Cristina Aubá

LYMPHATICOVENULAR ANASTOMOSES FOR LYMPHEDEMA TREATMENT: 18 MONTHS POSTOPERATIVE OUTCOMES

The purpose of this work was to report our initial experience with lymphaticovenular anastomoses (LVA), a controversial technique for lymphedema treatment. Although LVA technique was described many years ago, the procedure is not as widespread as it was supposed to be, taking into account the high impact that lymphedema has in the quality of life of patients. Thus, 12 patients, 5 with lower limb and 7 with upper limb lymphedema, underwent LVA surgery under local anesthesia. Two patients were excluded from the study due to the lack of follow‐up. At 18 months, 8 out 10 patients showed a variable objective reduction of the perimeter of the limbs and 9 patients presented a subjective clinical improvement. These results joined to the outcomes of the most experienced surgeons in this field are encouraging, although there are still many issues that need to be addressed with research to optimize the efficacy of this technique.

CD137 on inflamed lymphatic endothelial cells enhances CCL21-guided migration of dendritic cells

CD137/TNFR9/41BB was originally described as a surface molecule present on activated T and NK cells. However, its expression is broader among leukocytes, and it is also detected on hypoxic endothelial cells and inflamed blood vessels, as well as in atherosclerotic lesions. Here, we demonstrate that lymphatic endothelial cells (LECs) up‐regulate CD137 expression from undetectable baseline levels on stimulation with TNF‐α, LPS, and IL‐1β. CD137 cross‐linking with an agonistic mAb results in NF‐κB nuclear translocation, followed by up‐regulation of VCAM and a 3‐fold increase in the production of the chemokine CCL21. Accordingly, there is a 50% increase in CCR7‐dependent migration toward conditioned medium from activated LECs on CD137 cross‐linking with the agonistic mAb or the natural ligand (CD137L). Such an enhancement of cell migration is also observed with monocyte‐derived dendritic cells transmigrating across CD137‐activated LEC monolayers. Using explanted human dermal tissue, we found that inflamed skin contains abundant CD137+ lymphatic vessels and that ex vivo incubation of explanted human dermis with TNF‐α induces CD137 expression in lymphatic capillaries. More interestingly, treatment with CD137 agonistic antibody induces CCL21 expression and DC accumulation close to lymphatic vessels. Collectively, our results demonstrate that the inflammatory function of lymphatic vessels can be regulated by CD137.—Teijeira, A., Palazón, A., Garasa, S., Marré, D., Aubá, C., Rogel, A., Murillo, O., Martínez‐Forero, I., Lang, F., Melero, I., Rouzaut, A. CD137 on inflamed lymphatic endothelial cells enhances CCL21‐guided migration of dendritic cells. FASEB J. 26, 3380–3392 (2012). www.fasebj.org

Lymphatic endothelium forms integrin-engaging 3D structures during DC transit across inflamed lymphatic vessels.

Dendritic cell (DC) transmigration across the lymphatic endothelium is critical for the initiation and sustenance of immune responses. Under noninflammatory conditions, DC transit across the lymphatic endothelial cell (LEC) has been shown to be integrin independent. In contrast, there is increasing evidence for the participation of integrins and their ligands in DC transit across lymphatic endothelium under inflammation. In this sense, we describe the formation of ICAM-1 (CD54)-enriched three-dimensional structures on LEC/DC contacts, as these DCs adhere to inflamed skin lymphatic vessels and transmigrate into them. In vitro imaging revealed that under inflammation ICAM-1 accumulated on microvilli projections surrounding 60% of adhered DCs. In contrast, these structures were scarcely formed in noninflammatory conditions. Furthermore, ICAM-1-enriched microvilli were important in promoting DC transendothelial migration and DC crawling over the LEC surface. Microvilli formation was dependent on the presence of β-integrins on the DC side and on integrin conformational affinity to ligand. Finally, we observed that LEC microvilli structures appeared in close vicinity of CCL21 depots and that their assembly was partially inhibited by CCL21-neutralizing antibodies. Therefore, under inflammatory conditions, integrin ligands form three-dimensional membrane projections around DCs. These structures offer docking sites for DC transit from the tissue toward the lymphatic vessel lumen.

