Objective: To assess long-term results and present experience with a high-porosity hydroxyapatite ceramic for obliterating large open mastoid cavities. Study-Design: Cross-sectional cohort study. Setting: Tertiary academic referral center. Patients: All patients who underwent tympanomastoid surgery for chronic middle ear disease or revision surgery with reduction of an open mastoid cavity using a highly porous hydroxyapatite matrix material (HMM) between May 2005 and June 2013 were assessed for eligibility. Twenty three patients (56.9 ± 18.3 yr) were included. Intervention: Primary middle ear surgery or revision surgery using a HMM. Main Outcome Measures: Pure-tone average, computed tomography (CT), and magnetic resonance imaging (MRI) to investigate osseoinduction, osseointegration and presence of cholesteatoma, current quality of life assessed by Zurich Chronic Middle Ear Inventory and change in quality of life post-intervention assessed by the Glasgow Benefit Inventory. Results: Patients were reexamined after a mean follow-up period of 88.3 months (SD 21.4 mo) after obliteration of the open mastoid cavity with HMM. Compared with visit 1, patients showed a significantly reduced ABG at visit 2 (29.22 dB ± 2.71 dB versus 12.77 dB ± 3.46 dB). CT scan was carried out in 21 patients (91%) patients and 17 patients (74%) underwent MRI. Revision surgery was required in a total of 17 cases (74%). In four patients recurrent cholesteatoma was found at follow up. Conclusions: Poor cavity obliteration, a high rate of revision surgery and difficult differentiation between recurrent cholesteatoma and granulation tissue in CT scan was observed.

Inverted (Schneiderian) sinonasal papilloma (ISP) is a neoplasm derived from mucosa of the sinonasal tract characterized by local aggressive growth, a tendency to recur and an association with sinonasal carcinoma. The etiology of ISP remains unclear. Recently, identical mutations in exons 19 and 20 of the oncogene EGFR were reported in ISP and ISP-associated sinonasal carcinoma. Nevertheless, it remains unclear whether recurring ISPs show identical EGFR mutations at different time points or whether these mutations are identical throughout the respective ISP sample. We used Sanger sequencing to test 60 formalin-fixed paraffin embedded ISP samples from 40 patients regarding mutations in exons 19 and 20 of EGFR—together with exon 15 of BRAF. Overall, 32 samples of 22 patients showed a mutation in EGFR exon 20, whereas 28 samples of 18 patients showed none. No mutation in EGFR exon 19 was found in any sample. Four samples of four patients showed a BRAF exon 15 mutation. Interestingly, samples of four patients exhibited genetic heterogeneity, enabling us to report this in ISP for the first time.

BackgroundHistopathologic differentiation between the stages of Barrett’s carcinogenesis is often challenging. Liver–intestine (LI)-cadherin, an intestine-specific marker, is involved in intestinal metaplasia development in gastric and colon cancers and could be of value in diagnosis and differentiation.AimsTo examine the expression of LI-cadherin in the sequence of Barrett’s carcinogenesis and to evaluate its association with clinicopathological data.MethodsLI-cadherin expression was immunohistologically investigated, by use of anti-CDH17 antibody, in gastric mucosa (GM) biopsies taken from the cardia (n = 9), in Barrett’s esophagus (BE) without intraepithelial neoplasia (without IEN) (n = 9) and BE with low-grade IEN (n = 11), and in esophageal adenocarcinoma (ADC) (n = 13).ResultsThe immunoreactivity score was highest in adenocarcinoma (mean IRS = 4.0), and dropped gradually from BE with IEN and BE without IEN (mean IRS = 2.0) to cardia mucosa (IRS = 0). Similarly, the intensity of staining and the percentage of positive cells increased during the sequential stages of BE carcinogenesis. Comparative analysis showed that LI-cadherin expression was significantly different between cardiac epithelium and ADC. Also, percentage of positive cells in GM was significantly different from that in BE with IEN. LI-cadherin IRS was lower for tumors with poor differentiation than for moderately differentiated tumors, but the difference was not statistically significant.ConclusionsLI-cadherin is a sensitive marker of intestinal metaplasia and can be helpful for early histologic diagnosis of Barrett’s esophagus; it is, however, not significantly different between BE with and without IEN, and cannot be used to distinguish between these.

Theoretically, von Willebrand factor (VWF) should be capable of binding all factor VIII (FVIII), but an unbound FVIII (uFVIII) plasma fraction remains. In patients' status post deep-vein thrombosis (DVT), an altered uFVIII fraction and high FVIII levels might be indicative of dysfunctional FVIII regulation. Out of 928 consecutive DVT patients, 321 were found to have high FVIII levels. After excluding 183 patients with known causes for high FVIII levels, plasma samples with unexplainably high FVIII levels were available from 84 patients. To capture the FVIII-VWF-complex, superparamagnetic polystyrene beads with covalently attached streptavidin were coated with biotinylated anti-rabbit Ig and incubated with rabbit anti-human VWF-Ig. Slowly thawed plasma samples were added to cooled beads, which were then separated by a magnetic particle concentrator. The uFVIII fraction was calculated by dividing the FVIII activity in the supernatant of the FVIII-VWF-complex-free sample by the FVIII activity in the supernatant of the control sample. Additionally, the VWF residuum in the supernatant was determined. Compared to age- and sex-matched blood donors, thrombosis patients showed a significantly higher plasma FVIII/VWF ratio (median: 1.3 vs. 1.0, p<0.001). uFVIII fraction data were adjusted for VWF residuum. After forward stepwise logistic regression, uFVIII had an odds ratio of 0.48 (95% CI 0.34-0.65), i.e. the uFVIII fraction was reduced in thrombosis patients. Analysis of covariance confirmed these results: In thrombosis patients, the estimated mean of the uFVIII fraction was significantly lower (6.34% vs. 7.58%, p<0.001). In conclusion, thrombosis patients with high FVIII levels showed a higher FVIII/VWF ratio, similar to mice with defective FVIII clearance. The clearly reduced uFVIII fraction lends further support to the hypothesis of a modified FVIII clearance.

Optical coherence tomography (OCT) and confocal laser scanning microscopy (CLSM) are light-based imaging techniques that allow for a visualization of microscopic tissue properties in vivo. Our study was to examine whether they allow for differentiation of inverted papilloma (IP) from nasal polyps (NP). Five cases of IP and NP, respectively, were investigated intraoperatively with OCT and CLSM. Biopsies were taken of the investigated area and were analyzed ex vivo with OCT and CLSM and then underwent HE-staining for standard light microscopy. On OCT images, IP showed the characteristic inverted character of the epithelium, that was thicker with a high degree of variability of thickness compared to the thin and homogenous epithelium of NP. In addition, the characteristic stromal edema of NP could be visualized. On CLSM images, the typical epithelial invaginations of IP appeared as crypts, while in NP the highly organized cylindric epithelium could be visualized. In vivo, OCT acquired images of sufficient quality to visualize these characteristics, while CLSM did not. Our study demonstrates that OCT and CLSM can distinguish IP from NP. Further technical development is required to apply the techniques clinically to guide intranasal biopsies or even to make them dispensable.