A 2-Year Follow-up Study of an Absorbable Implant to Treat Nasal Valve Collapse.

The safety and effectiveness of an absorbable implant for lateral cartilage support have been recently demonstrated in subjects with nasal valve collapse (NVC) at 12 months postprocedure. This follow-up study aimed to assess whether the safety and effectiveness of the implant persist in these patients for 24 months after the procedure. Thirty subjects with Nasal Obstruction Symptom Evaluation (NOSE) score ≥ 55 and isolated NVC were treated; 14 cases were performed in an operating suite under general anesthesia and 16 cases were performed in a clinic-based setting under local anesthesia. The implant, a polylactic acid copolymer, was placed with a delivery tool within the nasal wall to provide lateral cartilage support. Subjects were followed up through 24 months postprocedure. Fifty-six implants were placed in 30 subjects. The mean preoperative NOSE score was 76.7 ± 14.8, with a range of 55 to 100. At 24 months, the mean score was 32.0 ± 29.3, reflecting an average within-patient reduction of -44.0 ± 31.1 points. There were no device-related adverse events in the 12 to 24 months period. There were five subjects who exited the study prior to the 24-month follow-up. Four of the five subjects who exited were elected for further intervention and one subject was lost to follow-up. This study demonstrates safety of an absorbable implant for lateral nasal wall support and symptom improvement in some subjects with NVC at 24 months postprocedure.

Activin-A Is a Pro-Inflammatory Regulator in Type-2-Driven Upper Airway Disease.

BACKGROUND: Allergic upper airway disease involves pro-inflammatory type-2 cytokines such as IL-5 and regulatory tissue repair mediators, in particular transforming growth factor (TGF)-ß1. The TGF-ß-superfamily member activin-A displays multiple biological functions and shares certain signalling pathways with TGF-ß1. We aimed to examine the coregulation of mucosal activin-A and TGF-ß1 in acute allergic and chronic Th2-driven upper airway disease. METHODS: We investigated mucosal cytokine expression profiles and kinetics using RT-PCR after nasal allergen challenges in patients with seasonal allergic rhinitis. Furthermore, we analysed mucosal specimens from patients with chronic upper airway disease with nasal polyps using ELISPOTs and confocal microscopy. In addition, we stimulated nasal mucosa ex vivo from patients with nasal polyps as well as primary nasal cell cultures from healthy donors. RESULTS: Mucosal activin-A expression revealed increasing correlation with IL-5 and TGF-ß1 at 0.25, 6, and 24 h, respectively, and was significantly upregulated at 6 h after allergen challenge. The correlated expression was found to be more pronounced in chronic disease with nasal polyps, showing substantially (48-fold) increased activin-A-producing cells in nasal polyps by ELISPOT, while submucosal downstream signalling as determined by confocal microscopy was decreased. Ex vivo stimulations of nasal tissue suggested that activin-A and TGF-ß1 mutually regulate each other's expression at the mRNA level and, when combined, enhance IL-5 expression. CONCLUSION: Activin-A in allergic upper airway disease acts as a pro-inflammatory mediator and TGF-ß1 modifier. Our data in the upper airways oppose the view of potentially anti-inflammatory properties in contrast to lymphatic compartments.

Pharyngotomy in head and neck squamous cell carcinoma: functional and oncological aspects.

BACKGROUND: Head and Neck Surgery constantly has to oppose non-invasive organ preservation methods and therefore should be evaluated especially with regard to clinical and functional outcome. We will discuss the role of pharyngotomy in the treatment of HNSCC. METHODS: Seventy-three patients with carcinoma of the oral cavity, oro-/hypopharynx and supraglottis underwent lateral/median pharyngotomy. Functional and oncological parameters were retrospectively assessed and set into clinical context. RESULTS: The 5-year recurrence-free-interval (RFI) was significantly higher with surgery and adjuvant radio(chemo)therapy (80%; mean RFI: 92 months) when compared to conservative treatment (68%; mean RFI: 68 months). The 5-year overall-survival (OS) after surgery and conservative treatment was 71% and 54%, respectively. Compared to other surgical techniques (mean RFI: 82 months), pharyngotomy demonstrated a significant higher 5-year RFI (mean RFI: 89 months). CONCLUSIONS: Pharyngotomy achieves good exposure and clear resection margins that result in a notably good oncological outcome with a minimum of functional loss. In particular, among UICC IV oropharyngeal HNSCC, pharyngotomy is superior in OS and RFI to conservative methods.

