Fluorescence grid analysis for the evaluation of piecemeal surgery in sinonasal inverted papilloma: a proof-of-concept study.

PURPOSE: Local recurrence occurs in ~ 19% of sinonasal inverted papilloma (SNIP) surgeries and is strongly associated with incomplete resection. During surgery, it is technically challenging to visualize and resect all SNIP tissue in this anatomically complex area. Proteins that are overexpressed in SNIP, such as vascular endothelial growth factor (VEGF), may serve as a target for fluorescence molecular imaging to guide surgical removal of SNIP. A proof-of-concept study was performed to investigate if the VEGF-targeted near-infrared fluorescent tracer bevacizumab-800CW specifically localizes in SNIP and whether it could be used as a clinical tool to guide SNIP surgery. METHODS: In five patients diagnosed with SNIP, 10 mg of bevacizumab-800CW was intravenously administered 3 days prior to surgery. Fluorescence molecular imaging was performed in vivo during surgery and ex vivo during the processing of the surgical specimen. Fluorescence signals were correlated with final histopathology and VEGF-A immunohistochemistry. We introduced a fluorescence grid analysis to assess the fluorescence signal in individual tissue fragments, due to the nature of the surgical procedure (i.e., piecemeal resection) allowing the detection of small SNIP residues and location of the tracer ex vivo. RESULTS: In all patients, fluorescence signal was detected in vivo during endoscopic SNIP surgery. Using ex vivo fluorescence grid analysis, we were able to correlate bevacizumab-800CW fluorescence of individual tissue fragments with final histopathology. Fluorescence grid analysis showed substantial variability in mean fluorescence intensity (FImean), with SNIP tissue showing a median FImean of 77.54 (IQR 50.47-112.30) compared to 35.99 (IQR 21.48-57.81) in uninvolved tissue (p < 0.0001), although the diagnostic ability was limited with an area under the curve of 0.78. CONCLUSIONS: A fluorescence grid analysis could serve as a valid method to evaluate fluorescence molecular imaging in piecemeal surgeries. As such, although substantial differences were observed in fluorescence intensities, VEGF-A may not be the ideal target for SNIP surgery. TRIAL REGISTRATION: NCT03925285.

Cochlear aqueduct flow resistance depends on round window membrane position in guinea pigs.

The resistance for fluid flow of the cochlear aqueduct was measured in guinea pigs for different positions of the round window membrane. These different positions were obtained by applying different constant pressures to the middle ear cavity. Fluid flow through the aqueduct was induced by small pressure steps superimposed on these constant pressures. It was found that the resistance for fluid flow through the aqueduct depended on the round window position but not on flow direction. The results can be explained by special fibrous structures that connect the round window with the entrance of the aqueduct. It was also found that the equilibrium inner ear pressure depends on middle ear pressure, indicating that the aqueduct does not connect the inner ear with a cavity with constant pressure.

Change of guinea pig inner ear pressure by square wave middle ear cavity pressure variation.

The inner ear fluid pressure of guinea pigs was measured during square wave middle ear cavity pressure variation. Time constants were derived for the slopes of the inner ear pressure recovery curves after middle ear pressure change. A "single exponential" function did not fit well and therefore more complicated functions were used for this purpose. For middle ear pressure increasing from zero to a few centimetres of water, returning to zero again, decreasing from zero to minus a few centimetres of water and then returning to zero again, time constants for the inner ear pressure recovery curves were on average 15.0, 8.6, 2.5 and 2.5 s, respectively. The results could not be described using a linear model with constant window membrane compliance and cochlear aqueduct flow resistance. A possible explanation for the large difference in time constants for positive or negative middle ear pressure changes is a dependence on aqueduct flow resistance or round window membrane position.

[Perceptual disorders in a Turkish woman: hallucinations or pseudohallucinations?]. / Waarnemingsstoornissen bij een Turkse vrouw: hallucinaties of pseudohallucinaties?

'Hallucinations' were diagnosed in a 41-year-old Turkish woman after the death of her father. The nature of hallucinations is often difficult to understand in patients of Turkish (or Moroccan) origin, as they can be diagnosed as a psychotic feature, or as a sign of dissociation, reexperiences, mourning, personality disorder or depression. Most of the time the symptoms can be regarded as culture-bound phenomena of psychosocial stress, often accompanied by somatoform complaints. In those cases they should be diagnosed as pseudohallucinations. Drug interventions only play a supportive role in the treatment of these symptoms. Joining the patients' explanatory model and exploring the psychological meaning of symptoms may be a rather difficult process which, however, may result in fewer symptoms in the end.

Monitoring inner ear pressure changes in normal guinea pigs induced by the Meniett20.

The inner ear fluid pressure of guinea pigs was measured during a series of complex oscillating middle ear pressure changes induced by the Meniett20 (Pascal Medical, Sweden), a possible therapeutic pressure generator to be used by patients with Meniere's disease. Middle ear pressure changes were transferred instantly to the inner ear, although inner ear pressure declined while middle ear pressure stayed relatively stable. An average undershoot of -1.0 cm H2O with respect to the steady-state pressure was seen after application of a pressure pulse, which was released in a few seconds. The results did not fully comply with a simple linear model in which a constant flow resistance between the inner ear and cerebrospinal space was assumed.