Severe midface necrosis after liver failure induced fungal infection: A case report on the outcome after reconstruction.

INTRODUCTION: Reconstruction of the complex anatomy of the midface is challenging and requires meticulous preparation. Immunosuppression therapy increases patient susceptibility to infection and can compromise wound healing. PRESENTATION OF CASE: A 22-year-old male presented with acute hepatic failure and underwent liver transplantation. The subsequent immunosuppressing therapy resulted in an invasive fungal infection in the midface involving the left lower eyelid, skin and soft tissue of the cheek and the underlying maxilla and zygoma. After multiple revisions, a primary surgical closure of the defect was performed with a free partial myocutaneous latissimus dorsi flap. 3 years post-transplantation the patient was referred to our hospital with no nasal airflow on the right side and completely obliterated nasal airway on the left side. He experienced trouble with the left eye tearing up and double vision when looking upward. Furthermore, he was troubled by missing 4 teeth in the left upper jaw. Lastly, he was not entirely satisfied with the general cosmetic outcome. These issues were addressed in two stages of surgery while considering that the patient was immunosuppressed. DISCUSSION: The patient did not suffer any complications or adverse side effects. Overall, the patient was satisfied with the results, and a questionnaire showed a clear improvement in patient reported outcome on both functional and cosmetic results of the problems addressed. CONCLUSION: Here we present how to plan a complex 3D midface reconstruction on an immunosuppressed patient and a questionnaire follow up on patient reported outcome. The patient reported overall satisfaction.

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.

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.

Comparison between stromal vascular fraction and adipose derived stem cells in a mouse lymphedema model.

Background: Lymphedema is one of the most common complications following breast cancer. Axillary lymph node dissection and radiotherapy are two well-known risk factors resulting in either removal or damage to the lymph nodes. As stem cells are known for their regenerative capabilities, they could theoretically repair/restore the damaged lymph vessels leading to a decrease in lymphedema.Methods: We evaluated the treatment of SVF and ASC on a mouse lymphedema model. Forty-five mice were allocated into three groups containing 15 mice each. The SVF group was injected with 100 µl containing 1 × 106 SVF, the ASC group with 100 µl ml containing 1 × 106 ASC and the NS with 100 µl ml of NS. Volumes of the mice were assessed weekly by µCT hindlimb volumetry for a total of 8 weeks. Lymph vessel morphometry was assessed by cross-sections of both hindlimbs stained for anti-LYVE1. Lymphatic function was assessed by lymphatic clearance.Results: The volume change between the groups was non-significant throughout all 8 weeks. The immunohistochemistry showed a statistically significant difference between the hindlimbs in ASC vs. NS group p = 0.032, 95% CI [-2121, -103].Conclusion: The volume of the hindlimbs showed that treatment with SVF or ASC yielded very similar results compared to the control group when assessed after 8 weeks. In week two the biggest difference between ASC and NS was seen but the difference diminished during the 8 weeks. The secondary outcomes showed that the lymph vessel lumen decreased when treated with ASC compared to the control group. Lymphoscintigraphy yielded non-significant results.

Quantification of tissue volume in the hindlimb of mice using microcomputed tomography images and analysing software.

When studying illnesses that cause disturbance in volume such as lymphedema, reliable quantification of tissue volume is important. Lymphedema results in swelling and enlargement of extremities and can be both physically and psychologically stressful to the patient. Experiments in rodent models provide a cost-effective research platform and are important for preclinical research on lymphedema. When performing such research, it can be crucial to measure the changes in tissue volume. Researchers must ensure that the risk of measurement error, when measuring the tissue volume, is as low as possible. The main goal of this article was to perform a comprehensive examination of the intra- and interrater agreement and hereby assess the risk of measurement error when using microcomputed tomography (µCT) images to measure hindlimb volume. We examined the agreement between four raters with different levels of prior experience and found that the risk of measurement error is extremely low when using this method. The main limitation of this method is that it is relatively expensive and time-consuming. The main advantages of this method are that it is easily learned and that it has a high intra- and interrater agreement, even for raters with no prior measuring experience.

A Revised Method for Inducing Secondary Lymphedema in the Hindlimb of Mice.

Animal models are of paramount importance in the research of lymphedema in order to understand the pathophysiology of the disease but also to explore potential treatment options. This mouse model allows researchers to induce significant lymphedema lasting at least 8 weeks. Lymphedema is induced using a combination of fractioned radiotherapy and surgical ablation of lymphatics. This model requires that the mice get a dose of 10 Gray (Gy) radiation before and after surgery. The surgical part of the model involves ligation of three lymph vessels and extraction of two lymph nodes from the mouse hindlimb. Having access to microsurgical tools and a microscope is essential, due to the small anatomical structures of mice. The advantage of this model is that it results in statistically significant lymphedema, which provides a good basis for evaluating different treatment options. It is also a great and easily available option for microsurgical training. The limitation of this model is that the procedure can be time consuming, especially if not practiced in advance. The model results in objectively quantifiable lymphedema in mice, without causing severe morbidity and has been tested in three separate projects.