Nerve regeneration through nerve autografts and cold preserved allografts using tacrolimus (FK506) in a facial paralysis model: a topographical and neurophysiological study in monkeys.

OBJECTIVE:Nerve regeneration through cold preserved nerve allografts is demonstrated, and treatment of nerve allografts with FK506 induces better regeneration than other immunosuppressants. We study nerve regeneration through cold preserved nerve allografts temporarily treated with FK506 and compare it with the regeneration obtained using classic nerve autografts in a facial paralysis model in monkeys. METHODS:A trunk of the facial nerve on both sides was transected in eight monkeys and immediately repaired with a 3 to 4 cm nerve autograft or allograft. FK506 was administered to the animals of the allograft group for 2 months, and nerve allografts were cold preserved for 3 weeks. At periods of 3, 5, and 8 months after surgery, quantitative electrophysiological assessment and video recordings were performed. At the end of the study, quantitative analysis of neurons in the facial nucleus was carried out, and axons were stereologically counted. RESULTS:After the regenerative period, neuronal density was higher in the autograft group. However, distal axonal counts were similar in both groups. Serial electrophysiological recordings and histology of nerve allografts showed that the grafts were partially rejected after cessation of the immunosuppressant. CONCLUSION:The regeneration through nerve allografts temporarily treated with FK506 does not achieve the electrophysiological results and neuronal counts achieved with nerve autografts, but axonal collateralization in the allografts induces a similar activation of mimic muscles.

NERVE REGENERATION THROUGH NERVE AUTOGRAFTS AFTER LOCAL ADMINISTRATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR WITH OSMOTIC PUMPS. Commentary

OBJECTIVETo determine whether or not administration of brain-derived neurotrophic factor (BDNF) with osmotic pumps at the site of the proximal stump of a peripheral nerve autograft can improve peripheral nerve regeneration. METHODSThe tibialis branch of the sciatic nerve was transected and grafted with a 20-mm nerve autograft. Wistar rats (Harlan iberica, Barcelona, Spain) (n = 70) were divided into four groups: a nongrafted control group (Group I, n = 10), a grafted but nontreated control group (Group II, n = 20), a grafted saline-treated group (Group III, n = 20), and a grafted and BDNF-treated group (Group IV, n = 20). BDNF was delivered at a rate of 6 μg/day for 2 weeks after nerve repair using osmotic pumps subcutaneously implanted with a connecting tube, the distal end of which faced the proximal stump of the nerve graft. The animals were euthanized at 6 weeks. Spinal motoneurons were quantified as well as axons at the tibialis branch 5 mm distal to the distal nerve repair site. Neuron size was categorized as large (>25 μm) or small (<25 μm). RESULTSThe statistical comparisons between the mean number of neurons in Groups II and III showed no statistical differences (P = 0.27), but there were statistically significant differences between Groups II and IV (P = 0.02) and III and IV (P = 0.02). Labeling of neurons in the group treated with BDNF represents 76% of neurons found on the nonoperated control Group I, which, in turn, is superior to the 51% of neurons found in the nontreated autograft Groups II and III. Regarding the size of motoneurons, there were no statistically significant differences between groups (P > 0.1). Finally, there were no statistically significant differences among Groups II, III, and IV regarding the number of distal axons. CONCLUSIONBDNF delivered through osmotic pumps was found to have a significant capacity for improving the presence of motoneurons in the ventral spinal horn and, thus, capacity to improve nerve regeneration through nerve autografts. However, in this study, BDNF did not specifically protect against injury to motoneurons, depending on the soma size.

Chest wall reconstruction using iliac bone allografts and muscle flaps.

