to placebo treatment. Baseline characteristics were similar in both groups. One year after treatment, no objective improvements were observed in the treatment or placebo groups. In contrast, significant subjective improvements were noted for both the treatment and placebo groups. CONCLUSION: This trial failed to confirm a benefit of ADRCs and lipotransfer in the treatment of BCRL. These non-confirmatory results suggest that ADRC and lipotransfer should not be recommended for alleviating BCRL at this time. However, we cannot exclude that repeated treatments or higher doses of ADRCs or lipotransfer could yield a clinical effect.

Surgical treatment algorithm for breast cancer lymphedema-a systematic review.

Background: Various surgical treatments are increasingly adopted and gaining popularity for lymphedema treatment. However, challenges persist in selecting appropriate treatment modalities targeted for individual patients and achieving consensus on choice of treatment as well as outcomes. The systematic review aimed to create a treatment algorithm incorporating the latest scientific knowledge, to provide healthcare professionals and patients with a tool for informed decision-making, when selecting between treatments or combining them in a relevant manner. This systematic review evaluated and synthesized the evidence on the effectiveness of three surgical treatments for breast cancer-related lymphedema (BCRL): lymphovenous anastomosis (LVA), vascularized lymph node transfer (VLNT), and liposuction. Methods: We conducted a systematic search of electronic databases on 18 June 2023, including Medline, Embase, Cochrane Library, Google Scholar, and ClinicalTrials.org. Eligible studies were randomized controlled trials, non-randomized comparative studies, and observational studies that assessed the outcomes of LVA, VLNT, or liposuction in managing BCRL. The primary results of interest were changes in arm volume, lymphatic flow, and quality of life. Two independent reviewers performed the study selection and data extraction. Following this, we systematically reviewed and conducted a risk of bias assessment. Results were qualitatively presented, and a treatment algorithm was developed based on the available data. Results: We identified 16,593 papers, after removal of duplicates. Following assessment of studies, 73 articles met the inclusion criteria, including 2,373 patients. We were not able to conduct a meta-analysis due to considerable heterogeneity in the methodologies and outcome measures across the studies. Liposuction appears effective for patients presenting with non-pitting lymphedema. LVA indicates variable success rate, with some evidence indicating a reduction in limb volume and symptomatic relief amongst early stages of lymphedema. VLNT showed promising results for limb volume reduction and symptom improvement in patients presenting with mild and moderate lymphedema. Conclusions: Liposuction, LVA, and VLNT seem to be effective treatments for BCRL, when targeted for the appropriate patient. Well-conducted high evidence clinical studies in the field are still lacking to uncover the efficacy of surgical treatment for BCRL.

Iterative qualitative approach to establishing content validation of a patient-reported outcome measure for arm lymphedema: the LYMPH-Q Upper Extremity Module.

BACKGROUND: Breast cancer-related lymphedema (BRCL) is one of the most common causes of upper extremity (UE) lymphedema in developed nations and substantially impacts health-related quality of life. To advance our understanding of the epidemiology and treatment of BRCL, rigorously developed and validated patient-reported outcome measures (PROMs) are needed. This study aimed to demonstrate the iterative content validity of a modular UE lymphedema-specific PROM called the LYMPH-Q UE module. METHODS: A multi-step iterative qualitative approach was used. Semi-structured interview data from in-depth qualitative interviews with adult women (18 years and older) with BCRL were used to develop the first set of the LYMPH-Q UE scales. The content validity of these scales was demonstrated with patient and clinician feedback. Over the course of cognitive debriefing interviews, additional concepts of lymphedema worry and impact on work were identified as missing from the LYMPH-Q UE module. Subsequently, two new qualitative studies (a focus group and in-depth concept elicitation interviews with patients) were conducted, and two new scales were developed to measure lymphedema worry and impact on work life and their content validity was demonstrated. RESULTS: Qualitative data from in-depth and cognitive interviews with 15 (age 40-74 years) and 16 (age 38-74 years) women with BRCL, respectively, and feedback from 12 clinical experts, were used to develop and demonstrate the content validity of six LYMPH-Q UE scales measuring symptoms, function, appearance, psychological, information, and arm sleeve. Additionally, data from in-depth interviews with 12 (age 35-72 years) women with UE lymphedema and four focus groups (n = 16 women; age 35-74 years) was used to develop and assess the content validity of two new LYMPH-Q UE scales measuring lymphedema worry and impact on work life. The content validity of the previously established six scales was also demonstrated in these subsequent qualitative studies. CONCLUSION: The LYMPH-Q UE is a modular PROM developed using international guidelines for PROM development and can be used in clinical practice, research, and quality improvement to enhance patient-centered shared decision-making. This study's innovative and iterative approach to content validation demonstrates that the LYMPH-Q UE is a comprehensive measure that includes important concepts relevant to patients with UE lymphedema.

