Christian Rohrmeier

Evidence for a role of epithelial mesenchymal transition during pathogenesis of fistulae in Crohn's disease

Background: The pathogenesis of fistulae in Crohns disease (CD) patients is barely understood. We recently showed that more than two‐thirds of CD fistulae are covered with flat, mesenchymal‐like cells (transitional cells [TC]) forming a patchy basement membrane. Epithelial‐to‐mesenchymal transition (EMT) is a process of reprogramming epithelial cells, allowing them to migrate more effectively and giving epithelial cells an “invasive” potential. EMT has been suggested to be crucial in fibrosis found in different tissues and diseases. We therefore investigated whether EMT could be involved in the pathogenesis of fistulae formation in CD. Methods: In all, 18 perianal fistulae, 2 enteroenteric, and 1 enterovesical fistulae from 17 CD patients were analyzed. In addition 2 perianal fistulae of non‐CD patients were studied. Hematoxylin and eosin staining, immunohistochemistry for the expression of cytokeratins 8 and 20, &bgr;6‐integrin, E‐cadherin, &bgr;‐catenin, vimentin, and TGF‐&bgr;1 and 2 were performed according to standard techniques. Results: The TC covering perianal or enteroenteric fistulae were strongly positive for cytokeratins 8 and 20 but negative for vimentin, indicating their epithelial origin. &bgr;6‐Integrin and TGF‐&bgr; had the highest staining intensities in the transitional zone between the epithelium and the TC. Expression of junctional proteins such as E‐cadherin was reduced in TC as compared to regular fistulae epithelium. In addition, a translocation of &bgr;‐catenin from the membrane to the cytoplasm was observed. Conclusions: Our data for the first time indicate an expression pattern of epithelial and mesenchymal markers in TC associated with fistulae formation that is characteristic for EMT. Studying the pathways of EMT during intestinal fistulae formation may help to develop new therapeutic strategies.

Predictors of cervical lymph node metastasis in salivary gland cancer

This study compares clinicopathological parameters with novel molecular markers for predicting cervical lymph node metastasis in salivary gland cancer.

Triple test as predictive screen for unilateral weakness on caloric testing in routine practice.

Objective To investigate in vertigo patients in routine practice to what extent a rapid and straightforward triple bedside test (spontaneous nystagmus, head-shaking nystagmus, and the head impulse test) can predict a normal result on caloric testing. Study Design Prospective, single-blind, diagnostic study. Setting Tertiary referral center. Patients 151 patients (78 male and 73 female subjects; mean age, 52.5 ± 16.4 yr) presenting with acute or recent symptoms of vertigo. Intervention Diagnostic evaluation. Main Outcome Measure The negative predictive value (NPV) of the triple test in relation to a normal caloric test response. Results In unilateral weakness (UW) on caloric testing (UW, ≥25%), the triple test had sensitivity of 63.6%, specificity of 85.4%, a positive predictive value (PPV) of 71.4%, and an NPV of 80.4%. In other words, 80.4% of patients with a negative triple test also had a normal response on caloric testing. In pronounced canal paresis (UW, ≥50%), the triple test had sensitivity of 81.8%, specificity of 81.4%, a PPV of 55.1%, and an NPV of 94.1%. Significant differences were found between 2 subgroups assessed by examiners with differing levels of experience (p < 0.05). Conclusion The triple test represents a good screening tool that quickly and reliably excludes unilateral weakness and in particular pronounced canal paresis on caloric testing.

Positive frozen section margins predict local recurrence in R0-resected squamous cell carcinoma of the head and neck

OBJECTIVES The purpose of this study was to analyse the impact of surgical margins on tumour recurrence and survival of patients with carcinomas of the head and neck. MATERIAL AND METHODS A cohort of 156 patients with primary squamous cell carcinoma of the head and neck treated by local resection with negative margins and neck dissection between 2004 and 2012 was investigated. Margin status in frozen sections and permanent paraffin tissues were analysed and compared to clinical and histopathological parameters as well as to tumour recurrence (local, regional and distant) and disease-specific survival (DSS). RESULTS Close margins (<5mm) on permanent sections were correlated to high-grade differentiation (p=0.070), lymphangiosis (p=0.009) and positive neck nodes (p=0.025) implicating regional and distant recurrence (p=0.001) as well as unfavorable DSS (p=0.002). Positive margins on initial frozen section analysis revised into negative margins during further surgery were the strongest predictor for local recurrence in uni- and multivariate analysis (p<0.001, hazard ratio 3.34). However, positive frozen section margins were not significantly predictive for DSS (p=0.150). Significant predictors for DSS in univariate analysis were local recurrence (p=0.026), T-stage (p=0.02), N-stage (p<0.001), grading (p=0.02) and lymphangiosis (p=0.001). Multivariate DSS analysis revealed lymph node metastasis (p=0.005) and local recurrence (p=0.017) as significant negative predictors. CONCLUSION Close margins on permanent sections are associated with aggressive tumour characteristics, regional and distant metastasis implicating worse DSS. The accuracy of frozen section analysis seems limited as positive frozen section margins revised into negative margins bear a high risk of local recurrence.

The nasal cycle during wakefulness and sleep and its relation to body position

To compare the occurrence, duration, and relative amplitudes of the nasal cycle (NC) during wakefulness and sleep, and to investigate the relationship of the NC to body position.

