Novel Discovery of the Somatostatin Receptor (SSTR2) in Pleomorphic Adenomas via Immunohistochemical Analysis of Tumors of the Salivary Glands.

Reliable preoperative diagnosis between salivary gland tumor entities is difficult. In this monocentric retrospective study, we examined the somatostatin receptor 2 (SSTR2) status of salivary gland tumors after salivary gland tumor resection via immunohistochemistry (IHC), and stains were compared in analogy to the HER2 mamma scale. A total of 42.3% of all pleomorphic adenoma (PA) tumors (42 of 99, 95% confidence interval 32.5-52.8%) demonstrated ≥20% of cells displaying the SSTR2 as compared to just 1% of all other tumors (1/160, 95% CI 0.02-3.4%). The other tumor was a neuroendocrine carcinoma. PA had a higher intensity of SSTR2 staining, with 90.9% staining ≥ an intensity of 2 (moderate). Tumors with an intensity of SSTR2 expression equal to or greater than 2 had an 89.9% likelihood of being a PA (95% CI: 82.2-95.0%, AUC: 0.928). Only one Warthin tumor demonstrated a 'strong' SSTR2 staining intensity. No Warthin tumor showed a percentage of cells staining for SSTR2 above ≥20%. This result demonstrates consistent and strong expression of SSTR2 in PAs as compared to Warthin tumors, which may allow physicians to utilize radioligand-somatostatin analog PET CT/MR imaging to diagnose the PA. SSTR2 positivity, if shown to be clinically relevant, may allow peptide receptor radionuclide therapy in the future.

[Laryngeal-preservation surgery in laryngeal cancer]. / Kehlkopferhaltende Operationen bei Larynxkarzinomen.

After oral cavity and pharyngeal cancer, laryngeal cancer is the third most common malignant tumor in the head and neck region. According to the current German S3 guideline on the diagnosis, treatment, and follow-up of laryngeal cancer, larynx-preserving surgical interventions are part of the standard treatment of this disease, even in advanced tumor stages. However, in order to achieve the desired function-preserving effect, an exact indication is of crucial importance. In this article, the most important larynx-preserving interventions and their indications but also the respective contraindications are presented, with the aim of illuminating the surgical treatment options up to just before total laryngectomy.

Efficacy of human C1 esterase inhibitor concentrate for treatment of ACE-inhibitor induced angioedema.

BACKGROUND: ACE inhibitor (ACEi) induced angioedema predominantly affects the upper aerodigestive tract. As ACEi induced angioedema is mediated by bradykinin, therapeutic response to antihistamines and glucocorticoids remains unsatisfactory. In bradykinin mediated hereditary angioedema, C1-esterase inhibitor (C1INH) is an effective and approved treatment since many years. Our aim was to evaluate the therapeutic effect of C1INH in ACEi induced angioedema. METHODS: We performed a double-blind, parallel-group, multicentre randomised placebo-controlled trial between December 2013 and September 2018. Eligible were adults with ACEi induced angioedema with airway obstruction. Participants were randomised 1:1 to single doses of either C1INH (20 IU/kg) or placebo (0.9% NaCl) i.v in addition to standard care (i.v. 500 mg prednisolone and 2.68 mg clemastine) i.v. Composite symptom scores were assessed at baseline and up to 48 h, at discharge and 1 week after discharge. Physician assessed time to complete oedema resolution (TCER) and time to onset of relief (TOR). RESULTS: 30 patients (16 C1INH, 14 placebo) were randomised and dosed. 25 (9 C1INH, 12 placebo) completed the study. TCER was 29.63 h ± 15.56 h in the C1INH and 17.29 h ± 10.40 h in the placebo arm (p = 0.0457). TORs were 4.13 h ± 3.38 h and 2.86 h ± 1.29 h for C1INH and placebo, respectively (p = 0.4443). There were no adverse events related to study medication. CONCLUSIONS: In the context of baseline application of steroids and antihistamines C1INH was inferior in the treatment of ACEi induced angioedema when compared to placebo with respect to time to complete resolution of symptoms. Eudra-CT Number: 2012-001670-28.

