Ossification of the vascular pedicle in microsurgical fibular free flap reconstruction of the head and neck.

BACKGROUND AND PURPOSE: The fibular free flap, often used for osseous reconstruction following extirpation of head and neck malignancies, has been associated with heterotopic periosteal ossification. We aimed to determine the frequency and radiologic characteristics of this process and describe its clinical correlates. MATERIALS AND METHODS: Surgical records for 2 years and neck imaging reports for 10 years were evaluated to identify patients with fibular free flap reconstruction and CT and/or PET/CT imaging available for review. The images were evaluated for the quality, type, and contour of ossification, and the reports were reviewed for associated clinical findings and radiologic impressions. RESULTS: Of 32 patients with posttreatment CT or PET/CT imaging, ossification was evident in 16 patients (50%) as early as 1 month following fibular free flap reconstruction. In 8 patients, it mimicked a new bone; in 5, it appeared as linear attenuation; in 2, as multiple short segments; and in 1 patient, a mixed appearance was found. No associated FDG uptake was seen on PET/CT. On MR imaging, these findings were extremely subtle or not appreciable. In only 1 patient was new bone associated with symptoms. CONCLUSIONS: Periosteal ossification of the vascular pedicle is commonly evident on CT following fibular free flap, even as early as 1 month after reconstruction, though the finding is not typically noted on imaging. While symptoms related to new bone are uncommon, they may mimic recurrent tumor. The location and pattern of ossification and the absence of a soft-tissue mass or FDG uptake are useful distinguishing imaging features.

Oncocytoma: the vanishing parotid mass.

Parotid gland oncocytoma is an uncommon, benign salivary neoplasm composed of mitochondria-rich oncocytes. The purpose of this study was to correlate MR imaging and histopathology of parotid gland oncocytomas and to define the features that may distinguish these neoplasms from other benign and malignant parotid gland tumors. The MR imaging features in 9 patients with a pathologic diagnosis of oncocytoma were retrospectively reviewed. The imaging features were strikingly similar for 8 of the 9 patients. All lesions appeared T1 hypointense but isointense to the native parotid gland on fat-saturated T2 and postcontrast T1 imaging. On MR imaging, parotid gland oncocytomas share specific imaging characteristics that have not been described for benign or malignant parotid gland tumors. Oncocytomas are isointense to native parotid gland on fat-saturated T2 and T1 postcontrast MR images. Preoperative identification of correct histology may help surgical planning.

Fatal cerebral oedema in adult diabetic ketoacidosis.

In this report, a case of adult onset fatal cerebral oedema as a rare complication of diabetic ketoacidosis (DKA) is described and confirmed at post-mortem pathological examination. The pathogenesis of cerebral oedema due to DKA is still unknown. Potential mechanisms include the administration of sodium bicarbonate leading to intracellular acidosis, excessive fluid infusion causing swelling of brain tissue, or reduction of plasma osmolarity by a rapid fall in glucose levels causing osmotic swelling.

Sulf-2, a heparan sulfate endosulfatase, promotes human lung carcinogenesis.

Heparan sulfate (HS) proteoglycans (HSPGs) bind to multiple growth factors/morphogens and regulate their signaling. 6-O-sulfation (6S) of glucosamine within HS chains is critical for many of these ligand interactions. Sulf-1 and Sulf-2, which are extracellular neutral-pH sulfatases, provide a novel post-synthetic mechanism for regulation of HSPG function by removing 6S from intact HS chains. The Sulfs can thereby modulate several signaling pathways, including the promotion of Wnt signaling. We found induction of SULF2 transcripts and Sulf-2 protein in human lung adenocarcinoma and squamous cell carcinoma, the two major classes of non-small-cell lung carcinomas (NSCLCs). We confirmed widespread Sulf-2 protein expression in tumor cells of 10/10 surgical specimens of human lung squamous carcinomas. We studied five Sulf-2(+) NSCLC cell lines, including two, which were derived by cigarette-smoke transformation of bronchial epithelial cells. shRNA-mediated Sulf-2 knockdown in these lines caused an increase in 6S on their cell surface and in parallel reversed their transformed phenotype in vitro, eliminated autocrine Wnt signaling and strongly blunted xenograft tumor formation in nude mice. Conversely, forced Sulf-2 expression in non-malignant bronchial epithelial cells produced a partially transformed phenotype. Our findings support an essential role for Sulf-2 in lung cancer, the leading cancer killer.

