Dupilumab for chronic rhinosinusitis with nasal polyps: real-life retrospective 12-month effectiveness data.

BACKGROUND: Dupilumab, an IL-4/13 receptor inhibitor, is approved for the treatment of uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: We evaluated the effectiveness and safety of dupilumab for CRSwNP based on retrospective 12-month follow-up data of 41 patients. We analysed nasal endoscopy scores, patient-reported outcome measures (PROMs), 12-item SniffinSticks odor identification test (SSIT-12), total serum IgE, serum Eosinophilic Cationic Protein (ECP), and total blood eosinophil count (BEC). We performed statistical analysis using non-parametric ANOVA-type models and Spearman's correlation. RESULTS: At month 1, endoscopy scores, PROMs and SSIT-12 showed meaningful improvements that were maintained until month 12. Initial elevations in both median ECP and BECs returned to near baseline levels by month 12. The percentage of patients withBEC ≤ 0.6 remained increased at month 12 (42.1%) compared to baseline (19.5%). Total serum IgE levels decreased progressively and correlated with nasal polyp scores at month 12. "Adequate response" was reached in 86.8% of our cohort. CONCLUSIONS: Our data suggest that dupilumab is effective for the treatment of CRSwNP. The potential for short- and long-term BEC elevations in some CRSwNP patients should be carefully monitored.

Comparison of manual and automated digital image analysis systems for quantification of cellular protein expression.

OBJECTIVE: Quantifying protein expression in immunohistochemically stained histological slides is an important tool for oncologic research. The use of computer-aided evaluation of IHC-stained slides significantly contributes to objectify measurements. Manual digital image analysis (mDIA) requires a user-dependent annotation of the region of interest (ROI). Others have built-in machine learning algorithms with automated digital image analysis (aDIA) and can detect the ROIs automatically. We aimed to investigate the agreement between the results obtained by aDIA and those derived from mDIA systems. METHODS: We quantified chromogenic intensity (CI) and calculated the positive index (PI) in cohorts of tissue microarrays (TMA) using mDIA and aDIA. To consider the different distributions of staining within cellular sub-compartments and different tumor architecture our study encompassed nuclear and cytoplasmatic stainings in adenocarcinomas and squamous cell carcinomas. RESULTS: Within all cohorts, we were able to show a high correlation between mDIA and aDIA for the CI (p<0.001) along with high agreement for the PI. Moreover, we were able to show that the cell detections of the programs were comparable as well and both proved to be reliable when compared to manual counting. CONCLUSION: mDIA and aDIA show a high correlation in acquired IHC data. Both proved to be suitable to stratify patients for evaluation with clinical data. As both produce the same level of information, aDIA might be preferable as it is time-saving, can easily be reproduced, and enables regular and efficient output in large studies in a reasonable time period.

[Effects of the SARS-CoV­2 pandemic on the otolaryngology university hospitals in the field of research, student teaching and specialist training]. / Auswirkungen der SARS-CoV­2-Pandemie auf die universitäre Hals-Nasen-Ohren-Heilkunde im Bereich der Forschung, Lehre und Weiterbildung.

BACKGROUND: From spring 2020, SARS-CoV­2 began to spread worldwide, with what is now known as the first wave of the pandemic, starting in March 2020. This resulted in restructuring and shift of resources at many hospitals. The aim of our work was to detect the effects of the pandemic on the german Oto-Rhino-Laryngology (ORL) university hospitals in terms of research, student teaching and further specialist training. MATERIAL AND METHODS: The chairmen of the 39 ORL university hospitals in Germany were asked about the effects of the pandemic on research, student teaching and ORL specialist training (residency) in the period from March to April 2020 using a structured online survey. RESULTS: All 39 chairmen took part in the survey. Of these, 74.4% (29/39) stated that their research activities had deteriorated as a result of the pandemic. In 61.5% (24/39) pandemic-related research issues were addressed. All hospitals reported a restriction for in-house teaching and 97.5% (38/39) introduced new digital teaching methods. During the observation period, 74.4% of the chairmen did not see ORL specialist training (residency)at risk. CONCLUSION: Our results provide an insight into the heterogeneous effects of the pandemic. The fast processing of pandemic-related research topics and the introduction of innovative digital concepts for student teaching impressively demonstrates the great innovative potential and the ability of the ORL university hospitals to react quickly in order to maintain their tasks in research, student teaching and ORL specialist training in the best possible way even during the pandemic.

