Transorbital endoscopic approaches to the skull base: a systematic literature review and anatomical description

Neurosurgical Review - Transorbital endoscopic approaches are increasing in popularity as they provide corridors to reach various areas of the ventral skull base through the orbit. They can be used...     

Paediatric focal nodular hyperplasia: A case study of typical contrast-enhanced ultrasound findings with quantitative analysis and correlated with magnetic resonance imaging

IntroductionFocal nodular hyperplasia, a benign liver tumour, is the second most common focal benign liver lesion, after a cavernous haemangioma. Contrast-enhanced ultrasound is used increasingly for the diagnostic work up and follow-up of focal liver lesions in adults, but is particularly valuable in the paediatric population, with the ability to reduce radiation and the nephrotoxic contrast agents used in computed tomography or magnetic resonance imaging. Confident recognition of focal nodular hyperplasia is important; it is benign, usually asymptomatic, of no clinical significance, of no clinical consequence or malignant potential. We present a case of focal nodular hyperplasia of the liver with its characteristic findings on conventional ultrasound, contrast-enhanced ultrasound with quantitative analysis and correlated with magnetic resonance imaging.Case presentation: A 15-year-old female with right upper quadrant abdominal pain was referred for liver ultrasound. A focal liver lesion was detected on B-mode ultrasound examination, and colour Doppler demonstrated no specific features. Contrast-enhanced ultrasound examination demonstrated early arterial enhancement, with a characteristic spoke-wheel pattern, centrifugal uniform filling of the lesion on the late arterial phase and sustained enhancement on the portal venous phase. Quantitative contrast-enhanced ultrasound has been performed, showing a typical curve of enhancement, as well as characteristic parametric images, supporting the interpretation of contrast-enhanced ultrasound and assisting the diagnosis. Magnetic resonance imaging demonstrated a central T2 hyperintense scar and similar enhancement characteristics as contrast-enhanced ultrasound on T1 gadolinium-enhanced sequences.ConclusionContrast-enhanced ultrasound is a useful technique for the differentiation of benign from malignant liver lesions and has the potential to establish the diagnosis of focal nodular hyperplasia, based on the enhancement pattern, which is similar to that observed on magnetic resonance imaging but can be better appreciated with superior temporal, contrast and spatial resolution of contrast-enhanced ultrasound.     

The effect of ions at the surface of calcium oxalate monohydrate crystals on cell-crystal interactions

Magnesium is an abundant ion in biologic systems, including renal tubular fluid; however, the precise role of magnesium during the interaction of calcium oxalate crystals with cells has not been previously defined. In addition, the respective roles of calcium and hydrogen ions during the cell-crystal bonding interaction remain poorly defined. Here we report an atomic level three-dimensional study of a single crystal of calcium oxalate monohydrate (COM; whewellite) which was bathed in a solution of magnesium hexahydrate for 1 year. Magnesium was not incorporated into the structure of whewellite to any significant degree. Instead, COM accepted magnesium primarily as an adsorbate in a binding configuration which, as a surface phenomenon, is controlled by localized charge effects. The effect of magnesium and calcium on the efficiency of calcium oxalate crystal binding to renal cells was also investigated. When present in supraphysiologic concentrations (greater than 0.1 M), magnesium progressively inhibited adhesion of pre-formed COM crystals to cultured renal cells. Therefore, even though magnesium does not incorporate into the crystal structure of calcium oxalate, magnesium can exert important surface effects and change the interaction of pre-formed COM with molecules anchored on the cell surface. Similarly, binding was nearly blocked when the exogenous calcium concentration was > or =0.1 M (supraphysiologic range), although in lower concentrations (within the physiologic range) exogenous calcium promoted crystal adhesion. Finally, the ambient hydrogen ion concentration also influenced calcium oxalate crystal interactions with renal cells, with maximal binding occurring at a pH of 4. Therefore, hypercalciuria and/or an acidic urine could each promote renal stone formation via increased crystal adhesion to renal cells, a previously under-appreciated potential mechanism.     