Epidermal growth factor receptor variant III in head and neck squamous cell carcinoma is not relevant for targeted therapy and irradiation.

BACKGROUND: The epidermal growth factor receptor (EGFR) is an important regulator of cell growth and survival, and is highly variable in tumor cells. The most prevalent variation of the EGFR extracellular domain is the EGFR variant III (EGFRvIII). Some studies imply that EGFRvIII may be responsible for the poor response to the monoclonal EGFR-antibody Cetuximab, used therapeutically in head and neck squamous cell carcinoma (HNSCC). Due to inconsistent data in the literature regarding EGFRvIII prevalence and clinical relevance in HNSCC, especially its predictive value, we examined EGFRvIII-transfected cell lines and patient tissue samples. RESULTS: In contrast to other recent publications, we were able to demonstrate EGFRvIII expression in HNSCC. However, we noted that the different detection methods yielded inconsistent results. Furthermore, our EGFRvIII transfected and EGFR wild type cell lines exhibited similar characteristics and response rates in the performed in vitro experiments. MATERIALS AND METHODS: We conducted various inhibition and combined irradiation experiments using three EGFRvIII-transfected cell lines. Moreover, a patient cohort of 149 cases consisting of formalin fixed and paraffin embedded (FFPE) and fresh-frozen specimens was assayed via reverse transcriptase PCR (rtPCR) with gel electrophoresis and sequencing for EGFRvIII prevalence. In the rtPCR assays, we used five previously published EGFRvIII primers and EGFRvIII-positive glioblastoma tissue as a positive control. In addition, immunohistochemical staining was conducted. CONCLUSIONS: EGFRvIII can be detected in HNSCC patient samples. Nevertheless, the low prevalence and similar response rates to targeted drugs and irradiation in vitro cast doubt regarding the clinical relevance of EGFRvIII in HNSCC.

Absorbable Implant to Treat Nasal Valve Collapse.

Objective To evaluate the safety and effectiveness of an absorbable implant for lateral cartilage support in subjects with nasal valve collapse (NVC) with 12 months follow-up. Methods Thirty subjects with Nasal Obstruction Symptom Evaluation (NOSE) score ≥ 55 and isolated NVC were treated; 14 cases were performed in an operating suite under general anesthesia and 16 cases were performed in a clinic-based setting under local anesthesia. The implant, a polylactic acid copolymer, was placed with a delivery tool within the nasal wall to provide lateral cartilage support. Subjects were followed up through 12 months postprocedure. Results Fifty-six implants were placed in 30 subjects. The mean preoperative NOSE score was 76.7 ± 14.8, with a range of 55 to 100. At 12 months, the mean score was 35.2 ± 29.2, reflecting an average within-patient reduction of -40.9 ± 31.2 points. The majority (76%) of the subjects were responders defined as having at least one NOSE class improvement or a NOSE score reduction of at least 20%. There were no adverse changes in cosmetic appearance at 12 months postprocedure. Three implants in three subjects required retrieval within 30 days postprocedure and resulted in no clinical sequelae. Conclusion This study demonstrates safety and effectiveness of an absorbable implant for lateral cartilage support in subjects with NVC at 12 months postprocedure.

Palatoglossus coupling in selective upper airway stimulation.

