Bilateral Brachiocephalic Vein and Superior Vena Cava Reconstruction With an Aortic Allograft.

Malignant thymoma can be invasive and may require radical resection. Here we present a case with phrenic nerve, right upper lobe, bilateral brachiocephalic vein, and superior vena cava involvement. Total venous reconstruction was performed with a cryopreserved aortic allograft by using the aortic root, ongoing transverse arch, and innominate arterial branch. The patient then had postoperative radiotherapy for a total of 63 Gy over 35 treatment days. Follow-up imaging demonstrated no evidence of recurrence and intermediate-term patency but with homograft calcification developing at 4 years.

Stability of patient-specific features of altered DNA replication timing in xenografts of primary human acute lymphoblastic leukemia.

Genome-wide DNA replication timing (RT) profiles reflect the global three-dimensional chromosome architecture of cells. They also provide a comprehensive and unique megabase-scale picture of cellular epigenetic state. Thus, normal differentiation involves reproducible changes in RT, and transformation generally perturbs these, although the potential effects of altered RT on the properties of transformed cells remain largely unknown. A major challenge to interrogating these issues in human acute lymphoid leukemia (ALL) is the low proliferative activity of most of the cells, which may be further reduced in cryopreserved samples and difficult to overcome in vitro. In contrast, the ability of many human ALL cell populations to expand when transplanted into highly immunodeficient mice is well documented. To examine the stability of DNA RT profiles of serially passaged xenografts of primary human B- and T-ALL cells, we first devised a method that circumvents the need for bromodeoxyuridine incorporation to distinguish early versus late S-phase cells. Using this and more standard protocols, we found consistently strong retention in xenografts of the original patient-specific RT features. Moreover, in a case in which genomic analyses indicated changing subclonal dynamics in serial passages, the RT profiles tracked concordantly. These results indicate that DNA RT is a relatively stable feature of human ALLs propagated in immunodeficient mice. In addition, they suggest the power of this approach for future interrogation of the origin and consequences of altered DNA RT in ALL.