Implications of Von Hippel-Lindau Syndrome and Renal Cell Carcinoma

Von Hippel-Lindau syndrome (VHLS) is a rare hereditary neoplastic disorder caused by mutations in the vhl gene leading to the development of tumors in several organs including the central nervous system, pancreas, kidneys, and reproductive organs. Manifestations of VHLS can present at different ages based on the affected organ and subclass of disease. In the subclasses of VHLS that cause renal disease, renal involvement typically begins closer to the end of the second decade of life and can present in different ways ranging from simple cystic lesions to solid tumors. Mutations in vhl are most often associated with clear cell renal carcinoma, the most common type of renal cancer, and also play a major role in sporadic cases of clear cell renal carcinoma. The recurrent, multifocal nature of this disease presents difficult challenges in the long-term management of patients with VHLS. Optimization of renal function warrants the use of several different approaches common to the management of renal carcinoma such as nephron-sparing surgery, enucleation, ablation, and targeted therapies. In VHLS, renal lesions of 3 cm or bigger are considered to have metastatic potential and even small lesions often harbor malignancy. Many of the aspects of management revolve around optimizing both oncologic outcome and long-term renal function. As new surgical strategies and targeted therapies develop, the management of this complex disease evolves.  This review will discuss the key aspects of the current management of VHLS

Isotopic Evaluation of Ocean Circulation in the Late Cretaceous North American Seaway

During the mid- and Late Cretaceous period, North America was split by the north–south oriented Western Interior Seaway. Its role in creating and maintaining Late Cretaceous global greenhouse conditions remains unclear. Different palaeoceanographic reconstructions portray diverse circulation patterns1, 2, 3. The southward extent of relatively cool, low-salinity, low-δ18O surface waters critically distinguishes among these models, but past studies of invertebrates could not independently assess water temperature and isotopic compositions. Here we present oxygen isotopes in biophosphate from coeval marine turtle and fish fossils from western Kansas, representing the east central seaway, and from the Mississippi embayment, representing the marginal Tethys Ocean. Our analyses yield precise seawater isotopic values and geographic temperature differences during the main transition from the Coniacian to the early Campanian age (87–82 Myr), and indicate that the seaway oxygen isotope value and salinity were 2‰ and 3‰ lower, respectively, than in the marginal Tethys Ocean. We infer that the influence of northern freshwater probably reached as far south as Kansas. Our revised values imply relatively large temperature differences between the Mississippi embayment and central seaway, explain the documented regional latitudinal palaeobiogeographic zonation4, 5 and support models with relatively little inflow of surface waters from the Tethys Ocean to the Western Interior Seaway2, 3