Anke Schlüter

Tendon Elongation with Bovine Pericardium in Patients with Severe Esotropia after Decompression in Graves’ Orbitopathy—efficacy and Long-term Stability

ABSTRACT Background/Aims: We performed a retrospective analysis to examine clinical results, establish a dose-effect coefficient and analyze the long-term efficacy of tendon elongation with bovine pericardium (Tutopatch®) for surgical correction of severe esotropia, occurring after three-wall orbital decompression for dysthyroid optic neuropathy in patients with Graves’ orbitopathy (GO). Methods: Tendon elongation of the medial rectus muscle (MR) was performed in our institution using an interponate of bovine pericardium in 60 patients (27 underwent unilateral and 33 bilateral surgery). Success-rate (total horizontal deviation of 10 prism-diopters (PD) or less and evidence of binocular single vision with or without prism glasses) and horizontal motility were examined 3 months, 1 and >4 years after surgery. A dose-effect coefficient for deviation reduction (PD) per recession distance (mm) was established. Results: Horizontal deviations between 28–80Δ were corrected. Diplopia in primary-gaze disappeared in 65% of the patients after 3 months and in 83% after one year (including 12 patients who underwent subsequent surgery after 3-month follow-up). Patients with deviations ≤40Δ after unilateral and ≤50Δ after bilateral tendon elongation showed higher primary success-rates after 3 months (78% and 72%). Vertical deviations (≤10Δ) were corrected by the procedure in 28% without need of recession of the inferior rectus (IR). Only 3 patients showed overcorrection after one year. One of these underwent revision surgery, in which the interponate was no longer discernible from surrounding fibrotic scar tissue. At >4-year follow-up (4.3–15years) effects were stable and 95% of patients showed fusion in primary gaze. Median dose-effect coefficient was lower after tendon elongation (1.8Δ/mm) compared to conventional medial rectus recession in patients with GO. Horizontal motility was slightly decreased, but much more symmetric around primary gaze. Conclusion: Tendon elongation with a bovine pericardium implant is a safe surgical method, suitable to correct severe esotropia after decompression surgery. A lower dose-effect has to be taken into account. Patients with esotropia ≥42Δ should not be treated with unilateral, but bilateral tendon elongation, to avoid undercorrections. In patients with deviations ≥52Δ it has to be further investigated if the application of even higher elongation distances is viable or if another approach—the recession of more than one rectus muscle has to be performed simultaneously to handle the severe restriction. Generally, a step-by-step approach is advisable, since small vertical deviations could also be corrected in a third of patients with the procedure and the dose-effect was more variable as in medial recessions without tendon elongation.

Multimodal assessment of orbital immune cell infiltration and tissue remodeling during development of graves disease by 1H19F MRI: Orbital Inflammation and Remodeling by 1H/19F MRI

To evaluate key molecular and cellular features of Graves orbitopathy (GO) by simultaneous monitoring of alterations in morphology, inflammatory patterns, and tissue remodeling.

Stromal versus tumoral inflammation differentially contribute to metastasis and poor survival in laryngeal squamous cell carcinoma

In solid tumors the biology and clinical course are strongly influenced by the interaction of tumor cells and infiltrating stromal host cells. The aim of this study was to assess the relative importance of stromal vs. tumoral inflammation for metastasis and survival in patients with laryngeal squamous cell carcinoma (LSCC). In 110 patients with tissues from histologically proven LSCC the expression of CD45, CD11b, CD3, MMP-9 and COX-2 was semiquantitatively analyzed in stromal regions and tumor nests. CD45, CD11b, CD3 and MMP-9 positive cells were more abundant in stroma whereas COX-2 was predominantly expressed in epithelial tumor nests. High expression of stromal CD45 and CD11b on immune cells in tumor regions correlated with COX-2 expression on tumor cells. High levels of CD45 in stroma as well as CD11b and COX-2 in tumor nests were associated with increased metastasis. In contrast, high frequencies of CD3 cells in the tumor core area were associated with reduced metastasis. Overall survival was reduced in patients with high stromal CD45, high tumoral CD11b and high tumoral COX-2 expression. This is the first study which separately analyzes peritumoral stroma and tumor core area in laryngeal squamous cell carcinoma in terms of CD45, CD11b, CD3, MMP-9 and COX-2 expression. Our results indicate that stroma and tumor islands need to be considered as two separate compartments in the inflammatory tumor microenvironment. Inflammatory stromal leukocytes, abundant myeloid cells in tumor regions and high expression of COX-2 on tumor cells are linked to metastatic disease and poor overall survival.