Ultrasound-Guided Needle Aspiration vs. Surgical Incision of Parotid Abscesses.

OBJECTIVE: Standard treatment of parotideal abscesses consists of surgical drainage. This often has to be carried out in general anesthesia and carries the risk of iatrogenic injury of the facial nerve. Ultrasound-guided needle aspiration is an alternative therapy. Up until now a lack of systematic data concerning this subject exists. The study at hand aims to answer the question whether needle aspiration is a viable alternative for surgical drainage. METHODS: All patients who had been treated surgically (n = 39) or via ultrasound-guided needle aspiration (n = 18) at our clinic were included into this monocentric retrospective analysis. RESULTS: There was no statistically significant difference (p = 0.142) regarding the mean abscess volume in both groups (5.7 vs. 10.1 mL). Therapy of the abscesses on average required 1.88 (1-5) ultrasound-guided needle aspirations or 1.10 (1-4) surgical interventions. There was a trend to a shorter inpatient treatment period (5.88 vs. 7.33 days) after ultrasound-guided needle aspiration. This trend did not reach statistical significance (p = 0.301). Facial nerve alterations did not occur in any of the patients. Postoperative bleeding did never occur after needle aspirations but in 2% of the patients after surgical abscess revision. CONCLUSION: Ultrasound-guided needle aspiration is safe and effective in the treatment of parotid abscesses.

Prevalence of Castleman's disease in patients suffering from cervical lymphadenopathy.

Objectives: To determine the prevalence of Castleman's disease (unicentric/idiopathic multicentric CD) in a retrospective cohort according to the newly defined international diagnostic criteria in patients, who underwent a lymph node removal at a tertiary care university hospital over a period of 10 years. Study design: Retrospective chart review. Material and methods: All Patients with cervical lymphadenopathy coded by ICD-10-CM with "I88.9," "R59.0," or "D47.Z2" between January 2010 and December 2020 and who underwent a lymph node extirpation were identified. In cases who met the diagnostic criteria for a potential unicentric or idiopathic multicentric CD (iMCD) diagnosis, the lymph node tissue was re-evaluated by a pathologist. Results: A total of 714 patients with cervical lymphadenopathy were included into this single-center retrospective study. After exclusion of patients with diseases that may mimic iMCD and cases for which material to perform histological re-evaluation was lacking, a subset of 75 patients with "nonspecific lymphadenitis" or "reactive hyperplasia of lymph node" was identified, who underwent a renewed histopathological examination. One case fulfilled both the major and minor criteria of an iMCD diagnosis, and further 15 cases matched the histological criterion of an iMCD diagnosis (one of the two major diagnostic criteria), so that a UCD diagnosis according to the new criteria could be accepted. Conclusion: In this cohort, the subsequent application of the new diagnostic criteria led to further cases of CD (1.9% compared to 0.1% before) being recognized. Although incidence and prevalence of UCD and iMCD are low, clinicians should keep in mind this differential diagnosis as effective therapies are available. Level of Evidence: 4.

Persisting sicca complaints in sarcoidosis.

Background: Sarcoidosis is a systemic inflammatory disease that is characterized by non-caseating granulomas. Besides the lung as classical site of involvement, extrapulmonary manifestations are common, for example cervical lymph nodes or the salivary glands. The aim of this investigation is the analysis of the long-term course of glandular symptoms with a focus on persisting sicca symptoms. Materials and methods: All patients with the diagnosis of sarcoidosis over a period of 20 years in the departments of otorhinolaryngology, nephrology and pneumology were identified. In addition to clinical examinations and functional evaluation of the salivary glands, a sonographic examination of the salivary glands was carried out. Results: A total of 76 patients were included in the study (age 35.1 ± 21.6 years). At baseline, 32 out of 76 patients were suffering from xerostomia, 36 from dry eyes. While other salivary gland symptoms, such as gland enlargement, pain or facial nerve impairment, dissolved during the further course of the disease, xerostomia was still present in 29 and dry eyes in 35 out of 76 patients at the time of follow-up (which took place on average after 88.2 months). Conclusion: Sicca symptoms persist in patients with the diagnosis of sarcoidosis, while other salivary gland symptoms completely dissolve during the further course of the disease. This development appears to be independent of the type of therapy and should be considered during the follow-up of these patients, since sicca symptoms can cause further ocular, oral and dental damage.