[Effects of the SARS-CoV-2 pandemic on the otorhinolaryngology university hospitals in the field of medical care]. / Auswirkungen der SARS-CoV-2-Pandemie auf die universitäre Hals-Nasen-Ohrenheilkunde im Bereich der Krankenversorgung.

INTRODUCTION: Since December 2019, the SARS-CoV-2 virus has been rapidly spreading worldwide. In Germany, an exponential increase in the number of infections was registered at the beginning of March 2020 and led to a call of the Ministry of Health to create more capacity for intensive medical treatment in hospitals. The aim of the present study was to determine the effects of the SARS-CoV-2 pandemic on Oto-Rhino-Laryngology (ORL) university hospitals regarding patient care. MATERIALS AND METHODS: An online survey was sent out to all chairmen of the 39 ORL university hospitals in Germany. The answers to the questions referred to the defined period from March 15th to April 15th 2020 and were carried out using the online survey tool "SurveyMonkey". 87 questions focused on general information, health care, and structural effects in the respective institution. RESULTS: All chairmen of the 39 university hospitals in Germany participated in the survey. The collected data prove the considerable impact on organizational, structural and medical aspects of patient care. For example, the surveyed clinics reported a decrease in outpatient cases by 73.8 % to 26.2 ±â€Š14.2 % and in surgical treatments by 65.9 % to 34.1 ±â€Š13.9 %. In contrast, emergency treatment remained unchanged or even increased in 80 % of the facilities and surgical treatment of emergency patients remained unchanged or even increased in more than 90 %. Emergency outpatient and surgical treatment of patients was provided throughout the pandemic in all facilities. In total, about 35 000 outpatients and about 12 000 surgical cases were postponed. As a result of the acute structural changes, the potential danger of falling below current treatment standards was seen in individual areas of patient care. DISCUSSION: The assessment of the impact of the SARS-CoV-2 pandemic is heterogeneous. The majority of the chairmen are critically aware of the risk of falling below current medical treatment standards or guidelines. In the phase of an exponential increase in the number of infections, significant changes in treatment processes had to be accepted for understandable reasons. However, with the currently significantly reduced number of infections, falling below treatment standards and guidelines should not be allowed to remain constant and tolerated. SUMMARY: This study shows a differentiated picture with regard to the effects of the SARS-CoV-2 pandemic on outpatient, inpatient and operative patient care at the ORL university hospitals in Germany and illustrates the importance of these institutions for ensuring patient care during this critical phase.

[Sleep endoscopy and complete concentric collapse in CPAP failure]. / Schlafendoskopie und komplett konzentrischer Weichgaumenkollaps bei CPAP-Nutzungsproblemen.

INTRODUCTION: First-line treatment for patients with obstructive sleep apnea (OSA) is continuous positive airway pressure (CPAP) therapy. However, many patients cannot use CPAP sufficiently. With drug-induced endoscopy (DISE), it is possible to assess the collapse pattern in the upper airway. The aim of this work was to evaluate a collective of patients with CPAP usage problems using DISE, in order to evaluate their usage problems and therapy recommendations. METHODS: Over a period of 5 years, all patients with an apnea-hypopnea index (AHI) of at least 15/h were retrospectively evaluated using DISE. The recommended treatment options were then analyzed. RESULTS: Data analysis of 210 patients showed that about two thirds reported mask problems as the cause of non-adherence to CPAP. A complete concentric collapse (CCC) could be excluded in 75%. These patients had a lower AHI and more frequent tonsillectomy (TE) than patients with CCC. Double the number of patients with a body mass index (BMI) > 35 kg/m2 had a CCC compared to those with a BMI < 35 kg/m2. Among patients with similar BMI and AHI, CCC was twice as likely to be found in patients without TE. CONCLUSION: The course of treatment recommended for OSA often differs, depending on CCC, BMI > 35 kg/m2, and previous TE.

Balloon Eustachian Tuboplasty in children.