Robot-assisted lymphovenous anastomosis surgery for lymphocele in the groin.

We present the first-in-human robot-assisted microsurgery on a lymphocele in the groin involving a man in his late 60s who had been coping with the condition for 12 months. Despite numerous efforts at conservative treatment and surgical intervention, the lymphocele persisted, leading to a referral to our clinic.Diagnostic techniques, including indocyanine green lymphography and ultrasound, identified one lymphatic vessel draining into the lymphocele. The surgical intervention, conducted with the assistance of a robot and facilitated by the Symani Surgical System (Medical Microinstruments, Calci, Italy), involved a lymphovenous anastomosis and excision of the lymphocele. An end-to-end anastomosis was performed between the lymphatic and venous vessels measuring 1 mm in diameter, using an Ethilon 10-0 suture.The surgery was successful, with no postoperative complications and a prompt recovery. The patient was discharged 3 days postoperatively and exhibited complete recovery at the 14-day follow-up. This case marks the first use of robot-assisted microsurgical lymphovenous anastomosis to address a groin lymphocele, highlighting the benefit of advanced robotic technology in complex lymphatic surgeries.

Identifying health-related quality of life concepts to inform the development of the WOUND-Q.

OBJECTIVE: The impact of hard-to-heal wounds extends beyond traditional clinical metrics, negatively affecting a patient's health-related quality of life (HRQoL). Yet treatment outcomes are seldom measured from the patient's perspective. The purpose of the present study was to perform in-depth qualitative interviews with patients diagnosed with varying types of hard-to-heal wounds to identify outcomes important to them. METHOD: Participants were recruited from wound care clinics in Canada, Denmark, the Netherlands and the US, and were included if they had a hard-to-heal wound (i.e., lasting ≥3 months), were aged ≥18 years, and fluent in English, Dutch or Danish. Qualitative interviews took place between January 2016 and March 2017. An interpretive description qualitative approach guided the data analysis. Interviews were audio-recorded, transcribed and coded line-by-line. Codes were categorised into top-level domains and themes that formed the final conceptual framework. RESULTS: We performed 60 in-depth interviews with patients with a range of wound types in different anatomic locations that had lasted from three months to 25 years. Participants described outcomes that related to three top-level domains and 13 major themes: wound (characteristics, healing); HRQoL (physical, psychological, social); and treatment (cleaning, compression stocking, debridement, dressing, hyperbaric oxygen, medication, suction device, surgery). CONCLUSION: The conceptual framework developed as part of this study represents the outcome domains that mattered the most to the patients with hard-to-heal wounds. Interview quotes were used to generate items that formed the WOUND-Q scales, a patient-reported outcome measure for patients with hard-to-heal wounds.

Surgical lymphedema models in the mice hindlimb-A systematic review and quality assessment.