Inhalative Treatment of Laryngitis Sicca in Patients with Sjögren's Syndrome-A Pilot Study.

Xerostomia and keratoconjunctivitis sicca are the main symptoms of Sjögren's syndrome. Often patients also suffer from laryngeal complaints, but there is a lack of specific treatment options. The aim of this study was to evaluate the effect of a liposomal inhalation therapy. Patients with Sjögren's syndrome were included and received a two-month period of liposomal inhalation therapy. The effect was evaluated by standardized questionnaires (patient-reported indices) and measurement of unstimulated whole salivary flow and glandular stiffness. Forty-five patients were included in this study. A comparison of baseline and therapeutic values demonstrated a significant improvement of the EULAR Sjögren's syndrome patient reported index (ESSPRI) with a baseline of 5.0 ± 2.1 and a therapeutic value of 4.1 ± 2.4 (p = 0.012). This improvement was mainly based on the item on dryness within this score. Overall, the therapy was well tolerated. In conclusion, an inhalative application of liposomes had a beneficial effect on the reported dryness in patients with Sjögren's syndrome. A first insight into the effect of inhalation therapy on laryngeal symptoms could thus be obtained and at the same time the basis was created on which case calculations can be carried out in the future.

Obstruction level associated with outcome in hypoglossal nerve stimulation.

PURPOSE: Selective hypoglossal nerve stimulation (sHNS) constitutes an effective surgical alternative for patients with obstructive sleep apnea (OSA). sHNS results in tongue protrusion and consecutive alleviation of obstructions at the tongue base level (lower obstructions). Furthermore, obstructions at the soft palate level (upper obstructions) may be prevented through palatoglossal coupling as seen on sleep endoscopy. However, it has not been studied if the distribution of obstruction level during a whole night measurement is a relevant factor for the treatment outcome. METHODS: Obstruction levels were measured with a manometry system during a whole night of sleep in 26 patients with OSA (f = 1, m = 25; age 59.4 ± 11.3; BMI = 29.6 ± 3.6) either before (n = 9) or after sHNS implantation (n = 12). Five patients received a measurement before and after implantation. Obstructions were categorized into velar (soft palate and above), infravelar (below soft palate), and multilevel obstructions. An association between obstruction level and treatment outcome was calculated. RESULTS: The mean distribution of preoperative obstruction level could be divided into the following: 38% velar, 46% multilevel, and 16% infravelar obstructions. Patients with a good treatment response (defined as AHI < 15/h and AHI reduction of 50%) had fewer preoperative velar obstructions compared to non-responder (17% vs. 54%, p-value = 0.006). In patients measured after sHNS implantation, a significantly higher rate of multilevel obstructions per hour was measured in non-responders (p-value = 0.012). CONCLUSIONS: Selective hypoglossal nerve stimulation was more effective in patients with fewer obstructions at the soft palate level. Manometry may be a complementary diagnostic procedure for the selection of patients for HNS.

Management of patients with seasonal allergic rhinitis: Diagnostic consideration of sensitization to non-frequent pollen allergens.

