Reconstrucción de la fosa poplítea con colgajo fasciocutáneo de la arteria safena / Reconstruction of the popliteal fossa with fasciocutaneous flap of the saphenous artery

INTRODUCCIÓN. Los defectos de la fosa poplítea suponen un desafío reconstructivo para el cirujano plástico, dada la relación íntima de esta área con la articulación de la rodilla y la neurovasculatura vital subyacente. El propósito de éste informe fie compartir la experiencia en la utilización de un colgajo fasciocutaneode la arteria safena. CASO CLÍNICO. Paciente de 5 años de edad que sufrió quemadura térmica en miembros inferiores con dos años y medio de evolución, ameritó injertos, presentó contractura por tejido cicatricial en fosa poplítea, dificultó la deambulación y desarrollo neuro osteomuscular. Se realizó reconstrucción de la fosa poplítea con colgajo fasciocutáneo de la arteria safena. RESULTADOS. El colgajo fasciocutáneo de la arteria safena dio cobertura al defecto en fosa poplítea izquierda tras retiro del tejido cicatricial que producía contractura, limitaba la marcha y el desarrollo neuro osteo-muscular. Seis meses postquirúrgicos brindó cobertura cutánea definitiva y estable en el área crítica, que permitió la deambulación con movimientos de extensión y flexión de rodilla conservados. DISCUSIÓN. Este colgajo al igual que en otros estudios que respaldan su ejecución brindó excelentes resultados en defectos de partes blandas a nivel de la articulación de la rodilla. CONCLUSIÓN. El colgajo fasciocutáneo de la arteria safena demostró utilidad para la reconstrucción del defecto de la fosa poplítea, posibilitó una cobertura definitiva, funcional y estética, restableció los ángulos de movilidad y favoreció el desarrollo pondoestatural del paciente.

INTRODUCTION. Defects of the popliteal fossa pose a reconstructive challenge for the plastic surgeon, because of the intimate relation of this area with the knee joint and the near vital neurovasculature; the purpose of this report was to share the experience of using a fasciocutaneous flap of the saphenous artery. CLINICAL CASE. A 5 year old patient who suffered thermal burn in lower limbs with two and a half years of evolution, he nedeed grafts and presented tissue contracture because the scar in the popliteal fossa hindered ambulation and neuro-osteomuscular growth. Reconstruction of the popliteal fossa was made it with a fasciocutaneous flap of the saphenous artery. RESULTS. The fasciocutaneous flap of the saphenous artery covered the defect in the left popliteal fossa after removal of the scar tissue that caused contracture, limited to walk and growth. Six months after surgery the flap provided definitive and secure skin coverage in the critical area, which allowed to walk with preserved knee extension and flexion movements. DISCUSSION. This flap was useful for the recons-truction of the defect of the popliteal fossa and provided excellent results in soft tissue defects in this area of the knee joint. CONCLUSION. The fasciocutaneous flap of the saphenous artery proved useful for the reconstruction of the popliteal fossa defect, it permited a definitive, functional and esthetic coverage, reestablished the angles of mobility and helped with the patient growth

Reconstrucción de miembro superior posterior a lesión catastrófica por quemadura / Upper extremity reconstruction after a catastrophic injury from burning