OBJECTIVES/HYPOTHESIS: Selective upper airway stimulation (sUAS) of the hypoglossal nerve is a useful therapy to treat patients with obstructive sleep apnea. Is it known that multiple obstructions can be solved by this stimulation technique, even at the retropalatal region. The aim of this study was to verify the palatoglossus coupling at the soft palate during stimulation. STUDY DESIGN: Single-center, prospective clinical trail. METHODS: Twenty patients who received an sUAS implant from April 2015 to April 2016 were included. A drug-induced sedated endoscopy (DISE) was performed before surgery. Six to 12 months after activation of the system, patients' tongue motions were recorded, an awake transnasal endoscopy was performed with stimulation turned on, and a DISE with stimulation off and on was done. RESULTS: Patients with a bilateral protrusion of the tongue base showed a significantly increased opening at the retropalatal level compared to ipsilateral protrusions. Furthermore, patients with a clear activation of the geniohyoid muscle showed a better reduction in apnea-hypopnea index. CONCLUSIONS: A bilateral protrusion of the tongue base during sUAS seems to be accompanied with a better opening of the soft palate. This effect can be explained by the palatoglossal coupling, due to its linkage of the muscles within the soft palate to those of the lateral tongue body. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:E378-E383, 2017.

Multimodal ultrasonographic algorithm in the differentiation of submandibular masses.

CONCLUSION: The multimodal diagnostic algorithm is a simple diagnostic tool in the pre-operative assessment of submandibular masses that enables one-stage surgical concepts. BACKGROUND: The pre-operative assessment of submandibular masses is of major clinical impact. This study assesses the diagnostic utility of a newly introduced diagnostic algorithm in the differentiation of submandibular masses based on epidemiological and B-mode ultrasonographic data. METHODS: One hundred and eighty-eight patients with submandibular triangle masses were included. Epidemiological and ultrasonographic data of 128 consecutively included patients were assessed and structured in a multimodal algorithm. The diagnostic algorithm was prospectively validated in a further 60 patients. RESULTS: Single epidemiological and ultrasonographic data do not reliably predict the lesional entity. The multimodal diagnostic algorithm achieved a diagnostic sensitivity/specificity of 100%/100% in sialolithiasis, 44%/100% in benign submandibular gland diseases (BSD), 94%/96% in nodal lymphoma/unspecific lymphadenitis, and 91%/84% in carcinomas. Reduced sensitivity in BSD or specificity in carcinomas increased after intra-operative fresh frozen section in patients suspected for BSD.

Multimodal Ultrasonographic Pathway of Parotid Gland Lesions.

Purpose To evaluate a multimodal pathway in solitary circumscribed parotid gland lesions (PL) to predict tumor dignity and to avoid repeat surgery. Materials and Methods 202 patients with PL underwent medical history, clinical examination, high-resolution B-mode ultrasound (US), real-time sonoelastography (RTE), color-coded duplex sonography (CDS), and contrast-enhanced ultrasound (CEUS). Malignancy was suspected when: 1. patients reported on previous cutaneous head and neck (H&N) malignancy; 2. patients presented synchronous cutaneous H&N malignancy and/or facial palsy; 3. US visualized poorly defined tumor borders and/or pathological cervical lymph nodes; 4. PL showed poor vascularization in CDS with enhanced perfusion kinetics in CEUS; 5. PL showed moderate/strong vascularization with delayed perfusion kinetics. Intraoperative frozen section was performed in PLs suspicious for malignancy, and surgery was extended when malignancy was confirmed. The sensitivity, specificity, negative, and positive predictive values (NPV/PPV) were calculated. Results Histology revealed 170 benign and 32 malignant PLs. Medical history, clinical examination, and B-mode US identified malignancy with a sensitivity/specificity of 77 %/98 %. After application of CDS and CEUS in the multimodal pathway, the sensitivity of malignant tumors increased to 91 %. The decreased specificity (81 %) was equalized by intraoperative frozen section (PPV 48 %, NPV 98 %). After application of the multimodal pathway, only 1 patient underwent repeat surgery. Conclusion The multimodal pathway is a useful method to predict dignity in PLs and reduces the number of repeat surgeries.

Clinicopathological characteristics of head and neck Merkel cell carcinomas.