BACKGROUND: Diagnosis of pollen allergies is mainly based on test allergens for skin prick testing. In the minimum battery of test inhalant allergens recommended by the Global Allergy and Asthma European Network 10 pollen allergens are included. Complementary other pollen allergens may need to be considered; however, respective awareness may not always be granted. Furthermore, at least in Germany, the situation may be even more complicated by the fact that test allergens need regulatory approval. A decline in commercially available test allergens may result in a diagnostic gap regarding patients with non-frequent allergies. How many patients with non-frequent pollen allergies would be affected by this gap? The data presented here partly answer this question. METHODS: The study consisted of a descriptive and an analytical part. In the descriptive part, sensitization to frequent pollen allergens (alder, hazel, birch, sweet grasses; according to the German Therapy Allergen Ordinance) and to respective non-frequent pollen allergens (cypress, Japanese cedar, ash, plane tree, olive, Bermuda grass, wall pellitory, plantain, goosefoot, mugwort, ragweed, and saltwort) was measured in adult patients with physician-diagnosed allergic rhinitis from two German federal states, namely North-Rhine Westphalia (n = 360) and Bavaria (n = 339), using skin prick testing and/or ISAC technology. Furthermore, respective regional pollen data were assessed. In the analytical part, sensitization data were correlated with each other and with anamnestic data on symptom periods. RESULTS: Sensitization to frequent pollen allergens ranged from 45% (sIgE to Aln g 1/Alder, NRW) to 72% (prick test reactivity to birch, NRW). Sensitization to non-frequent pollen allergens ranged from 0% (sIgE to Amb a 1/ragweed, NRW) to 41% (prick test reactivity to olive, Bavaria). Sensitization data partly correlated with each other and in connection with symptom periods showed a partly similar seasonal pattern as pollen data. CONCLUSIONS: Sensitization to non-frequent pollen allergens have to be considered when examining patients with respective seasonal symptoms, and test (and respective therapy) allergens for non-frequent pollen allergies need to be available. Further prerequisites for adequate patient management would be a nationwide pollen monitoring system giving continuous pollen data and a systematic sensitization monitoring at patient level.

Liposomal Inhalation after Tracheostomy-A Randomized Controlled Trial.

BACKGROUND: Tracheostomy is a common procedure in critical care. The aim of this study was to evaluate the application of a liposomal inhalation compared to standard physiologic saline (SPS) inhalation on basis of objective and subjective parameters of airway inflammation. METHODS: We evaluated in this two-armed, double-blinded and randomized control group study the effect of liposomal compared with SPS inhalation in newly tracheotomized patients. The primary endpoint was defined as trend of tracheobronchial IL-6 secretion at day 1 compared to day 10. Further objective and subjective parameter were evaluated. RESULTS: Fifty patients were randomized in each arm. Tracheal IL-6 levels decreased significantly only after liposomal inhalation. Both inhalative agents seem to have an effect on the respiratory impairment after tracheostomy. Subjective patient impairment was reduced significantly from day 1 to day 10 after tracheostomy with liposomal inhalation. CONCLUSIONS: Liposomal inhalation demonstrated an advantage over SPS inhalation in newly tracheotomized patients.

Etiology and predictors of cluster attacks of hereditary angioedema that recur despite pharmaceutical treatment.

Introduction: Hereditary angioedema (HAE) is a disease that leads to recurrent swelling of the skin and mucous membranes, including the upper airway tract. Apart from being deadly, these attacks can be debilitating, which leads to a poor quality of life in patients. Clinicians are occasionally confronted with patients who have recurrent attacks despite treatment with C1 esterase inhibitor concentrate or ß2-receptor antagonists. The goal of this study was to investigate repeated attacks that occur 48 hours to 7 days ("cluster attacks") after treatment, to determine why they occur and the factors that may be associated with them, and thus to prevent their occurrence. Methods: We conducted a multicenter mixed retrospective-prospective study with data acquired from all documented attacks in our patients with collective (n = 132) between 2015 and 2018. Results: Eighty-five percent (n = 132) of our total patient collective (N = 156) agreed to participate in the study. Nine percent of these patients (n = 12) had cluster attacks, with a total of 48 cluster attacks. The data procured from the patients were mixed retrospective-prospective. Approximately 72% of all the cluster attacks were caused by exogenous stimuli (41% due to psychological stress, 29% due to physical stimuli, and 2% due to menstruation). Cluster attacks occurred in 7% of the patients who received prophylactic therapy in comparison with 12.5% of patients who received on-demand therapy. Cluster attacks comprised 48.4% of all the attacks that patients with cluster-attacks (n= 9) experienced. In addition, the patients who were underdosing their C1 esterase inhibitor treatment had cluster attacks more often. A lower "time to repeated attack" was seen in the patients who received on-demand therapy compared with those who received prophylactic therapy. Discussion: The percentage of the patients who had attacks as a result of exogenous triggers was higher in the cluster-attack group (70.5%) compared with the general HAE population (30-42%). Repeated attacks, therefore, were strongly associated with external triggers. The patients who received prophylactic treatment and who experienced cluster attacks were highly likely to have been underdosing, which may explain the repeated attacks despite treatment. In the patients prone to cluster attacks, prophylaxis should be considered.