INTRODUCCIÓN. Las lesiones catastróficas del miembro superior han sido lesiones devastadoras que afectaron a muchas estructuras esenciales como la mano, antebrazo, brazo y órganos adyacentes, que casi siempre conducen a una incapacidad significativa, de forma directa o mediante el impacto psicosocial que se relacione con la ausencia o atrofia de miembros. OBJETIVO. Demostrar la versatilidad y efectividad del uso del colgajo paraescapular para cubrir defectos severos postraumáticos en un miembro superior catastrófico. Así como, dar a conocer resultados de una amputación digital que preserve la mayor funcionalidad de la mano. CASO CLINICO. Paciente masculino de 37 años, que sufrió quemadura eléctrica de alto voltaje de tercer grado del 30,0% de superficie corporal total. Se realizó tratamiento con colgajo paraescapular para defecto axilar y amputación digital funcional en manos. RESULTADOS. Al quinto mes postquirúrgico se evidenció todos los movimientos conservados en la extremidad superior sin retracción a nivel axilar. Tras la rehabilitación se consiguió conservar en las manos gran porcentaje de fuerza prensil y motricidad fina. DISCUSIÓN. El colgajo paraescapular permitió una reconstrucción temprana y definitiva del defecto extenso, mejorando la funcionalidad de la extremidad superior derecha. La amputación digital preservó una máxima longitud funcional, permitiendo una curación rápida de las heridas, disminuyendo costos y estancia hospitalaria. CONCLUSIÓN. El colgajo paraescapular brindó cobertura a defectos de hombro y axila que permitió recuperar todos los ángulos de movilidad de la extremidad afectada, sin retracción de la piel. La amputación funcional de rayos en la mano admitió conservar fuerza prensil y motora, mejorando la calidad de vida.

INTRODUCTION. Catastrophic injuries of the upper limb have been devastating injuries that affected many essential structures such as the hand, forearm, arm and adjacent organs, which almost always lead to a significant disability, directly or through the psychosocial impact that is related to the absence or atrophy of members. OBJECTIVE. Prove the versatility and effectiveness of the use of the paraescapular flap to cover severe post-traumatic defects in a catastrophic upper limb. As well as, present results of a digital amputation that preserves the greatest functionality of the hand. CLINICAL CASE. A 37 year old male patient, who suffered a third degree high voltage electrical burn of 30,0% of total body surface area. Treatment was performed with paracapular flap for axillary defect and functional digital amputation in hands. RESULTS. By the fifth postoperative month, all movements preserved in the upper extremity without retraction at the axillary level were evident. After the rehabilitation it was possible to keep in the hands a great percentage of prehensile strength and fine motor skills. DISCUSSION. The paraescapular flap allowed an early and definitive reconstruction of the extensive defect, improving the functionality of the right upper extremity. The digital amputation preserved a maximum functional length, allowing a quick healing of the wounds, reducing costs and hospital stay. CONCLUSION. The paraescapular flap provided coverage for shoulder and axilla defects, which allowed recovery of all the angles of mobility of the affected limb, without retraction of the skin. The functional amputation of rays in the hand allowed conserving prehensile and motor strength, improving the quality of life.

Reconstrucción compleja con matriz de regeneración dérmica acelular en el paciente quemado / Complex reconstruction with acellular dermal regeneration matrix in the burned patient

INTRODUCCIÓN. Las quemaduras de gran extensión que han afectado a las extremidades produciendo efectos funcionales y de calidad de vida permanente, han sido el reto que enfrenta la cirugía reparadora. OBJETIVO. Demostrar la efectividad del uso de la matriz de regeneración dérmica acelular para lograr una cobertura cutánea definitiva y funcional en el tratamiento de las heridas profundas producidas por quemaduras. CASO CLINICO. Paciente masculino de 29 años de edad, que sufrió quemadura térmica con cemento de contacto y fuego, presentó una quemadura del 45% de superficie corporal total, se realizó el tratamiento con matriz dérmica acelular con enfoque en lesión de tercer grado en toda una extremidad superior. RESULTADOS. El paciente tras 6 meses de reconstrucción no presentó limitación funcional, cicatrices estéticamente aceptables. DISCUSIÓN. Los sustitutos dérmicos ayudaron en el tratamiento de defectos de cobertura cutánea. La matriz dérmica acelular y su uso en el paciente quemado, permitió brindar una cobertura cutánea precoz y permanente, con resultados óptimos, evitando generar heridas profundas en sitios donantes, lo que disminuyó la morbilidad en el paciente con quemaduras graves. CONCLUSIÓN. El uso de matriz dérmica acelular permitió la regeneración de nueva dermis y tejido en corto tiempo concediendo cobertura definitiva de las lesiones sin dejar secuelas funcionales y con cicatrices aceptables.