Sulphated endothelial ligands for L-selectin in lymphocyte homing and inflammation.

Lymphocytes from the blood home to secondary lymphoid tissues through a process of tethering, rolling, firm adhesion and transmigration. Tethering and rolling of lymphocytes is mediated by the interaction of L-selectin on lymphocytes with sulphated ligands expressed by the specialized endothelial cells of high endothelial venules (HEVs). The sulphate-dependent monoclonal antibody MECA79 stains HEVs in peripheral lymph nodes and recognizes the complex of HEV ligands for L-selectin termed peripheral node addressin. High endothelial cell GlcNAc-6-sulphotransferase/L-selectin ligand sulphotransferase is a HEV-expressed sulphotransferase that contributes to the formation of the MECA79 epitope and L-selectin ligands on lymph node HEVs. MECA79-reactive vessels are also common at sites of chronic inflammation, suggesting mechanistic parallels between lymphocyte homing and inflammatory trafficking.

Sulfation of L-selectin ligands by an HEV-restricted sulfotransferase regulates lymphocyte homing to lymph nodes.

Lymphocytes home to lymph nodes, using L-selectin to bind specific ligands on high endothelial venules (HEV). In vitro studies implicate GlcNAc-6-sulfate as an essential posttranslational modification for ligand activity. Here, we show that genetic deletion of HEC-GlcNAc6ST, a sulfotransferase that is highly restricted to HEV, results in the loss of the binding of recombinant L-selectin to the luminal aspect of HEV, elimination of lymphocyte binding in vitro, and markedly reduced in vivo homing. Reactivity with MECA 79, an adhesion-blocking mAb that stains HEV in lymph nodes and vessels in chronic inflammatory sites, is also lost from the luminal aspects of HEV. These results establish a critical role for HEC-GlcNAc6ST in lymphocyte trafficking and suggest it as an important therapeutic target.

Vascular endothelial junction-associated molecule, a novel member of the immunoglobulin superfamily, is localized to intercellular boundaries of endothelial cells.

During the process of lymphocyte homing to secondary lymphoid organs, such as lymph nodes and tonsils, lymphocytes interact with and cross a specialized microvasculature, known as high endothelial venules. There is a great deal of information available about the first steps in the homing cascade, but molecular understanding of lymphocyte transmigration through the intercellular junctions of high endothelial venules is lacking. In analyzing expressed sequence tags from a cDNA library prepared from human tonsillar high endothelial cells, we have identified a cDNA encoding a novel member of the immunoglobulin superfamily. The protein, which we have termed VE-JAM ("vascular endothelial junction-associated molecule"), contains two extracellular immunoglobulin-like domains, a transmembrane domain, and a relatively short cytoplasmic tail. VE-JAM is prominently expressed on high endothelial venules but is also present on the endothelia of other vessels. Strikingly, it is highly localized to the intercellular boundaries of high endothelial cells. VE-JAM is most homologous to a recently identified molecule known as Junctional Adhesion Molecule, which is concentrated at the intercellular boundaries of both epithelial and endothelial cells. Because the Junctional Adhesion Molecule has been strongly implicated in the processes of neutrophil and monocyte transendothelial migration, an analogous function of VE-JAM during lymphocyte homing is plausible.

Identification of endoglycan, a member of the CD34/podocalyxin family of sialomucins.

CD34 and podocalyxin are structurally related sialomucins, which are expressed in multiple tissues including vascular endothelium and hematopoietic progenitors. These glycoproteins have been proposed to be involved in processes as diverse as glomerular filtration, inhibition of stem cell differentiation, and leukocyte-endothelial adhesion. Using homologies present in the cytoplasmic tails of these proteins, we have identified a novel member of this family, which we designate endoglycan. This protein shares a similar overall domain structure with the other family members including a sialomucin domain, but also possesses an extremely acidic amino-terminal region. In addition, endoglycan contains several potential glycosaminoglycan attachment sites and is modified with chondroitin sulfate. Endoglycan mRNA and protein were detected in both endothelial cells and CD34(+) bone marrow cells. Thus, CD34, podocalyxin, and endoglycan comprise a family of sialomucins sharing both structural similarity and sequence homology, which are expressed by both endothelium and multipotent hematopoietic progenitors. While the members of this family may perform overlapping functions at these sites, the unique structural features of endoglycan suggest distinct functions for this molecule.