Pre-operative cellular dissociation grading in biopsies is highly predictive of post-operative tumour stage and patient outcome in head and neck squamous cell carcinoma.

BACKGROUND: Pre-operative treatment planning in head and neck squamous cell carcinoma (HNSCC) is mainly dictated by clinical staging, which has major shortcomings. Histologic grading is irrelevant due to its lack of prognostic impact. Recently, a novel grading termed Cellular Dissociation Grade (CDG) based on Tumour Budding and Cell Nest Size was shown to be highly prognostic for resected HNSCC. We aimed to probe the predictive and prognostic impact of CDG in the pre-operative biopsies of HNSCC. METHODS: We evaluated CDG in n = 160 pre-therapeutic biopsies from patients who received standardised treatment following German guidelines, and correlated the results with pre- and post-therapeutic staging data and clinical outcome. RESULTS: Pre-operative CDG was highly predictive of post-operative tumour stage, including the prediction of occult lymph node metastasis. Uni- and multivariate analysis revealed CDG to be an independent prognosticator of overall, disease-specific and disease-free survival (p < 0.001). Hazard ratio for disease-specific survival was 6.1 (11.1) for nG2 (nG3) compared with nG1 tumours. CONCLUSIONS: CDG is a strong outcome predictor in the pre-treatment scenario of HNSCC and identifies patients with nodal-negative disease. CDG is a purely histology-based prognosticator in the pre-therapeutic setting that supplements clinical staging and may aide therapeutic stratification of HNSCC patients.

Bradykinin Receptor B1 and C-Reactive Protein as Prognostic Factors for Pharyngocutaneous Fistula Development After Laryngectomy.

Pharyngocutaneous fistulae (PCF) are one of the most common complications after laryngectomy. Predisposing risk factors have been studied, yet knowledge to determine which patients are prone to developing a fistula remains scarce. This study aims to establish prognostic parameters to identify individual patients at risk for PCF development. As PCF and inflammation seem to be interwoven, this work focuses on markers able to detect an inflammatory response. We retrospectively analyzed all patients who had undergone a laryngectomy at our clinic in the years 2007 to 2017 (n = 182). Immunohistochemical expression of bradykinin type 1 and 2 receptor and vascular endothelial growth factor receptor 2 was studied in all available tumor samples. Additionally, the clinical inflammation parameters 'body temperature', 'pain', 'c-reactive protein (CRP)', and 'leucocytes' were postoperatively tracked in all patients. The times between fistula diagnosis, therapeutic approach, and hospital discharge were recorded. We found a strong correlation between inflammation and the formation of a fistula. High bradykinin 1 receptor expression in the tumor samples correlated with postoperative PCF development. Persistently elevated CRP and leukocyte levels beyond the 6th postoperative day were also risk factors. A decreased time lapse between PCF diagnosis and surgical revision clearly correlated with a shorter hospital stay. In this study, we identified a bradykinin 1 receptor positive patient group at high risk for development of PCF. We recommend close monitoring for fistula formation in these patients to ensure timely intervention.

Radiofrequency resection in oral and oropharyngeal tumor surgery.