BACKGROUND: Lymphedema constitutes a major unsolved problem in plastic surgery. To identify novel lymphedema treatments, preclinical studies are vital. The surgical mouse lymphedema model is popular and cost-effective; nonetheless, a synthesis and overview of the literature with evidence-based guidelines is needed. The aim of this review was to perform a systematic review to establish best practice and support future high-quality animal studies exploring lymphedema treatments. METHODS: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching four databases (PubMed, Embase, Web of Science, and Scopus) from inception-September 2022. The Animals in Research Reporting In Vivo Experiments 2.0 (ARRIVE 2.0) guidelines were used to evaluate reporting quality. Studies claiming to surgically induce lymphedema in the hindlimb of mice were included. RESULTS: Thirty-seven studies were included. Four main models were used. (1) Irradiation+surgery. (2) A variation of the surgery used by (1) + irradiation. (3) Surgery only (SPDF-model). (4) Surgery only (PLND-model). Remaining studies used other techniques. The most common measurement modality was the caliper. Mean quality coefficient was 0.57. Eighteen studies (49%) successfully induced sustained lymphedema. Combination of methods seemed to yield the best results, with an overrepresentation of irradiation, the removal of two lymph nodes, and the disruption of both the deep and superficial lymph vessels in the 18 studies. CONCLUSION: Surgical mouse hindlimb lymphedema models are challenged by two related problems: (1) retaining lymphedema for an extended period, that is, establishing a (chronic) lymphedema model (2) distinguishing lymphedema from post-operative edema. Most studies failed to induce lymphedema and used error-prone measurements. We provide an overview of studies claiming to induce lymphedema and advocate improved research via five evidence-based recommendations to use: (1) a proven lymphedema model; (2) sufficient follow-up time, (3) validated measurement methods; (4) ARRIVE-guidelines; (5) contralateral hindlimb as control.

Diagnostic Accuracy of Up-Front PET/CT and MRI for Detecting Cervical Lymph Node Metastases in T1-T2 Oral Cavity Cancer-A Prospective Cohort Study.

The diagnostic accuracy of up-front 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for detecting cervical lymph node metastases in patients with T1-T2 oral squamous cell carcinoma is reported with large discrepancies across the literature. We investigated the sensitivity, specificity, positive and negative predictive value, and accuracy of up-front PET/CT for detecting cervical lymph node metastases in this patient group and compared the performance to magnetic resonance imaging (MRI). In this prospective cohort study, 76 patients with T1-T2 oral squamous cell carcinoma underwent an up-front PET/CT and MRI at the Odense University Hospital from September 2013 to February 2016. Sentinel node biopsy and elective neck dissection were used for histopathological verification of the imaging modalities. Up-front PET/CT was significantly more sensitive than neck MRI (74% vs. 27%, p = 0.0001), but less specific (60% vs. 88%, p = 0.001). The accuracy of PET/CT and neck MRI was comparable (66% vs. 63%, p = 0.85), the PPV was slightly in favor of neck MRI (56% vs. 62%, p = 0.73), the NPV was slightly in favor of PET/CT (77% vs. 63%, p = 0.16). Neither PET/CT nor neck MRI should stand alone for N-staging T1-T2 oral cavity cancer.

Missed cancer in the Danish head and neck cancer fast-track program: results from a tertiary cancer center.

BACKGROUND: The Danish head and neck cancer fast-track program is a national standardized pathway aiming to reduce waiting time and improve survival for patients suspected of cancer in the head and neck (HNC). Until now, the frequency of missed cancer in the fast-track program has not been addressed. A missed cancer leads to treatment delay and may cause disease progression and worsening of prognosis. The study objective was to estimate the frequency of patients with missed cancers in the Danish HNC fast-track program and to evaluate the accuracy of the program. MATERIALS AND METHODS: Patients who were rejected from the HNC fast-track program because cancer was not found between 1 July 2012 and 31 December 2018 at Odense University Hospital, Denmark were included and followed for three years. Patients were categorized into groups depending on the diagnostic evaluation. Group 1 included patients evaluated with standard clinical work-up without imaging and biopsy. Group 2 included patients evaluated with imaging and/or biopsy in addition to the standard clinical work-up. The local cancer database and electronic patient records were reviewed to determine if a missed cancer had occurred within the follow-up period. RESULTS: A total of 8345 HNC fast-track courses were initiated during the study period. 1499 were patients suspected of recurrent cancer and were excluded leaving 6846 patients to be assessed for eligibility. Of these, 3752 patients were rejected because cancer was not found. Ten patients were subsequently diagnosed with cancer within the follow-up period resulting in an overall frequency of 0.15%. For group 1 and 2, the frequency was 0.04% and 0.10%, respectively. The sensitivity of the fast-track program was 99.67% and the negative predictive value was 99.73%. CONCLUSION: The frequency of missed cancer in a tertiary HNC center following the Danish fast track program is low.