Endonasal ballon dilatation of the Eustachian tube (BET) is a promising treatment for Eustachian tube dysfunction with encouraging results over the last years in adults. In addition, in children, single studies demonstrated promising results, but revealed the necessity for broader and additional studies. Our retrospective analysis presents outcomes with BET in children with chronic obstructive dysfunction of the Eustachian tube, showing resistance to the conventional therapy after adenotomy with paracentesis or grommets (ventilation tubes). The data of 52 children, having undergone BET from April 2011 to April 2016, were retrospectively evaluated. Most children in our study presented middle ear effusion (47%), adhesive (21%), chronic otitis media (13%), or recurrent acute otitis media (11%). In 24 (37%) children, we combined BET with a paracentesis, in 5 (8%) patients with a tympanoplasty type I and in 3 (5%) patients with a type III. All children were assessed using an audiogram, tympanometry, and tubomanometry (50 mbar) before and after BET. In addition, we evaluated the results of the Lübecker questionnaire, which we performed before and after BET. The childrens' ear-related and quality of life-related symptoms, such as pressure equalization, ear pressure, hearing loss, pain and limitation in daily life, and satisfaction pre- and postoperatively, were analyzed. In the majority of patients, we could see an improvement in the ear pressure, hearing loss, limitation in daily life, and satisfaction with recurrent inflammations, underlined by better outcomes in the tubomanometry and the tympanogram. BET in children is a safe, efficient, and promising method to treat chronic tube dysfunction, especially as a second line treatment, when adenotomy, paracentesis, or grommets failed before.

[Reconstruction with supraclavicular island flaps : An option in oncological treatment of head and neck carcinomas]. / Rekonstruktion mit dem supraklavikulären Insellappen : Eine Alternative in der onkologischen Therapie von Kopf-Hals-Karzinomen.

BACKGROUND: Reconstruction of defects after extirpation of head and neck cancer is a highly challenging and complex surgical undertaking. Commonly used techniques, e.g., the radial forearm flap, the anterior lateral thigh flap, or flaps harvested from the chest-deltopectoral or pectoralis major-share numerous disadvantages, such as donor-site morbidity, poor color matching for cutaneous reconstruction, and excessive tissue bulk. The use of a supraclavicular artery island flap is a long-forgotten but increasingly popular option for reconstruction in the head and neck area. MATERIALS AND METHODS: In the period 03/2013-02/2016, a total of 12 patients were treated with a supraclavicular island flap after surgical resection of carcinoma of the oral cavity, pharynx, parotid, or facial skin. RESULTS: Using examples, reconstruction of the lateral tongue and tongue base following resection of a squamous cell carcinoma, and reconstruction of the parotideal region after total parotidectomy and neck dissection for a skin spinalioma that had infiltrated the parotid are reported. In both patients, the flap healed without problems and led to very good functional and cosmetic outcomes. CONCLUSION: The supraclavicular island flap is a reliable and versatile flap for reconstruction in the head and neck region. Minimal donor-site morbidity, excellent cosmetic properties, and the relative ease of preparation and use compared to other distant flaps render it an excellent reconstructive tool for ENT surgeons.

[Submental artery island flaps for reconstruction in the head and neck region]. / Der submentale Insellappen zur Rekonstruktion im Kopf-Hals-Bereich.

BACKGROUND: Reconstruction of defects after extirpation of head and neck neoplasms is a highly challenging and complex surgical undertaking. Commonly used techniques, such as the radial forearm flap or anterior lateral thigh flap, have numerous disadvantages, e.g., donor-site morbidity, poor color match for cutaneous reconstruction, and excessive tissue bulk for intraoral reconstruction. Use of a submental artery island flap is a relatively new and increasingly performed option for reconstruction in the head and neck region. MATERIALS AND METHODS: From March 2013 to August 2015, 12 patients were treated with a submental island flap after surgical resection of intraoral carcinomas or cutaneous neoplasms of the lower half of the face. CASE DESCRIPTION: This paper reports on two cases. The first case describes reconstruction of the floor of the mouth using a pull-through technique after resection of a squamous cell carcinoma. The submental flap was pedicled on the contralateral side, since neck dissection of regions I-V had been performed on the ipsilateral side. The second case is a reconstruction of the lower midface with parts of the upper lip, after removal of a cutaneous spinalioma. In a N0 neck, no neck dissection was performed. The flap healed without problems in both patients, leading to a very good functional and cosmetic outcome. CONCLUSION: The submental island flap demonstrates reliability and versatility for head and neck reconstructions. Its minimal donor site morbidity, excellent cosmetic match, pliability, and relative ease of dissection and application confer a definite advantage over distant flaps.