OBJECTIVE: Various techniques are available for the transoral resection of oral and oropharyngeal tumors. The application of radiofrequency proved successful in the resection of pathologies and achieved a good combination of radicality and hemostasis. The objective of this case series it to evaluate the feasibility of radiofrequency-assisted resection of oral and oropharyngeal tumors. METHODS: Patients presenting with oral or oropharyngeal tumors eligible for transoral resection were included. The excision was performed with a 4 MHz microsurgical radiofrequency generator using a monopolar needle. Radiofrequency was evaluated with perioperative (bleeding, tissue sticking, coagulation), objective (wound healing, complications) and subjective postoperative parameters (visual analogue scale of pain, impaired food intake, impaired speak). The surgical specimens were examined regarding entity, width of coagulation margins and the quality of the resection margins and compared to laser-assisted resected specimen. RESULTS: Twenty-five patients were included. 13 patients suffered from benign and 12 patients from malign lesions. Intraoperative bleeding was described as self-limiting in most of the cases and only in some cases the application of additional light pressure was required. Intraoperative tissue sticking was described as none or as resolvable by activation of the radiofrequency generator. Coagulation was limited to the area of resection. No impairment of wound healing or postoperative complications could be observed. Pain, impaired food intake and speak declined steadily. Radiofrequency-assisted resected specimen showed better assessability compared to laser-assisted resected specimen (p < 0.001). Resection margins were predominantly smooth. The width of the coagulation zones was 1593.75 µm on average. CONCLUSION: Radiofrequency is a suitable tool for the resection of oral and oropharyngeal tumors with a favourable intraoperative performance regarding the peri-incisional bleeding control and a continuous decline of postoperative morbidity.

Cyclooxygenase activity in bradykinin-induced dermal extravasation. A study in mice and humans.

BACKGROUND: Non-allergic angioedema is largely driven by increased plasma levels of bradykinin and over-activation of bradykinin receptor type II (B2), but the specific downstream signalling pathways remain unclear. The aim of this study was to identify signal transduction events involved in bradykinin-induced dermal extravasation. METHODS: Quantification of dermal extravasation was accomplished following intradermal (i.d.) injection of bradykinin or the B2 agonist labradimil in mice with endothelial NO-synthase (eNOS) deficiency and in C57BL/6J mice pre-treated with vehicle, NO-synthase or cyclooxygenase (COX) inhibitors. In the multicentre clinical study ABRASE, 38 healthy volunteers received i.d. bradykinin injections into the ventral forearm before and after oral treatment with the COX inhibitor ibuprofen (600 mg). The primary endpoint of ABRASE was the mean time to complete resolution of wheals (TTCR) and the secondary endpoint was the change of maximal wheal size. RESULTS: Neither NOS inhibitors nor eNOS deficiency altered bradykinin-induced extravasation. In striking contrast, the COX inhibitors ibuprofen, diclofenac, SC560 and celecoxib significantly diminished this extravasation when given before injection. As for diclofenac, a similar but significantly lower effect was observed when given after i.d. injection of bradykinin. Similar results were obtained when bradykinin was replaced by labradimil. In volunteers, ibuprofen significantly reduced TTCR (P < 0.001) and maximal wheal size (P = 0.0044). CONCLUSION: These data suggest that COX activity contributes to bradykinin-induced dermal extravasation in mice and humans. In addition, our findings may open new treatment options and point to a potential activity of drugs interfering with the release of the COX substrate arachidonic acid, e.g. glucocorticoids.

Tumor Budding and Cell Nest Size Are Highly Prognostic in Laryngeal and Hypopharyngeal Squamous Cell Carcinoma: Further Evidence for a Unified Histopathologic Grading System for Squamous Cell Carcinomas of the Upper Aerodigestive Tract.

Squamous cell carcinoma (SCC) is the most common cancer of the head and neck region including-among others-laryngeal (LSCC) and hypopharyngeal (HSCC) subsites. LSCC/HSCC are heterogenous diseases with respect to patient outcome. Currently, tumor stage-based patient stratification is essential to predict prognosis and thus selection of the appropriate treatment modalities. In contrast, the prognostic impact of the current HSCC/LSCC grading system according to the WHO classification is limited. Recently, a novel grading system based on tumor budding activity (BA) and cell nest size (CNS) has been introduced for SCC in different anatomic regions of the upper aerodigestive tract. To test and transvalidate this grading scheme in LSCC and HSCC, we retrospectively correlated BA, CNS, and additional histomorphologic parameters with clinicopathologic data of 157 treatment-naive patients. In doing so, we demonstrate that a 3-tiered novel grading system (well-differentiated [nG1], intermediately [nG2], and poorly differentiated [nG3]) based on a sum score for BA and CNS is highly and independently prognostic for patient survival in LSCC/HSCC, strongly outperforming the current WHO grading scheme with a hazard ratio for disease-specific survival of 6.6 for nG2 and 13.4 for nG3 cases (P<0.001). This finding contributes to a growing body of evidence that a CNS and BA-based pan-entity grading system in SCC might be useful and seems to capture differences in underlying SCC biology crucial for survival.