Technically we can divide full-thickness thoracic reconstruction into 2 parts: providing a rigid support and ensuring well-vascularized coverage. Since 1986, the authors’ center has had ample experience with bone banks and the use of cryopreserved bone grafts, which led them to consider the possibility of using these grafts for full-thickness chest wall reconstruction. They describe 3 patients in whom resection of the tumor and reconstruction of the thorax were carried out using iliac bone allografts covered with muscle flaps (1 pectoralis major and 2 rectus abdominis). None of the patients experienced breathing difficulties, pain, or instability after 14 months, 18 months, and 11 years of follow-up. The result of the reconstruction was excellent in all 3 patients in terms of function and aesthetics. The advantage of allografts compared with synthetic materials is their potential integration; they can become part of the host patient’s living tissue.

Smile reconstruction through bilateral muscular transplants neurotized by hypoglossal nerves.

Free transplant of gracilis muscle is the criterion-standard technique in dynamic rehabilitation of long-standing facial paralysis in which the facial musculature is atrophied. When the facial nerve is not available because of a bilateral lesion, other sources are the masseteric, hypoglossal, or accessory nerves. Although the use of hypoglossal nerve has been relegated to the background because of the morbidity caused by its loss, there are special situations in which the hypoglossal nerve should be considered the first option as donor motor nerve. The present article discusses the case of a patient with dynamic reanimation of bilateral facial paralysis with free-muscle transfer neurotized to the hypoglossal nerve. End-to-side coaptation of gracilis motor nerve and hypoglossal motor nerve allows neurotization of the transplanted muscle with minimum repercussion in speech or swallowing and can provide an adequate spontaneous smile with time.

Role of Biofilms in Breast Implant Associated Infections and Capsular Contracture

Breast implants are used for cosmetic breast enlargement, correction of asymmetries and congenital defects and for reconstruction after mastectomy for breast cancer or cancer risk reduction. Breast implant associated complications still represent a significant challenge for clinicians and have a significant negative impact on patient satisfaction, hospital length of stay, and associated costs. Breast implant related infection is one of the leading causes of morbidity that complicates breast implantation representing around 2 % of interventions in most series. Cellulitis, periimplant infection, fistula presence and/or implant exposure often mandate immediate device removal. However, there been some reports of attempted implant salvage in certain patients. Other potential complication is capsular contracture. Contracture of this capsule around a soft implant leads to a painful, tight capsular contracture. It has been postulated that contracture might be related to a chronic infection with propionibacteria, coagulase-negative staphylococcus and other skin organisms. Rates of capsular contracture may range between 1 and 33 %. Cause of capsular contracture and, accordingly, treatment and prevention, remains to be elucidated.

Prevention of a foot amputation: a large arteriovenous malformation reconstructed with a composite free flap.

A case of a patient with a large arteriovenous malformation in the medial plantar aspect and dorsum of the foot is presented. Embolization and surgical management of the malformation allowed a successful outcome, avoiding amputation of the foot and preventing recurrence of the lesion. Although arteriovenous malformations are not frequent entities, they have to be considered in the differential diagnosis of lesions that may affect the lower extremities. The earlier the diagnosis and treatment of these malformations, the lower the morbidity. In large arteriovenous malformations, before radical treatment is envisaged, surgery combined with embolization may achieve good results.

Tratamiento quirúrgico de los hemangiomas

The therapeutic approach to haemangiomas has changed slightly in recent years, moving from a generally conservative attitude to a more aggressive one in some cases. Chronic unaesthetic alterations that might be caused by haemangiomas, psychosocial traumas that can be caused during childhood, together with a better understanding of the behaviour of this type of lesions and advances in safer and more efficient surgical techniques are the basic factors behind this change of attitude. The present paper concentrates on the surgical treatment of haemangiomas, explaining their indications according to the stage of evolution at which they are found, and the surgical techniques employed to resect the lesion with the least morbidity. Similarly, a detailed treatment is given to those lesions that, because of their specific facial anatomical localization, require a special surgical treatment.