[The value of supracricoid partial laryngectomy in moderately advanced laryngeal cancer (T3-T4a)]. / Stellenwert der suprakrikoidalen Teilresektion beim moderat fortgeschrittenen Glottiskarzinom (T3-T4a).

BACKGROUND: Transoral laser microsurgery (TLM) is the method of choice for partial laryngectomy in Germany. In advanced stages, chemoradiotherapy is increasingly indicated for organ preservation. OBJECTIVE: This report considers the indications for and outcomes of supracricoid partial laryngectomy (SPL), also known as crico-hyoido-(epiglotto)-pexy, as an option for surgical organ preservation in moderately advanced laryngeal cancer (T3-T4a), in the well-defined gap between TLM and chemoradiotherapy protocols in Germany. METHODS: Retrospective evaluation of functional and oncological outcomes of all SPLs conducted between 2008 and 2014. During this period, 17 SPLs with resection of rpT2 (n = 2), (r)pT3 (n = 11), and (r)pT4a (n = 4) were performed with resection of one arytenoid. Mean age was 58 years (range 47-75 years). In 5 patients, SPL was for a first or second local recurrence after TLM or open partial laryngectomy. Adjuvant radiotherapy was received by 7 patients staged pT4a or pN+. RESULTS: Salvage laryngectomy with adjuvant radiotherapy was required by 2 patients. The remaining patients (n = 15) had a mean tumor-free follow-up of 4 years with a functional intact larynx: these patients can eat and drink, have a closed tracheotomy, and a good voice. After 3 years tumor-free follow-up with a functional intact larynx, 2 patients died due to cardiac comorbidity at the age of 76 years. DISCUSSION: SPL is a rare but valuable option for surgical larynx preservation in stage pT3-4a laryngeal cancer.

Fibroblast growth factor 2 is of prognostic value for patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: Patients with locally advanced SCCHN have a poor prognosis. This study investigated the prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients treated with surgery followed by radiotherapy. PATIENTS AND METHODS: The impact of FGF-2-expression and 11 additional potential prognostic factors on loco-regional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 146 patients. Additional factors included age, gender, performance status, pre-radiotherapy hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papilloma virus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model. RESULTS: On multivariate analysis, improved LRC was significantly associated with FGF-2-negativity [risk ratio (RR): 7.33; 95%-confidence interval (CI): 2.88-19.05; p<0.001], lower T-category (RR: 2.42; 95%-CI: 1.47-4.33; p<0.001), lower N-category (RR: 12.36; 95%-CI: 3.48-78.91; p<0.001), and pre-radiotherapy hemoglobin levels ≥ 12 g/dl (RR: 4.18; 95%-CI: 1.73-10.53; p=0.002). No factor was significantly associated with improved MFS. Lower T-category showed a trend (RR: 1.59; 95%-CI: 0.97-2.82; p=0.069). Better OS was significantly associated with FGF-2-negativity (RR: 5.10; 2.22-11.80; p<0.001), lower T-category (RR: 2.17; 95%-CI: 1.38-3.68; p < 0.001), lower N-category (RR: 3.86; 95%-CI: 1.60-10.85; p=0.002), and pre-radiotherapy hemoglobin levels ≥ 12 g/dl (RR: 3.20; 95%-CI: 1.46-7.30; p=0.004). HPV-positivity showed a trend (RR: 2.36; 95%-CI: n.a.; p=0.054). CONCLUSIONS: Tumor cell expression of FGF-2 proved to be an independent prognostic factor for LRC and OS. This factor can help personalize treatment and stratify patients in future trials.