Short term treatment of secondary lymphedema with hyaluronidase injections reduces mouse hindlimb lymphedema.

Lymphedema is a common complication following breast cancer treatment with axillary lymphadenectomy and radiotherapy. Currently, there is no curative treatment for this disease, hence there is a need for new therapeutic suggestions. The aim of this study was to investigate the effect of hyaluronidase (HYAL) injections after inducing hindlimb lymphedema in 36 female C57BL/6 mice. HYAL injections were administered every second day for 14 days in three groups: (1) HYAL for 1 week followed by saline for 1 week, (2) HYAL for 2 weeks, and (3) saline injections for 2 weeks. Volume of the lymphedema limb was weekly assessed with micro-computed tomography (µ-CT) scans for a total course of 6 weeks. Lymph vessel morphometry was assessed in the end of the study after staining cross-sections of the hindlimb for anti-LYVE-1 blindly. Lymphatic function was assessed by lymphoscintigraphy to assess lymphatic clearance. There was a significant reduction of the volume of lymphedema in mice treated with HYAL-7 compared with mice treated with HYAL-14 (p < 0.05) and saline (p < 0.05). No differences were detected in lymph vessel morphometry and the lymphoscintigraphy between groups. Short-term treatment with HYAL-7 might be a potential therapeutic suggestion for secondary lymphedema induced in mouse hindlimbs. In the future, clinical studies are needed to investigate the potential of HYAL treatment in human beings.

Arm and thigh plasty after massive weight loss.

Massive weight loss patients are often left with significant excess skin, which is associated with reduced quality of life and physical limitations due to the symptoms from the excess skin including pendulation, skin maceration, wounding, pain, and infection. The arm and thigh plasty are procedures that reduce the patient's physical symptoms and increase the quality of life by removing excess skin and shaping the remaining tissue. The aim of this review is to describe patient selection for the arm and thigh plasty, discuss indications, surgical principles, and common complications.

Treatment of Breast Cancer-Related Lymphedema With Topical Tacrolimus: A Prospective, Open-Label, Single-Arm, Phase II Pilot Trial.

PURPOSE: Breast cancer-related lymphedema (BCRL) is a chronic, progressive side effect of breast cancer treatment, occurring in one-third of patients treated with axillary lymph node dissection and nodal radiotherapy. Cluster of differentiation 4-positive (CD4+) cells plays a key role in BCRL by facilitating inflammation and inhibiting lymphangiogenesis. Tacrolimus is an anti-inflammatory and immunosuppressive macrolide that targets CD4+ cells. Treatment of lymphedema with topical tacrolimus has revealed promising results in preclinical trials. This clinical trial was aimed at evaluating the feasibility, safety, and effect of tacrolimus in women with stage I or II BCRL, according to the International Society of Lymphology. METHODS: We conducted this open-label, single-arm, phase II pilot trial from September 2020 to April 2021. Eighteen women with BCRL stage I or II BCRL were treated with topical tacrolimus for 6 months and followed up at 3 and 6 months. The primary outcome was arm volume, and secondary outcomes were the lymphedema index (L-Dex), health-related quality of life (HRQoL), lymph flow and function, and safety and feasibility of the trial design. RESULTS: The mean lymphedema arm volume and L-Dex reduced significantly by 130.44 ± 210.13 mL (p < 0.05; relative reduction: 3.6%) and 3.54 ± 4.98 (p < 0.05), respectively, and health-related quality of life scores was improved significantly (p < 0.05). According to the MD Anderson scale, in terms of lymph flow and function, three patients (16.7%) showed improvement, while none showed worsening. Lymph flow or function showed no change according to the Arm Dermal Backflow scale. CONCLUSION: In this trial, treatment with tacrolimus was safe and feasible in women with stage I or II BCRL. Tacrolimus alleviated BCRL in terms of improved arm volume, L-Dex, and HRQoL. Assessments of lymph flow and function were positive, although inconclusive. Larger randomized controlled trials are required to verify these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04541290.

Body Contouring Surgery Improves Long-Term Satisfaction with Appearance and Health-Related Quality of Life after Bariatric Surgery.