BACKGROUND: There are still controversies about the therapeutic strategies and subsequent outcome in head and neck Merkel cell carcinoma. METHODS: Clinicopathological data of 23 Merkel cell carcinomas, 93 cutaneous head and neck squamous cell carcinomas (HNSCCs), 126 malignant melanomas, and 91 primary parotid gland carcinomas were comprehensively analyzed. Merkel cell carcinomas were cytokeratin 20 (CK20)/neuron-specific enolase (NSE)/chromogranin A (CgA)/synaptophysin (Syn)/thyroid transcription factor-1 (TTF-1)/MIB1 immunostained. RESULTS: All Merkel cell carcinomas underwent wide local excision. Parotidectomy/neck dissection was performed in 40%/33% cutaneous Merkel cell carcinoma and 100%/100% in parotid gland Merkel cell carcinoma. Five-year recurrence-free interval (RFI)/overall survival (OS) was significantly higher in malignant melanoma (81/80%) than in cutaneous Merkel cell carcinoma/HNSCC. Interestingly, 5-year RFI/OS was significantly higher in Merkel cell carcinoma (61%/79%) than in HNSCC (33%/65%; p < .0001) despite comparable TNM classifications and treatment regimens. There were neither differences of RFI/OS between parotid gland Merkel cell carcinoma and parotid gland carcinomas, nor in the immunohistochemical profile. CONCLUSION: Five-year RFI/OS was significantly better in cutaneous Merkel cell carcinoma when compared with TNM classification matched HNSCC. Five-year RFI/OS was comparable in parotid gland Merkel cell carcinoma and other primary parotid gland malignancies. © 2016 Wiley Periodicals, Inc. Head Neck 39: 92-97, 2017.

Selective upper airway stimulation for obstructive sleep apnea: a single center clinical experience.

Selective upper airway stimulation (UAS) is a novel therapy for patients with obstructive sleep apnea (OSA). The aim of this study was to analyze the application and outcome of UAS in patients with moderate to severe OSA in the clinical routine of a tertiary referral center. The design of this study is single-center, prospective clinical trial. Thirty-one patients who received a UAS device (Inspire Medical Systems) were included. Treatment outcome was evaluated at 2, 3, 6, and 12 months after surgery. Data collection included demographics, body mass index (BMI), apnea hypopnea index (AHI), oxygen saturation and desaturation index (ODI), Epworth Sleepiness Score (ESS), adverse events, and adherence to therapy. Sher criteria were used to evaluate treatment response. The mean age was 59.6 years with thirty patients being male. Mean BMI was 28.8 kg/m2. The mean pre-implantation AHI of 32.9/h could be reduced to 7.1/h after 12 months (p < 0.001). The mean pre-implantation ODI of 30.7/h could be reduced to 9.9/h after 12 months (p = 0.004). The mean pre-implantation ESS of 12.6 could be reduced to 5.9 after 12 months (p = 0.006). Serious adverse events did not occur. Therapy adherence was a usage of 6.6 h/night after 12 months. OSA severity and subjective daytime sleepiness were improved in patients with moderate to severe OSA after receiving UAS therapy. Patients maintained high adherence to therapy use after 12 months. It is encouraging that UAS has been shown to be successfully implemented in the routine clinical management of OSA outside of a clinical trial setting.

Evidence and evidence gaps of medical treatment of non-tumorous diseases of the head and neck.

Unfortunately, the treatment of numerous otolaryngological diseases often lacks of evidence base because appropriate studies are missing. Whereas sufficient high-quality trials exist for the specific immunotherapy of allergic rhinitis and in a limited measure also for the angiotensin-converting enzyme inhibitor induced angioedema, the evidence for Menière's disease or for pharmacotherapy of postoperative laryngeal edema is rather poor. This contribution will discuss the trial situation and evidence of the respective diseases.

Effect of liposomal local therapy on salivary glands in acoustic radiation force impulse imaging in Sjögren's syndrome.