Annexin II is present on renal epithelial cells and binds calcium oxalate monohydrate crystals

Attachment of newly formed crystals to renal epithelial cells appears to be a critical step in the development of kidney stones. The current study was undertaken to identify potential calcium oxalate monohydrate (COM) crystal-binding proteins on the surface of renal tubular cells. Apical membranes were prepared from confluent monolayers of renal epithelial cells (MDCKI line), and COM crystal affinity was used to isolate crystal-binding proteins that were then subjected to electrophoresis and electroblotting. Microsequencing of the most prominent COM crystal-binding protein (M(r) of 37 kD) identified it as annexin II (Ax-II). When exposed proteins on the surface of intact monolayers were biotinylated and then isolated using streptavidin agarose beads, Ax-II was detected, suggesting that at least a portion is exposed on the apical cell surface. Ax-II was not completely extracted by 0.1 M Na(2)CO(3), suggesting that at least a portion of cellular Ax-II is an intrinsic membrane-bound protein. Using confocal immunofluorescence microscopy, Ax-II was visualized together with Caveolin-1 (Cav-1) on the apical membrane of intact MDCKI cells. Cells pretreated with a monoclonal anti-Ax-II antibody bound significantly fewer COM crystals, whereas anti-LDL receptor antibody did not decrease COM binding, further suggesting a functional role for Ax-II during adhesion of crystals to intact cells. These results suggest that Ax-II avidly binds COM crystals and is present on the apical surface of MDCKI cells. Therefore, in the intact nephron, Ax-II could mediate adhesion of COM crystals to cells, and altered exposure of Ax-II on the surface of renal tubular cells could promote crystal retention and possibly kidney stone formation.     

Isolation from human calcium oxalate renal stones of nephrocalcin, a glycoprotein inhibitor of calcium oxalate crystal growth. Evidence that nephrocalcin from patients with calcium oxalate nephrolithiasis is deficient in gamma-carboxyglutamic acid.

We have determined that the organic matrix of calcium oxalate kidney stones contains a glycoprotein inhibitor of calcium oxalate crystal growth (nephrocalcin) that resembles nephrocalcin present in the urine of patients with calcium oxalate stones and differs from nephrocalcin from the urine of normal people. Pulverized calcium oxalate renal stones were extracted with 0.05 M EDTA, pH 8.0; nephrocalcin eluted in five peaks using DEAE-cellulose column chromatography, and each peak was further resolved by Sephacryl S-200 column chromatography. Four of the five DEAE peaks corresponded to those usually found in nephrocalcin from urine; the fifth eluted at a lower ionic strength than any found in urine. Amino acid compositions and surface properties of nephrocalcins isolated from kidney stones closely resembled those of nephrocalcins isolated from urine of stone-forming patients: they differed from normal in lacking gamma-carboxyglutamic acid residues, and in forming air-water interfacial films that were less stable than those formed by nephrocalcin from normal urine.     

Genetic alterations between primary head and neck squamous cell carcinoma and recurrence after radiotherapy

BACKGROUND:

In the attempt to characterize the genetic bases of recurrent head and neck squamous cell carcinoma (HNSCC) after radiotherapy (RT), the authors compared the molecular profiles of primary tumors and recurrences.

METHODS:

TP53 gene status and instability at 10 microsatellite markers were determined in pre‐RT lesions and corresponding local recurrences in a series of 16 HNSCCs.

RESULTS:

Eight (50%) HNSCCs showed both TP53 and microsatellite instability (MSI) status concordance in pre‐ and postirradiation biopsies; 3 (18.7%) showed discordance of both TP53 and MSI status; and finally 5 (31.2%) had discordance at only 1 genetic test. Accordingly, the authors interpreted as true recurrence the 8 concordant cases, and as true second primary malignancies the 3 discordant ones. In the remaining 5 cases with partial DNA correspondence, the exact nature of the new lesion only partially related to the original cancer is a matter of discussion. Patients showing the same mutations among pre‐ and post‐RT HNSCCs had a longer disease‐free interval (DFI) and better survival than those showing discordant genetic features (log‐rank test, P = .0045).

CONCLUSIONS:

Post‐RT recurrent HNSCCs are genetically heterogeneous. The genetic characterization of the recurrence, especially in those cases with a particularly short DFI showing partially discordant mutations, might have a useful clinical relevance in the restaging process. Cancer 2010. © 2010 American Cancer Society.