Androgen receptor expression: prognostic value in locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: This study investigated the prognostic value of androgen receptor (AR) expression of tumor cells in patients treated with surgery and subsequent radio(chemo)therapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN). MATERIAL AND METHODS: The impact of AR and 11 additional factors on locoregional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively studied in 163 patients with nonmetastatic stage III/IV SCCHN. Additional factors included age, gender, ECOG performance status, pre-radiotherapy (pre-RT) hemoglobin levels, tumor site, histologic grade, T category, N category, HPV status, extent of resection, and concurrent chemotherapy. RESULTS: On multivariate analysis, improved LRC was significantly associated with pre-RT hemoglobin levels≥12 g/dl (risk ratio [RR] 2.22; 95% confidence interval [CI] 1.19­4.13; p=0.013), tumor site (RR 1.39; 95% CI 1.14­1.70; p=0.001), lower T category (RR 1.67; 95% CI 1.18­2.44; p=0.003), and lower N category (RR 4.18; 95% CI 1.90­10.55; p<0.001). Improved MFS was associated with AR expression (RR 2.21; 95% CI 1.01­5.41; p=0.048), better ECOG performance status (RR 3.19; 95% CI 1.50­7.14; p=0.003), lower T category (RR 2.24; 95% CI 1.47­3.65; p<0.001), and lower N category (RR 5.33; 95% CI 2.07­16.63; p<0.001). OS was positively associated with AR expression (RR 1.99; 95% CI 1.06­4.00; p=0.032), better ECOG performance status (RR 2.20; 95% CI 1.20­4.09; p=0.010), pre-RT hemoglobin levels≥12 g/dl (RR 2.13; 95% CI 1.19­3.82; p=0.012), lower T category (RR 1.81; 95% CI 1.30­2.62; p<0.001), and lower N category (RR 3.41; 95% CI: 1.65­7.80; p<0.001). CONCLUSION: Tumor cell expression of AR was an independent prognostic factor for MFS and OS and should be considered in future prospective trials.

Prognostic impact of VEGF and FLT-1 receptor expression in patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: This study investigated the prognostic value of tumor cell expression of vascular endothelial growth factor (VEGF) and its receptor fms-related tyrosine kinase 1 (FLT-1) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) who had been treated with adjuvant radiotherapy or radiochemotherapy. MATERIAL AND METHODS: The impact of tumor cell VEGF and FLT-1 expression plus 11 additional factors on loco-regional control (LRC), metastases-free survival (MFS) and overall survival (OS) was retrospectively evaluated in 157 patients. The additional factors were age, gender, performance status, pre-radiotherapy (pre-RT) hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papillomavirus (HPV) status, extent of resection and chemotherapy. RESULTS: On multivariate analysis, improved LRC was significantly associated with an absence of VEGF expression (risk ratio, RR: 5.02; p = 0.009), lower T-category (RR: 2.00; p < 0.001), lower N-category (RR: 3.75; p < 0.001) and pre-RT hemoglobin levels ≥ 12 g/dl (RR: 2.20; p = 0.029). Improved MFS was significantly associated with an absence of VEGF expression (RR: 7.46; p = 0.002), lower T-category (RR: 1.97; p = 0.002), lower N-category (RR: 3.29; p = 0.005) and a favorable tumor location (RR: 1.34; p = 0.033); HPV positivity showed a trend towards improved MFS (RR: 1.43; p = 0.09). Improved OS was significantly associated with an absence of VEFG expression (RR: 3.22; p = 0.041), pre-RT hemoglobin levels ≥ 12 g/dl (RR: 2.47; p = 0.009), lower T-category (RR: 1.92; p < 0.001) and lower N-category (RR: 3.39; p < 0.001). FLT-1 expression was significantly associated with LRC and OS in the univariate but not in the multivariate analysis. CONCLUSION: VEGF expression proved to be an independent negative predictor for LRC, MFS and OS in patients treated for locally advanced SCCHN with adjuvant radiotherapy or radiochemotherapy. FLT-1 expression was not significant in multivariate analyses.

[Cervical manifestation of malignant schwannoma]. / Zervikale Manifestation eines malignen Schwannoms.

BACKGROUND: Malignant schwannomas are rare malignant mesenchymal tumors often associated with neurofibromatosis. They occur less frequently in the head and neck than in other regions. PATIENT: A case history of a primary malignant schwannoma of the head and neck area in a 27-year-old man is reported. The tumor was located in the left submandibular region. The patient did not have any functional deficits. The tumor was totally removed. There have been no signs of either recurrence or metastasis within the two years following diagnosis and surgery. DISCUSSION: The microscopic and immunohistochemical findings are presented, and the importance and therapy of this very rare malignant tumor of the head and neck area are discussed. CONCLUSION: Malignant schwannoma in the head and neck region is rare. Radical resection is the treatment of choice.

Primary non-Hodgkin's lymphoma of the temporal bone.

A rare case of primary non-Hodgkin's lymphoma in the mastoid cells of a 2-year-old boy is presented and the available literature reviewed.