The purpose of this study was to evaluate the utility of acoustic radiation force impulse (ARFI) imaging as a monitoring tool for the effect of a liposomal local therapy in patients with dry mouth symptoms due to primary Sjögren's syndrome (pSS). Fifty patients with pSS, diagnosed according to the American-European Consensus Group (AECG) criteria, were included. Clinical data were collected, and sonographic examination including ARFI imaging of the parotid and submandibular glands was performed. Subjective symptoms were evaluated via visual analogue scales (VAS), and the unstimulated whole salivary flow was measured. After a two-month period of liposomal local therapy, sonographic examination was repeated and both subjective and objective symptoms were re-evaluated. Before local treatment, the mean ARFI value of parotid glands was 2.96 m/s (SD 0.97). Mean ARFI value of the submandibular glands was 2.09 m/s (SD 0.71). After the two-month treatment period, a significant decline of ARFI values in the parotid glands to a value of 2.34 m/s (SD 0.70, p < 0.001) could be observed. The submandibular glands did not show any significant change. Further, a significant reduction of the subjective sensation of dry mouth symptoms could be observed (p = 0.0001). With the application of ARFI imaging, a decline in parotid gland stiffness could be observed in patients with primary Sjögren's Syndrome accompanied by a significant improvement of the subjective sensation of dry mouth symptoms. The seromucous submandibular glands did not show any changes compared to the serous parotid glands.

Reproducibility of Acoustic Radiation Force Impulse Imaging in Thyroid and Salivary Glands with Experienced and Inexperienced Examiners.

Acoustic radiation force impulse (ARFI) imaging enables the sonographic measurement of tissue stiffness. The aim of this study was to evaluate if experience in ARFI imaging influences the reproducibility of ARFI imaging of the head and neck. Three experienced sonographers and three inexperienced sonographers performed ARFI imaging of thyroid, submandibular and parotid glands in 10 healthy volunteers. The examination was repeated after 2 wk. Ten single ARFI measurements were done in every gland. Inter-rater and intra-rater reliability was analyzed using the intra-class correlation coefficient (ICC). Moderate agreement was observed between experienced and inexperienced examiners (ICC = 0.46). In salivary glands, agreement was fair between the groups (ICC = 0.33), whereas in separate evaluations, inter-rater reliability in the submandibular glands was moderate (ICC = 0.52), and that in the parotid glands, only poor (ICC = 0.09). For ARFI imaging of the thyroid gland, there was moderate agreement between the groups (ICC = 0.50). The intra-rater reliability for the salivary and thyroid glands together and separately was strong in both groups. ARFI imaging of the thyroid and salivary glands did exhibit good reproducibility. ARFI imaging of the thyroid gland reached the highest levels of inter- and intra-observer agreement in both groups. ARFI imaging in salivary glands is only reproducible with experienced examiners.

Preservation of Endothelial and Smooth Muscle Function of Human Saphenous Vein Transplants.

OBJECTIVES: Methods for conservation and preservation of vascular grafts are often controversially discussed. Furthermore, immunologic monitoring or immunotherapy for allogeneic graft is not considered necessary in many cases. The present study was initiated to examine the cellular vitality and functional efficiency of vein transplant during preservation. MATERIALS AND METHODS: Twenty-seven human vein segments (vena saphena magna) were stored after explant in University of Wisconsin solution or histidine-tryptophan-ketoglutarate solution at 4 °C. After 3, 24, 48, 72, and 96 hours, vein functionality was tested. Ring segments were fixed by triangles in Krebs-Henseleit buffer. Contractile function was measured after addition of potassium chloride solution (80 mM) and phenylephrine (0.2, 2, or 20 µM). To investigate endothelium-dependent vasorelaxation, 1 µM acetylcholine was added. RESULTS: Of 27 segments, 5 showed endothelium-dependent relaxation. Vasorelaxation continued for up to 48 hours after administration of acetylcholine in University of Wisconsin solution and for up to 24 hours in histidine-tryptophane-ketoglutarate solution. At 48 hours, potassium chloride solution-induced vasocontraction was 17% more effective than phenylephrine in University of Wisconsin solution. University of Wisconsin solution was significantly more effective than histidine-tryptophane-ketoglutarate solution in terms of preservation of phenylephrine (0.2, 2 µM)-induced vasocontraction. Phenylephrine (2 µM)-induced contraction was retained in University of Wisconsin solution after 24 hours by 81% and after 48 hours by 55%, with comparable results in histidine-tryptophane-ketoglutarate solution of only 62% and 34% after 24 and 48 hours. CONCLUSIONS: At 48 hours, human saphenous vein transplants had better endothelium and smooth muscle function when preserved in University of Wisconsin solution versus histidine-tryptophane-ketoglutarate solution.

