Endoscopic endonasal resection of skull base chondrosarcomas: technique and early results.

OBJECT: The authors of this study sought to report the technique and early clinical outcomes of a purely endonasal endoscopic approach for resection of petroclival chondrosarcomas. METHODS: Between 2010 and 2014, 8 patients (4 men and 4 women) underwent endonasal endoscopic operations to resect petroclival chondrosarcomas at 2 institutions. The patients' mean age was 44.8 years (range 30-64 years). One of the patients had previously undergone radiation therapy and another a staged craniotomy. Using volumetric software, an independent neuroradiologist assessed the extent of the resections on MRI scans taken immediately after surgery and at the 3-month follow-up. Immediate complications and control of symptoms were also recorded. In addition, the authors reviewed the current literature on surgical treatment of chondrosarcoma. RESULTS: The mean preoperative tumor diameter and volume were 3.4 cm and 9.8 cm(3), respectively. Six patients presented with cranial neuropathies. Endonasal endoscopic surgery achieved > 95% resection in 5 of the 8 patients and < 95% resection in the remaining 3 patients. One of the 6 neuropathies resolved, and the remaining 5 partially improved. One instance of postoperative CSF leakage required a reoperation for repair; no other complications associated with these operations were observed. All of the patients underwent adjuvant radiotherapy. CONCLUSIONS: According to the authors' experience, the endoscopic endonasal route is a safe and effective approach for the resection of appropriately selected petroclival chondrosarcomas.

Imaging evaluation of the suprahyoid neck.

Evaluating the complex anatomy of the suprahyoid neck on imaging studies can be a daunting task without a sound understanding of anatomy and a systematic approach. In this article, the suprahyoid neck is divided into characteristic anatomic spaces, which allow for the accurate localization of both normal structures and abnormal pathology in the neck. Once a lesion is localized to a specific suprahyoid space, imaging characteristics and clinical data can be used in a logical fashion to provide a clinically useful imaging differential diagnosis.

Giant hemorrhagic myelolipoma in a patient with sickle cell disease.

Adrenal myelolipoma is a rare, benign tumor consisting of adipose tissue and hematopoetic elements. It is generally diagnosed as an incidental finding due to its nonfunctioning, asymptomatic nature (Meaglia and Schmidt J Urol 147:1089, 1992). With increasing size, however, as seen in this case, myelolipomas can cause flank pain and abdominal distention. This lesion was diagnosed in a young male with sickle cell disease during a vaso-occlusive crisis.

Inducible nitric oxide synthase mediates prostaglandin h2 synthase nitration and suppresses eicosanoid production.

Nitric oxide (NO) modulates the biological levels of arachidonate-derived cell signaling molecules by either enhancing or suppressing the activity of prostaglandin H(2) isoforms (PGHS-1 and PGHS-2). Whether NO activates or suppresses PGHS activity is determined by alternative protein modifications mediated by NO and NO-derived species. Here, we show that inducible NO synthase (iNOS) and PGHS-1 co-localize in atherosclerotic lesions of ApoE(-/-) mouse aortae. Immunoblotting and immunohistochemistry revealed Tyr nitration in PGHS-1 in aortic lesions but markedly less in adjacent nonlesion tissue. PGHS-2 was also found in lesions, but 3-nitrotyrosine incorporation was not detected. 3-Nitrotyrosine formation in proteins is considered a hallmark reaction of peroxynitrite, which can form via NO-superoxide reactions in an inflammatory setting. That iNOS-derived NO is essential for 3-nitrotyrosine modification of PGHS-1 was confirmed by the absence of 3-nitrotyrosine in lesions from ApoE(-/-)iNOS(-/-) mice. Mass spectrometric studies specifically identified the active site residue Tyr385 as a 3-nitrotyrosine modification site in purified PGHS-1 exposed to peroxynitrite. PGHS-mediated eicosanoid (PGE(2)) synthesis was more than fivefold accelerated in cultured iNOS(-/-) versus iNOS-expressing mouse aortic smooth muscle cells, suggesting that iNOS-derived NO markedly suppresses PGHS activity in vascular cells. These results further suggest a regulatory role of iNOS in eicosanoid biosynthesis in human atherosclerotic lesions.

Involvement of the mitogen-activated protein kinase cascade in peroxynitrite-mediated arachidonic acid release in vascular smooth muscle cells.

Eicosanoid production is reduced when the nitric oxide (NO.) pathway is inhibited or when the inducible NO synthase gene is deleted, indicating that the NO. and arachidonic acid pathways are linked. We hypothesized that peroxynitrite, formed by the reaction of NO. and superoxide anion, may cause signaling events leading to arachidonic acid release and subsequent eicosanoid generation. Western blot analysis of rat arterial smooth muscle cells demonstrated that peroxynitrite (100-500 microM) and 3-morpholinosydnonimine (SIN-1; 200 microM) stimulate phosphorylation of extracellular signal-regulated kinase (ERK), p38, and cytosolic phospholipase A(2) (cPLA(2)). We found that peroxynitrite-induced arachidonic acid release was completely abrogated by the mitogen-activated protein/ERK kinase (MEK) inhibitor U0126 and by calcium chelators. With the p38 inhibitor SB-20219, we demonstrated that peroxynitrite-induced p38 phosphorylation led to minor arachidonic acid release, whereas U0126 completely blocked p38 phosphorylation. Addition of arachidonic acid caused p38 phosphorylation, suggesting that arachidonic acid or its metabolites are responsible for p38 activation. KN-93, a specific inhibitor of Ca(2+)/calmodulin-dependent kinase II (CaMKII), revealed no role for this kinase in peroxynitrite-induced arachidonic acid release in our cell system. Together, these results show that in response to peroxynitrite the cell initiates the MEK/ERK cascade leading to cPLA(2) activation and arachidonic acid release. Thus studies investigating the role of the NO. pathway on eicosanoid production must consider the contribution of signaling pathways initiated by reactive nitrogen species. These findings may provide evidence for a new role of peroxynitrite as an important reactive nitrogen species in vascular disease.