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

BACKGROUND: Patients 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. METHODS: Tissue-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

Evaluation of the application of rhino-septal splints in endoscopic transsphenoidal skull base surgery.

The endoscopic transnasal route for the surgical removal of tumors in the sellar region is frequently associated with nasal complications such as synechiae or impaired nasal breathing. In this study, we investigated the impact of septal splints on avoiding surgery-related co-morbidities. 49 patients in whom endoscopic transnasal, transsphenoidal surgery for sellar tumors was performed between 2012 and 2014 were studied. In 30 of these, nasal septal splints were applied at the end of surgery to both sides of the septum and left in situ for 10 days (group 1), 19 patients received no splints (group 2). A standardized postsurgical follow-up investigation with endoscopic nasal examination, rhinomanometry and olfactory testing was performed on average 2 months postoperatively. Patients' subjective nose-related discomfort at follow-up was assessed descriptively using a set of standardized self-rating statements on nasal problems. Synechias occurred less likely with nasal septal splints (n = 15; 50 %) than without (n = 16; 84.2 %). Moreover, multiple synechiae were predominantly observed in the group without septal splints (n = 10 vs. n = 2). Rhinomanometry showed improved flow-V150-inspiration scores when splints were used (with significant differences between groups for the left nostril: p = 0.039 and p = 0.022, resp.). In accordance, impaired nasal breathing after surgery was reported more frequently by 76.9 % of patients without splints, but only 56 % of patients with splints. Our results provide support for the application of nasal septal splints when operating endoscopically on tumors in the sellar region to reduce postoperative synechias and to improve nasal breathing.

Motor recovery as assessed with isometric finger movements and perfusion magnetic resonance imaging after acute ischemic stroke.

OBJECTIVE: Recovery from hemiparetic stroke is variable. An important goal for clinicians and clinical researchers is to identify predictors of recovery. The initial phase after acute ischemic stroke is considered to be of major importance for neurological outcome. The authors sought to determine in patients with acute ischemic stroke whether early motor recovery, as measured by repetitive isometric index-thumb oppositions, is correlated with ischemic lesion volume. METHODS: Thirty-six acute hemiparetic stroke patients with residual hand function were investigated. The European Stroke Scale (ESS) score was determined on admission and at discharge. Performance of repetitive index finger-thumb pinch movements was measured daily during the 1st 8 days after stroke onset. Brain ischemia volume was determined digitally in time-to-peak magnetic resonance images of per-fusion. RESULTS: The recovery of patients with (P = 0.002) and without (P < 0.001) thrombolysis as assessed with the ESS was paralleled by an increase in isometric grip force and movement rate (P < 0.05). Recovery was predicted by the area of moderately impaired perfusion indicated by the per-fusion mismatch volume (r = 0.578, P < 0.001). CONCLUSIONS: In acute stroke, recovery of hand function is predicted by the volume of salvageable ischemic tissue, as determined by the perfusion mismatch.

Effect of C1-Esterase-inhibitor in angiotensin-converting enzyme inhibitor-induced angioedema.

OBJECTIVES/HYPOTHESIS: The study objective was to generate pilot data to evaluate the effectiveness and safety of C1-esterase-inhibitor concentrate (C1-INH) compared to standard treatment in patients with angiotensin-converting enzyme inhibitor (ACEi)-induced angioedema affecting the upper aerodigestive tract. STUDY DESIGN: Proof-of-concept case series with historical control. METHODS: Adult patients with angioedema in the upper aerodigestive tract presenting to the emergency department were included. After establishing the diagnosis of ACEi-induced angioedema based on patient history and thorough clinical examination, all patients were administered 1,000 international units (IU) of C1-INH intravenously. A historical control group consisting of adult patients with ACEi-induced angioedema who had been treated with intravenous corticosteroids and antihistamines at the same institution over the past 8 years was used for comparison. The most important parameters assessed were the time to complete resolution of symptoms and the need for intubation or tracheotomy. RESULTS: Ten patients were included in the C1-INH group and 47 in the corticosteroid/antihistamine group. The time to complete resolution of symptoms was considerably longer in the historical control group (33.1 ± 19.4 hours) than in the C1-INH group (10.1 ± 3.0 hours). No intubation or tracheotomy was needed in the C1-INH group (0/10 patients), whereas three out of the 47 historical controls required tracheotomy and two were intubated (5/47). CONCLUSION: The results suggest a role for C1-INH as an effective and safe therapeutic option in patients with ACEi-induced angioedema, which needs to be confirmed by further larger and double-blinded studies. LEVEL OF EVIDENCE: 4.

The role of tumour FoxP3 as prognostic marker in different subtypes of head and neck cancer.