Nanofiltrated C1-esterase-inhibitor in the prophylactic treatment of bradykinin-mediated angioedema.

BACKGROUND: Patients suffering from bradykinin-induced angioedema show recurrent swelling of subcutaneous and submucosal structures. Increased bradykinin levels lead to an increase in vascular permeability and edema formation. Current therapy consists of B2 bradykinin receptor antagonists, C1-esterase-inhibitor (C1-INH) concentrate, or the kallikrein inhibitor ecallantide. In most cases the treatment of acute attacks is sufficient. Prophylactic therapy is recommended only in severe cases. C1-INHc has been shown a safe and efficient option. Its effect on the quality of life has not yet been analyzed. STUDY DESIGN AND METHODS: Patients with inadequate disease control despite an "on-demand therapy" including C1-INHc and/or the B2 receptor antagonist icatibant were switched to long-term prophylaxis consisting in an individual dose of intravenous C1-INHc (Cinryze). None of the patients had been previously treated with ecallantide. Disease-specific quality-of-life questionnaires and patient records were used for evaluation. Disease control, quality of life, adverse events, and administered dosage per month were compared for 6 months on on-demand therapy and the following 6 months under prophylactic therapy. RESULTS: Data of seven patients with hereditary angioedema (HAE) and one patient with acquired angioedema were evaluated. Prophylactic therapy with Cinryze led to a significant and clinically relevant reduction in the overall attack frequency from 6.7 to 2.3 per month without relevant side effects. The frequency of severe attacks was reduced by 89% and quality of life significantly improved. CONCLUSION: Prophylaxis with Cinryze led to a significantly improved quality of life in our cohort of patients with high-frequency bradykinin-induced angioedema attacks that were not sufficiently treated with on-demand medication.

Management and prevention of acute bleedings in the head and neck area with interventional radiology.

BACKGROUND: The Interventional Neuroradiology is becoming more important in the interdisciplinary treatment of acute haemorrhages due to vascular erosion and vascular tumors in the head and neck area. The authors report on acute extracranial haemorrhage in emergency situations but also on preventive embolization of good vascularized tumors preoperatively and their outcome. METHODS: Retrospective analysis of 52 patients, who underwent an interdisciplinary approach of the ORL Department and the Interventional Neuroradiology over 5 ½ years at the Department of Otorhinolaryngology, Klinikum Rechts der Isar, Technical University of Munich, Germany. Their outcome was analysed in terms of success of the embolization, blood loss, survival rate and treatment failures. RESULTS: 39/52 patients were treated for acute haemorrhage. Twenty-five of them attributable to vascular erosion in case of malignant tumors. Affected vessels were the common carotid artery as well as its internal and external parts with branches like the ascending pharyngeal, the facial and the superior thyroid artery. Altogether 27/52 patients were treated for malignant tumors, 25/52 were attributable to acute haemorrhage due to epistaxis, after tonsillectomy, benign tumors and bleeding attributable to inflammations. Treatment of all patients consisted either of an unsuccessful approach via exposure, package of the bleeding, electrocoagulation or surgical ligature followed by embolization or the primary treatment via interventional embolization/stenting. CONCLUSIONS: The common monitoring of patients at the ORL and interventional neuroradiology is an important alternative especially in the treatment of severe acute haemorrhage, following vascular erosion in malignant tumors or benign diseases. But also the preoperative embolization of good vascularized tumors must be taken into account to prevent severe blood loss or acute intraoperative bleeding.

Diagnostic utility of Acoustic Radiation Force Impulse (ARFI) imaging in primary Sjoegren`s syndrome.