BACKGROUND: Patient-reported outcomes are crucial in bariatric surgery (BaS) and body contouring surgery (BC) because patients' goals include improvement in appearance and health-related quality of life (HR-QOL). The BODY-Q is a patient-reported outcome measure developed to measure change in satisfaction with appearance and HR-QOL in BaS and BC patients. The aim of this study was to examine BODY-Q scores over the entire weight loss journey, and to investigate the impact of BC after BaS. METHODS: Patients completed the BODY-Q before and after BaS and BC at four hospital departments in Denmark between 2015 and 2019. Cross-sectional scores were analyzed by phase of weight loss journey using one-way analysis of variance. Scores for patients who provided longitudinal assessments were analyzed using repeated measures analysis of variance and paired t test. The impact of BC was examined over time after BaS, using an independent t test from before BaS through more than 7 years after BaS. RESULTS: The study included 1527 patients who provided 2285 BODY-Q assessments. The cross-sectional analysis by phase of weight loss journey showed higher scores after BaS, lower scores before BC, and highest-level scores after BC. The longitudinal analysis showed higher postoperative mean scores compared with preoperative scores for both BaS and BC. The analysis over time after BaS revealed lower mean scores in patients who did not receive BC. CONCLUSION: The authors' results provide evidence of the positive impact of BaS and BC on patients' lives and emphasize the importance of considering BC to finalize the weight loss journey, as it helps to maintain improvements in appearance and HR-QOL. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Microsurgical replantation of a traumatic total scalp avulsion.

We present a rare case of microsurgical replantation of a total scalp avulsion. A woman in her mid-60s was renovating a tractor when her hair was caught in a column drill resulting in traumatic scalp avulsion. The avulsed scalp involved the eyebrows and the entire hair-covered part of the scalp. The prehospital management and the conservation packing of the scalp was very effective. Microsurgical replantation was achieved with anastomoses of the left superficial temporal artery and one temporal vein on each side. The combination of the prehospital treatment and our university hospital setup made it possible to reattach the scalp with an ischaemia time of approximately 5 hours. A functional and aesthetically pleasing outcome was achieved, and the patient was discharged 6 days postoperatively with a vital scalp and no complaints. Five months postoperatively, she has no sign of alopecia and is regaining sensation and function of the scalp.A woman in her mid-60s was renovating a tractor when her hair was caught in a column drill resulting in traumatic scalp avulsion. The avulsed scalp involved the eyebrows and the entire hair-covered part of the scalp. The prehospital management and the conservation packing of the scalp was very effective.

[Alternatives to wire localization of non-palpable breast lesions].

With the introduction of screening mammography, the proportion of smaller, clinically recognised tumors has increased. In cases in which lesions cannot be palpated, a guidewire or a wireless marker is placed. Wire localization is associated with several limitations, despite its status as gold standard. Several wireless methods that meet these limitations have been developed. Methods that increase efficiency and patient satisfaction. This review provides an overview of the existing literature on intra-operative localization methods, and the risk of re-resection associated with excision of non-palpable mammary lesions.

Can prophylactic incisional negative pressure wound therapy Reduce Wound Complications After Inguinal Lymph Node Dissection for Melanoma? Results from a Randomized Controlled Trial.

Background: Inguinal lymph node dissection (ILND) is associated with a high complication rate. Retrospective studies suggest that incisional negative pressure wound therapy (iNPWT) might reduce complications, especially seroma, following ILND. Methods: This was a prospective multicenter, randomized (1:1), open-labeled, parallel-group trial. Patients with macrometastic melanoma to the inguinal lymph nodes and eligible for ILND were randomized to receive either iNPWT for 14 postoperative days or conventional wound dressing. The primary outcome was seroma incidence. Secondary outcomes included surgical-site infection, wound rupture, wound necrosis, hematoma, rehospitalization and readmission rates between groups. All outcomes were registered 3 months after ILND and analyzed according to the intention-to-treat principle. Results: The trial was terminated early due to a low recruitment rate as a consequence of a change in the national treatment protocol, and the estimated sample size was not reached. Twenty patients were included and randomized in the study. The trial showed less seroma formation between the iNPWT 6/11 (55%) and control 7/9 (78%) groups; however, this was not statistically significant (p = 0.29). Similarly, there were no differences in the rates of surgical-site infection (p = 0.63), wound rupture (p = 0.19), wound necrosis (p = 0.82), hematoma (p = 0.19), reoperation (p = 0.82) or readmission (p = 0.34) between groups. Conclusion: There was a tendency toward fewer complications in the iNPWT group, however this trial was underpowered and could not confirm the hypothesis that iNPWT reduces complications after ILND. Future randomized controlled trials are required to fully evaluate the treatment potential of iNPWT. Trial registration: The trial was prospectively registered at https://clinicaltrials.gov/ct2/show/NCT03433937.