Expression of the forkhead transcription factor (FoxP3)--an established marker of regulatory T cells--has been found in other cell types as well, including tumour cells. Recent studies indicated that high tumour FoxP3 expression might be associated with a poor outcome of patients with several types of solid cancers. Here, we investigated the role of FoxP3 expressed by the tumour cells in the prognosis of larynx and oro-hypopharynx squamous cell carcinoma (LSCC and OHSCC)--two major subtypes of head and neck cancer. To this end, we analysed by immunohistochemistry the expression of tumour FoxP3 in tissues from 83 LSCC and 89 OHSCC patients in relation to overall survival. In multivariate analysis we found that high tumour FoxP3 expression significantly associated with poor survival in OHSCC but not in LSCC patients. In further studies, we combined the prognostic value of FoxP3 with selected markers of inflammation (cyclooxygenase-2; COX2) or with markers of enhanced tumour migration/invasion (AHNAK and CORTACTIN). Interestingly, we found that the combination of FoxP3 and AHNAK (in LSCC) or FoxP3 and CORTACTIN (in OHSCC) had significantly stronger prognostic values than either marker analysed individually. Combination of FoxP3 and COX2 enhanced the prognostic accuracy only in OHSCC. Thus, our study identifies novel individual and combination markers that might have enhanced and distinct prognostic relevance in different subtypes of head and neck cancer.

Detection of circulating tumor cell subpopulations in patients with head and neck squamous cell carcinoma (HNSCC).

BACKGROUND: Since image based diagnostic tools fail to detect early metastasis in head and neck squamous cell carcinoma (HNSCC) it is crucial to develop minimal invasive diagnostic methods. A promising approach is to identify and characterize circulating tumor cells (CTC) in the peripheral blood of HNSCC patients. In this pilot study, we assessed which non-hematopoietic cell types are identifiable and whether their numbers differ in pre- and postoperative blood samples. METHODS: 20 ml citrated peripheral blood was taken from 10 HNSCC patients before and after curative resection. CTC were enriched using density gradient centrifugation. CTC presence was verified by multi-immunofluorescence staining against cytokeratin (CK; epithelial), N-cadherin (mesenchymal); CD133 (stem-cell), CD45 (hematopoietic) and DAPI (nucleus). Individual cell type profiles were analyzed. RESULTS: We were able to detect cells with epithelial properties like CK+/N-cadherin-/CD45- and CK+/CD133-/CD45- as well as cells with mesenchymal features such as N-cadherin+/CK-/CD45- and cells with both characteristics like N-cadherin+/CK+/CD45-. We also observed cells showing stem cell-like features like CD133+/CK-/CD45- and cells with both epithelial and stem cell-like features such as CD133+/CK+/CD45-. The number of CK positive cells (p = 0.002), N-cadherin positive cells (p = 0.002) and CD133 positive cells (p = 0.01) decreased significantly after resection. Kaplan-Meier test showed that the survival was significantly shorter when N-cadherin+ cells were present after resection (p = 0.04; 474 vs. 235 days; [HR] = 3.1). CONCLUSIONS: This is - to the best of our knowledge- the first pilot study identifying different CTC populations in peripheral blood of HNSCC patients and showing that these individual cell type profiles may have distinct clinical implications.

Initial ischemic event: perfusion-weighted MR imaging and apparent diffusion coefficient for stroke evolution.

PURPOSE: To prospectively determine if the degree of acute perfusion or diffusion abnormalities measured prior to treatment onset help predict the evolution of brain infarction on magnetic resonance (MR) images. MATERIALS AND METHODS: Local ethics committee approval and informed consent were obtained. On parametric maps obtained in 64 patients (mean age, 64 years +/- 13 [standard deviation]; 37 men and 27 women) with acute middle cerebral artery infarction, lesion volumetry was performed to determine time to peak, mean transit time, cerebral blood volume, and apparent diffusion coefficient obtained within 3 hours of symptom onset. The infarct lesions were assessed on T2-weighted MR images obtained at follow-up on day 8. Cerebrovascular changes were determined on MR angiograms. Inferential and correlation statistics were used. RESULTS: A perfusion delay of more than 6 seconds relative to the nonaffected hemisphere on time-to-peak maps helped to predict the lesion volume on T2-weighted images (r = 0.686, P < .001). In contrast, neither the volume nor the degree of the diffusion abnormality helped to predict the infarct volume (r < 0.46). This was because in one subgroup of patients there was an increase and in one subgroup there was a decrease in infarct volume on the T2-weighted images (P < .001). There was a greater prevalence (P < .02) of cerebral artery abnormalities in the patients with larger infarcts. Clinically, the neurologic impairment was more severe (P < .01) and the mean arterial pressure higher (P < .04) in these patients. CONCLUSION: The results suggest that in acute stroke the severity of the initial ischemic event as determined on time-to-peak maps indicates hemodynamic compromise in addition to internal carotid artery or middle cerebral artery occlusion, because of abnormalities in other cerebral arteries.