INTRODUCTION. Extensive burns that have affected the extremities producing functional defects and permanent quality of life, have been the challenge facing reconstructive surgery. OBJECTIVE. Demonstrate the effectiveness of the use of the dermal acellular regeneration matrix to achieve a definitive and functional skin coverage in the treatment of deep injuries caused by burns. CLINICAL CASE. A 29-year-old male patient, who suffered thermal burn with contact cement and fire, presented a burn of 45% of total body surface area, was treated with acellular dermal matrix with focus on third degree lesion in an entire upper extremity. RESULTS. The patient after 6 months of reconstruction didn´t present functional limitation, aesthetically acceptable scars. DISCUSSION. Dermal substitutes helped in the treatment of skin coverage defects. The acellular dermal matrix and its use in the burned patient, allowed to provide a precocious permanent skin coverage, with optimal results, avoiding generating deep wounds in donor sites, which decreased the morbidity in the patient with severe burns.

Loss of amphiregulin reduces myoepithelial cell coverage of mammary ducts and alters breast tumor growth.

BACKGROUND: Amphiregulin (AREG), a ligand of the epidermal growth factor receptor, is not only essential for proper mammary ductal development, but also associated with breast cancer proliferation and growth. In the absence of AREG, mammary ductal growth is stunted and fails to expand. Furthermore, suppression of AREG expression in estrogen receptor-positive breast tumor cells inhibits in-vitro and in-vivo growth. METHODS: We crossed AREG-null (AREG-/-) mice with the murine luminal B breast cancer model, MMTV-PyMT (PyMT), to generate spontaneous breast tumors that lack AREG (AREG-/- PyMT). We evaluated tumor growth, cytokeratin-8 (K8)-positive luminal cells, cytokeratin-14 (K14)-positive myoepithelial cells, and expression of AREG, Ki67, and PyMT. Primary myoepithelial cells from nontumor-bearing AREG+/+ mice underwent fluorescence-activated cell sorting and were adapted to culture for in-vitro coculture studies with AT-3 cells, a cell line derived from C57Bl/6 PyMT mammary tumors. RESULTS: Intriguingly, PyMT-induced lesions progress more rapidly in AREG-/- mice than in AREG+/+ mice. Quantification of K8+ luminal and K14+ myoepithelial cells in non-PyMT AREG-/- mammary glands showed fewer K14+ cells and a thinner myoepithelial layer. Study of AT-3 cells indicated that coculture with myoepithelial cells or exposure to AREG, epidermal growth factor, or basic fibroblast growth factor can suppress PyMT expression. Late-stage AREG-/- PyMT tumors are significantly less solid in structure, with more areas of papillary and cystic growth. Papillary areas appear to be both less proliferative and less necrotic. In The Cancer Genome Atlas database, luminal-B invasive papillary carcinomas have lower AREG expression than luminal B invasive ductal carcinomas. CONCLUSIONS: Our study has revealed a previously unknown role of AREG in myoepithelial cell development and PyMT expression. AREG expression is essential for proper myoepithelial coverage of mammary ducts. Both AREG and myoepithelial cells can suppress PyMT expression. We find that lower AREG expression is associated with invasive papillary breast cancer in both the MMTV-PyMT model and human breast cancer.

A novel neuregulin - jagged1 paracrine loop in breast cancer transendothelial migration.