Graves’ orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model

Graves’ orbitopathy (GO) is the most common extra thyroidal complication of Graves’ disease (GD) and occurs predominantly in women but more severe in men. The reason for this effect of gender on GO is unknown. Herein we studied the manifestation of GO in both sexes of an induced mouse model in absence of additional risk factors present in patients like advanced age, genetic variabilities or smoking. Male and female mice were immunized with human TSHR A-subunit encoding plasmid. Both sexes comparably developed autoimmune hyperthyroidism characterized by TSHR stimulating autoantibodies, elevated T4 values, hyperplastic thyroids and hearts. Autoimmune mice developed inflammatory eye symptoms and proptosis, although males earlier than females. Serial in vivo1H/19F-magnetic resonance imaging revealed elevated inflammatory infiltration, increased fat volume and glycosaminoglycan deposition in orbits of both sexes but most significantly in female mice. Histologically, infiltration of T-cells, extension of brown fat and overall collagen deposition were characteristics of GO in male mice. In contrast, female mice developed predominately macrophage infiltration in muscle and connective tissue, and muscle hypertrophy. Apart from sex-dependent variabilities in pathogenesis, disease classification revealed minor sex-differences in incidence and total outcome. In conclusion, sex does not predispose for autoimmune hyperthyroidism and associated GO.

CD31 and VEGF are prognostic biomarkers in early-stage, but not in late-stage, laryngeal squamous cell carcinoma

BackgroundPatients suffering from squamous cell carcinoma of the larynx (LSCC) with lymphatic metastasis have a relatively poor prognosis and often require radical therapeutic management. The mechanisms which drive metastasis to the lymph nodes are largely unknown but may be promoted by a pro-angiogenic tumor microenvironment. In this study, we examined whether the number of microvessels and the expression level of vascular endothelial growth factor (VEGF) in the primary tumor are correlated with the degree of lymph node metastasis (N-stage), tumor staging (T) and survival time in LSCC patients.MethodsTissue-Microarrays of 97 LSCC patients were analyzed using immunohistochemistry. The expression of VEGF was scored as intensity of staining (low vs high) and the number of CD31-positive vessels (median </≥7 vessels per visual field) was counted manually. Scores were correlated with N-stage, T-stage and 5-year overall survival rate.ResultsA high expression of angiogenic biomarkers was not associated with poor overall survival in the overall cohort of patients. Instead high CD31 count was associated with early stage cancer (p = 0.004) and in this subgroup high VEGF expression correlated with poor survival (p = 0.032). Additionally, in early stage cancer a high vessel count was associated with an increased recurrence rate (p = 0.004).ConclusionOnly in the early stage subgroup a high expression of angiogenic biomarkers was associated with reduced survival and an increased rate of recurrence. Thus, biomarkers of angiogenesis may be useful to identify high risk patients specifically in early stage LSCC.

Ungewöhnliche Ausbreitung eines Nasopharynxkarzinoms

Im Folgenden soll ein Fall vorgestellt werden, bei dem bei Erstdiagnose eines Nasopharynxkarzinoms eine Tumorausdehnung bis in den auseren Gehorgang vorlag. Eine 69-jahrige Patientin stellte sich mit Otalgie, Hypakusis und rezidivierenden Paukenergussen links vor. In den letzten funf Monaten waren auswartig dreimal Paukenrohrchen eingesetzt und eine Biopsie des Nasopharynx, ohne Malignitatsnachweis, durchgefuhrt worden. Otoskopisch links zeigte sich der Befund einer eitrig, granulierenden Myringitis. In der Endoskopie des Nasopharynx imponierte eine exulzerierende Raumforderung. Die hierauf durchgefuhrte Computertomographie zeigte eine ausgedehnte, teils nekrotische Raumforderung des Nasopharynx links mit zirkularem Wachstum und diffuser Ausdehnung links parapharyngeal, in den weichen Gaumen und bis in den linken Oropharynx. Die darauf folgende Panendoskopie sicherte ein gering differenziertes Plattenepithelkarzinom des Nasopharynx. Bei therapierefraktarer granulierender Myringitis wurde zudem Gewebe im Bereich des Gehorgangs und Trommelfells bioptisch asserviert und so der histologische Nachweis einer Infiltration durch das Nasopharynxkarzinom erbracht. In der anschliesenden MRT bestatigte sich das Wachstum des Nasopharynxkarzinoms per continuitatem uber die Tuba Eustachii bis ins Mittelohr und den auseren Gehorgang. Therapie: Anschliesend erfolgte die definitive Radio-Chemo-Therapie. Nasopharynxkarzinome werden haufig durch Paukenergusse symptomatisch, auserst selten zeigt sich jedoch eine Infiltration der Tuba Eustachii und der Paukenhohle per continuitatem. Bei Raumforderungen im Gehorgang und Mittelohrprozessen sollten Manifestationen von per continuitatem gewachsenen Nasopharynxtumoren als Differentialdiagnose in Betracht gezogen werden. Der Erstautor gibt keinen Interessenkonflikt an.