Diagnostic lymph node extirpation in CUP syndrome - useful or damaging?

OBJECTIVE: In a proportion of patients with cervical lymph node metastasis no primary can be found even with modern imaging and careful clinical examination (cancer of unknown primary syndrome = CUP syndrome). The ideal diagnostic approach is still debated on. METHODS: The clinical data of 75 patients (median age: 61.8 years; 16 females and 59 males), which have been treated for cervical squamous cell carcinoma of unknown primary syndrome in our hospital were retrospectively analyzed. RESULTS: In 12% of patients (n = 9) the primary demarcated in a time period of up to 5.3 years after diagnosis. In the patients who did not receive adjuvant radiotherapy (n = 13), primary became apparent in 38%. Diagnostic lymph node extirpation delayed time until therapeutic neck dissection on average for 3 weeks. In 62% of patients with previous lymph node extirpation (pN2a-N2c), a modified radical neck dissection was required compared to 41% when the surgical site was not operated on. CONCLUSIONS: In 12% of patients' primary demarcated in the course of the disease. A diagnostic lymph node extirpation was compared to direct therapeutic neck dissection after frozen section analysis associated with a three weeks delayed therapy and higher rate of modified radical neck dissection.

Sonographic differentiation between lymphatic and metastatic diseases in cervical lymphadenopathy.

OBJECTIVES/HYPOTHESIS: The spectrum of differential diagnosis in cervical lymphadenopathy is extremely broad. In lymphoma and inflammatory diseases, surgical approaches are restricted to diagnostic lymph extirpation, whereas metastatic outgrowth into regional lymph nodes usually requires neck dissection. Lymph node surgery has to manage the balancing act between sufficient radicality and preservation of functional structures. The current study, therefore, aimed to identify parameters to differentiate between lymph nodes of lymphatic and metastatic origin. STUDY DESIGN: Single-center, retrospective cohort study. METHODS: Clinical and sonographic parameters from all patients who underwent diagnostic cervical lymphadenectomy from 2010 to 2015 (N = 262) were included in this retrospective analysis. Parameters with significant differences between the two subgroups were utilized to create a clinical algorithm to distinguish between cervical lymphadenopathy of lymphatic and metastatic genesis. RESULTS: Statistically significant differences between the two subgroups could be shown for clinical (gender, age, nicotine/alcohol abuse, B symptoms, history of cutaneous melanoma, or lymphoma) and ultrasonographic parameters (string-of-beads confirmation, bilaterality, homogenous echostructure, localization in level I, long-to-short axis ratio, and hilar vascularity). The proposed algorithm yielded a sensitivity of 92.4% for metastatic disease. CONCLUSIONS: The implemented algorithm based on ultrasonographic and clinical criteria contributes to one-step surgical approaches that guarantee a sufficient radicality with a minimum of functional loss. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:859-863, 2018.

Potential Biomarkers for the Diagnosis of Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema.

BACKGROUND: Angiotensin-converting enzyme inhibitor-induced angioedema (ACEi-AE) is the most frequent drug-induced angioedema. The aim of this study was to evaluate potential biomarkers for the detection of the risk to develop an ACEi-AE. METHODS: Adult patients who started antihypertensive treatment with ramipril were included and followed up for 4-6 weeks. At baseline, 3 days, and 4-6 weeks after onset of therapy, blood samples were obtained. RESULTS: Twenty-four patients could be enrolled. The thromboxane values were very heterogeneous, and none of the group differences observed was statistically significant. The values obtained for 6-keto-prostaglandin F1α (6-keto-PGF1α) showed a statistically significant increase with 10 mg/day doses under ramipril therapy. CONCLUSIONS: In this small patient population, it could be shown that determination of 6-keto-PGF1α is feasible. It may prove to be a valuable blood marker for assessing the risk of developing ACEi-AE.

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.