BACKGROUND: The interaction of breast cancer cells with other cells in the tumor microenvironment plays an important role in metastasis. Invasion and intravasation, two critical steps in the metastatic process, are influenced by these interactions. Macrophages are of particular interest when it comes to studying tumor cell invasiveness. Previous studies have shown that there is paracrine loop signaling between breast cancer cells and macrophages involving colony stimulating factor 1 (CSF-1) produced by tumor cells and epidermal growth factor (EGF) production by macrophages. In this paper, we identify a novel paracrine loop between tumor cells and macrophages involving neuregulin (NRG1) and notch signaling. METHODS: The aim of this study was to determine the role of NRG1, a ligand of the ErbB3 receptor, in macrophage stimulation of tumor cell transendothelial migration and intravasation. We used fluorescence-activated cell sorting (FACS) and western blot to determine ErbB3 and NRG1 expression, respectively. An in vitro transendothelial migration (iTEM) assay was used to examine the effects of short hairpin (sh)RNA targeting NRG1 in tumor cells and clustered regularly interspaced short palindromic repeats (CRISPR) knockout of jagged 1 (JAG1) in macrophages. Orthotopic xenograft injections in mice were used to confirm results in vivo. RESULTS: In our system, macrophages were the primary cells showing expression of ErbB3, and a blocking antibody against ErbB3 resulted in a significant decrease in macrophage-induced transendothelial migration of breast cancer cells. Stimulation of macrophages with NRG1 upregulated mRNA and protein expression of JAG1, a ligand of the Notch receptor, and JAG1 production by macrophages was important for transendothelial migration of tumor cells. CONCLUSIONS: This study demonstrates that stimulation of macrophages by tumor cell NRG1 can enhance transendothelial migration and intravasation. We also demonstrate that this effect is due to induction of macrophage JAG1, an important ligand of the Notch signaling pathway.

Rac3 regulates breast cancer invasion and metastasis by controlling adhesion and matrix degradation.

The initial step of metastasis is the local invasion of tumor cells into the surrounding tissue. Invadopodia are actin-based protrusions that mediate the matrix degradation necessary for invasion and metastasis of tumor cells. We demonstrate that Rac3 GTPase is critical for integrating the adhesion of invadopodia to the extracellular matrix (ECM) with their ability to degrade the ECM in breast tumor cells. We identify two pathways at invadopodia important for integrin activation and delivery of matrix metalloproteinases: through the upstream recruiter CIB1 as well as the downstream effector GIT1. Rac3 activity, at and surrounding invadopodia, is controlled by Vav2 and ßPIX. These guanine nucleotide exchange factors regulate the spatiotemporal dynamics of Rac3 activity, impacting GIT1 localization. Moreover, the GTPase-activating function of GIT1 toward the vesicular trafficking regulator Arf6 GTPase is required for matrix degradation. Importantly, Rac3 regulates the ability of tumor cells to metastasize in vivo. The Rac3-dependent mechanisms we show in this study are critical for balancing proteolytic activity and adhesive activity to achieve a maximally invasive phenotype.

Tumor cell intravasation.

The process of entering the bloodstream, intravasation, is a necessary step in the development of distant metastases. The focus of this review is on the pathways and molecules that have been identified as being important based on current in vitro and in vivo assays for intravasation. Properties of the vasculature which are important for intravasation include microvessel density and also diameter of the vasculature, with increased intravasation correlating with increased vessel diameter in some tumors. TGFB signaling can enhance intravasation at least in part through induction of EMT, and we discuss other TGFB target genes that are important for intravasation. In addition to TGFB signaling, a number of studies have demonstrated that activation of EGF receptor family members stimulates intravasation, with downstream signaling through PI3K, N-WASP, RhoA, and WASP to induce invadopodia. With respect to proteases, there is strong evidence for contributions by uPA/uPAR, while the roles of MMPs in intravasation may be more tumor specific. Other cells including macrophages, fibroblasts, neutrophils, and platelets can also play a role in enhancing tumor cell intravasation. The technology is now available to interrogate the expression patterns of circulating tumor cells, which will provide an important reality check for the model systems being used. With a better understanding of the mechanisms underlying intravasation, the goal is to provide new opportunities for improving prognosis as well as potentially developing new treatments.