Occurence of a round window membrane rupture in patients with sudden sensorineural hearing loss.

BackgroundAim of the present study was to evaluate the occurence of a round window membrane rupture and the effects of hearing restoration after exploratory tympanotomy and sealing of the round window (niche) in patients with unilateral sudden deafness.MethodsRetrospective analysis of patients’ charts in a tertiary referral center. Charts of 69 patients with sudden deafness followed by exploratory tympanotomy were retrospectively analyzed. Pure-tone audiometry data before and after tympanotomy were compared to determine the outcome of hearing recovery. The postoperative hearing test values were documented 3 weeks after tympanotomy. All surgical reports were reviewed with regard to the surgical technique performed and the intraoperative findings.Results18.8% of the patients revealed a visible perilymphatic fistula in the round window niche. 89.8% of the patients reported no typical history for a round window membrane rupture. All patients were treated with an exploratory tympanotomy under local anesthesia and an intravenous corticosteroid treatment regimen. The majority of the surgeons used a fat plomb to cover the round window. Postoperative hearing was significantly improved compared to the preoperative hearing test data. No patient showed a worsened hearing curve after the treatment.ConclusionMost patients suffering from unilateral sudden deafness had no visible perilymphatic fistula. In our study population, the majority of patients reported no typical history of a pressure elevation in the inner ear. Exploratory tympanotomy is a safe procedure that may support hearing recovery in patients with sudden deafness in addition to the established treatment regimen including high-dose steroids.

Genomic aberrations of MDM2, MDM4, FGFR1 and FGFR3 are associated with poor outcome in patients with salivary gland cancer.

Fibroblast growth factor receptor 1 and 3 (FGFR1, FGFR3) impact on tissue homoeostasis, embryonic development and carcinogenesis. Murine double minute protein 4 (MDM4) and mouse double minute 2 homologue (MDM2) are regulators of p53-protein and may be the origin of an apoptosis overpowering cascade. A collective of 266 carcinomas of salivary glands were investigated for MDM2, MDM4, FGFR1 and FGFR3 aberrations by fluorescence in situ hybridization (FISH). The results were matched with clinicopathological parameters and with expression of PTEN and p53. MDM2 gene amplification (n = 9) and chromosomal aberrations (trisomy, n = 47; high polysomy, n = 7) are linked to high-grade malignancy (P < 0.001), lymph node metastasis (P = 0.001), advanced tumour size (P = 0.013) and stage (P < 0.001), gender (P = 0.002) and age (P = 0.001). MDM4 gene amplification (n = 19) and chromosomal aberrations (trisomy, n = 34; high polysomy, n = 31) are correlated to high-grade malignancy (P < 0.001), lymph node metastasis (P = 0.008), advanced tumour size (P = 0.039), stage (P = 0.004) and loss of PTEN (P < 0.001). Only, high-grade malignancy (P < 0.001), lymph node metastasis (P = 0.036) and advanced tumour stage (P = 0.025) are associated with FGFR3 amplification (n = 1) or chromosomal aberrations (low polysomy, n = 61; high polysomy, n = 55) but not with MDM4 alterations. FGFR1 amplifications (n = 5) and chromosomal aberrations (trisomy, n = 38; high polysomy, n = 30) are associated with high-grade malignancy (P < 0.001), advanced tumour size (P = 0.026) and stage (P = 0.004), gender (P = 0.016) and age (P = 0.023). Aberrations of MDM2, MDM4, FGFR1 and FGFR3 correlate with aggressive tumour growth and nodal metastasis. MDM2 (P < 0.001), MDM4 (P = 0.005) and FGFR3 (P = 0.006) alterations are associated with worse overall survival of patients with salivary gland cancer.

Die wichtigsten Kriterien für dauerhaften Erfolg

Bei richtiger Indikation und Durchführung ist die Tränenwegschirurgie außerordentlich erfolgreich. Sowohl die externe Dacryocystorhinostomie als auch die endonasale Variante kann in über 80 % der Fälle die Tränenwege dauerhaft offen halten.

Levels of monocyte chemoattractant protein-1 differ from the norm in patients with sudden sensorineural hearing loss

Background: The aim of this study was to evaluate the role of cytokines and soluble adhesion molecules in patients with sudden sensorineural hearing loss (SSNHL) with respect to their pure-tone audiometry values. Material and Methods: This study analyses blood samples of 51 patients with SSNHL. Serum levels of ICAM-1, VCAM-1, E-selectin, IL-6, IL-8, and MCP-1 were evaluated by ELISA. Pure-tone audiometry data were compared before and after a systemic steroid treatment regimen. The subjects with SSNHL were compared to a control group of 44 patients with normal hearing and matching age and gender. The data complete our previous data collection. Results: There is trend toward suppressed levels of MCP-1 in sera of SSNHL patients. There were no statistically significant differences concerning ICAM-1, VCAM-1, E-selectin, IL-6, IL-8, and MCP-1 between SSNHL patients and controls. Puretone audiometry of the SSNHL group showed a significant improvement in hearing after systemic steroid therapy and a median follow-up of 4 months. Conclusions: Further prospective studies are necessary to prove the role of MCP-1 and other cytokines in SSNHL in order to develop adequate treatment regimens.