Papel de la yeyunoplastia en la reconstrucción esofágica compleja / Role of jejunoplasty in complex esophageal reconstruction

Introducción: La reconstrucción esofágica es un proceso quirúrgico técnicamente muy complejo, gravado por una importante morbilidad. Clásicamente se han utilizado la gastroplastia y la coloplastia, aunque la yeyunoplastia ya fue descrita por Roux en 1907. Parece demostrado que la plastia de yeyuno libre es una muy buena opción en el tratamiento de la enfermedad del esófago cervical, pero no está tan claro el papel de la yeyunoplastia supercharged en la reconstrucción del esófago torácico. El objetivo de este estudio es el análisis de las reconstrucciones esofágicas realizadas en nuestra unidad y que precisaron de un injerto de yeyuno. Métodos: Estudio retrospectivo de las reconstrucciones esofágicas realizadas con yeyunoplastias en nuestra unidad entre enero de 2011 y diciembre de 2019. Se analizan datos epidemiológicos, indicaciones, técnica quirúrgica y morbimortalidad. Resultados: Se realizaron 67 procedimientos quirúrgicos de reconstrucción esofágica compleja de los que 10 fueron yeyunoplastias: 5 yeyunos libres en esófago cervical y 5 supercharged en esófago torácico con abordaje transesternal. La morbilidad, mortalidad, estancia media y tiempo de retirada de la alimentación enteral fueron menores en los yeyunos libres que en los supercharged. Conclusiones: En nuestro grupo la yeyunoplastia supercharged es la última opción para la reconstrucción del esófago torácico; el acceso por esternotomía media nos permite un excelente abordaje del mediastino anterior y los vasos mamarios internos. El yeyuno libre sería la primera elección —con indemnidad del resto de esófago— en la reconstrucción del esófago cervical. (AU)

Introduction: Esophageal reconstruction is a very complex surgical procedure, burdened by significant morbidity. Gastroplasty and coloplasty have classically been used. Free jejunal plasty has shown to be a very good option in the treatment of cervical esophagus pathology, but the role of supercharged jejunoplasty in thoracic esophagus reconstruction is still controversial. Methods: A retrospective study of esophageal reconstructions with jejunoplasties performed in our unit between January 2011 and December 2019. Epidemiological data, indications, surgical technique, and morbidity and mortality were analyzed. Results: 67 procedures of esophageal reconstruction were performed, 10 of which were jejunoplasties: 5 free jejunums and 5 supercharged. Morbidity, mortality, mean stay and withdrawal time from enteral feeding were lower in free than in supercharged jejunums. Conclusions: Supercharged jejunoplasty was the last option for reconstruction of the thoracic esophagus. Median sternotomy access provides an excellent approach to the anterior mediastinum and the internal mammary vessels. The free jejunum would be the first choice, with the indemnity of the rest of the esophagus, in the reconstruction of the cervical esophagus. (AU)

Role of jejunoplasty in complex esophageal reconstruction.

INTRODUCTION: Esophageal reconstruction is a very complex surgical procedure, burdened by significant morbidity. Gastroplasty and coloplasty have classically been used. Free jejunal plasty has shown to be a very good option in the treatment of cervical esophagus pathology, but the role of supercharged jejunoplasty in thoracic esophagus reconstruction is still controversial. METHODS: A retrospective study of esophageal reconstructions with jejunoplasties performed in our unit between January 2011 and December 2019. Epidemiological data, indications, surgical technique, and morbidity and mortality were analyzed. RESULTS: 67 procedures of esophageal reconstruction were performed, 10 of which were jejunoplasties: 5 free jejunums and 5 supercharged. Morbidity, mortality, mean stay and withdrawal time from enteral feeding were lower in free than in supercharged jejunums. CONCLUSIONS: Supercharged jejunoplasty was the last option for reconstruction of the thoracic esophagus. Median sternotomy access provides an excellent approach to the anterior mediastinum and the internal mammary vessels. The free jejunum would be the first choice, with the indemnity of the rest of the esophagus, in the reconstruction of the cervical esophagus.

PDGFR-induced autocrine SDF-1 signaling in cancer cells promotes metastasis in advanced skin carcinoma.

Advanced and undifferentiated skin squamous cell carcinomas (SCCs) exhibit aggressive growth and enhanced metastasis capability, which is associated in mice with an expansion of the cancer stem-like cell (CSC) population and with changes in the regulatory mechanisms that control the proliferation and invasion of these cells. Indeed, autocrine activation of PDGFRα induces CSC invasion and promotes distant metastasis in advanced SCCs. However, the mechanisms involved in this process were unclear. Here, we show that CSCs of mouse advanced SCCs (L-CSCs) express CXCR4 and CXCR7, both receptors of SDF-1. PDGFRα signaling induces SDF-1 expression and secretion, and the autocrine activation of this pathway in L-CSCs. Autocrine SDF-1/CXCR4 signaling induces L-CSC proliferation and survival, and mediates PDGFRα-induced invasion, promoting in vivo lung metastasis. Validation of these findings in patient samples of skin SCCs shows a strong correlation between the expression of SDF1, PDGFRA, and PDGFRB, which is upregulated, along CXCR4 in tumor cells of advanced SCCs. Furthermore, PDGFR regulates SDF-1 expression and inhibition of SDF-1/CXCR4 and PDGFR pathways blocks distant metastasis of human PD/S-SCCs. Our results indicate that functional crosstalk between PDGFR/SDF-1 signaling regulates tumor cell invasion and metastasis in human and mouse advanced SCCs, and suggest that CXCR4 and/or PDGFR inhibitors could be used to block metastasis of these aggressive tumors.

Cancer Stem-like Cells Act via Distinct Signaling Pathways in Promoting Late Stages of Malignant Progression.

Cancer stem-like cells (CSC) play key roles in long-term tumor propagation and metastasis, but their dynamics during disease progression are not understood. Tumor relapse in patients with initially excised skin squamous cell carcinomas (SCC) is characterized by increased metastatic potential, and SCC progression is associated with an expansion of CSC. Here, we used genetically and chemically-induced mouse models of skin SCC to investigate the signaling pathways contributing to CSC function during disease progression. We found that CSC regulatory mechanisms change in advanced SCC, correlating with aggressive tumor growth and enhanced metastasis. ß-Catenin and EGFR signaling, induced in early SCC CSC, were downregulated in advanced SCC. Instead, autocrine FGFR1 and PDGFRα signaling, which have not been previously associated with skin SCC CSC, were upregulated in late CSC and promoted tumor growth and metastasis, respectively. Finally, high-grade and recurrent human skin SCC recapitulated the signaling changes observed in advanced mouse SCC. Collectively, our findings suggest a stage-specific switch in CSC regulation during disease progression that could be therapeutically exploited by targeting the PDGFR and FGFR1 pathways to block relapse and metastasis of advanced human skin SCC.