Inter- and Intrarater Reliability and Agreement Among Danish Head and Neck Pathologists Assessing Extranodal Extension in Lymph Node Metastases from Oropharyngeal Squamous Cell Carcinomas.

BACKGROUND: Extranodal extension (ENE) in lymph node metastases is one of the most important prognostic factors in head and neck squamous cell carcinomas. Studies have shown inconsistency among pathologists in the assessment of ENE. The aims of this study were: (1) to determine the interrater and intrarater reliability and agreement in the assessment of ENE among Danish pathologists and (2) to test if a standardized assessment method may increase interrater agreement. METHODS: Four Danish head and neck pathologists assessed ENE presence or absence in 120 histological slides from lymph nodes with oropharyngeal squamous cell carcinoma metastases (first round). Subsequently, guidelines were introduced to the pathologists and a new assessment was performed (second round). Finally, two of the pathologists assessed the slides to determine intrarater reliability and agreement (third round). RESULTS: Interrater kappa coefficients varied between 0.57 and 0.67 in the first round and between 0.59 and 0.72 in the second round. The intrarater agreement between round 2 and 3 was 0.88 for pathologist 1 and 0.92 for pathologist 2 with resulting kappa coefficients of 0.76 (95% CI 0.64-0.88) and 0.84 (95% CI 0.74-0.94), respectively. CONCLUSION: We found a moderate level of reliability and agreement among pathologists for ENE in lymph node metastases from oropharyngeal squamous cell carcinomas. The intrarater reliability and agreement was generally higher than interrater measures. Interrater agreement was slightly improved by standardized assessment.

Reconstruction of a knee defect in a morbidly obese patient with a pedicled reverse anterolateral thigh flap.

The anterolateral thigh (ALT) flap is widely used in the reconstruction of a variety of soft tissue defects. Descriptions of patients with severe obesity in the literature are scarce. We report a case where a reverse pedicled fasciocutaneous ALT flap was successfully used for resurfacing of a knee defect measuring 12×6 cm in a patient with a body mass index (BMI) of 47.3. The flap was supercharged to the greater saphenous vein to optimise flap survival. Reconstruction of the soft tissue of the knee was achieved as planned. There were no flap or donor site complications.

Microcomputed tomography versus plethysmometer and electronic caliper in the measurements of lymphedema in the hindlimb of mice.

Lymphedema affects 20% of women diagnosed with breast cancer. It is a pathology with no known cure. Animal models are essential to explore possible treatments to understand and potentially cure lymphedema. The rodent hindlimb lymphedema model is one of the most widely used. Different modalities have been used to measure lymphedema in the hindlimb of mice, and these are generally poorly assessed in terms of the interrater agreement; thus, there could be a risk of measuring bias and poor reproducibility. We examined the interrater agreement of µCT-scans, electronic caliper thickness of the paw and plethysmometer in the measurement of lymphedema in the hindlimb of mice. Three independent raters assessed 24 C57BL6 mice using these three modalities four times (week 1, 2, 4 and 8) with a total of 96 samples. The mean interrater differences were then calculated. The interrater agreement was highest in the µCT-scans, with an extremely low risk of measurement bias. The interrater agreement in the plethysmometer and electronic caliper was comparable with a low to moderate risk of measurement bias. The µCT-scanner should be used whenever possible. The electronic caliper should only be used if there is no µCT-scanner available. The plethysmometer should not be used in rodents of this size.