OBJECTIVES: The purpose of the study was to assess the diagnostic utility of acoustic radiation force impulse (ARFI) imaging in primary Sjögren's syndrome (pSS). METHODS: One hundred fifty-seven patients with sicca symptoms and/or salivary gland swelling were included. Sicca symptoms, Schirmer test, unstimulated whole saliva (UWS), SS-A/B antibodies, and histology were assessed according to American-European Consensus group (AECG) criteria. All patients underwent high-resolution ultrasound and ARFI imaging of the parotid (PG) and submandibular glands (SMG). RESULTS: Seventy patients were classified as having pSS. The remaining 87 patients suffered from idiopathic sicca (n = 24), rheumatoid arthritis (n = 12), sarcoidosis (n = 9), cutaneous/systemic lupus erythematosus (n = 7), scleroderma (n = 2), dermatomyositis (n = 1), HBV/HCV (n = 2), and panarteritis nodosa (n = 1), and disorders in 29 patients were classified as not otherwise specified. ARFI values of the PG were significantly higher in the pSS versus non-pSS groups (2.86 ± 0.07 m/s vs. 2.15 ± 0.11 m/s, p < 0.0001). ARFI imaging demonstrated diagnostic sensitivity and specificity of 81 % and 67 %, respectively. CONCLUSIONS: In addition to histology, ARFI imaging was the most important diagnostic tool for identifying early pSS. KEY POINTS: • Early stages in Sjögren's syndrome become apparent with major salivary gland enlargements. • Schirmer and unstimulated whole saliva tests demonstrated insufficient sensitivity/specificity for early-stage diagnosis. • Acoustic radiation force impulse imaging is a reliable tool for diagnosing early disease stages.

Oncogenes and tumor suppressor genes in squamous cell carcinoma of the tongue in young patients.

OBJECTIVES: The occurrence of squamous cell carcinoma of the tongue (SCCT) of young patients increased. There are still controversies about patient prognosis. The underlying molecular mechanisms remain unclear. METHODS: 276 patients (66 ≤45, 210 >45 years) with SCCT were included. Clinical parameters and survival data were assessed. Oncogenes and tumor suppressors were analyzed via immunohistochemistry (p53, CXCR4, p16, EGFR) and qPCR (CDK4, CDKN2A, TP53, MDM2, AKT1, PIK3CA, NRAS, HRAS, KRAS, HGF, MET, EGF, ATM, BRCA1, E2F1, FHIT, RUNX3, STK11, BCL2, CTNNB1). RESULTS: The median overall survival was 142 (≤45 years) and 34 months (>45 years) (p < 0.0001; HR [95%CI]: 0.37 [0.30-0.58]). Disease specific survival in patients ≤45 years was with 181 months significantly higher than in patients >45 years (p < 0.0001; HR [95%CI]: 0.33 [0.26-0.57]). Immunhistochemistry visualized a comparable expression of analyzed proteins. QPCR demonstrated in patients ≤45 years a higher expression of genes that are associated with carcinogenesis (CTNNB1, STK11, CDKN2A, HGF, MET) as well as tumor suppressors that constitute an enhanced radio-sensitivity (ATM, BRCA1E2F1, FHIT). CONCLUSION: Derogation of the WNT-CTNNB1-STK11 and CDKN2A-HGF-MET pathway can constitute the carcinogenesis, while the higher expression of radio-sensitizers ATM, BRCA1E2F1 and FHIT can explain the better OS/DSS in young patients.

Orbital complications:diagnosis of different rhinological causes.

To evaluate the clinical course of orbital complication using a standardised diagnostic pathway. Seventy-three patients with orbital complications underwent a multimodal diagnostic pathway comprising ENT examination, leucocytes/CRP, CT-/MRI-scanning and disease-related data. Twenty-nine patients suffered from rhinosinusitis, 28 from mucoceles, 13 patients from neoplasms and three patients from rheumatic disorders. Clinical examination diagnosed 60 patients with eyelid swelling, 55 patients with ocular pain, 14 patients with diplopia, 4 patients with exophthalmus, 29 patients with visual field defect and 4 patients with visual loss. The diagnostic pathway identified acute rhinosinusitis with a sensitivity/specificity of 90 %/90 %, mucoceles with 79 %/100 %, neoplasms with 100 %/96 % and granulomatosis with polyangiitis with 100 %/100 %, respectively. All patients left the hospital in good general condition and with regular ocular motility; two patients suffered persistent visual loss. The standardised application of a widely accepted diagnostic pathway reliably distinguishes different causes of orbital complication.