The six major genes involved in hereditary susceptibility for pheochromocytoma (PCC)/paraganglioma (PGL) (RET, VHL, NF1, SDHB, SDHC, and SDHD) have been recently integrated into the same neuronal apoptotic pathway where mutations in any of these genes lead to cell death. In this model, prolyl hydroxylase 3 (EglN3) abrogation plays a pivotal role, but the molecular mechanisms underlying its inactivation are currently unknown. The aim of the study was to decipher specific alterations associated with the different genetic classes of PCCs/PGLs. With this purpose, 84 genetically characterized tumors were analyzed by means of transcriptional profiling. The analysis revealed a hypoxia-inducible factor (HIF)-related signature common to succinate dehydrogenase (SDH) and von Hippel-Lindau (VHL) tumors, that differentiated them from RET and neurofibromatosis type 1 cases. Both canonical HIF-1α and HIF-2α target genes were overexpressed in the SDH/VHL cluster, suggesting that a global HIF deregulation accounts for this common profile. Nevertheless, when we compared VHL tumors with SDHB cases, which often exhibit a malignant behavior, we found that HIF-1α target genes showed a predominant activation in the VHL PCCs. Expression data from 67 HIF target genes was sufficient to cluster SDHB and VHL tumors into two different groups, demonstrating different pseudo-hypoxic signatures. In addition, VHL-mutated tumors showed an unexpected overexpression of EglN3 mRNA that did not lead to significantly different EglN3 protein levels. These findings pave the way for more specific therapeutic approaches for malignant PCCs/PGLs management based on the patient's genetic alteration.

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RESUMENTRATAMIENTO QUIRÚRGICO DE DUPLICIDAD PENEANA COMPLETA La duplicidad peneana es una anomalía rara, con una incidencia de 1 entre 5.500.000. Normalmente está asociada a otras malformaciones como duplicidad vesical, cloaca, ano imperforado, duplicidad de recto y sigma y a deformidades vertebrales.Los autores presentan la técnica quirúrgica que aplicaron para la resolución de un caso raro de duplicidad peneana completa en un individuo de sexo masculino, de cuatro años de edad, sin otras malformaciones sistémicas asociadas.Palabras clave: Duplicidad peneana. Cirugía reconstructiva. ABSTRACT SURGICAL TREATMENT OF COMPLETE PENILE DUPLICATIONPenile duplication is a rare anomaly with an incidence of 1 in 5,500,000. It is almost associated with other malformations like double bladder, presence of the cloaca, imperforate anus, duplication of the recto sigmoid and vertebral deformities.The authors present the surgical technique to resolve a rare case of complete penile duplication in a 4 years old child, without any other malformation.

abnormal high-level duodenal compartment. When duodenum coarses between the abdominal aorta and superior mesenteric artery (duodenal interposition), the left renal vein entrapment occurs even at < 90 aortomesenteric degrees.Three-dimensional PEEK printed extravascular stent was chosen to elevate the superior mesenteric artery and lower the duodenum position, thus relieving left renal vein compression. This extravascular application has significant advantages over open surgery, endovascular stenting and artificial vessel procedures with expanded polytetrafluoroethylene. It provides better cellular vitality by ensuring soft tissue proliferation. By reducing external acceleration and centrifugal force, a three-dimensional printed PEEK extravascular stent reduces adverse side effects. Such a stent has a distinctive personalized design, good stiffness, and durability that allows blood vessel growth, preventing stent migration and thrombosis. Therefore, it is suitable for both adult and pediatric patients. According to the abdominal ultrasound and MSCT scan, the post-operative follow-up results are satisfactory one year after surgery. The patient feels well, the blood flow in the left renal vein is not obstructed, and the blood flow velocity was average. The external stent is in place.

No abstract

RESUMENTRATAMIENTO QUIRÚRGICO DE DUPLICIDAD PENEANA COMPLETA La duplicidad peneana es una anomalía rara, con una incidencia de 1 entre 5.500.000. Normalmente está asociada a otras malformaciones como duplicidad vesical, cloaca, ano imperforado, duplicidad de recto y sigma y a deformidades vertebrales.Los autores presentan la técnica quirúrgica que aplicaron para la resolución de un caso raro de duplicidad peneana completa en un individuo de sexo masculino, de cuatro años de edad, sin otras malformaciones sistémicas asociadas.Palabras clave: Duplicidad peneana. Cirugía reconstructiva. ABSTRACT SURGICAL TREATMENT OF COMPLETE PENILE DUPLICATIONPenile duplication is a rare anomaly with an incidence of 1 in 5,500,000. It is almost associated with other malformations like double bladder, presence of the cloaca, imperforate anus, duplication of the recto sigmoid and vertebral deformities.The authors present the surgical technique to resolve a rare case of complete penile duplication in a 4 years old child, without any other malformation.